Enforcement Regulations of the Pharmaceutical Affairs Law CHAPTER I PHARMACIES Article 1. (Application for Establishment) A person wishing to obtain a license for the establishment of a pharmacy pursuant to the provisions of Article 5, Paragraph 1 of the Pharmaceutical Affairs Law (Law No.145, 1960; hereafter referred to as "the Law") must submit an application using Form No.1 to the prefectural governor. 2. The following documents are to be attached to the application form mentioned in the previous paragraph. However, this shall not apply when the fact that the forms have been submitted to the prefectural governor or submitted to the Minister via the prefectural governor as the recipient of forms for applications or notifications of licenses, etc. pursuant to the provisions of the Law (hereinafter "applications, etc.") is entered in the application form concerned,: (1) A floor plan of the pharmacy (2) When the applicant is a corporation, a copy of the registration (3) A medical certificate from a physician indicating whether or not the applicant (the directors of the company when the applicant is a corporation) is suffering from a mental illness or is addicted to narcotics, marijuana, opium or stimulants (4) When a person other than the applicant is the manager of the pharmacy, a copy of the employment contract or another document that proves the employment relationship between the applicant and the manager of the pharmacy (5) When a pharmacist is to be employed in the pharmacy in pharmaceutically related work in a position other than the manager of the pharmacy, a copy of the employment contract or another document that proves the employment relations between the applicant and the pharmacist. (6) When the applicant intends to handle radiopharmaceuticals (radiopharmaceuticals as specified in Article 1, Item 1 of the Radiopharmaceutical Manufacturing and Handling Regulations, MHW Ordinance No. 4, 1961; hereinafter the same definition) (excluding the handling of radiopharmaceuticals in amounts not exceeding those specified by the Minister), documents showing the type of radiopharmaceuticals handled and outlining the facilities required to handle the radiopharmaceuticals 3. When the applicant is a corporation and it is confirmed by the prefectural governor that work will not be impaired based on an evaluation of the tasks performed by the director, it shall be possible to submit, in place of the medical certificate in Item (3) of the preceding paragraph, a document certifying that the director concerned does correspond to Article 6, Item 2 (d) of the Law (excluding incompetent; the same hereinafter). Article 2. (License Certificate Form) The license certificate will be issued on Form No.2. Article 3. (Display of the License) A person establishing a pharmacy (hereafter referred to as "proprietor of a pharmacy") must display the license for the establishment of the pharmacy in a clearly visible place in the pharmacy. Article 4. (Application for Issue of a Revised License) When alterations are to be made in items in the license for the establishment of the pharmacy, the proprietor of the pharmacy may apply for issue of a revised license. 2. The application in the previous paragraph is to be made on Form No.3. This application form, with the license for the establishment of the pharmacy attached, is to be submitted to the governor of the prefecture where the pharmacy is located. Article 5. (Application for Reissuance of the License) When the proprietor of a pharmacy damages, soils or loses his license for the establishment of the pharmacy, he may apply to have the license reissued. 2. The application in the previous paragraph is to be made on Form No.4. This application form is to be submitted to the governor of the prefecture where the pharmacy is located. When the original license has been damaged or soiled, it must be attached to the application form. 3. If the proprietor of a pharmacy finds the lost license after he has been issued a new license, he must return the original license immediately to the governor of the prefecture where the pharmacy is located. Article 6. (Return of the License) When a license for the establishment of a pharmacy is canceled pursuant to the provisions of Article 75, Paragraph 1 of the Law, or when the business is suspended or closed, the proprietor of the pharmacy must return the license immediately to the governor of the prefecture where the pharmacy is located. Article 7. (Application for License Renewal) Applicants for renewal of the pharmacy license pursuant to the provisions of Article 5, Paragraph 2 of the Law must submit an application of Form No.5, with the pharmacy license attached, to the governor of the prefecture where the pharmacy is located. Article 8. (Items Entered in the License Register) The items to be entered in the pharmacy license register are as follows: (1) License number and date (2) Name of the proprietor of the pharmacy (or the name of the corporation if applicable; the same hereinafter) and his address (or the address of the corporation if applicable; the same hereinafter) (3) The name and address of the pharmacy (4) The name and address of the manager of the pharmacy (4-2) The name and address of any pharmacist employed in the pharmacy in pharmaceutically related work other than in the position of manager (5) When radiopharmaceuticals are to be handled, the type of radiopharmaceuticals involved (6) When business such as the sale of drugs etc. is also to be conducted in the pharmacy, the type of such business (7) The average number of prescriptions filled daily pursuant to the provisions of Article 1 of the Ordinance (MHW Ordinance No.3, 1964) which stipulates the number of pharmacists in a pharmacy or first-class sales business. Article 9. (Exception to the Use of the Name Pharmacy) Pursuant to the proviso of Article 7 of the Law, the name "Yakkyoku" (meaning pharmacy) may be used for the dispensaries of hospitals and clinics. Article 10. (Storage of Drugs) The manager of the pharmacy must store and display drugs separately from other articles. Article 11. (Methods of Performing Tests) The proprietor of a pharmacy shall have the manager of his pharmacy perform tests on drugs which the manager confirms to be necessary for the appropriate control of the drugs. However, in cases where the manager of the pharmacy confirms that it is difficult to perform such tests using the facilities and utensils of the pharmacy concerned, the proprietor of the pharmacy shall be able to perform the test by utilizing a test organization specified by the Minister. 2. When the proprietor of the pharmacy performs tests as specified in the proviso of the preceding paragraph, the results specified of the test shall be confirmed by the manager of the pharmacy. Article 11-2. (Records Concerning Management of a Pharmacy) The proprietor of a pharmacy shall keep records in his pharmacy for the recording of items related to the management of the pharmacy. 2. The proprietor of pharmacy shall record in the records specified in the preceding paragraph items related to tests, disposal of defective goods and other aspects of the management of his pharmacy. 3. The proprietor of a pharmacy shall preserve the records specified in Paragraph 1 for a period of 3 years from the date of the final entry. Article 11-3. (Records Related to Transfer of Drugs) The proprietor of a pharmacy shall enter the items stated below in the records, when he has received drugs designated by the Minister, or sold or transferred such drugs to the proprietor of other pharmacies, pharmaceutical manufacturers or distributors, or hospitals, clinics or veterinary clinics [clinics pursuant to the provisions of Article 2, Paragraph 2 of the Veterinary Service Law (Law No.46, 1992); includes the residences of persons who undertake the health care of domestic animals by veterinarians only by means of house calls; the same hereinafter]: (1) Name of drug (2) Quantity (3) Manufacturing lot number or code (4) Date of sale or transfer (5) Name of buyer or transferee 2. The proprietor of a pharmacy shall preserve the records mentioned in the preceding paragraph for a period of 3 years from the date of entry. Article 12. (Notification of Changes) Changes which must be reported in accordance with the provisions in Article 10 of the Law are as follows: (1) The name or address of the proprietor of the pharmacy or the manager ofthe pharmacy (1-2) The name of a pharmacist, other than the proprietor of the pharmacy or the manager of the pharmacy, who is employed in the pharmacy in pharmaceutically related work (2) When the pharmacy is established by a corporation, the names of the directors involved in the business (3) The name of the pharmacy (4) A major part of the structure or equipment of the pharmacy (5) Any type of additional business such as the sale of drugs which is performed in the pharmacy (6) When radiopharmaceuticals are handled, the type of radiopharmaceuticals. 2. The notifications in the preceding paragraph shall be submitted on Form No.6. 3. The documents specified in the following items in accordance with the type of notification in each item shall be attached to the notification in the preceding paragraph. However, this shall not apply when the fact that the forms have been submitted to the prefectural governor or submitted to the Minister via the prefectural governor as the recipient of applications, etc. is entered in the application form concerned. (1) Notification concerning the name of the proprietor of the pharmacy in Paragraph 1, Item (1): a copy of the family register, an abstract of the family register or a certificate of entry in the family register of the proprietor of the pharmacy (a copy of the registration when the proprietor of the pharmacy is a corporation) (2) Notification concerning items in Paragraph 1, Item (1) or Item (1-2) (excluding cases where the new manager or pharmacist employed in the pharmacy in pharmaceutically related work is the proprietor): copy of the employment contract or other documents proving the employment relations between the proprietor of the pharmacy and the new manager or pharmacist employed in the pharmacy in pharmaceutically related work. (3) Notification concerning items in Paragraph 1, Item (2): a medical certification from a physician indicating that the new directors are not suffering from a mental disease, and are not addicted to narcotics, marijuana, opium or stimulants. 4. When the applicant is a corporation and it is confirmed by the prefectural governor that work will not be impaired based on an evaluation of the tasks performed by the director, it shall be possible to submit, in place of the medical certificate in Item (3) of the preceding paragraph, a document certifying that the director concerned does correspond to Article 6, Item 2 (d) of the Law. Article 12-2. (Notification of Number of Prescriptions Filled) The proprietor of the pharmacy shall notify the governor of the prefecture where the pharmacy is located, by the 31st of March each year, of the total number of prescriptions filled (total number of prescriptions filled as specified in Article 1 of the MHW Ordinance specifying the number of pharmacists in pharmacies and first class retailers; the same hereinafter) However, this requirement does not apply in the following cases: (1) Pharmacy whose period of business in the previous year has been less than 3 months; (2) Pharmacy for which the result obtained by dividing the total number of prescriptions filled in the previous year by the total number of business days in the same year does not exceed 40. 2. The notifications in the preceding paragraph shall be made on Form No.6-2. Article 13. (Form for Notification of Business Suspension, Closure, etc.) Notifications of closure or business suspension of a pharmacy or of resuming business which has been suspended pursuant to the provisions of Article 10 of the Law are to be submitted on Form No.7. CHAPTER II MANUFACTURERS AND IMPORTERS OF DRUGS, etc. Article 14. (Application for Manufacturing License) Applications for licenses to manufacture drugs, quasi-drugs, cosmetics or medical devices (hereafter referred to as"drugs, etc".) pursuant to the provisions of Article 12, Paragraph 1 of the Law shall be submitted to the Minister or prefectural governor who has the licensing authority concerned pursuant to the provisions of this Article 12, Paragraph 1 of the Law and Article 15-3 of the Enforcement Ordinance of the Law (Cabinet Order No.11, 1961; hereinafter "the Ordinance") on Form No.8 (original and one copy when submitted to the minister, original when submitted to the prefectural governor). 2. The documents specified in the following items shall be attached to the application in the preceding paragraph. However, this shall not apply when the fact that the forms have been submitted to the prefectural governor or submitted to the Minister via the prefectural governor as the recipient of applications, etc. is entered in the application form concerned. (1) A floor plan of the manufacturing plant (2) When the applicant is a corporation, a copy of the registration (3) A medical certificate from a physician indicating that the applicant (the directors of the company when the applicant is a corporation) is not suffering from a mental disease, and are not addicted to narcotics, marijuana, opium or stimulants. (4) When a person other than the applicant is manager of the manufacturing plant, a copy of the employment contract or another document that proves the employment relationship between the applicant and the manager of the manufacturing plant. (5) When the applicant intends to handle radiopharmaceuticals (excluding the handling of radiopharmaceuticals in amounts not exceeding those specified by the Minister), documents showing the type of radiopharmaceuticals handled and outlining the facilities required to handle the radiopharmaceuticals (6) When the application in the preceding paragraph is for a license pursuant to the provisions of Article 13-2, Paragraph 1 of the Law, documents showing that the substances to be manufactured by the applicant are the drugs pursuant to the provisions of Item 2 of the same paragraph, and other necessary documents 3. When the applicant is a corporation and it is confirmed by the Minister (prefectural governor when the licensing authority concerned has been transferred to the prefectural governor pursuant to the provisions of Article 15-4 of the Ordinance) that work will not be impaired based on an evaluation of the tasks performed by the director, it shall be possible to submit, in place of the medical certificate in Item (3) of the preceding paragraph, a document certifying that the director concerned does correspond to Article 6, Item 2 (d) of the Law. Article 14-2. (Applications for Renewal of Manufacturing Licenses) Applications for renewal of manufacturing licenses for drugs etc. pursuant to the provisions of Article 12, Paragraph 3 of the Law shall be submitted on Form No. 8-2 to the Minister or the prefectural governor with authority to grant the license concerned (original and one copy when submitted to the Minister, or original when submitted to the prefectural governor). 2 The following documents shall be attached to the application in the preceding paragraph. (1) License certificate (2) When the application of for renewal of a license in Article 12, Paragraph 1 pursuant to Article 13-2, Paragraph 1 of the Law, the documents in Paragraph 2, Item 6 of the preceding article. Article 15. (Issuance of the Certificate of Manufacturing License) When the Minister or a prefectural governor grants a license for the manufacture of drugs, etc., the license shall be issued to the applicant on Form No.9. This shall also apply in the renewal of such licenses. Article 16. (Manufacturing License Register) The Minister or the prefectural governors shall keep a register of the licenses for the manufacture of drugs, etc. The following items shall be entered in these registers. (1) License number and date (2) Name and address of manufacturer (3) Name and address of manufacturing plant (4) Products manufactured or the category as specified in Article 1-3, Paragraph 1 of the Ordinance and the manufacturing process performed in the factory concerned (5) In cases of categories pursuant to the provisions of Article 1-3-2, Paragraph 1 of the Ordinance or special repairers pursuant to the provisions of Article 23-3, Paragraph 1, that fact shall be mentioned. (6) Name and address of the manager or responsible technician of the manufacturing plant 2. The Minister or the prefectural governor may have all or part of the register specified in the preceding paragraph prepared in the form of a magnetic disk (including materials on which specific items can be reliably recorded by corresponding methods; the same hereinafter). Article 17. (Approval for the Manufacture of Drugs, etc.) Applications for approval to manufacture drugs, etc. pursuant to the provisions of Article 14, Paragraph 1 of the Law shall be made on Form No.10 (original and two copies when submitted to the Minister, original and one copy when submitted to the prefectural governor). Article 18. (Medical Devices Not Requiring Approval) Medical devices not requiring approval persuant to the provisions of Article 14, Paragraph 1 of the Law are those listed in the Attached Table 1 [Electrically- driven devices (excluding those exclusively for household use) shall be limited to those which comply with Japanese Industrial Standard (hereinafter, "JIS") T1001 based on the Industrial Standardization Law (Law No. 185, 1949]. However, those with structures, methods of use, indications, effects, performance, etc. distinctly different from those of existing medical devices shall be excluded. Article 18-2. (Items Not Suitable as Drugs, etc.) Items not suitable as drugs, etc. as specified in Article 14, Paragraph 2, Item 3 (with application mutatis mutandis in Article 14, Paragraph 6) of the Law shall be those drugs quasi-drugs, cosmetics or medical devices for which an application has been submitted with properties or qualities extremely unsuitable with respect to public health and hygiene. Article 18-3. (Data to be Attached to Approval Application Forms) The data which must be attached to application forms submitted pursuant to the provisions of Article 17 or 19 of these Regulations as provided in Article 14, Paragraph 3 (with application mutatis mutandis in Article 14, Paragraph 6) of the Law shall be the data listed below by classifications of approvals and according to active ingredients, administration route, dose form, structure and performance of the applicable drugs, etc. However, it shall not be necessary to attach the data in cases where it is confirmed that the item is well known in the medical and pharmaceutical fields or there is some other justifiable reason. (1) Approvals for drugs a. Data concerning the origin of the drug, the background of its discovery and the conditions of use in foreign countries b. Data concerning the physicochemical properties, specifications and test methods c. Data concerning stability d. Data concerning acute, subacute and chronic toxicity, teratogenicity and other types of toxicity e. Data concerning pharmacological action f. Data concerning absorption, distribution, metabolism and excretion g. Data concerning clinical trial results (2) Approvals for quasi-drugs a. Data concerning the origin of the quasi-drug, the background of its discovery and the conditions of use in foreign countries b. Data concerning the physicochemical properties, specifications and test methods c. Data concerning stability d. Data concerning safety e. Data concerning indications (3) Approvals for cosmetics a. Data concerning the origin of the cosmetic, the background of its discovery, and the conditions of use in foreign countries b. Data concerning the physicochemical properties c. Data concerning safety (4) Approvals for medical devices a. Data concerning the origin of the medical device, the background of its discovery and the conditions of use in foreign countries b. Data concerning the physicochemical properties, specifications and test methods c. Data concerning stability d. Data concerning safety including electrical safety, biological safety and safety with respect to radiation e. Data concerning performance f. Data concerning the results of clinical trials 2. The tests required for preparing the data specified in each item of the preceding paragraph shall be performed in test facilities, etc. where it is confirmed that they have facilities, equipment and personnel necessary for securing the reliability of test results and that they are properly operated and managed. 3. Applicants shall submit to the Minister or to the prefectural governors any negative findings with respect to the quality, efficacy, or safety of drugs, etc., for which an application has been submitted, even if the test required for preparing such data was not performed in the test facilities, etc. specified in the preceding paragraph. 4. In addition to the data specified in each item of the first paragraph of this Article and in the preceding paragraph, applicants should submit relevant materials such as samples of the drugs, etc. to the Minister or the prefectural governors when the Minister or the governors request them on finding that they are necessary for the examination for the approval of the drugs, etc. in question. Article 18-4. (Deferment of Submission of Data Attached to Approval Applications for Drugs Related to Special Licenses Before Approval) When the Minister or prefectural governor confirms that the applicant is unable to attach data specified in Paragraph 1, Item (1), a to f of the preceding article for drugs to be manufactured or imported under special license before approval, submission may be deferred during the corresponding period. Article 18-4-2. (Drugs Designated by MHW Ordinance) Drugs specified in the last part of Article 14, Paragraph 3 (with application mutatis mutandis in Article 6) of the Law shall be the drugs in the following items (excluding drugs not used in direct contact with the bodies of humans or animals and drugs adhering to the skin of humans or animals among drugs used exclusively for the diagnosis of disease, drugs which proprietors of pharmacies manufacture using the facilities and equipment in their pharmacies, drugs for which the approval authority has been transferred to the prefectural governors pursuant to the provisions of Article 15-4 of the Ordinance, and drugs for exclusive use with animals). (1) Drugs in the Japanese Pharmacopoeia and drugs already approved for manufacture or import [excluding new drugs pursuant to the provisions of Article 14-4, Paragraph 1, Item (1) of the Law for which the reexamination period specified in the same item (period after the extension when the period is extended pursuant to the provisions of Article 14-4, paragraph 2) from the date of manufacturing or import approval has not elapsed, or drugs designated by the Minister pursuant to the provisions of Article 14-4, Paragraph 1, Item (2) for which the period specified by the Minister as specified in the same item has not elapsed] and drugs with different active ingredients or routes of administration (2) Prescription drugs pursuant to the provisions of Article 1-5, Item 1(b) (hereinafter "prescription drugs")[excluding those specified in the preceding item). Article 18-4-3. (Reliability Criteria of Application Data) The data pursuant to the provisions of the last part of Article 14, Paragraph 3 (with application mutatis mutandis in Article 14, Paragraph 6) shall be collected and compiled as specified in the MHW Ordinance on Implementation Standards for Non-Clinical Studies on Safety of Drugs (MHW Ordinance No.21, 1997) and MHW Ordinance on Implementation Standards for Clinical Studies on Drugs (MHW Ordinance No.28, 1997), as well as the following items. (1) The data shall be compiled correctly based on the results of analyses and studies performed in order to compile the data concerned. (2) When results are obtained in analyses or studies specified in the previous item which cast doubts on the quality, efficacy or safety of drugs in applications, these results of the analyses and studies shall also be investigated and evaluated, and the results obtained shall be entered in the data concerned. (3) The data which form the basis of the data concerned shall be retained until the date when a decision is made on the approval pursuant to the provisions of Article 14. However, this shall not apply when such retention is confirmed to by extremely difficult based on the properties of the data. Article 19. (Approval of Partial Changes in the Approved Items) Applications for approval of partial changes in the approved items for the manufacture of drugs, etc. submitted pursuant to the provisions of Article 14, Paragraph 6 of the Law are to be made by submitting an application on Form No.11 (oryiginal and two copies when submitted to the Minister, original and one copy when submitted to the prefectural governor). Article 20. (Approval Register) The Minister or the prefectural governors shall keep a register of the approvals specified in Article 14 of the Law. The following items shall be entered in this register. (1) Approval number and date of approval (2) Name and address of recipient of approval (3) Name of item approved (4) Ingredients and quantities or form, structure and dimensions of approved item (5) Indications, effects, performance or application of approved item (6) Directions, dosage, method of operation or use of approved item (7) Standards and test methods of approved item 2. The Minister or the prefectural governor may have all or part of the register specified in the preceding paragraph prepared in the form of a magnetic disk. Article 20-2. (Applications for Reviews for the Organization for Drug ADR Relief, R & D Promotion and Product Review) Applications for reviews performed by the Organization for Drug ADR Relief, R & D Promotion and Product Review (hereinafter referred to as "the Drug Organization") pursuant to the provisions of Article 14-2, Paragraph 3 of the Law shall be made by submitting an application using Form No.11-2. 2. The application specified in the preceding paragraph shall be attached to the application form for approval of the drug concerned pursuant to the provisions of Article 14, Paragraph 1 or Paragraph 6 of the Law. However, this shall not apply to reviews performed pursuant to the provisions of the last part of Article 14, Paragraph 4 (with application mutatis mutandis of Article 14, Paragraph 6). Article 20-3. (Notification of Results of Reviews by the Drug Organization) Notification of the results of reviews to the Minister pursuant to the provisions of Article 14-2, Paragraph 4 of the Law shall be made using Form No.11-2-2. Article 20-4. (Applications for Reviews by Designated Review Organizations) Applications for reviews pursuant to the provisions of Article 14-3, Paragraph 3 of the Law by designated review organizations pursuant to the provisions of Paragraph 1 of the same article shall be submitted using Form No. 11-2-3. 2. The applications in the preceding paragraph shall be attached to applications for approval of the product in the application concerned pursuant to the provisions of Article 14, Paragraph 1 or Paragraph 6 of the Law. Article 20-5. (Notification of Results of Reviews by Designated Review Organizations) Notification of the results of reviews to the Minister pursuant to the provisions of Article 14-3, Paragraph 4 shall be made using Form No. 1-2-4. Article 21. (Applications for Reexamination of New Drugs, New Medical Devices, etc.) Applications for reexamination of the drugs or medical devices in the items of Article 14-4, Paragraph 1 pursuant to the provisions of the same paragraph of the Law shall be made by submitting an application on Form No.11-2-5 (one original and two copies). Article 21-2. (Drugs Designated by MHW Ordinance) Drugs designated by MHW ordinance pursuant the provisions of Article 14-4, Paragraph 1, Item 1-a of the Law are drugs other than orphan drugs which require reviews of the results of use, including disease, disability, death suspected to be caused by adverse reactions or infections suspected to be due to use ("adverse reactions, etc." in Article 21-4 and Article 21-4-2) adverse reactions, for a period of more than 6 years from the date of approval to manufacture the drug concerned. 2. Drugs designated by MHW ordinance pursuant to the provisions of Article14-4, Paragraph 1, Item (1)(b) of the Law are drugs which have clearly different administration methods (excluding routes of administration) or doses but have the same active ingredients and routes of administration as drugs which have already been approved for manufacture or import [excluding drugs specified in Item (1)(a)] or otherwise differ only slightly from drugs which have already been approved for manufacture or import [excluding drugs specified in Item (1)(a)]. Article 21-2-2. (Medical Devices Designated by MHW Ordinance) Medical devices designated by MHW ordinance pursuant to the provisions of Article 14-4, Paragraph 1, Item (1)(a) of the Law are medical devices other than orphan medical devices which require reviews of the results of use, including onset of disorders, disease, disability or death suspected to be due to the effects of disorders, and infections suspected to be caused by use ("disorders, etc." in Article 21-4) problems, for a period of more than 4 years from the date of approval to manufacture the medical device concerned. 2. Medical devices designated by MHW ordinance pursuant to the provisions of Article 14-4, Paragraph 1, Item (1)(b) are medical devices which have clearly different methods of use or performance but have the same structure as medical devices which have already been approved for manufacture or import [excluding medical devices specified in Item (1)(a)] or otherwise differ only slightly from medical devices which have already been approved for manufacture or import [excluding medical devices specified in Item (1)(a)]. Article 21-3. (Data to be Attached to Reexamination Application Forms) The data to be attached to the application forms in the Article 21 pursuant to the provisions of Article 14-4, Paragraph 4 of the Law shall be data concerning the results of using the drug or medical devices applied for, data submitted with reports pursuant to the provisions of Article 21-4, Paragraph 2, and research reports concerning the indications, efficacy and safety of the drug or medical device after its manufacture was approved. 2. Data submitted pursuant to provisions of the preceding paragraph shall comply with the provisions of Article 18-3, Paragraph 2. 3. A person who files an application for reexamination pursuant to the provisions of Article 14-4, Paragraph 1 shall comply with the provisions of Article 18-3, Paragraph 3. In this case,"the Minister or the prefectural governor" in this paragraph shall read"the Minister." 4. In addition to the data required pursuant to the provisions of Article 18-3, Paragraph 3 which apply mutatis mutandis Paragraph 1 and the preceding paragraph of this article, the applicant shall submit to the Minister any data which the Minister requests on finding that they are necessary for reexamination of drugs or medical devices in question. Article 21-3-2. (Range of Drugs Subject to Reexamination Data Compliance Reviews) Drugs specified by MHW Ordinance pursuant to the provisions of the last part of Article 14-4, Paragraph 4 of the Law shall be the drugs in each item of Article 14, Paragraph 1. Article 21-3-3. (Reliability Criteria of Reexamination Data) The provisions of Article 18-4-3 shall apply mutatis mutandis to the data pursuant to the provisions of the last part of Article 14-4, Paragraph 4 of the Law. In this case, MHW Ordinance on Implementation Standards for Non-Clinical Studies on Safety of Drugs (MHW Ordinance No.21, 1997) in the Article shall read "MHW Ordinance on Standards for Postmarketing Surveillance of Drugs (MHW Ordinance No.10, 1997), MHW Ordinance on Implementation Standards for Non-Clinical Studies on Safety of Drugs (MHW Ordinance No.21, 1997)" and "the date when a decision is made on the approval pursuant to the provisions of Article 14" shall read "the date of completion of the reexamination pursuant to the provisions of Article 14-4, Paragraph 1". Article 21-4. (Surveillance of the Results of Use of New Drugs or Medical Devices and Reports of the Results) A person who has received approval pursuant to the provisions of Article 14 of the Law for manufacture of drugs (excluding prescription drugs) or medical devices specified in the following items shall survey the adverse reactions, etc., problems, etc. and other results of use of the drug concerned for the period specified in the following items . (1) New drugs or medical devices as specified in Article 14-4, Paragraph 1, Item 1 of the Law : the period specified in the same item (the period after the extension when an extension has been made pursuant to the provisions of Article 14-3, Paragraph 2) (2) Drugs or medical devices designated by the Minister of pursuant to the provisions of Article 14-4, Paragraph 1, Item 2: the period from the date on which manufacturing approval was obtained until the day before the start of the period designated by the Minister pursuant to the provisions of the same item. 2. Persons specified in the preceding paragraph shall report the following to the Minister on the basis of the results of the investigation specified in the same paragraph. (1) Name of the drug concerned (2) Approval number and date of approval (3) Surveillance period and number of cases investigated (4) Amount of drug shipped (5) Outline of investigation, results of surveillance and results of analysis (6) Incidence of each type of adverse reaction, etc. or problems, etc. (7) List of patients in whom adverse reactions appeared or patients affected by other problems 3. The report in the preceding paragraph shall be filed within 2 months after the end of each one year period commencing on the date of approval to manufacture the drug or medical device investigated (the period specified by the Minister in the case of drugs or medical devices designated by the Minister). Article 21-4-2. (Periodic Safety Update Reports) Persons who have received approval to manufacture prescriptions drugs specified in the items of Article 21-4, Paragraph 1 pursuant to the provisions of Article 14 must undertake surveillance of the incidence of adverse reactions, etc. and other results of use for the prescription drug concerned for the period specified in each item of Article 21-4, Paragraph 1 [including surveillance of a drug with the same ingredients as the prescription drug concerned when the drug is used in foreign countries (hereinafter "drug with the same ingredients"). 2. Persons specified in the previous item shall report the following items to the Minister based on the results of the surveillance specified in the same paragraph. (1) Name of the prescription drug or drug with the same ingredients (hereinafter "prescription drug, etc. concerned") (2) Approval date and number (date when manufacture or marketing was confirmed in the foreign country concerned for drugs with the same ingredients) (3) Surveillance period and number of patients subject to surveillance (4) Quantities of shipment of prescription drug concerned, etc. (5) Outline of the surveillance results and results of analysis (6) Appearance of adverse reactions, etc. by type of the prescription drug, etc. concerned. (7) Lists of patients with adverse reactions, etc. of prescription drug, etc. concerned. (8) Measures taken to prevent the onset or the spread of hazards for public health or hygiene due to prescription drug, etc. concerned or taken to assure proper use of the prescription drug, etc. concerned. (9) Package insert of the prescription drug concerned, etc. (10) Information on the quality, efficacy and safety of the prescription drug, etc. concerned and other information required for proper use of the prescription drug, etc. concerned 3. The reports specified in the previous paragraph shall be submitted every 6 months for 2 years and thereafter once a year from the date specified by the Minister (at periods specified by the Minister for drugs designated by the Minister) within 2 months from the completion of the period (3 months when the data obtained by the surveillance in Paragraph 1 is in a language other than Japanese) when drugs requiring surveillance are approved for manufacture. 4. When the date of completion of the period specified in the previous paragraph (referred to as "deadline of the report" in this paragraph) comes after the date of completion of the period specified in Paragraph 1, the report of the surveillance related to the deadline of the report concerned shall be submitted within 9 months after the start of the surveillance concerned notwithstanding the provisions in the previous paragraph. Article 21-4-3. (Application for Reexamination Data Compliance Reviews to the Organization for Drug ADR Relief, R&D Promotion and Product Review) Applications for reviews to the Drug Organization pursuant to the provisions of Article 14-2, Paragraph 3 with application mutatis mutandis in Article 14-4-2 shall be submitted using Form No. 11-2-6. 2. The application in the preceding paragraph shall be attached to the application for reexamination pursuant to the provisions of 14-4, Paragraph 1 for the product in the application concerned. Article 21-4-4. (Notification of the Results of Reexamination Data Compliance Reviews by the Drug Organization) Notification of the results of the reviews to the Minister pursuant to the provisions of Article 14-2, Paragraph 4 with application mutatis mutandis in Article 14-4-2 shall be made using Form No. 11-2-7. Article 21-5. (Applications for Reevaluation of Drugs and Medical Devices) Applications for the reevaluation of drugs or medical devices pursuant to the provisions of Article 14-5 of the Law shall be made by submitting an application on Form No.11-3 (one original and two copies) 2. For data submitted for reevaluation of drugs or medical devices pursuant to the provisions of Article 14-5 of the Law, the provisions of Article 18-3, Paragraph 2 shall apply mutatis mutandis. 3. A person who files an application for reevaluation of drugs or medical devices pursuant to the provisions of Article 14-5 of the Law shall comply with the provisions of Article 18-3, Paragraph 3. In this case, "the Minister or the governor of the prefecture" in the paragraph shall read "the Minister". 4. Drugs specified by MHW Ordinance pursuant to the provisions of the last part of Article 14-5, Paragraph 4 shall be the drugs designated by the Minister in Paragraph 1 of the same article. 5. The provisions of Article 18-4-3 shall be applied mutatis mutandis for data pursuant to the provisions of Article 14-5, Paragraph 4. In this case, MHW Ordinance on Implementation Standards for Non-Clinical Studies on Safety of Drugs (MHW Ordinance No.21, 1997) in the Article shall read "MHW Ordinance on Standards for Postmarketing Surveillance of Drugs (MHW Ordinance No.10, 1997), MHW Ordinance on Implementation Standards for Non-Clinical Studies on Safety of Drugs (MHW Ordinance No.21, 1997)" and "the date when a decision is made on the approval pursuant to the provisions of Article 14" shall read "the date of completion of the reevaluation pursuant to the provisions of Article 14-4, Paragraph 1". Article 21-6. (Notification of Transfer) In the event of an inheritance or merger involving a person who has received an approval to manufacture a drug, etc. pursuant to the provisions of Article 14 of the Law (hereinafter in this Article and in Article 26-2-3 referred to as the "recipient of approval") or if a recipient of approval transfers the data and information referred to below with the intent of assigning his status as the recipient of approval of a drug, etc. with respect to which the recipient of approval has received approval to manufacture under Article 14 of the Law, the person who has become the recipient of approval shall, in any case other than inheritance, before transfer, and in the case of inheritance, without delay after transfer, notify the Minister [or the prefectural governor, if authority to grant said approval has been delegated to the prefectural governor pursuant to the provisions of Article 15-4 of the Ordinance]. (1) Data which were submitted with an application for approval pursuant to Article 14, Paragraph 1 of the Law or for approval of a partial change in such approval pursuant to Article 14, Paragraph 6 of the Law, or data which are the basis for such data. (2) Data which were submitted with an application for reexamination pursuant to Article 14-4, Paragraph 1 of the Law, or data which are the basis for such data. (3) Data which were submitted with a report pursuant to the provisions of Article 14-4, Paragraph 6 of the Law, or data which are the basis for such data. (4) Data which were submitted with an application for reevaluation pursuant toArticle 14-5, Paragraph 1 of the Law, or data which are the basis for such data. (5) Records concerning designated medical devices pursuant to the provisions of Article 77-5, Paragraph 1 of the Law and data related to these records (6) Other data or information relating to quality, efficacy or safety. 2. The notifications in the preceding paragraph shall be made by submitting anotification by Form No.11-4 (original and one copy when submitted to the Minister and original when submitted to the prefectural governor). 3. Documentation certifying that the person giving notice is the successor to the position of the recipient of approval shall be attached to the notification form referred to in the preceding paragraph. 4. The notifications in Paragraph 1 shall be submitted via the governor of the prefecture where the person submitting the notification is domiciled. Article 22. (Supervision of Drug Manufacture Not Requiring a Pharmacist) For supervision of the manufacture of the drugs specified in the following items pursuant to the proviso of Article 15, Paragraph 1 of the Law, a technician as specified in the following items may be used in place of a pharmacist. 1) Drugs specified in Article 1-2, Paragraph 1, Item 5 of the Ordinance: persons corresponding to either a or b. a. Person with at least 5 years of experience in work such as identification of the types of natural drugs in cases of work related to the manufacture or marketing of natural drugs. b. Person of learning and experience confirmed by the Minister to be at least equivalent to the person in a. 2) Drugs specified in Article 1-2, Paragraph 1, Item 7 of the Ordinance (excluding those used for verterinary treatment; hereinafter referred to as "therapeutic gases"): persons corresponding to a, b or c as follows. a. A person who has completed a course specializing in pharmacology or chemistry in a middle school based on the former Middle School Ordinance (Imperial Ordinance No.36, 1943) (hereinafter referred to as "former middle school") or in a senior high school based on the School Education Law (Law No.26, 1947) (hereinafter referred to as a "high school") or an equivalent or higher level school. b. A person who has been employed for at least 3 years in work related to the manufacture of therapeutic gases after completion of a course majoring in pharmacology or chemistry at a former middle school, high school or an equivalent or higher level school. c. A person whom the Minister has confirmed as having learning and experience equivalent to or greater than the persons described in items a and b. 3) Absorbent cotton or gauze (excluding sterile gauze, sterile absorbent cottonand sterile purified absorbent cotton): A person corresponding to a, b or c a. A person who has completed a course specializing in pharmacology or chemistry in a university based on the former University Ordinance (Imperial Ordinance No.388, 1918), a technical higher school based on the former Technical Higher School Ordinance (Imperial Ordinance No.61, 1903) or a university or technical senior high school based on the School Education Law (Law No.26, 1947) (hereinafter referred to as a "university, etc.") b. A person who has been employed for more than 3 years in work related to the manufacture of drugs or quasi-drugs after completing a course majoring in pharmacology or chemistry at a former middle school, a high school or an equivalent or higher level school. c. A person whom the Minister has confirmed as having knowledge and experience equivalent to or greater than the persons described in the preceding items. Article 22-2. (Approval of Supervisor) Applications for approvals pursuant to the provisions of Article 15, Paragraph 1 or 2 of the Law shall be made by submitting an application on Form No.12 (original and one copy when submitted to the Minister and original when submitted to the prefectural governor). 2. The re′sume′of the person who is to become a supervisor at the applicable manufacturing facility shall be attached to the application form referred to in the preceding paragraph. Article 22-3. (Respect for the Opinions of Supervisors, etc.) Manufacturers of drugs or medical devices shall respect the opinions stated by drug manufacturing supervisors or responsible technicians and confirmed necessary for fulfilling their duties pursuant to the provisions of Article 9 Paragraph 1 with application mutatis mutandis in Article 15, Paragraph 3 and Article 17, Paragraph 2. However, this shall not apply to manufacturers of drugs by application of the Pharmaceutical Manufacturing Control and Quality Control regulations (MHW Ordinance No.3, 1994), manufacturers of medical devices by application of the Medical Device Manufacturing Control and Quality Control Regulations (MHW Ordinance No. 40, 1995) and manufacturers of drugs and medical devices by application of the Ordinance on Manufacturing Control and Quality Control for Two or More Manufacturing Processes for One Drug, Quasi-drug, Cosmetic or Medical Device Product in Article 1-2, Paragraph 1, Items 1, 2 and 4 of the Enforcement Ordinance of the Law (MHW Ordinance No. 26, 1994). Article 23. (Records of Manufacture, Tests, etc.) The supervisor or responsible technician at a factory manufacturing drugs, etc. shall keep records concerning manufacture, tests and other matters related to the management of the factory and shall preserve them for 3 years [where there is an obligation to display the period of efficacy (including the expiry date; the same hereinafter) for drugs for which such records are kept, for the efficacy period plus one year]. However, this shall not apply when there is an obligation to prepare and preserve records pursuant to the provisions of Regulations for Manufacturing Control and Quality Control of Drugs, Regulations for Manufacturing Control and Quality Control of Medical Devices or the Ordinance concerning Manufacturing Control and Quality Control when the manufacturing processes of one drug, quasi-drug, cosmetic or medical device are performed in two or more factories in Article 1-2, Paragraph 1, Items (1), (2) and (4) of the Enforcement Ordinance of the Law. Article 23-2. (Documentation Related to Control of Installation) Manufacturers of medical devices which must be assembled at the time of installation (hereinafter referred to as "installation control medical devices") designated by the Minister as requiring control of assembly in order not to jeopardize public health and hygiene (excluding cases where the manufacturing involves repair of existing medical devices; the same hereinafter) must prepare documentation concerning the methods of assembly and the method of confirmation of the quality of installation control medical devices (hereinafter referred to as "installation control specifications") for each installation control medical device. 2. Manufacturers of installation control medical devices must control the installation by appropriate methods based on the installation control specifications concerned when they install the installation control medical devices concerned themselves. 3. Manufacturers of installation control medical devices must conclude a written contract including articles related to reports of installation control and transfer installation control specifications for the installation control medical devices concerned with other persons when the manufacturers entrust the installation of installation control medical devices to other persons. 4. Manufacturers of installation control medical devices must transfer installation control specifications to the sellers of installation control medical devices when sellers or leasers of medical devices (referred to as "sellers, etc." in the remainder of this paragraph and in Article 42-2 and Article 45-2) who sell or lease installation control medical devices. 5. Manufacturers of installation control medical devices must transfer installation control specifications for the installation control medical devices concerned to the person issuing the notification when notifications pursuant to the provisions of Paragraph 6 of the next article (including application mutatis mutandis in Article 23-4) for installation control medical devices are received. 6. Manufacturers of installation control medical devices must provide education and training concerning installation control of installation control medical devices for persons installing installation control medical devices. 7. Manufacturers of medical devices must prepare records and retain them for a period of 3 years from the date of preparation when they perform installation control, transfer installation control specifications or perform education and training pursuant to the provisions of preceding Paragraph 2 to 6. Article 23-3. (Manufacturing Control and Quality Control of Special Repairers) Manufacturers of medical devices [limited to those whose manufacturing activities involve repair of existing medical devices (limited to medical devices in attached table 1-2; referred to as "special repair medical devices" in the remainder of this article); hereinafter referred to as "special repairers") must prepare the following documentation for each factory. (1) Documentation concerning the contents of the work (2) Documentation showing repair procedures and other repair work 2. Special repairers must repair special repair medical devices by proper methods based on the documentation specified in Item (2) in the preceding paragraph. 3. Special repairers must have the following work performed by the responsible technician in the factory concerned when they receive complaints concerning the quality of medical devices which they have repaired themselves except in cases where it is clear that the matter in the complaint was not caused in the factory where the repair concerned was performed. (1) Clarify the cause of the matter in the complaint and take the required measures when it is necessary to improve the manufacturing control and quality control related to the repair. (2) Prepare complaint processing records which include the contents of the complaint concerning the special repair medical device, the results of clarification of the cause, and the improvement measures, and retain these records for a period of 3 years from the date of preparation. 4. Special repairers must have the following work performed by the responsible technician in the factory concerned when they recall medical devices which they have repaired themselves for reasons related to quality, etc. except in cases where it is clear that the reason for the recall did not arise in the factory where the repair concerned was performed. (1) Clarify the cause of the recall and take the required measures when it is necessary to improve the manufacturing control and quality control related to the repair. (2) Take appropriate measures for classification of the recalled medical device after a fixed period of storage. (3) Prepare recall processing records which include the contents of the recall concerning the special repair medical device, the results of clarification of the cause, and the improvement measures, and retain these records for a period of 3 years from the date of preparation. 5. Special repairers must have the following work performed by the responsible technician (1) Undertake education and training of workers concerning manufacturing control and quality control related to repair of special repair medical devices. (2) Prepare records of implementation of education and training and retain the records for a period of 3 years from the date of preparation. 6. Special repairers must notify the manufacturer or importer and seller of the medical devices concerned ["manufacturer, etc." in Article 42-2, Paragraph 5, Item (2)] beforehand when they repair a medical devices (excluding very small repairs; the same in the next paragraph). 7. Special repairers must enter their own name and address on the medical device concerned or its immediate container or wrapper when they have repaired a medical device. 8. Special repairers must notify the person who requested the repair of the special repair medical device of the contents of the repair in writing. Article 23-4. (Manufacturing Control and Quality Control of Repairers Other Than Special Repairers) The provision of Paragraph 3, Paragraph 4, Paragraph 6 and Paragraph 7 of the preceding article shall apply mutatis mutandis to manufacturers of medical devices (limited to cases where such manufacture consists of repair of existing medical devices) other than special repairers. In this case, "the following" in Paragraph 3 of the same article shall read "Item 1" and "the following in Paragraph 4 shall read "in Items 1 and 2". Article 23-5. (Installation Control of Repairers) The provisions of Article 23-2, Paragraph 2, Paragraph 3 and Paragraph 7 shall apply mutatis mutandis to repairers of installation control medical devices. Article 24. (Qualifications of Responsible Technicians) Responsible technicians of factories manufacturing quasi-drugs as specified in Article 17, Paragraph 1 of the Law shall be persons as stipulated in any one of the following: (1) A pharmacist (2) A person who has completed a course majoring in pharmacology or chemistry in a university, etc. (3) A person who has been employed for more than 3 years in work related tothe manufacture of drugs or quasi-drugs after completing a course majoring in pharmacology or chemistry in a former middle school) or a high school or an equivalent to higher level school. (4) A person whom the Minister has confirmed as having knowledge and experience equivalent to or greater than the persons described in the preceding Item (3). 2. Responsible technicians in a factory for the manufacture of cosmetics as specified in Article 17, Paragraph 1 of the Law shall be persons as stipulated in any one of the following: (1) A pharmacist (2) A person who has completed a course majoring in pharmacology or chemistry in a former middle school or a high school, or an equivalent or higher level school (3) A person who has been employed for more than 3 years in work related to the manufacture of drugs or cosmetics after completing a course in pharmacology or chemistry in a former middle school or a high school, or an equivalent or higher level school (4) A person whom the Minister has confirmed as having knowledge and experience equivalent to or greater than the persons described in the preceding Item (3). 3. Responsible technicians in a factory for the manufacture of medical devices as specified in Article 17, Paragraph 1 of the Law (excluding cases where the manufacturing performed in the factory concerned is the repair of existing medical devices; the same in the following paragraphs) shall be persons as stipulated in any one of the following: (1) Persons having completed a course majoring in physics, chemistry, metallurgy, electricity, mechanics, pharmacology, medicine or dentistry in a university, etc. (2) A person who has been employed for more than 3 years in work related to the manufacture of medical devices after completing a course majoring in physics, chemistry, metallurgy, electricity, mechanics, pharmacology, medicine or dentistry in university, etc. (3) A person who has completed a course designated by the Minister after being employed for at least 5 years in work related to the manufacture of medical devices. (4) A person whom the Minister has confirmed as having knowledge and experience equivalent to or greater than the persons described in the preceding Item (3). 4. Notwithstanding the provisions of the previous paragraph, a person corresponding to any one of the following items may serve as the responsible technician in a factory manufacturing medical devices pursuant to the provisions of Article 18. (1) A person who has completed a course majoring in physics, chemistry, metallurgy, electricity, mechanics, pharmacology, medicine or dentistry in a university, etc. (2) A person who has been employed for more than 3 years in work related to the manufacture of medical devices after completing a course majoring in physics, chemistry, metallurgy, electricity, mechanics, pharmacology, medicine or dentistry in a university, etc. (3) A person whom the Minister has confirmed as having knowledge and experience equivalent to or greater than the persons described in the preceding Item (3). 5. Responsible technicians in factories producing medical devices pursuant to the provisions of Article 17, Paragraph 1 of the Law (limited to factories where the manufacturing performed is repair of existing medical devices) shall be persons as stipulated in any one of the following items in accordance with the classifications in the following items. (1) Special repairers: a person corresponding to (a) or (b). (a) A person who has completed a basic course designated by the Minister (referred to as a "basic course" hereinafter in this paragraph) or a specialized course designated by the Minister after being employed for more than 3 years in work related to the repair of medical devices. (b) A person whom the Minister has confirmed as having knowledge and experience equivalent to or greater than the person described in Item (a). (2) Repairers other than special repairers: a person corresponding to (a) or (b). (a) A person who has completed a basic course after being employed for more than 3 years in work related to the repair of medical devices. (b) A person whom the Minister has confirmed as having knowledge and experience equivalent to or greater than the person described in Item (a). Article 25. (Application for License to Change Manufactured Articles) An application to allow a change or addition to the manufactured drugs, etc. pursuant to Article 18, Paragraph 1 of the Law shall be submitted on Form No.13 to the Minister or prefectural governor with the authority to grant the license concerned pursuant to the provisions of the same paragraph and Article 15-3 of the Ordinance (original and two copies when submitted to the Minister and original and one copy when submitted to the prefectural governor). 2. When an application is submitted for a license in the preceding paragraph pursuant to the provisions of Article 13-2, Paragraph 1 with application mutatis mutandis in Article 18, Paragraph 2 of the Law, the documents in Article 14, Paragraph 2, Item 6 shall be attached to the application form in the preceding paragraph. 3. An application for a change in or addition to categories concerning partial processing factories pursuant to the provisions of Article 1-3, Paragraph 1 of the Ordinance as specified in Article 18, Paragraph 1 of the Law applied with the reading changed pursuant to the provisions of Article 1-3, Paragraph 2 of the Ordinance shall be submitted on Form No.13-2 to the Minister or prefectural governor with the authority to grant the license concerned pursuant to the provisions of Article 8, Paragraph 1 and Article 15-3 of the Ordinance (original and two copies when submitted to the Minister and original and one copy when submitted to the prefectural governor). 4. Applications for license to change or add the categories specified by MHW ordinance based on repaired products and repair methods pursuant to the provisions of Article 1-3-2, Paragraph 1 of the Ordinance by application of the provisions of Article 18, Paragraph 1 of the Law with the changes in reading specified in Article 1-3-2, Paragraph 2 of the Ordinance shall be made by submitting Form No. 13-2-2 to the Minister or prefectural governor with the authority to grant the license concerned pursuant to the provisions of Article 8, Paragraph 1 and Article 15-4 of the Ordinance (original and two copies when submitted to the Minister and original and one copy when submitted to the prefectural governor). Article 26. (Notification of Changes of Supervisor, etc. of a Manufacturing Facility) A notification of change pursuant to the provisions of Article 19 of the Law shall be submitted with respect to the following items: (1) Name or address of the manufacturer or the supervisor or responsible technician in the manufacturing factory. (2) Directors engaged in the business, when the manufacturer is a corporation. (3) Name of the factory. (4) Major parts of the structural facilities of the factory. (5) Item manufactured or the category specified in Article 1-3, Paragraph 1 or Article 1-3-2, Paragraph 1 of the Ordinance and the manufacturing process performed in the factory concerned (only when the manufacture of the item, manufacturing for the category concerned or part of the process in the manufacturing concerned is to be discontinued). 2. The notifications referred to in the previous paragraph shall be submitted on Form No.6 (original and one copy when submitted to the Minister and original when submitted to the prefectural governor). 3. The provisions of Article 12, Paragraph 3 and Paragraph 4 of these Regulations shall apply, mutatis mutandis to the notifications referred to in Paragraph 1 of this article. In this case, "prefectural governor as the recipient" in the proviso of Article 12, Paragraph 3 shall read "Minister or prefectural governor as the recipient" and "prefectural governor" in Paragraph 4 shall read "Minister (prefectural governor when the authority pursuant to the provisions of Article 19 of the Law is transferred to the prefectural governors pursuant to the provisions of Article 15-4 of the Ordinance). Article 26-2. (Range of Drugs and Medical Devices for Which Special Manufacture in Two or More Factories Is Not Applicable) Drugs specified by MHW Ordinance pursuant to provisions of Article 1-3, Paragraph 1 of the Ordinance shall be as follows. (1) Biological products (excluding drugs specified in Article 1-2, Paragraph 1, Item 4 of the Ordinance) (2) Radiopharmaceuticals (3) Drugs designated by the Minister pursuant to the provisions of Article 43, Paragraph 1 of the Law (excluding those in the preceding two items) (4) Bulk drugs used exclusively for the manufacture of other drugs (excluding those specified in Article 1-2, Paragraph 1, Item 5 of the Ordinance and the preceding three items) (5) Therapeutic gases (6) Drugs specified in Article 1-2, Paragraph 1, Item 6 of the Ordinance (hereinafter "drugs manufactured in pharmacies") 2. The medical devices specified by MHW ordinance in Article 1-3, Paragraph 1 of the Ordinance are medical devices other than those in attached table 1-3. Article 26-2-2. (Categories Specified by MHW Ordinance) The categories specified by MHW ordinance pursuant to the provisions of Article 1-3, Paragraph 1 of the Ordinance shall be as follows. (1) Drugs specified in Article 1-2, Paragraph 1, Item 1 or 2 of the Ordinance (2) Drugs specified in Article 1-2, Paragraph 1, Item 4 of the Ordinance (3) Drugs specified in Article 1-2, Paragraph 1, Item 5 of the Ordinance (4) Sterile preparations specified in Article 6 of the Buildings and Facilities Regulations of Pharmacies, etc. (Ordinance No.2, 1961) (hereinafter referred to as "sterile preparations") (5) Drugs other than those specified in the preceding items 2. The categories of quasi-drugs specified by MHW ordinance pursuant to the provisions of Article 1-3, Paragraph 1 of the Ordinance shall be as follows. (1) Quasi-drugs used for the prevention of nausea and other feelings of discomfort or prevention of bad breath (limited to those for internal application) (2) Quasi-drugs for use in repelling or preventing of rodents, flies, mosquitoes, fleas, etc. in order to maintain human health (3) Cotton products (including paper cotton) for hygienic use (4) Quasi-drugs other than those in the preceding three items 3. The categories of cosmetics specified by MHW ordinance pursuant to the provisions of Article 1-3, Paragraph 1 of the Ordinance shall be all cosmetics. 4. The categories of medical devices specified by MHW ordinance pursuant to the provisions of Article 1-3, Paragraph 1 of the Ordinance shall be as follows. (1) Medical devices in Items 1 to 34 of attached table 1-3 (2) Medical devices in Item, 35 of attached table 1-3 5. The categories of medical devices specified by MHW ordinance pursuant to the provisions of Article 1-3-2, Paragraph 1 of the Ordinance shall be those in attached table 1-4. Article 26-2-3. (Preservation of Data) The recipient of approval shall preserve the data described in the following Items for the period specified; provided, however, that this shall not apply to any data which is recognized by its nature as particularly difficult to preserve. (1) Data which was the basis for data submitted with the application for approval pursuant to the provisions of Article 14 of the Law shall be preserved for 5 years from the date of approval; provided, however, that data applicable to drugs or medical devices which shall be subject to reexamination pursuant to the provisions of Article 14-4, Paragraph 1 of the Law, shall be preserved until reexamination has been completed if the period between the date of approval and the date of completion of reexamination exceeds 5 years. (2) Data which was the basis for data submitted with the application for reexamination of a drug pursuant to the provisions of Article 14-4, Paragraph 1 of the Law, except for data referred to in the preceding item, shall be preserved for 5 years from the date of completion of reexamination. (3) Data which was the basis for data submitted with the application for reexamination of a drug or medical device pursuant to the provisions of Article 14-5 of the Law, except data referred to in the preceding two items, shall be preserved for 5 years from the date of completion of reexamination. 2. A manufacturer of drugs, etc. shall preserve data which was the basis for matters concerning disease, disability or death suspected as an adverse reaction of the product concerned, an infection suspected to be due to use of the product concerned or any other item related to the efficacy and safety of the drug, quasi-drug, cosmetic or medical device (hereinafter referred to as the matters concerning side effects, etc.) reported to the Minister pursuant to the provisions of Article 77-4-2 of the Law for 5 years from the date of the applicable report. 3. The proviso of Paragraph 1, excluding the subsequent items, of this article shall apply to the preservation of the data in the preceding paragraph. Article 26-2-4. (Prohibition of Recontracting, etc. in Manufacture in Two or More Factories) When part of the manufacturing process of a drug, etc. is performed in the factory of another manufacturer, the manufacturer concerned must not subcontract all or part of the manufacturing process for which he has been contracted to another manufacturer. 2. When a manufacturer of drugs performs the manufacturing process of a sterile preparation, liquid preparation for external application (excluding eye drops), liquid for external use or poultice in two or more factories, the manufacturing process must be divided in such a way that the drug concerned does not correspond to drugs specified in Article 56 of the Law. Article 26-2-5. (Changes in License Conditions) A person who has received a license pursuant to the provisions of Article 12 of the Law (including those pursuant to the provisions of Article 18 of the Law) shall be able to request a change in the conditions related to the license concerned pursuant to the provisions of Article 79 of the Law. 2. The request in the preceding paragraph shall be submitted on Form No.13-2-3. Article 26-3. (Approval of Drugs, etc. Manufactured Abroad) An application for approval of drugs, etc. manufactured abroad pursuant to the provisions of Article 19-2, Paragraph 1 of the Law shall be submitted on Form 13-2-4 to the Minister (original and two copies). 2. The provisions in Article 18-3 and Article 18-4 shall apply mutatis mutandis to the data to be attached to application in the previous paragraph. In this case, "the Minister or prefectural governors" in Article 18-3, Paragraphs 3 and 4 and Article 18-4 shall read "the Minister". 3. The following documents shall be attached to the application referred to in Paragraph 1. However, this shall not apply when it is mentioned in the application concerned that the documents were submitted to the Minister at the time of application, etc. (1) If an applicant is a corporation, evidence of incorporation. (2) Documents which indicate whether or not an applicant (including directors involved in the business if the applicant is a corporation) is a person pursuant to the provisions of Article 19-2, Paragraph 2 of the Law. (3) Documents which certify that an in-country caretaker has been established. (4) A copy of resident card of the in-country caretaker. If the in-country caretaker is a corporation, a certified copy of the corporate register. (If an in-country caretaker is a representative of the office located in Japan of a foreign corporation, a certified copy of the registration of the office.) (5) Documents which indicate that sub-items (a) through (e) of Item (1) of Article 26-5 are not applicable to an in-country caretaker (including the directors involved in the business where an applicant is a corporation; this also applies to Item (1) of Article 26-5). (6) Documents which evidence whether an in-country caretaker is a person specified in sub-items (a) through (d) of the Item (2) of Article 26-5, in accordance with the classification of approval described in said clauses. (7) If an in-country caretaker has employed a person to engage in the business pursuant to the proviso of Article 26-5, Item (2),(hereinafter referred to as "an in-country administrative employee"), copies of the employment contract and other documents which certify the relationship between the in-country caretaker and the in-country administrative employee and documents which certify that he or she is the person specified respectively in (a) through (d) of the item in accordance with the classification of approval described in sub-items (a) through (d). Article 26-4. (Register of Approval of Drugs, etc. Manufactured Abroad) The Minister shall establish a register of approval pursuant to the provisions of Article 19-2 of the Law, and record the following matters in addition to the matters mentioned in each item of Article 20, Paragraph 1. (1) Name and location of plant which manufactures the items in question. (2) Name and address of the in-country caretaker. (3) Name and address of the in-country administrative employee, if any. 2. The Minister or the prefectural governor may have all or part of the register specified in the preceding paragraph prepared in the form of a magnetic disk. Article 26-5. (Standards for In-Country Caretaker) Standards for an in-country caretaker pursuant to the provisions of Article 19-2, Paragraph 3 of the Law shall be as follows: (1) The in-country caretaker shall not be any of the following (a) through (e). a. A person whose license has been canceled under the provisions of Article 75, Paragraph 1 of the Law and with respect to whom the period of 3 years has not elapsed since the date of cancellation. b. A person who was an in-country caretaker of a recipient of approval for foreign manufacturing, whose approval has been canceled in whole or in part due to liability pursuant to the provisions of Article 75-2, Paragraph 1 of the Law, and for whom the period of 3 years has not elapsed since the date of cancellation that was related to the in-country caretaker. c. A person who has been sentenced to imprisonment or more serious penalty, and less than 3 years has elapsed since the execution of such penalty was completed or suspended. d. Other than persons to whom Item (a), (b) or (c) applies, a person who has infringed the Law, the Narcotic and Psychotropic Drug Control Law (Law No. 14 of 1953), the Poisonous and Powerful Substances Control Law (Law No.303 of 1950) or any other law or regulation relating to pharmaceuticals, and less than 2 years has elapsed since the date of the infringement. e. A person adjudged incompetent, a mental patient, or a person addicted to narcotics, marijuana, opium, or stimulants. (2) The in-country caretaker for each approval classified in sub-items (a) through (d) below shall conform to the description in the applicable classification; provided, however, that this shall not apply if an in-country caretaker for the applicable classification employs in his office a person conforming to the description in the corresponding classification to engage in the actual business. a. Approval of drugs - a pharmacist. Except that with regard to the approval of biological products or other drugs designated by the Minister - a physician, a person with knowledge of bacteriology or other technician approved by the Minister. b. Approval of quasi-drugs A person who falls under any of the Items of Article 24, Pargraph 1. c. Approval of cosmetics A person described in any of the Items of Article 24, Paragraph 2. d. Approval of medical devices A person described in any of the Items of Article 24, Paragraph 3. (3) The in-country caretaker shall comply with following sub-items (a) through (d) below: a. Establish books to record matters concerning the offering of information to importers and any other business of the in-country caretaker, and preserve such records for 3 years from the date of the last recording. b. Preserve the following documents (i) to (v): (i) documents in which persons who have obtained approval pursuant to the provisions of Article 19-2 of the Law (hereinafter, recipients of foreign manufacturing approval) recorded the matters approved pursuant to the provisions of Article 19-2 of the Law. (ii) one copy of the data submitted by the recipient of foreign manufactur-ing approval with the application for approval pursuant to the provisions of Article 19-2 of the Law. (iii) one copy of the data submitted by the recipient of foreign manufacturing approval with the application for review pursuant to Article 14-4, Paragraph 1 of the Law as applied pursuant to the provisions of Article 19-4 of the Law. (iv) one copy of the data submitted by the recipient of foreign manufacturing approval with the application for reevaluation of drugs pursuant to Article 14-5 of the Law as applied pursuant to the provisions of Article 19-4 of the Law. (v) documents in which the recipient of foreign manufacturing approval described the matters reported by him to the Minister pursuant to the provisions of Article 14-4, Paragraph 6 of the Law as applied pursuant to the provisions of Article 19-4 of the Law, and the matters concerning side effects etc., reported to the Minister pursuant to the provisions of Article 75-2, Paragraph 1, Item e of the Law. c. Preserve the data which were the basis for matters concerning side effects etc. reported to the Minister pursuant to the provisions of Article 77-4-2 of the Law for five years from the date of report. This rule shall not apply to the data which are recognized to be extremely difficult to preserve because of their nature. d. Give due regard to the opinion of an in-country administrative employee, if any. Article 26-6. (Application for Approval of Qualifications for Control of Biological Products, etc. Manufactured Abroad) The application for approval pursuant to the proviso in the preceding Article, Item (2)a. shall be submitted (one original and one copy) on Form No.13-3. In this case, the application shall be made through the governor of the prefecture where the in-country caretaker (including one expected to be in-country caretaker) resides (where the office is located in case of a representative of a foreign corporation which has an office in Japan ; the same in Article 26-10, Paragraph 2). 2. Resume of the physician, the technician with knowledge of bacteriology or other technicians concerned with the approval in question shall be attached to the application mentioned in the preceding paragraph. Article 26-7. (Notification of Change Relating to In-country Caretaker) Changes of which notification should be filed in accordance with the provisions of Article 19-3 of the Law shall be as follows: (1) Name or address of an in-country caretaker or an in-country administrative employee (2) Directors engaged in the business if the in-country caretaker is a corporation (3) In-country administrative employees 2. The notification of change of in-country caretaker pursuant to the provisions of Article 19-3 of the Law (referred to in the next paragraph as "notification of change of in-country caretaker") and the notification in the preceding paragraph shall be submitted for each product on Form No. 13-4 (one original and one copy). 3. The documents specified in the following items in accordance with the type of notification in each item shall be attached to the notification in the preceding paragraph. However, this shall not apply when the fact that the forms have been submitted to the Minister as the recipient of applications, etc. is entered in the application form concerned. (1) Notification concerning the name of the in-country caretaker in Paragraph 1, Item (1): a copy of the family register, an abstract of the family register or a certificate of entry in the family register of the proprietor of the pharmacy (a copy of the registration when the in-country caretaker is a corporation) (2) Notification concerning the address of the in-country caretaker in Paragraph 1, Item (1): Document in Article 26-3, Paragraph 2, Item 4 concerning the address after a change of the in-country caretaker (3) Notification concerning the items in Paragraph 1, Item 2: Document showing that the directors after the change do not correspond to (a) to (e) in Article 26-5, Paragraph 5, Item 1. (4) Notification concerning the items in Paragraph 1, Item 3: copy of the employment contract or other documents proving the employment relation between the in-country caretaker and the in-country administrative employees, and documents showing that the in-country administrative employees correspond to the persons specified in Article 26-5, Item 2. Article 26-8. (Supply of Information) A recipient of foreign manufacturing approval shall supply the in-country caretaker with the following information: (1) Name and address of the importer. (2) Information concerned with the matters provided in Article 52 of the Law (including application mutatis mutandis in Articles 60 or 62 of the Law) or Article 63-2 of the Law, and the reason for the change in case of changes in information. (3) In addition to the matters mentioned in the above two Items, the information which the in-country caretaker requires for conducting his business. 2. When a recipient of foreign manufacturing approval changes an in-country caretaker, he shall have the former in-country caretaker transfer to the new in-country caretaker the record books referred to in Item (3)(a), the documents referred to in Item (3)(b), and the data referred to in Item (3)(c) of Article 26-5, and the information referred to in the preceding paragraph. 3. When the in-country caretaker before the change in the preceding paragraph has obtained manufacturing approval for designated medical devices pursuant to the provisions of Article 77-5, Paragraph 1 of the Law, the in-country caretaker concerned shall transfer records concerning the designated medical devices and data related to these records to the in-country caretaker after the change. Article 26-9. (Record Books Relating to the Business of a Recipient of Foreign Manufacturing Approval) A recipient of foreign manufacturing approval shall maintain books, record the matters relating to information supplied to the importer and other business of the recipient of foreign manufacturing approval of drugs manufactured abroad. Such books shall be preserved for 3 years from the date of the final entry. Article 26-10. (Notification of Change Regarding Recipient of Foreign Manufactur- ing Approval) When a recipient of foreign manufacturing approval changes any of the following items, he shall notify the Minister to that effect within 30 days. (1) Name or address of a recipient of foreign manufacturing approval. (2) With respect to a recipient of foreign manufacturing approval who is a corporation, the directors engaged in the business. (3) The factory which manufactures the approved items, or name of the factory. 2. The notification in the preceding paragraph shall be submitted on Form No.13-4 (one original and one copy) for each article via the governor of the prefecture where the in-country caretaker resides. 3. If the notification in Paragraph 1 is concerned with matters mentioned in Item (1) of the same paragraph, or with the matters mentioned in Item (2) of the same paragraph, the documents certifying the matters referred to in Item (1) or documents indicating whether a new director is a person described in Article 19-2, Paragraph 2 of the Law, as the case may be, respectively shall be attached to the notification form referred to in the preceding paragraph. Article 26-11. (Procedure for Application, etc. by Recipient of Foreign Manufactur- ing Approval) The application, notification, report, submission, and other procedures to be made to the Minister by a person who is to receive approval under the provisions of Article 19-2 of the Law, or by a recipient of foreign manufacturing approval, shall be filed by an in-country caretaker including a person who is designated to become an in-country caretaker [in the case of an application for approval under the proviso of Article 26-5, Item (2)(a)]. Article 26-12. (Preservation of Data by Recipient of Foreign Manufacturing Approval) The provisions of Article 26-2-3, Paragraph 1 shall apply mutatis mutandis with respect to a recipient of foreign manufacturing approval. 2. A recipient of foreign manufacturing approval shall preserve data which is the basis for matters concerned with side effects reported to the Minister pursuant to the provisions of Article 75-2, Paragraph 1, Item (3), for 5 years from the date of report to the Minister. 3. The proviso of Article 26-2-3, Paragraph 1 shall apply with respect to preservation of data (except items (1) to (3)) described in the preceding paragraph. Article 26-13. (Application Mutatis Mutandis) The provisions of Articles 18-2 and Articles 18-4 through 19 and Articles 20-2 through 21-6 shall apply mutatis mutandis to approvals pursuant to the provisions of Article 19-2 of the Law. In this case, "Form No.11" in Article 19 shall read"Form No. 13-5", "Form No.11-2" in Article 20-2 shall read"Form No.13-6", "Form No.11-2-3" in Article 20-4 shall read"Form No.13-6-2", "Form No.11-2-4" in Article 21 shall read "Form No.13-7", "Form No.11-2-6" in Article 21-4-3 shall read "Form No.13-7-2", "Form No.11-3" in Article 21-5 shall read "Form No.13-8" "Form No.11-4" in Article 21-6, Paragraph shall read "Form No.13-9" and in Article 21-6, Paragraph 4, "where the person submitting the notification" shall read "where the in-country caretaker of the person to whom the status of the person receiving approval is transferred is domiciled (in the case of the representative of the office when a foreign corporation has an office in Japan, where that office is located)". Article 26-14. (Application for License of Importer) Application for a license to import drugs, etc. under the provisions of Article 22, Paragraph 1 of the Law, shall be submitted on Form No.8 (original and one copy when submitted to the Minister and original when submitted to the prefectural governor) to the Minister or prefectural governor with the authority to grant the license concerned pursuant to the provisions of Article 22, Paragraph 1 of the Law and Article 15-3 of the Ordinance. 2. The documents specified in the following items shall be attached to the application in the preceding paragraph. However, this shall not apply when the fact that the forms have been submitted to the prefectural governor or submitted to the Minister via the prefectural governor as the recipient of applications, etc. is entered in the application form concerned. (1) A floor plan of the manufacturing plant (2) When the applicant is a corporation, a copy of the registration (3) A medical certificate from a physician indicating that the applicant (the directors of the company when the applicant is a corporation) is not suffering from a mental disease, and are not addicted to narcotics, marijuana, opium or stimulants. (4) When a person other than the applicant is manager of the manufacturing plant, a copy of the emp loyment contract or another document that proves the employment relationship between the applicant and the manager of the manufacturing plant. (5) When the applicant intends to handle radiopharmaceuticals (excluding the handling of radiopharmaceuticals in amounts not exceeding those specified by the Minister), documents showing the type of radiopharmaceuticals handled and outlining the facilities required to handle the radiopharmaceuticals (6) When the manufacturer of drugs, etc. to be imported has obtained foreign manufacturing approval, a document certifying the import contract with the manufacturer with foreign manufacturing approval (7) When the application in the preceding paragraph is for a license pursuant to the provisions of Article 13-2, Paragraph 1 of the Law, documents showing that the substances to be manufactured by the applicant are the drugs pursuant to the provisions of Item 2 of the same paragraph, and other necessary documents 3. When the applicant is a corporation and it is confirmed by the Minister (prefectural governor when the licensing authority concerned has been transferred to the prefectural governor pursuant to the provisions of Article 15-4 of the Ordinance) that work will not be impaired based on an evaluation of the tasks performed by the director, it shall be possible to submit, in place of the medical certificate in Item (3) of the preceding paragraph, a document certifying that the director concerned does correspond to Article 6, Item 2 (d) of the Law. Article 26-14-2 (Application for Renewals of Import and Marketing Licenses) Applications for renewal of import and marketing licenses of drugs, etc. pursuant to the provisions of Article 22, Paragraph 3 of the Law shall be made by submitting Form No.8-2 (original and two copies when submitted to the Minister and original and one copy when submitted to the prefectural governor) to the Minister or the prefectural governor with the authority over the license concerned. 2. The following documents shall be attached to the application in the preceding paragraph. (1) License certificate (2) Document specified in Paragraph 2, Item 7 in the preceding article when applications are for renewal of licenses in Article 22, Paragraph 1 of the Law pursuant to the provisions of Article 13-2, Paragraph 1 with application mutatis mutandis in Article 23 of the Law Article 26-15. (Register of Licensed Importers) The provisions of Article 16 shall apply to the importation of drugs, etc. 2. If a person who manufactures drugs to be imported is a recipient of foreign manufacturing approval, the Minister or the prefectural governor shall record the name and address of the recipient of foreign manufacturing approval in a register concerning licenses of importers of drugs, etc. in addition to the matters provided in Article 16 as applied pursuant to the preceding paragraph. Article 26-16. (Application for License to Change Imported Items) An application for license to change or add imported drugs, etc. pursuant to the provisions of Article 18, Paragraph 1 of the Law as applied pursuant to Article 23 of the Law shall be submitted on Form No.13 (original and two copies when submitted to the Minister and original and one copy when submitted to the prefectural governor) to the Minister or prefectural governor with the authority over the license concerned pursuant to the provisions of Article 15-3 of the Ordinance. 2. When manufacturers of drugs to be imported have obtained foreign manufacturing approvals, they shall attach the documents in Article 26-14, Paragraph 2, Item 6 and when they apply for licenses in the preceding paragraph pursuant to the provisions of Article 13-2, Paragraph with application mutatis mutandis in Article 18, Paragraph 2 with application mutatis mutandis in Article 23 of the Law, they shall attach the documents in Article 26-14, Paragraph 2, Item 7 to the applications in the preceding paragraph. Article 26-17. (Notification of Change of Manager, etc. of Import Business) Notification of change pursuant to the provisions of Article 19 of the Law as applied pursuant to Article 23 of the Law shall be filed with respect to the following items: (1) Name or address of the importer or the manager or responsible technician at his place of business. (2) Directors engaged in the business, when the importer is a corporation. (3) Name of the place of business. (4) Major parts of the structure or facilities of the place of business. (5) Imported item (only when importation of the item is to be discontinued). (6) If the imported item is not a drug, etc. approved for manufacture abroad pursuant to Article 19-2, Paragraph 1 of the Law, the name of the country from which the item is imported, the name of the manufacturer or trade name in the country of origin. (7) If the imported item is a drug, etc. approved for manufacture abroad pursuant to Article 19-2, Paragraph 1 of the Law, the name of the recipient of approval for manufacture abroad of the applicable item or the name of country of residence (or, if a corporation, location of head office). 2. Notfications referred to in the preceding paragraph shall be submitted on Form 6 [original and one copy when submitted to the Minister and original when submitted to the prefectural governor (for notifications concerning items 6 and 7 of the preceding paragraph, original and two copies when submitted to the Minister and original and one copy when submitted to the prefectural governor)] 3. The provisions of Article 26, Paragraph 3 shall apply mutatis mutandis to the notifications referred to in Paragraph 1 of this Article. 4. Among the matters for notification described in Item (6) of Paragraph 1 of this Article, with respect to manufacturers of pharmaceutical drugs (except for all bulk drugs used exclusively in the manufacture of pharmaceuticals and natural extracts, tinctures, liquid extracts and similar items), evidence that no change has occurred in the quality, efficacy and safety of the relevant item because of change in the manufacturer must be attached to the notification mentioned in Paragraph 2. Article 27. (Application Mutatis Mutandis) The provisions of Articles 15, 17 to 23-2, Article 24 (excluding Paragraph 5), and 26-3 shall apply mutatis mutandis to import business concerning drugs, etc. In this case "Law" shall read "Law with application mutatis mutandis in Article 23 of the Law". Article 27-2. The provisions of Article 11-3 shall apply mutatis mutandis to the manufacturer or importer of drugs. Article 28. The provisions of Articles 3 through 6 and Article 13 shall apply mutatis mutandis to the manufacture (except manufacture in a pharmacy) or importation of drugs, etc. In this case, "application form" in Article 4, Paragraph 2 shall read "application form (original and one copy when submitted to the Minister and original when submitted to the prefectural governor. An application form submitted to the Minister shall have a ￥4,000 revenue stamp attached as fee)" and"the governor of the prefecture where the pharmacy is located" shall read "the Minister through the governor of the prefecture where the manufacturing factory or the place of business in located or the governor of the prefecture where the manufacturing factory or place of business in located", and "application form ...to the governor of the prefecture where the pharmacy is located" in Article 5, Paragraph 2 shall read "application form (original and one copy when submitted to the Minister and original when submitted to the prefectural governor). An application form submitted to the Minister shall have a ￥4,000 revenue stamp attached as fee", "to the Minister via the governor of the prefecture where the manufacturing factory or place of business is located or to the governor of the prefecture where the manufacturing factory or place of business is located"; and "the governor of the prefecture where the pharmacy is located" in Article 5, Paragraph 3 and Article 6 shall read "the Minister via the governor of the prefecture where the manufacturing factory or the place of business is located or the governor of the prefecture where the manufacturing factory or place of business is located"; and "notification" in Article 13 shall read "notification (original and one copy when submitted to the Minister and original when submitted to the prefectural governor)". 2. The provisions of Articles 3 through 7,11 and 13 shall apply to the manufacture of drugs in pharmacies. In this case, "Form No.5" in Article 7 shall read "Form No.14". CHAPTER II-2 DESIGNATED REVIEW ORGANIZATIONS Article 28-2. (Application for Designation) Persons who receive designations pursuant to the provisions of Article 23-2 of the Law shall submit an application form containing the following items to the Minister. (1) Name and address of the head office (2) Range of review work to be performed (3) Date on which the designation is to be received 2. The following documentation shall be attached to the application in the preceding paragraph. (1) Copies of articles of incorporation or the endowment and the register (2) List of property and balance sheet for the year prior to the year in which the application is made (list of property at the time of foundation for corporations founded during the year in which the application is made) (3) Business plan and budget for the year in which the application is made and the previous year (4) Document showing the decision making process for the application (5) The following documentation concerning executives (a) Documentation giving the name, addresses and personal histories of the executives (b) Documentation showing that the executives do not include anyone corresponding to Item (4)(a) or (b) in Article 23-3, Paragraph 2 of the Law. (6) Documentation giving the names of the personnel and the name in the case of a corporate body. (7) Documentation giving an outline of the work currently performed. (8) Plan for the implementation of review work including the following items. (a) Items concerning the time when review work is performed and holidays (b) The following items concerning the office where the review work is performed: (i) Name and address of the office where the review work is performed (ii) Outline of the review work (iii) Number of review personnel employed [persons specified in the provisions of Article 23-3, Paragraph 1, Item (1) of the Law; the same hereinafter] (c) Items concerning the method of receiving fees (d) Items concerning review equipment (e) Items concerning the methods of performing reviews (f) Items concerning appointment and dismissal of review personnel (g) Other items necessary for implementation of review work (9) Documentation giving the names and life histories of the review personnel and documentation showing that the requirements specified in Article 28-3 are met. (10) Documentation showing other items for reference. Article 28-3. (Requirements concerning Knowledge and Experience of Review Personnel) The requirements specified by MHW ordinance pursuant to the provisions of Article 23-3, Paragraph 1, Item (1) of the Law shall be as shown in the following items. (1) A pharmacist, physician, dentist or veterinarian (2) A person who has worked in the pharmaceutical regulatory field for more than 2 years and has adequate knowledge of medical devices. (3) A person whom the Minister has confirmed as having knowledge and experience equivalent to or greater than the person described in the preceding items. Article 28-4. (Number of Review Personnel) The number specified by MHW ordinance pursuant to the provisions of Article 23-3, Paragraph 1, Item (1) of the Law is three persons. Article 28-5. (Notices of Changes in Names, etc. of Designated Review Organizations) Notices of changes in the name or address of the head office pursuant to the provisions of Article 23-4, Paragraph 2 of the Law shall be made by submission of notices containing the following items. (1) The name or address of the designated review organization after the change (2) The date of the change (3) The reason for the change Article 28-6. (Review Methods) The methods specified by MHW ordinance pursuant to the provisions of Article 23-5, Paragraph 2 of the Law shall be methods which confirm that structure, method of use, indications, effects, performance, etc. of the medical devices in the application pursuant to the provisions of Article 14-3, Paragraph 3 of the Law are identical to those of medical devices which have already been approved for manufacture or import (hereinafter referred to as "approved medical devices") based on the following documentation. (1) Documentation pursuant to the provisions of Article 20-4, Paragraph 1 (including cases of application mutatis mutandis of Article 26-13 and Article 27) (2) Application documentation pursuant to the provisions of Article 17 (including cases of application mutatis mutandis of Article 27) and Article 26-3, Paragraph 1 and data pursuant to the provisions of Article 18-3, Paragraph 1 (including cases of application mutatis mutandis of Article 26-13 and Article 27). (3) Documentation containing the approved items and data attached to the approval application for the approved medical device Article 28-7. (Applications for Authorization of the Appointment or Dismissal of Executives) When designated review organizations wish to receive authorization to appoint or dismiss executives pursuant to the provisions of Article 23-6, Paragraph 1 of the Law, an application containing the following items must be submitted to the Minister. (1) Name and address of the person to be appointed or dismissed (2) Date of the appointment or dismissal (3) Reason for the appointment or dismissal Article 28-8. (Notice of Appointment or Dismissal of Review Personnel) Notice of appointment or dismissal of review personnel pursuant to the provisions of Article 23-6, Paragraph 2 of the Law shall be made by submission of a notice containing the following items. (1) Name of the person to be appointed or dismissed (2) Date of the appointment or dismissal (3) Reason for the appointment or dismissal Article 28-9. (Items Specified in the Review Work Regulations) Items related to the implementation of the review specified by MHW ordinance pursuant to the provisions of Article 23-8, Paragraph 1 of the Law shall be the items specified in Article 28-2, Paragraph 2, Item (8). Article 28-10. (Application of Approval of the Review Work Regulations) When designated review organizations wish to receive approval of review work regulations pursuant to the provisions of Article 23-8, Paragraph 1 of the Law, they shall submit the review work regulations with an application form stating that fact attached to the Minister. 2. When designated review organizations wish to receive approval to change review work regulations pursuant to the provisions of Article 23-8, Paragraph 1 of the Law, they shall submit an application form containing the following items to the Minister. (1) The items to be changed (2) The date of the change (3) The reason for the change Article 28-11. (Applications for Approval of Work Plans) When designated review organizations wish to obtain approval of work plans and balance sheets pursuant to the provisions of Article 23-9, Paragraph 1 of the Law, they shall submit the work plan and balance sheet with an application form stating that fact attached to the Minister. 2. When designated review organizations wish to receive approval to change work plans and balance sheets pursuant to the provisions of Article 23-8, Paragraph 1 of the Law, they shall submit an application form containing the following items to the Minister. (1) The items to be changed (2) The date of the change (3) The reason for the change Article 28-12. (Keeping of Account Books, etc.) Account books pursuant to the provisions of Article 23-10 of the Law shall be prepared for each office performing review work, shall be kept in the offices concerned and shall be preserved for a period of 5 years from the date of preparation. Article 28-13. (Items Entered in the Account Books) Items related to review work specified by MHW Ordinance pursuant to the provisions of Article 23-10 of the Law shall be as follows. (1) Name and address of the review applicant (2) Date of the application (3) Name of the product reviewed (4) Results of the review (5) Date of notification of the review results Article 28-14. (Applications for Approval to Suspend or Discontinue Review Work) When designated review organizations wish to receive approval pursuant to the provisions of Article 23-11, Paragraph 1 of the Law, they shall submit an application containing the following items to the Minister. (1) Range of review work to be suspended or discontinued (2) Date of the suspension or discontinuation and, in cases of suspension, the period (3) Reason for the suspension or discontinuation Article 28-15. (Items Required for Continuation of Review Work) When review work is continued pursuant to the provisions of Article 23-15, Paragraph 3 of the Law, the designated review organization (when the Minister cancels the designation of a designated review organization pursuant to the provisions of Article 23-13, Paragraph 1 or Paragraph 2 of the Law, that designated review organization) shall undertake the following items. (1) Transfer the review work to be continued to the Minister (2) Transfer the account books and documentation concerning the review work to be continued to the Minister (3) Other items confirmed to be necessary by the Minister CHAPTER III SELLING DRUGS AND SELLING AND LEASING MEDICAL DEVICES Article 29. (Application for First-Class License to Sell Drugs) Persons applying for a first-class license to sell drugs shall submit an application on Form No.15 to the prefectural governor [the mayor of the municipality or ward in the cases of first class sellers other than first class wholesalers pursuant to the provisions of Article 26, Paragraph 1 of the Law (hereinafter "first class sellers other than first class wholesalers") with stores located in municipalities (hereinafter "municipalities or wards with health centers") or special wards specified by cabinet order pursuant to the provisions of Article 5, Paragraph 1 of the Regional Insurance Law (Law No.101, 1947)]. 2. The provisions in Article 1, Paragraph 2 (except Item No. 5 in the case of persons applying for first-class licenses for wholesaling) and Paragraph 3 shall apply mutatis mutandis to applications in the preceding paragraph. In this case, "prefectural governors" in the same paragraph shall read "prefectural governors (the mayor of the municipality or ward in the cases of first class sellers other than first class wholesalers with stores located in municipalities or wards with health centers", and "Law" shall read "Law with application mutatis mutandis in Article 23 of the Law". Article 29-2. (Entries in the First-class License Register) The following matters shall be entered in the Register of Licensed First-Class Sellers: (1) License number and date. (2) Type of license. (3) Name and address of the owner of the first-class seller. (4) Name and address of the store. (5) Name and address of the supervisor of the first-class seller. (6) When radiopharmaceuticals are handled, the type of radiopharmaceuticals concerned. (7) If another business is operated at the store, the type of such business. (8) With respect to a person who has received a first-class license for wholesaling, the following matters: (a) Area of storage facilities for drugs. (b) Whether the person has received a license pursuant to the proviso in Article 26, Paragraph 3 of the Law, the number and date of the license, the types of purchasers, and articles for sale. (9) The following items are to be entered for persons other than those who have received a first-class license for wholesaling (except for those who have received licenses pursuant to the provisions of the proviso in Article 26, Paragraph 3 of the Law): If in addition to a manager of a first class seller, a pharmacist is engaged in pharmaceutically related work at the store, the name and address of the pharmacist. Article 29-3. (Application Mutatis Mutandis) The provisions of Articles 2 through 7, Articles 10 through 12, and Article 13 shall apply to persons who have received a license as a first-class seller [except that Paragraph 1, Item 1(2) shall apply to persons who have received a first-class license for wholesaling but have not received a license pursuant to the proviso in Article 26, Paragraph 3 of the Law]. In this case, "Form No.2" in Article 2 shall read"Form No.15-2", "prefectural governors" in Article 4, Paragraph 2, Article 5, Paragraph 2 and 3, Article 6, Article 7 and Article 12, Paragraph 4 shall read "prefectural governors (the mayor of the municipality or ward in the cases of first class sellers other than first class wholesalers with stores located in municipalities or wards with health centers")"Form No.5" in Article 7 shall read"Form No.15-3", in Article 11, Paragraph 1,"a test organization specified by the Minister" shall read"other test facilities of those who have received a first-class license for wholesaling, or a test organization specified by the Minister", in Paragraph 4, "Law" shall read "Law with application mutatis mutandis in Article 23 of the Law", in Article 12, Paragraph 3, "prefectural governors" shall read "prefectural governors (the mayor of the municipality or ward in the cases of first class sellers other than first class wholesalers with stores located in municipalities or wards with health centers". Article 29-4. (Applications for License to Change Persons to Whom Drugs Are Sold or Given) Persons wishing to receive a license under the proviso in Article 26, Paragraph 3 of the Law shall submit an application on Form No. 15-4 to the prefectural governor. 2. The provisions in Article 1, Paragraph 2 shall apply mutatis mutandis to the application in the preceding paragraph. In this case, "the following" in the same paragraph shall read "in Item 5". Article 29-5. (Form of License to Change Persons, etc. to Whom Drugs Are Sold) Notice of license provided for by the proviso in Article 26, Paragraph 3 of the Law shall be issued on Form No.15-5. Article 29-6. (Notification of Change) When a person who has received a license in accordance with the proviso in Article 26, Paragraph 3 of the Law changes or adds a purchaser or products for sale covered by the license, he shall notify the governor of the prefecture where the store is located within 30 days. 2. The notification in the preceding paragraph shall be submitted on Form No 6. Article 29-7. (Return of Notice of License to Change of Purchaser of Drugs, etc.) A person who has received a license under the provisions of the proviso in Article 26, Paragraph 3 of the Law shall immediately return the license certificate under the said provisions to the governor of the prefecture where the store is located if his first-class license for wholesaling has been canceled under the provisions of Article 75, Paragraph 1 of the Law, or he has closed the first-class wholesaling business. Article 29-8. (Application) The provisions in Articles 3 through 5 shall apply to the display as well as the application for alteration and reissuance of the license certificate under the proviso in Article 26, Paragraph 3 of the Law. Article 30. (Application for Second-Class License to Sell Drugs) Persons wishing to receive a second-class license to sell drugs shall submit an application on Form No. 16 to the prefectural governor. 2. The following documents shall be attached to the application referred to in the preceding paragraph. However, this shall not apply when the fact that the forms have been submitted to the prefectural governor or submitted to the Minister via the prefectural governor as the recipient of forms for applications, etc. is entered in the application form concerned,: (1) Floorplan of the store. (2) When the applicant is a corporation, a copy of the registration. (3) A medical report from a physician indicating whether or not the applicant (when the applicant is a corporation, the directors engaged in the business and the persons specified in Article 5 of the Ordinance) is suffering from a mental illness or is addicted to narcotics, marijuana, opium or stimulants. (4) When the applicant is a person to whom the provisions of Article 6 of theOrdinance apply, a school graduation certificate as specified in Article 6. 3. When the applicant is a corporation and it is confirmed by the prefectural governor that work will not be impaired based on an evaluation of the tasks performed by the director, it shall be possible to submit, in place of the medical certificate in Item (3) of the preceding paragraph, a document certifying that the director concerned does correspond to Article 6, Item 2 (d) of the Law. Article 30-2. (Qualifications for Taking Examinations under Article 28, Paragraph 2 of the Law) Persons who take an examination under Article 28, Paragraph 2 of the Law must be one of the following: (1) A person who has been employed in a pharmacy, a first-class seller, or a second-class seller for at least 3 years after graduation from a former middle school, a high school or an equivalent or higher level school (2) Other than the persons specified in the previous item, a person recognized by the prefectural governor as having knowledge and experience in the business of the second-class seller equal to or greater than those specified in the preceding two Items. Article 30-3. (Application Mutatis Mutandis) The provisions of Article 11-3 and Article 29-2 (except Items 6 and 9) shall apply mutatis mutandis to second-class sellers. Article 31. (Application for License to Sell Drugs by Household Distribution) Persons wishing to receive a license to sell drugs by household distribution shall submit an application on Form No.17 to the prefectural governor. (the mayor of the municipality or ward when stores are located in municipalities or wards with health centers) 2. The following documents shall be attached to the application referred to in the previous paragraph. However, this shall not apply when the fact that the forms have been submitted to the prefectural governor (the mayor of the municipality or ward when stores are located in municipalities or wards with health centers) or submitted to the Minister via the prefectural governor as the recipient of forms for applications, etc. is entered in the application form concerned.: (1) The documents specified in Article 30, Paragraph 2, Items 2 and 3. (2) A graduation certificate, certificate stating the number of years of businessexperience of the applicant, or other document which demonstrates that the applicant satisfies the provisions in Article 7 of the Ordinance. Article 32. (Application for Third-Class license to Sell Drugs) Persons wishing to receive a third-class license to sell drugs shall submit an application on Form No.18 to the prefectural governor. 2. The following documents shall be attached to the application referred to in the previous paragraph: (1) A floorplan of the store. (2) When the applicant is a corporation, a copy of the registration. Article 32-2. (Application Mutatis Mutandis) The provisions of Article 11-3 shall apply mutatis mutandis to persons engaged in third-class selling of drugs. Article 32-3. The provisions of Article 8 shall apply mutatis mutandis to the entries made in the register of licensed household distributors and the register of licensed third-class sellers. Article 33. The provisions of Articles 2 through 7 and Articles 12 and 13 shall apply mutatis mutandis to the selling of drugs (except for first-class selling). In this case,"Form No.2" in Article 2 shall read"Form No.15-2"; "prefectural governors" shall read "prefectural governors (the mayor of the municipality or ward in the cases of third class sellers with stores located in municipalities or wards with health centers)""Form No.5" in Article 7 shall read"Form No.15-3"; and, in Article 12,"directors" shall read "directors (including those specified in Article 5 of the Ordinance)" and"a major part of the structure and equipment of the pharmacy" shall read"a major part of the structure and equipment of the store (in the case of sales by household distribution, the business area)" and "prefectural governors" in Article 4, Paragraph 2, Article 5, Paragraph 2 and 3, Article 6, Article 7 and Article 12-2, Paragraph 1 shall read "prefectural governors (the mayor of the municipality or ward in the cases of third class sellers with stores located in municipalities or wards with health centers"). Article 34. Deleted. Article 35. (Obligations of Second-Class Distributors) Second-class sellers must maintain in person the structure and facilities of their store, drugs and other items and carry on their business in such a way that public health and hygiene are not endangered. 2. Second-class sellers must store and display drugs separately from other medically related products. Article 36. (Designated Drugs) The drugs specified in Article 29 of the Law are as given in Attached Table 1-2. Article 37. (Notification Items for Household Distribution) A household distributor or his employees must file notice pursuant to the provisions of Article 32 of the Law with respect to the following items: (1) Name and address of the household distributor. (2) Names and addresses of the persons engaging in household distribution. (3) The region of the distribution sales [broken down into counties, cities (into wards for cities which have a ward system) and special wards] as well as the period for such sales and the person to contact during this period. Article 38. (Identification Card of Household Distributor) Persons applying for the identification card as specified in Article 33, Paragraph 1 of the Law shall submit an application on Form No.21 to the governor of the prefecture where the applicant is domiciled. 2. The following documents shall be attached to the application in the preceding paragraph. However, this shall not apply when the fact that the forms have been submitted to the prefectural governor or submitted to the Minister via the prefectural governor [limited to documents in item (2)] as the recipient of forms for applications, etc. is entered in the application form concerned. (1) A photograph 4 cm long and 3 cm wide of the upper one third of the body, frontal view, hatless with no background taken within 6 months before the application (2) When the applicant is a salesman, a copy of the employment contract or other evidence of the relationship between the household distributor and the salesman. Article 39. The identification card in Article 33, Paragraph 1 of the Law shall be issued on Form No.22. 2. The period of validity of the identification card referred to in the preceding paragraph shall be from the day of issue until December 31 of the year following the year in which the card was issued. Article 40. (Application for the Addition of Designated Products) When a household distributor or a third-class seller applies for changes or additions with respect to products designated by the prefectural governor (the mayor of the municipality or ward in the cases of third class sellers with stores located in municipalities or wards with health centers; the same hereinafter in this article) in accordance with the provisions in Article 30, Paragraph 1 or Article 35 of the Law, he shall submit an application on Form No.23 to the prefectural governor. Article 41. (Medical Devices Requiring a Selling or Leasing Notification) The medical devices specified in Article 39, Paragraph 1 of the Law are as listed in Attached Table 2. However, notification of leasing of medical devices, shall be required only for leasers who undertake storage, display or other management of medical devices. Article 42. (Notification of Selling or Leasing of Medical Devices) Matters which must be reported by persons wishing to engage in the business of selling or leasing medical devices referred to in the preceding article pursuant to the provisions of Article 39, Paragraph 1 of the Law are as follows: (1) Name and address of the person making the notification. (2) Name and address of the site of business. (3) Outline of the structure and equipment of the business site. (4) Types of medical devices to be handled. (5) When another business is also conducted at the business site concerned, the type of such business. 2. The notifications in the preceding paragraph are to be submitted on Form No.24. 3. A floorplan of the business site concerned must be attached to the notification referred to in the preceding paragraph. However, this shall not apply when the fact that the forms have been submitted to the prefectural governor or submitted to the Minister via the prefectural governor as the recipient of forms for applications, etc. is entered in the application form concerned. Article 42-2 (Quality Assurance by Sellers and Leasers of Medical Devices) Sellers, etc. of medical devices shall assure the quality of the medical devices by appropriate methods. 2. When sellers, etc. receive complaints concerning the quality, etc. of medical devices which they have sold or leased, they shall clarify the cause of the items in the complaints and undertake the necessary measures when improvement of quality control is required except in cases where it is clear that the items in the complaint were not caused by them. 3. When sellers, etc. recall medical devices which they have sold or leased for reasons related to quality, etc., they must undertake the following in cases where the reason for the recall is definitely caused by display, storage, etc. of the medical device concerned. (1) Clarify the reason for the recall and take the required measures when improvements must be made in quality control. (2) Take appropriate disposal measures after the recalled medical device has been classified and stored for a fixed period. 4. Sellers and leasers of medical devices (limited to persons in the business of selling or giving medical devices to manufacturers, sellers or leasers, proprietors or hospitals, clinics or veterinary clinics or those in the business of leasing medical devices to the proprietors of hospitals, clinics or veterinary clinics) shall have persons corresponding to any of the following items (referred to as "selling managers" for sellers or "leasing managers" for leasers in the following paragraph) employed in each business office. (1) A person who has completed a course designated by the Minister after being employed for more than 3 years in work related to selling or leasing of medical devices. (2) A person confirmed by the Minister to have knowledge and experience equivalent to or greater than the person in the preceding item. 5. The seller, etc. shall have the selling manager or leasing manager undertake the following work. (1) When installation control medical devices are installed, control of the installation by appropriate methods based on the installation control criteria for the installation control medical devices concerned. (2) When used medical devices are sold, given or leased, notification of the manufacturer, etc. of the medical device concerned. Article 43. (Notification of Changes) Matters with respect to which changes must be reported in accordance with Article 40 of the Law are as specified in Article 42, Paragraph 1 of these Regulations. 2. The notifications referred to in the preceding paragraph are to be submitted on Form No.6. Article 44. (Forms for Notification of Suspensions, Closings, etc.) Notifications of closing or suspension of the business of selling or leasing medical devices, or reopening of suspended businesses as specified in Article 41 of these Regulations are to be submitted on Form No.7. Article 45. (Exceptions for Notifications) When pharmacies or stores selling drugs also engage in selling or leasing of medical devices or when the proprietor of the pharmacy or the store. When the applications or notifications in the following items are submitted, the notifications in the corresponding items with respect to the Pharmacy or the store concerned will be considered as submitted. However, this shall not apply when the applicant expresses a different intention. (1) Applications in Article 1, Paragraph 1, Article 29, Paragraph 1, Article 30, Paragraph 1 or Article 32, Paragraph 1: Notifications in Article 42, Paragraph 2 (2) Notifications in Article 12, Paragraph 2 (with application mutatis mutandis in Article 29-3 or Article 33): Notifications in Article 42, Paragraph 2 and Article 42, Paragraph 2 (3) Notifications in Article 13 (with application mutatis mutandis in Article 29-3 or Article 33): Notifications in Article 44 2. When the mayors of municipalities or special wards with health centers receive the applications or notifications in the preceding paragraph, they shall promptly forward a copy of the application or notification concerned to the prefectural governor. Article 45-2. (Installation Control by Sellers, etc.) The provisions of Article 23-2, Paragraph 2 to Paragraph 4 and Paragraph 7 shall apply mutatis mutandis to sellers, etc. of installation control medical devices. CHAPTER IV TESTS Article 46. (Test Applications and Testing Organizations) Applications for tests of drugs as specified in Article 43, Paragraph 1 of the Law or medical devices as specified in Article 43, Paragraph 2 of the Law shall be submitted on Form No.25 for each drug or medical device with the same manufacturing number. 2. Documents describing records of in-house tests must be attached to the applications referred to in the preceding paragraph. 3. The testing organizations in Article 8 of the Ordinance are the National Institute of Infectious Diseases for biological preparations and antibiotics and the National Institute of Health Sciences for other drugs and medical devices. 4. A revenue stamp equivalent in amount to the fee set by the Minister pursuant to the provisions of Article 8 of the Ordinance shall be attached to the application specified in Paragraph 1. Article 47. (Receiving and Labeling) When an applicant wishes to have a test performed, he shall place the drug or the medical device in the container or packaging used when the drug or medical device is sold or given (sold, given or leased in the case of medical devices; the same in the following paragraphs), and place it in a box or other container suitable to be sealed. The items listed below must be indicated on the outer box or container. (1) Name of the drug or medical device. (2) Manufacturing number (in the case of imports, the manufacturing number and the name of the manufacturer from whom the drug was imported). (3) Date of manufacture (in the case of imports, date of manufacture and date of import). (4) The quantity. 2. When an applicant wishes biological products to be tested, the requirements specified in the preceding paragraph shall be applied to these samples in the presence of a pharmaceutical inspector to collect the test samples as specified in Article 9 of the Ordinance. 3. When the drug or medical device is to be tested at two or more stages during manufacture, the provisions in the preceding two paragraphs shall not apply except in the case of the test at the final stage. Article 48. (Collection, etc. of Test Samples) When the pharmaceutical inspectors collect the test samples as specified in Article 9 of the Ordinance, they shall collect the samples in the amounts specified by the Minister, place them in suitable containers, seal the containers and inscribe the following items on the containers: (1) Name of applicant. (2) Name of drug or medical device. (3) Manufacturing number (in the case of imports, the manufacturing number and the name of the manufacturer from whom the drug was imported). (4) Date of manufacture (in the case of imports, date of manufacture and date of import). (5) The quantity. 2. When samples in the previous paragraph are collected in a box or other container pursuant to the provisions of Paragraph 1 of the preceding Article, the box or other container must be sealed. 3. The seal pursuant to the preceding paragraph on the box or other container containing the test sample must not be broken except in the following cases: (1) The pharmaceutical investigator breaks the seal in order to apply the seal pursuant to the provisions of Article 11 of the Ordinance. (2) The applicant breaks the seal after receiving notification of failure to pass a test. Article 49. (Certificate of Passing the Test) The certificate of passing the test pursuant to the provisions of Article 10 of the Ordinance is to be issued on Form No.26. Article 50. (Sealing by the Test Certificate) A seal described in Article 11 of the Ordinance shall be such that the drug or medical device cannot be taken out of the container or wrapper of a drug or medical device which has passed the test unless the seal is broken. Article 51. (Test Record Table) The applicant shall compile a test record table on Form No.27 for drugs and medical devices which have been tested. CHAPTER V HANDLING OF DRUGS, ETC. Article 52. (Range of Poisonous and Powerful Drugs) The poisonous and powerful drugs regulated pursuant to the provisions of Article 44, Paragraphs 1 and 2 of the Law are as listed in Attached Table 3. Article 53. (Register Concerning the Transfer of Drugs Requiring Directions or Prescriptions) Pursuant to the provisions of Article 49, Paragraph 2 of the Law, the following entries shall be recorded in a register concerning the sales or supply of drugs specified in Article 49, Paragraph 1 of the Law: (1) Name of drug. (2) The quantity. (3) Date of sale or supply. (4) The name and address of the physician, dentist or veterinarian who issued the prescription or directed the use of the drug, or the name and address of the hospital, clinic or veterinary clinic where such persons work. (5) Name and address of person receiving the drug. Article 53-2. (Matters to Be Indicated on Immediate Container, etc.) The items which must be indicated on the immediate container or wrapper of a drug pursuant to the provisions of Article 50, Item 11 of the Law are as follows: (1) For bulk drugs which are used exclusively in the manufacture of other drugs and natural drug extracts, tinctures, fluid extracts and similar items among the drugs designated by the Minister which do not require approvals as specified in Article 14, Paragraph 1 of the Law, the wording "for manufacturing only"; (2) For drugs designated by the Minister pursuant to the provisions of Article 11-3, Paragraph 1 of these Regulations, the wording "record"; (3) For drugs which have been approved pursuant to the provisions of Article 19-2 of the Law, the name of the recipient of approval for manufacturing abroad and the name of a country where he is domiciled, and the name and address of the in-country caretaker (hereinafter referred to as the name, etc. of the recipient of approval for manufacturing abroad, etc.). 2. When a drug is designated in the preceding paragraph, Item 2 and the word specified in the same item is indicated on the outer container or wrapper, reference to the word concerned on the immediate container or wrapper may be omitted. Article 54. (Exceptions to Labeling) With respect to the drugs listed below for which the matters specified in Items in Article 50 of the Law cannot be clearly indicated because the immediate containers and wrappings have small surfaces, when the items in the middle columm of the following table which are specified by the provisions in the Law given in the left column are indicated on the outer container or wrapper of the drug concerned, omissions or replacements of the item can be made as indicated in the right column of the table. (1) Drugs in ampules of 2 cc or less or in immediate containers or wrappers of the same size. (2) Drugs in ampules of more than 2 cc but not more than 10 cc or in immediate containers of the same size made of glass or other similar material on which the matters are printed directly. 2. If even the exceptions to labeling provided in the preceding paragraph cannot be clearly indicated on the immediate container or wrapper because space for inscription is extremely limited, the matters need not be indicated on the immediate container or wrapper of the drug provided the matters specified in Items in Article 50 of the Law are indicated on the outer container or wrapper, subject to the license by the Minister. Article 55. When the contents of drugs can be expressed by numerical count and the count is six units or less and this can be easily found without breaking the packaging, the contents as specified in Article 50, Item 4 of the Law need not be indicated on the immediate container or wrapper. Article 56. (Exceptions for Labeling of Drugs Used Only for Manufacture) When a drug is sold or given to a drug manufacturer to be used in the manufacture of another drug and the wording "For manufacture only" is indicated on the immediate container or wrapper, the provisions of Article 50, Items 7 to 9 and Article 52, Item 1 of the Law do not apply. Article 56-2. (Exceptions for Labeling of In Vitro Diagnostics) The items in the middle column of the following table specified in the Law as indicated in the left-hand column of the same table may be replaced by the items specified in the right-hand column of the table or may be omotted for in vitro diagnostic agents (drugs used exclusively for the diagnosis of diseases which are not used in direct contact with the human body; the same hereinafter) specified as prescription drugs. In cases where the items in the middle column of the following table specified in the Law as indicated in the left-hand column of the same table are entered on the outermost container or wrapper of in vitro diagnostic agents specified as prescription drugs which have "In vitro diagnostic agent" entered on their outer container or wrapper, the entry (including entries of items in the middle column of the same table specified in the Law as indicated in the left-hand column of the table which may be replaced by items as specified in the right-hand column of the table or which may be omitted as specified in the previous paragraph) may be replaced by the items shown in the right hand column of the following table or the entry may be omitted. Article 56-3. (Exceptions for Labeling of Drugs Exclusively for Dispensing) In cases where the proprietor of a pharmacy or a first class drug seller [limited to first class drug sellers in a certain prefecture for whom it is confirmed by the prefectural pharmaceutical association, a foundation established pursuant to the provisions of Article 34 of the Civil Code (Law No.89, 1896) to which pharmacists in the prefecture concerned belong, or by another organization that the immediate container or immediate wrapper of the drug for dispensing can be opened and repackaging for marketing can be undertaken properly] opens the immediate container or immediate wrapper of a drug and repackages the drug for marketing to the proprietor of a pharmacy for use in dispensing in the pharmacy concerned, the following items shall be entered on the immediate container or immediate wrapper of the repackaged drug, This provision is limited to cases where the proprietor of the pharmacy who purchases the repackaged drug concerned when it is sold possesses the package insert, container or wrapper with the items in the middle column of the following table pursuant to the provisions of the Law shown in the left column of the table. The entries in the middle column of the table pursuant to the provisions of the Law in the left column shall be replaced by the entries specified in the right column of the table or omitted. 1) The phrase "For dispensing" 2) The name of the person or company performing the repackaging and marketing 3) The name and address of the pharmacy or store which undertakes the repackaging and marketing 2. In cases where the entry in the middle column of the table in the preceding paragraph is replaced by the entry specified in the right column of the table or omitted for drugs pursuant to the provisions of the preceding paragraph, the provisions in each item of Article 52 of the Law shall not apply to the drugs concerned when the entries pursuant to each item of Article 52 for the drug concerned are made on the package insert, container or wrapper in the possession of the proprietor of the pharmacy as specified in the previous paragraph. Article 57. (Preparation of Package Inserts, etc.) Matters which must be indicated on inserts enclosed with the drug or on the container or wrapper of the drug in accordance withe the provisions of the Law must be especially clearly indicated. 2. When a name other than that specified in the Japanese Pharmacopoeia is indicated on the package insert or on the container or wrapper of a drug recognized in the Japanese Pharmacopoeia, the name specified in the Japanese Pharmacopoeia must also be indicated in such a way that it is at least as clear as the other name. Article 58. (Entries in Japanese) The matters specified in Articles 50 through 52 of the Law must be written in the Japanese language. Article 59. (Sealing) The sealing specified in Article 58 of the Law must be such that the drug cannot be removed unless the seal is broken, and it is not easy to return to the original sealed state once the seal has been broken. Article 59-2. (Labeling of Quasi-Drugs) The matters which must be indicated on the immediate container or wrapper of quasi-drugs pursuant to the provisions of Article 59, Item 8 of the Law are as follows: (1) For quasi-drugs whose standards are set pursuant to the provisions of Article 42, Paragraph 2 of the Law, matters specified in such standards to be indicated on the immediate container or wrapper. (2) For quasi-drugs which have been approved pursuant to the provisions of Article 19-2 of the Law, the name, etc. of the recipient of approval for manufacturing abroad, etc. Article 60. (Labeling of Cosmetics) The matters which must be indicated on the immediate containers or wrappers of cosmetics pursuant to the provisions of Article 61, Item 6 of the Law are as follows: (1) The quantity of the contents by weight, volume or numerical count etc., except for cosmetics with content of not more than 10 grams or 10 cc, or which contain 6 or fewer units and for which the quantity of the contents can be easily found without opening the packaging. (2) For cosmetics with standards set pursuant to the provisions of Article 42, Paragraph 2 of the Law, matters specified in such standards to be indicated on the immediate container or wrapper. (3) For cosmetics which have been approved pursuant to the provisions of Article 19-2 of the Law, the name, etc. of the recipient of approval for manufacturing abroad, etc. Article 60-2. (Labeling of Medical Devices) The matters which must be indicated on medical devices or on their immediate container or wrapper pursuant to the provisions of Article 63, Item 5 of the Law are as follows: (1) For medical devices with standards pursuant to the provisions of Article 42, Paragraph 2 of the Law, matters specified in such standards to be indicated on the medical device or its immediate container or wrapper; (2) For medical devices which have been approved pursuant to the provisions of Article 19-2 of the Law, the name, etc. of the recipient of approval for manufacturing abroad, etc. Article 60-3. (Labeling of Metals for Dental Use) The matters which must be indicated on metals for dental use or on their immediate container or wrapper pursuant to the provisions of Article 63, Item 5 of the Law are those given in the preceding article of these Regulations and the names of the ingredients of the metal for dental use concerned (generic name, if any) and their quantities. However, this does not apply when ingredients other than gold, silver, platinum, ruthenium, rhodium, palladium, osmium, iridium or iridosmine are present in amounts of not more than 5％ by weight. 2. The quantity indications in the preceding paragraph are to be expressed as percentages by weight. These values shall have one significant figure after the decimal point in the case of gold and mercury and shall be whole numbers in the case of alloys. Article 60-4. (Exceptions for Labeling of Quasi-Drugs) With respect to quasi-drugs(except for those not to be applied directly to the human body) for which the information specified in Article 59, Item 6 of the Law is indicated on any of the articles indicated below, the indication of the information concerned can be omitted from the immediate container or wrapper. (1) The outer container or wrapper. (2) The tag or display card which is firmly attached to the immediate container or wrapper. (3) For a sample in a small container which does not have any of the articles referred to in the preceding Items 1 and 2, a package leaflet included in the container. Article 61. (Exceptions for Labeling on Medical Devices) For the medical devices listed in attached Table 4, the information described in the middle column of the following table, required pursuant to provisions of the Law cited in the left-hand column of the same table, may be replaced by the information described in the right-hand column as provided therein. Article 61-2. (Maintenance and Inspections of Medical Devices) Medical devices which require items concerning maintenance and inspection entered in the package insert or on the container or wrapper are those in attached table 1-2. Article 62. (Application Mutatis Mutandis) With respect to quasi-drugs, the provisions of Articles 54 to 56, Article 57, Paragraph 1 and Article 58 of these Regulations shall apply mutatis mutandis. 2. With respect to cosmetics, the provisions of Articles 54 and 56, Article 57, Paragraph 1, and Articles 58 and 60-4 of these Regulations shall apply mutatis mutandis. 3. With respect to medical devices, the provisions of Article 57, Paragraph 1 and Article 58 of these Regulations shall apply mutatis mutandis. 4. When any of the preceding three paragraphs apply, the items indicated in Column 3 of the following table shall be changed to read as provided in Column 4 for the articles mentioned in Column 1 in the provisions in Column 2. CHAPTER VI SURVEILLANCE Article 62-2. (Reports) When the Minister, prefectural governor or the mayer of a municipality or special ward with a health center requests a report to be submitted by the operator of a pharmacy, hospital, clinic or veterinary clinic, the manufacturer, importer, or seller, leaser of medical devices, or the in-country caretaker of a drug, etc. or other persons who handle drugs, etc. in their business pursuant to the provisions of Article 69, Paragraph 1 of the Law or, when requesting a report from the recipient of approval of a drug, etc. manufactured abroad pursuant to the provisions of Article 75-2, Paragraph 1, Item 3 of the Law, he shall inform the reporting party of the reason for such report. Article 63. (Collection Certificate) When a pharmaceutical inspector collects samples of drugs, etc. or their raw materials pusuant to the provisions of Article 69, Paragraph 1 of the Law, he shall issue a collection certificate on Form No.28 to the party from whom the collection was made. Article 64. (Identification Certificate) The identification certificate required under Article 69, Paragraph 3 of the Law shall be prepared on Form No. 29. CHAPTER VII DESIGNATION OF ORPHAN DRUGS AND ORPHAN MEDICAL DEVICES Article 64-2. (Applications for Designation of Orphan Drugs or Orphan Medical Devices) Applications for designation of orphan drugs or orphan medical devices pursuant to the provisions of Article 77-2, Paragraph 1 of the Law shall be submitted on Form No. 30 (one original and two copies). 2. Data concerning the number of patients in Japan who would use the drug or medical device concerned, an outline of test results on toxicity, pharmacological action, etc. and other required data must be attached to the application form in the preceding paragraph. Article 64-3. (Upper Limit of Number of Patients) The number of patients specified by MHW ordinance pursuant to the provisions in Article 77-2, Paragraph 1, Item 1 of the Law shall be 50,000. Article 64-4. (Notification of Discontinuation of Research, etc.) Notifications of discontinuation of research, manufacture or import of orphan drugs or orphan medical devices pursuant to the provisions of Article 77-2-4 of the Law shall be submitted on Form No.31. CHAPTER VIII MISCELLANEOUS PROVISIONS Article 64-5. (Supply of Information) The recipient of approval for foreign manufacture or the in-country caretaker shall furnish the following information to importer-distributors who import the approved drugs, etc. (1) Terms of approval under Article 19-2, Paragraph 1 of the Law pertaining to the applicable product, and, in the case of an amendment, the matters amended and reasons therefor. (2) Information necessary for recording the matters stipulated in Article 50, 59, 61 or 63 of the Law and if an amendment has been made, the reasons for the amendment. (3) Information necessary for recording the matters stipulated in Article 52 (or as applied mutatis mutandis in Article 60 or 62) or Article 63-2 of the Law and if an amendment has been made, the reasons for the amendment. (4) A copy of the documents submitted at the time of the application for approval under Article 19-2 of the Law; a copy of the documents submitted at the time of the application for reexamination under Article 14-4, Paragraph 1 of the Law as applied mutatis mutandis in Article 19-4 of the Law; and a copy of the documents submitted at the time of the reevaluation of drugs or medical devices under Article 14-5 of the Law as applied mutatis mutandis in Article 19-4 of the Law. (5) Matters reported to the Minister under Article 14-4, Paragraph 5 of the Law as applied by Article 19-4 of the Law and matters relating to adverse reactions reported to the Minister pursuant to the provisions of Article 69, Paragraph 1 or Article 75-2, Paragraph 1, Item 3 of the Law. (6) Matters necessary for importer-distributors' business operations other than those referred to in the precceding items. Article 64-5-2. (Adverse Reaction Reports) When manufacturers or importers and marketers of drugs, persons who have obtained foreign manufacturing approvals or in-country caretakers learns of any of the events in the following items concerning the drugs which they manufacture, import or have obtained approval for, they shall report this fact to the Minister within the period specified for the event concerned. (1) The following events: 15 days (a) When any of the following events is suspected to be caused by an adverse reaction of the drug concerned or a drug used in a foreign country found to have the same ingredients as the drug concerned (hereinafter, "drug, etc. concerned" in this paragraph), and the onset of such an event, the number of cases, the incidence, the conditions of onset, etc. can not be predicted from the Precautions in the package insert or on the container or wrapper of the drug, etc. concerned. (1) Death (2) Disability (3) Cases which might be related to death or disability (4) Cases which require admission or prolongation of the period of admission to a hospital or clinic for treatment [excluding cases in (3)] (5) Severe cases corresponding to those in (1) to (4) (6) Congenital diseases or abnormalities in the next generation (b) Onset of events in Item (a)(1) to (6) caused by infections suspected to be due to the drug, etc. concerned. (c) Measures taken to prevent the onset or spread of risks to public health or hygiene, including discontinuation of manufacture, import and marketing, recall and disposal of a drug used in a foreign country found to have the same ingredients as the drug concerned. (2) The following events (excluding those in the previous item): 30 days (a) Onset of events in (a)(1) to (6) of the preceding item suspected to be caused by adverse reactions of the drug concerned. (b) Onset of events suspected to be caused by adverse reactions or infections suspected to be caused by use of the drug concerned, which could not be predicted from the Precautions in the package insert or on the container or wrapper of the drug concerned (excluding mild cases). (c) Research reports showing the possibility of the onset of cancer or other serious diseases, disabilities or death caused by adverse reactions or by infections due to use of the drug, etc. concerned; those showing marked changes in the onset trends, such as the number of cases, incidence or conditions of onset of events due to adverse reactions or due to infections due to use of the drug, etc. concerned; or those showing that the drug, etc. concerned does not have the indications for which approval was received. 2. When manufacturers or importers and marketers of medical devices, persons who have obtained foreign manufacturing approvals or in-country caretakers learns of any of the events in the following items concerning the medical devices which they manufacture, import or have obtained approval for, they shall report this fact to the Minister within the period specified for the event concerned. (1) The following events: 15 days (a) When any of events in Item (a)(1) to (6) in the previous paragraph is suspected to be caused by an adverse reaction of the medical device concerned or a medical device used in a foreign country found to have the same shape, structure, raw materials, method of use, indications, performance, etc. as the medical device concerned (hereinafter, "medical device, etc. concerned" in this paragraph), and the onset of such an event, the number of cases, the incidence, the conditions of onset, etc. can not be predicted from the Precautions in the package insert or on the container or wrapper of the drug, etc. concerned. (b) Onset of events in Item (a)(1) to (6) in the previous paragraph caused by infections suspected to be due to the medical device, etc. concerned. (c) A problem occurs with the medical device concerned and events in Item (a) are assumed to have occurred because of this problem. (d) Measures taken to prevent the onset or spread of risks to public health or hygiene, including discontinuation of manufacture, import and marketing, recall and disposal of a medical device used in a foreign country found to have the same shape, structure, raw materials, method of use, indications, performance, etc. as the medical device concerned. (2) The following events (excluding those in the previous item): 30 days (a) Onset of events in (a)(1) to (6) of the preceding item suspected to be affected by problems of the medical device concerned. (b) Onset of events suspected to be affected by problems of the medical device concerned or infections suspected to be caused by use of the medical device concerned, which could not be predicted from the Precautions in the package insert or on the container or wrapper of the medical device concerned (excluding mild cases). (c) A problem occurs with the medical device concerned and events in Item (a) or (b) are assumed to have occurred because of this problem. (d) Research reports showing the possibility of serious effects on the health of persons caused by problems of the medical device concerned or by infections due to use of the medical device, etc. concerned; those showing marked changes in the onset trends, such as the number of cases, incidence or conditions of onset of effects on the health of persons caused by problems of the medical device concerned or by infections due to use of the medical device, etc. concerned; or those showing that the medical device, etc. concerned does not have the indications or performance for which approval was received. 3. When manufacturers or importers and marketers of quasi-drugs or cosmetics, persons who have obtained foreign manufacturing approvals or in-country caretakers learn of research reports showing the possibility of onset of adverse events concerning the quasi-drugs or cosmetics which they manufacture, import or have obtained approval for, they shall report this fact to the Minister within 30 days. Article 64-5-3 (Recall Reports) When manufacturers or importers and marketers of drugs, quasi-drugs, cosmetics or medical devices, persons who have obtained foreign manufacturing approvals or in-country caretakers issue reports pursuant to the provisions of Article 77-4-3, they must report promptly after the start of the recall the following items to the Minister (to the prefectural governor when the authority concerned has been transferred to the prefectural governors pursuant to the provisions of Article 15-4 of the Ordinance). (1) The name and address of the person making the recall (2) The name of the drug, quasi-drug, cosmetic or medical device subject to the recall, the date of the license to manufacture or import the product concerned, and the approval number and date of the product concerned (3) The quantity of the product subject to recall, the manufacturing number or code, and the date of manufacture or import (4) The name and address of the manufacturing plant or sales office of the product concerned (5) The data on which recall was started (6) The method used for the recall (7) Other measures taken to prevent the onset or spread of hazards to public health or hygiene. However, this shall not apply when the fact that documents were submitted to the Minister at the time of application, etc. is specified in the notification. Article 64-6. (Designated Medical Devices) Designated medical devices pursuant to the provisions of Article 77-5, Paragraph 1 of the Law shall be as follows. (1) Implantation type cardiac pacemakers (2) Implantation type cardiac pacemaker leads (3) Defibrillators (limited to those which are used by implantation in the human body; the same in the following item) (4) Defibrillator leads (5) Artificial heart valves (6) Artificial valve rings (7) Artificial blood vessels (limited to those used in the coronary arteries, thoracic aorta and abdominal aorta) Article 64-7. (Items in Records of Designated Medical Devices) Items specified by MHW ordinance pursuant to the provisions of Article 77-5, Paragraph 1 of the Law shall be as follows. (1) Name, address, date of birth and gender of the users of designated medical devices (2) Name and manufacturing number or the equivalent of the designated medical device (3) Date when the designated medical device was implanted (4) Name and address of the medical institution which implanted the medical device (5) Other items required to prevent hazards to public health and hygiene caused by the designated medical device. Article 64-8. (Contracting out of Work such as Preparation of Records) The criteria specified by MHW ordinance pursuant to the provisions of 77-5, Paragraph 4 of the Law shall be sellers, leasers or importers distributors handling a designated medical device exclusively in Japan (excluding persons who have received approval for the medical device concerned pursuant to the provisions of Article 14 of the Law applied mutatis mutandis in Article 23 of the Law). 2. Items specified by MHW ordinance pursuant to the provisions of Article 77-5, Paragraph 4 of the Law shall be as follows. (1) The name and address of the person or the name of the representative in the case of a corporation which has received manufacturing approval and person entrusted with work such as preparation of records (hereinafter referred to as the "entrusted person" in this Article). (2) The name, approval number and approval date of the designated medical device concerned. 3. The notification pursuant to the provisions of Article 77-5, Paragraph 4 of the Law shall be submitted on Form No. 31-2 (one original and one copy) via the governor of the prefecture where the person submitting the notification is domiciled. 4. The following documentation shall be attached to the notification in the preceding paragraph. However, this shall not apply when it stator in the notification' concerned that these documents have been submitted to the minister with applications, etc. (1) Copy of the resident card of the contrusted person (copy of the register in the case of a corporation) (2) Documentation proving that the entrusted person meets the criteria specified in Paragraph 1 (3) Copy of the contract entrusting the work concerned Article 64-9. (Notification of Change in Persons Entrusted with Record Preparation Work) When persons who have received manufacturing approval change the items specified in Paragraph 2, Item (1) of the preceding article, they shall notify the Minister of the change within 30 days. 2. The notification in the preceding paragraph shall be submitted on Form No. 31-2 (one original and one copy) via the governor of the prefecture where the person submitting the notification is domiciled. 3. Documentation certifying the items which have been changed must be attached to the notification in the preceding paragraph. Article 64-10. (Retention of Records) Records concerning designated medical devices shall be retained for a period up to the time specified in any of the following items. (1) Death of the user of the designated medical device (2) Time when the designated medical device is no longer used (3) Time when reason for the retention of the records is no longer valid other than the times in the previous two items. Article 64-11. (Drugs Which Require Special Fees for Approval-Related Investiga- tions) The drugs specified in the proviso of Article 14, Paragraph 1, Item 3 (a), (1) of the Ordinance shall be drugs containing active ingredients (the nature in cases where the active ingredients are unclear; the same hereinafter) other than those stipulated in the following items (excluding drugs specified in Article 1-2, Paragraph 1, Item 4 of the Ordinance, drugs manufactured in pharmacies and drugs specified in Article 14, Paragraph 1, Item 3a, (1) c and d of the Ordinance). 1) Active ingredients of drugs in the Japanese Pharmacopoeia 2) Active ingredients of drugs approved pursuant to the provsions in Article 14, Paragraph 1 (including application of Article 23 mutatis mutandis) or Article 19-2, Paragraph 1 of the Law (excluding active igredients for which less 2 years has passed since approval was granted). 3) Active ingredients in drugs for which standards have been set pursuant to the provisions of Article 42, Paragraph 1 of the Law. Article 65. (Method of Paying Fees) Fees pursuant to the provisions of Article 78, Paragraph 1 of the Law shall be paid by attaching a revenue stamp equivalent to the amount of the fee for the application (limited to applications submitted to the Minister) to the application form. 2. Notwithstanding the preceding paragraph, the fees stipulated in each item of Article 14, Paragraph 2 of the Ordinance shall be paid in cash after notification of payment due has been issued. 3. Fees pursuant to provisions in Article 78, Paragraph 2 of the Law shall be paid by transfer to the bank account of the Drug Organization in a financial institution. 4. The fees pursuant to the provisions of Article 78, Paragraph 4 of the Law shall be paid by transfer to the account of the designated review organization established in a financial institution. Article 65-2. (Details of Calculating Travel Expenses) Trip expenses under Ordinance Article 14, Paragraph 2, Item 1 (hereinafter referred to as "travel expenses") shall be calculated as follows: (1) For purposes of calculating travel expense amounts, the location of the government offices referred to in the Law Relating to Travel Expenses of Government Officials (Law No. 114, 1950, hereinafter referred to as Travel Expense Law) Article 2, Paragraph 1, Item 6, from which a person travels to the location of facilities (hereinafter referred to as "facility location") to conduct tests or inspections for an examination or reexamination (herein-after referred to as "examination, etc.") shall be 2-2, Kasumigaseki 1-chome, Chiyoda-ku, Tokyo. (2) The preparation allowance stipulated in Article 6, Paragraph 1 of the Travel Expense Law shall not be included in the trip expense. (3) The number of days to complete the examination, etc. shall be the number of days stipulated as necessary by the Minister, not to exceed five (5) days. (4) The number of days for the trip shall be the number of days based on the next preceding item plus the number of days required for the round trip between office and the facility location. (5) The miscellaneous travel expenses described in Article 6, Paragraph 1 of the Travel Expense Law shall be calculated as 10,000 yen. (6) If the Minister does not provide a portion of travel expenses under Article 46, Paragraph 1 of the Travel Expense Law which is deemed unnecessary or in excess of actual expenses, the amount equivalent to such portion shall not be included in the travel expenses. Article 66. (Notification Relating to Exports) Information which must be reported by manufacturers or importers of drugs, etc. pursuant to the provisions of Article 15, Paragraph 1 of the Ordinance includes: (1) Name and address of the person submitting the notification. (2) Name and address of the factory or place of business. (3) Names of drugs, etc. manufactured for export or drugs, etc. which are to be imported and place where the drug, etc. is to be exported. 2. The information described in the preceding paragraph shall be submitted on Form No.32 (one original and one copy). 3. The provisions of the preceding paragraph notwithstanding, notifications specified in Article 15, Paragraph 1 of the Ordinance applicable to changes in the entries in notifications specified in the preceding paragraph shall be submitted on Form No. 6 (one original and one copy). Article 66-2. (Entries in Package Inserts for Drugs Given Special Licenses Before Approval) The words "Drug with special license before approval" must be entered in the package insert or on the container or wrapper of the drug pursuant to the provisions of Article 80, Paragraph 2 of the Law when the provisions of Article 52 of the Law are applied pursuant to the provisions of Article 15-2, Paragraph 5 of the Law. Article 66-3. (Notification of Clinical Trial Protocols for Drugs) Sponsors of clinical trials (limited to those on drugs; the same in the remainder of this article until Article 66-7) shall notify the Minister beforehand of the following items concerning the clinical trial protocol. (1) Ingredients and quantities of the drug which is the object of the clinical trial (hereinafter the "trial drug") (2) Manufacturing method of the trial drug (3) Anticipated indications of the trial drug (4) Anticipated dosage and administration of the trial drug (5) Objective, contents and period of the clinical trial (6) Name and address of the medical institution(s) performing the clinical trial (7) Names and titles of the physician or dentist supervising the work related to the clinical trial (hereinafter the coordinating investigator) in each medical institution performing the clinical trial (8) Names and titles of any physicians or dentists participating in the clinical trial under the supervision of the coordinating investigator) (9) Quantities of the trial drug, and drug product or substance and any other substance used for the purpose of comparison with the trial drug expected to be allocated to each medical institution performing the clinical trial (10) Anticipated numbers of subjects in each medical institution performing the clinical trial (11) The reason when the trial drug is supplied for a fee (12) Name and address of the person selected from among persons domiciled in Japan (including the representative of the office concerned in the case of foreign companies with offices in Japan) who can supervise the clinical trial in place of the sponsor in order to take the measures necessary to prevent the onset or spread of risks to public health and hygiene caused by the trial drug when the clinical trial sponsor is not domiciled in Japanese (hereinafter the "in-country caretaker" in this article and until Article 66-7) (13) The name and title of a physician or dentist entrusted to coordinate the interpretation of the clinical trial protocol or other details concerning the clinical trial (14) The names and titles of physicians or dentists who are members of a committee formed of a plurality of physicians or dentists and entrusted to coordinate the interpretation of the clinical trial protocol or other details concerning the clinical trial (15) When the clinical trial sponsor contracts out part of the work related to sponsoring or managing the clinical trial, the name and address of the person to whom this work was contracted out and the range of the work contracted out. 2. An outline of the results of studies on toxicity, pharmacological action, etc. and other required data shall be attached to the notification in the preceding paragraph. Article 66-4. (Notifications of Changes, etc. in Clinical Trial Protocols for Drugs) When persons submitting notifications in the preceding article have made changes in any of the matters in the notification concerned or in the in-country caretaker or when they discontinue or complete the clinical trial in the notification concerned, the contents, reasons, etc. shall be notified to the Minister. Article 66-5. (Procedures for Notifications, etc. of Clinical Trial Protocols for Drugs) When the sponsors of clinical trials or those undertaking clinical trials are not domiciled in Japan, the procedures related to the notification in the previous two articles shall be performed by the in-country caretaker. Article 66-6. (Cases Not Requiring Notifications of Clinical Trials for Drugs) Cases pursuant to the provisions of the proviso of Article 80-2, Paragraph 2 of the Law shall be cases other than clinical trials for drugs in the following items [excluding cases of bioequivalence tests for trial drugs in Items (2) to (6)]. (1) Drugs with different active ingredients than drugs in the Japanese Pharmacopoeia or drugs which have already been approved for manufacture or import. (2) Drugs with the same active ingredients but with different routes of administration than drugs in the Japanese Pharmacopoeia or drugs which have already been approved for manufacture or import. (3) Drugs with different compositions (combining ratios) of active ingredients, different indications or different dosage and administration than drugs in the Japanese Pharmacopoeia or drugs which have already been approved for manufacture or import (excluding drugs in the previous two items or drugs which are not intended to be used by, prescribed by or used under the directions of a physician or a dentist) (4) Drugs with different active ingredients from drugs in the Japanese Pharmacopoeia and drugs already approved for manufacture or import but with the same active ingredients as drugs already approved for manufacture or import for which the reexamination period pursuant to the provisions of Article 14-4, Paragraph 2, Item 1 (period after the extension when the period is extended pursuant to the provisions of Article 14-4, paragraph 2) from the date of manufacturing or import approval has not elapsed (5) Drugs which are biological products (excluding those specified in the previous four items) (6) Drugs manufactured using recombinant DNA technology (excluding those specified in the previous five items) Article 66-7. (Reports of Adverse Reactions in Clinical Trials for Drugs) When sponsors of clinical trials are informed of events concerning trial drugs specified in the following items, they shall report this to the Minister within the period specified for each of the items. (1) When any of the following events is suspected to be caused by an adverse reaction of the trial drug concerned or a drug used in a foreign country found to have the same ingredients as the trial drug concerned (hereinafter, "trial drug, etc. concerned" in this Article) or due to an infection suspected to be caused by use of the trial drug, etc. concerned, and the onset of such an event, the number of cases, the incidence, the conditions of onset, etc. can not be predicted from the outline of the trial drug (the document giving information about the quality, efficacy and safety of the trial drug concerned; hereinafter the same in this Article): 7 days (a) Death (b) Cases which might result in death (2) The following events (excluding those in the previous item): 15 days (a) Any of the following events suspected to be caused by an adverse reaction of the trial drug, etc. concerned, when the onset of such an event, the number of cases, the incidence, the conditions of onset, etc. can not be predicted from the outline of the trial drug, etc. concerned. (1) Events requiring admission to a hospital or clinic for treatment or extension of the period of hospitalization (2) Disability (3) Cases which might result in disability (4) Serious cases among the cases in (1) to (3) or (a) (1) and (2) in the previous item (5) Congenital diseases or abnormalities in the next generation (b) Onset of events, etc. in (a) or (b) of the previous item which are suspected to be due to an adverse reaction of the trial drug, etc. concerned or due to an infection suspected to be caused by use of the trial drug, etc. concerned. (c) Measures taken to prevent the onset or spread of risks to public health or hygiene, including discontinuation of manufacture, import and marketing, recall and disposal of a drug used in a foreign country found to have the same ingredients as the trial drug concerned. (d) Research reports showing the possibility of the onset of cancer or other serious diseases, disabilities or death caused by adverse reactions or by infections due to use of the trial drug, etc. concerned; those showing marked changes in the onset trends, such as the number of cases, incidence or conditions of onset of events due to adverse reactions or due to infections due to use of the trial drug, etc. concerned; or those showing that the trial drug, etc. concerned is not indicated for the diseases which are the object of the clinical trial. (limited to those for medical devices; hereinafter the same from this article to Article 70) Article 67. (Standards for Sponsoring Clinical Trials for Medical Devices) Sponsors of clinical trials (limited to those for medical devices; the same until Article 70) pursuant to the provisions of Article 80-2, Paragraph 1 of the Law shall comply with the following standards: (1) The tests relating to safety, performance, etc. required before sponsoring clinical trials shall be completed. (1-2) In order to take necessary measures against the occurrence or spread of hazards to public health and hygiene caused by the medical devices which are the objects of clinical trials (hereinafter "trial device" until Article 70), etc., if the sponsor of the clinical trials does not reside in Japan, he shall select a person who resides in Japan (including the representative of the Japan office of a foreign corporation having such an office) to sponsor clinical trials in his stead, and shall carry out the procedures relating to sponsoring through this person (hereinafter called the clinical trial in-country caretaker until Article 70). (2) The request shall be made in writing. (3) The results of the tests specified in Item (1) and other information required for the clinical trials shall be submitted. (4) The request shall be made to medical or research institutions (hereafter referred to as "medical institutions, etc.") which are able to properly conduct the trials, including being able to provide adequate clinical supervision and trial surveillance and being able to take necessary measures in the case of emergencies. (5) It shall be requested that, except in cases where it is decided by the investigator to be not medically desirable, the institution (medical institution requested to perform the clinical trial; hereinafter the same is required to explain the details of the clinical trial to the trial subjects and obtain their consent (in cases where subjects are not capable of giving their consent, the consent of those who can give consent on their behalf). (6) In cases where injury to health may occur due to use of the trial device, necessary measures for compensation shall be taken in advance. (7) The following matters shall be indicated in the Japanese language on the trial device or on its container or wrapper: (a) The fact that the drug is for trial use. (b) The name and address of the sponsor of the clinical trials (if the person does not reside in Japan, the name and country of the sponsor of the clinical trials and the name and address of the clinical trial in-country caretaker). (c) The chemical name or identifying symbol. (d) The manufacturing number or symbol. (e) Information relating to storage method, expiry date, etc., where applicable. (8) The following matters shall not be indicated in documents attached to the trial device or on the trial device or its container or wrapper (including the inner wrapper): (a) The anticipated brand name. (b) The anticipated indications or performance. (c) The anticipated method of use. (9) The trial device shall be delivered directly to the institution requested to perform the clinical trial and not through a third party such as a drug distributor, etc. (10) The matters indicated below concerning the trial device, etc. shall be recorded and preserved; provided, however, that, if the sponsor of the clinical trials does not reside in Japan, he shall have the clinical trial in-country caretaker keep the records. (a) Matters relating to manufacturing and testing. (b) The amount delivered and the date of delivery to the institution requested to perform the clinical trial. (11) When the sponsor of the clinical trials does not reside in Japan, and when the Minister instructs the sponsor to cancel or amend the trial request, or to take other measures deemed necessary in order to prevent the occurrence or spread of hazards to public health and hygiene due to use of trial devices, the sponsor of the clinical trials shall have the clinical trial in-country caretaker comply with the instruction. Article 68. (Notification of Trial Protocols, for Devices) Persons requesting clinical trials shall notify to the Minister the following matters relating to trial protocols: (a) Shape, structure, dimensions, raw materials, ingredients and quantities of the trial device (b) Manufacturing method of the trial device (c) Anticipated performance, method of use, and indications of the trial device (d) Anticipated method of operation or method of use of the trial device (e) The purpose, contents and period of the clinical trial. (f) The name and address of each institution performing the clinical trials, the name of the physician responsible for the clinical trial and the quantity of the trial device, etc. to be delivered to each institution. (g) The reason when the trial device is are provided for a fee. (h) If the person requesting clinical trials does not reside in Japan, the name and address of the clinical trial in-country caretaker. 2. A summary of the results of tests concerning safety, performance, etc. of the trial device and other necessary information shall be submitted with the information filed under the preceding paragraph. Article 69. (Report of Changes, etc.) When there is a change in the information submitted under the preceding article, or the clinical trial in-country caretaker is changed, or the trials concerned are terminated or completed, the person who submitted the information shall notify the Minister of the contents of the changes and reasons therefor. Article 69-2. (Procedures for Filing Trial Protocols) If the person who intends to request, or has requested, clinical trials does not reside in Japan, the procedures for submitting information pursuant to the preceding two articles shall be undertaken by the clinical trial in-country caretaker. Article 70. (Cases Not Requiring Notification of Clinical Trials for Medical Devices) Cases pursuant to the provisions of the proviso of Article 80-3, Paragraph 2 are cases other than clinical trials for medical devices with a clearly different structure, performance, etc. from medical devices already approved for manufacture or import or medical devices designated by the Minister pursuant to the provisions of Article 14, Paragraph 1 (excluding those which have no effect on the structure or function of the human body). Article 70-2. (Notification of Results of Examinations of Clinical Trial Protocols by the Organization for Drug ADR Relief, R&D Promotion and Product Review) Notification of the results of examinations performed for the Minister pursuant to the provisions of Article 80-4, Paragraph 3 of the Law shall be made on form No. 33. Article 71. (Accesory Medical Devices) Accessories referred to in the devices and instruments section, Item 84 of Table 1 of the Ordinance shall be those listed in Attached Table 5. Article 72. (Use of Japanese Language) Any application, notification, report or other document submitted to the Minister to prefectural governors or to mayors of municipalities or special wards with health centers shall be written in the Japanese language; provided, however, that this shall not apply to documents which for a special reason cannot be written in the Japanese language but to which a translation is attached. Article 73. (Procedures Using Flexible Disks) Documentation in the lower part of the following table pursuant to the provisions in the upper part of the table [limited to that related to drugs (excluding drugs produced in pharmacies), quasi-drugs, cosmetics or medical devices] may be replaced with a flexible disk or similar material designated by the Minister on which the items in each document concerned are recorded and documentation giving the name and address of the applicant, the person making the request or the person submitting the notification; an outline of the application, request or notification, and the date (referred to a "flexible disk, etc." in the following paragraph). 2. When a flexible disk, etc. is submitted in place of the documentation in the lower part of the table in the preceding paragraph pursuant to the provisions of the preceding paragraph, this flexible disk, etc. shall be considered as the documentation. Article 74. (Structure of Flexible Disks) The flexible disks in Paragraph 1 of the preceding article shall be 90 millimeter flexible disk cartridges in compliance with Japanese Industrial Standard No. X6223 Article 75. (Recording Method of Flexible Disks) Recording of the flexible disks specified in Article 73, Paragraph 1 shall be performed by the following methods. (1) The track format shall be as specified in JIS X6224 or JIS X6225 (2) The volume and file structure shall be as specified in JIS X0605. Article 76. (Label Attached to Flexible Disks) A label containing the following items shall be attached to the label region specified in JIS X6223 (1986) of the flexible disk specified in Article 73, Paragraph 1. (1) Name of the applicant, person making the request or person submitting the notification (2) Date of the application, request or notification