Japan drug and cosmetics regulation.pdf

Japan drug and cosmetics regulation.pdf

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  PMDA in Japan ØPMDA is the main regulatory body of PMDA located in- Tokyo Ø PMDA (Pharmaceuticals and Medical Devices Agency) is Japanese regulatory agency, working together with Ministry of health and labour welfare (MHLW). Ø It was established in April 01, 2004 Ø to serve in areas of review of drugs and medical devices, post-marketing safety measures, relief services for adverse health effects. Ø Our obligation is to protect the public health by assuring safety, efficacy and quality of pharmaceuticals and medical devices. Ø The role of the PMDA is to provide consultations concerning the clinical trials of new drugs and medical devices, and to conduct approval reviews and surveys of the reliability of application data — Capital -- Tokyo — Language -- Japanese — Ethnic groups -- 98.5% Japanese 0.5% Korea 0.4 % Brazilian — Currency -- yen — Market status -- second largest pharmaceutical marketing the world. — PMDA-JAPAN is carried out by Chief Executive Tatsuya Kondo. — PMDA focuses on 3 key services, which is a Safety triangle system. a Organization of PMDA:- Ø It consists 27 0ffices Ø It consists of the ministry proper, affiliated institutions, councils, local branches, and external organizations. Ø The ministry proper includes the Minister's Secretariat, 11 bureaus, and the Director- General for Policy Planning and Evaluation. Ø Councils include the Social Insurance Council, Pharmaceutical Affairs and Food Sanitation Council (PAFSC), and other organizations.
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  Ø Affiliated institutionsinclude the National Institute of Health Sciences and the National Institute of Infectious Diseases. Ø Local branches are regional bureaus of health and welfare and prefectural labor bureaus. The external organizations are the Social Insurance Agency and the Central Labor Relations Commission Organization chart PMDA three major functions:- Pharmaceutical laws and regulations:- Ø Pharmaceutical administration in Japan is based on various laws and regulations, consisting mainly of: 1. The Drugs and Medical Devices Law, 2. Law Concerning the Establishment for Pharmaceuticals and Medical Devices Organization, 3. Law Concerning Securing Stable Supply of Blood Products, 4. Poisonous and Deleterious Substances Control Law 5. Narcotics and Psychotropic Control Law 6. Cannabis Control Law, 7. Opium Law, and 8. Stimulants Control Law. Required document:- Ø Application form (written). Ø Application letter (XML). Ø Protocols. Ø Case report form. Ø IB ( investigator brochure). Ø Written reason with appropriate request for clinical trials. INVESTIGATIONAL NEW DRUG (IND) APPLICATION PROSESS:- Ø IND application to be prepared in the common technical document format (CTD) format. Ø Pre-IND meeting. Ø Subsequent to the application submission, PMDA evaluates the application with respect to the preclinical data and protocols for clinical studies etc. Ø It may probably take 30 days for initial IND and 14 days for second IND. Ø After PMDA completes the review, the IND fill will be transferred to the IRB board for the review. Ø IRB takes 1-4 weeks of time for the complete review. Ø Once IRB approved the review than the clinical trials on human beings will be started.
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  NEW DRUG APPLICATION(NDA) PROCESS:- — The entire process of approval review from review related inspections and clinical trial consultation to review works is undertaken by the PMDA. — Application forms for drug marketing authorization are submitted to the PMDA. — When application forms for new drug s marketing authorization are received by the PMDA, a compliance review of the application data (certification from source data), GCP on-site inspection, and detailed review are undertaken by review teams of the PMDA and the team prepares a review report. — The approval review process consists of expert meetings of review team members and experts to discuss important problems. — A general review conference attended by team members, experts and representatives of the applicant is held after the expert meeting. — It is necessary to submit a “list of persons involved in compilation of attached data” and a “list of competitive products and companies” in relation to persons who participated in clinical studies submitted as application data immediately after application submission, prior to the expert meeting, and prior to meeting of the Committee on Drugs.
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  PMDA review process Theevaluation process followed by the PMDA is as follows: 1. Interview (presentation, inquiries, and replies) 2. Team review 3. Inquiries and replies 4. Application for GMP inspection (about 6 months before the meeting of the Committee on Drugs) 5. Review report (1) 6. Expert meeting 7. Review report (2) 8. Report to MHLW for consultation to PAFSC COMPLETE OVERVIEW OF APPROVAL PROCESS IN JAPAN
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  JAPANESE PHARMACEUTICAL LAW 1.Pharmaceutical affair law 2. Pharmacist Law 3. Law Concerning the Establishment for Pharmaceuticals and Medical Devices Organization 4. Law Concerning Securing Stable Supply of Blood Products 5. Poisonous and Deleterious Substances Control Law, 6. Narcotics and Psychotropics Control Law, 7. Cannabis Control Law, 8. Opium Law 9. Stimulants Control Law Copyright Pharmaceutical affairs law has 11 chapters and 91 articles + Chapter 1—general provisions + Chapter 2: Prefectural pharmaceutical affairs councils + Chapter 7: Handling of drugs + Chapter 9-2: Handling of designated drug substances + Chapter 9-3: Designation of orphan drug CLASSIFICATION OF DRUG PRODUCTS 1. ETHICAL DRUGS 2. PRESCRIPTION DRUGS 3. OTC DRUGS Class I drug products Class II drug products Class III drug products 4. ORPHAN DRUGS APPROVAL APPLICATION FOR MARKETING A DRUG • When marketing a drug, it is necessary to obtain approval for each product by receiving examinations on both its efficacy and safety. • Only a MAH license holder can submit an approval application for a product. • To obtain product approval, the manufacturer in Japan needs to be licensed. For a foreign manufacturer, a Foreign Manufacturer Accredited Certificate (FMA) is required. • The application is sent to the PMDA and further examination is mainly conducted by this agency APPLICATION FEE FOR A NEW DRUG DESCRIPTION TOTAL FEE( YEN) 1. Drug containing new ingredient, drug for a new route of administration, drug with a new combination, biotechnology based existing drug (excluding an orphan drug) 31,068,900 2. Drug containing new ingredient, drug for a new route of administration, drug with a new combination, biotechnology based existing drug (orphan drug) 23,847,800 3. Drug with a new indication, drug with a new dosage form, drug for new dosage and drug with similar formulation (excluding an orphan drug) 14,230,600 4. Drug with a new indication, drug with a new dosage form, drug for new dosage and drug with similar formulation (orphan drug) 10,957,300
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  Required document : REQUIREDDOCUMENT CONTENTS MODULES Documents on origin or course of discovery and usage Status of development and comparison of package insert with similar drug. Module 1 Documents on manufacturing method and test methods Structure determination and physical – chemical property Module 3 Documents on stability Long term stability test, accelerated test Module 3 Documents on pharmacologic actions Test supporting efficacy /safety pharmacology Module 4 Documents on clinical test results Phase 1, phase 2, phase 3 Module Module 5 REVIEW PROCESS + Drugs Reviews + In the review of drug applications, PMDA reviewers, who have degrees in pharmaceutical science, medicine, veterinary medicine, physical science, biostatistics, or other specialties, form a team to evaluate the quality, pharmacology, pharmacokinetics, toxicology, clinical implications, and biostatistics regarding the particular drug product under review. During the review process, the reviewers exchange opinions with external experts (Expert Discussions) to ensure that more effective reviews are conducted by making use of their advanced expertise. In addition, PMDA participates in the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and has actively incorporated the guidelines agreed upon at ICH into its drug reviews. + PMDA strives to speed up the review process by setting target review times, while clarifying the standards for review by publishing the basic considerations for reviewers on its website. PMDA’s drug reviews encompass not only new drugs but also generic drugs, OTC drugs / “behind-the-counter (BTC)” drugs (requiring pharmacists’ advice) that can be purchased at pharmacies without a doctor’s prescription, and quasi-drugs. PMDA also conducts re- examinations and re-evaluations of approved drug products. In FY 2013, a total of 7118 drugs were approved, of which 4008 were prescription drugs (including 504 new drugs), 916 were OTC drugs / BTC drugs, 166 were in vitro diagnostics, and 2028 were quasi-drugs. PMDA Consultation & IND Application PMDA Review & Completion of Inquires IRB Approval & Contact With Hospital IRB Submissions & IRB meeting Reveiws Study Information
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  Review Process forDrug or Medical Device Application Medical Devices Reviews + Medical devices cover a wide range of products, from adhesive bandages and forceps to MRI and pacemakers, which are characterized by a variety of usage patterns and different levels of risk. Among these products, highrisk medical devices, including artificial hearts and pacemakers, are evaluated by PMDA. As with drug reviews, PMDA has set target review times for medical devices and is working hard to achieve these targets through various efforts, such as increasing the number of reviewers. + In evaluating medical devices, in addition to reviewers who possess expertise in medical engineering, biological engineering, and biomaterials, specialists with degrees in medicine, dentistry, pharmaceutical science, and other fields are involved in non-clinical, clinical, and biostatistical evaluations. During the review process, the reviewers exchange opinions with external experts (Expert Discussions) to enable more highly specialized reviews. + To promote international regulatory harmonization, PMDA participates in the International Medical Device Regulators Forum (IMDRF) and other meetings, while improving its review system by actively incorporating the topics discussed at international conferences as well as standards such as those of the International Organization for Standardization (ISO). + Cellular and Tissue-based Products (Regenerative Medicines) Reviews + What Are Cellular and Tissue-based Products? 1. Cellular and tissue-based products refer to: Products derived from human or animal cells / tissues processed by methods such as cell culture, and are those used for the purposes of: • reconstruction, restoration or formation of structures and functions of the human body; • prevention or treatment of diseases 2. Products transfected into human cells/tissues for the purpose of gene therapy. * Since these products are all derived from processed living cells/tissues, the products are characterized by their varied quality and in that their efficacy is difficult to be confirmed in some cases. TYPES OF REGISTRATION APPLICATION CLASSIFICATION OF APPLICATION MEDICAL DEVICES PHARMACEUTICALS QUASI DRUGS
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  CLASSIFICATION OF MEDICALDEVICE REGISTRATION OF MEDICAL DEVICES + Registration of medical devices and pharmaceuticals in Japan is complicated, and high costs and long timeframes. In some cases, Japanese regulators require clinical trials in Japan to be conducted. + Product registration in Japan needs to be pursued carefully and only after determining that there is a strong market demand for your product REGULATORY PATHWAY FOR MEDICAL DEVICE TODOKEDE, NINSHO AND SHONIN FOR MEDICAL DEVICE IN JAPAN + To market medical devices in Japan, the MAH must register the device through the following procedures. + Pre-market Submission (Todokede) - CLASS I Medical DEVICES + To register and market General Medical Devices (Class I devices), the MAH must file a Pre- Market Submission to PMDA. There is no review/assessment by the PMDA for Class I devices. + Pre-market Certification (Ninsho) - CLASS II MEDICAL DEVICES Only Class II devices which are specified as Controlled Devices are subject to Pre-market Certification. Class II devices other than Specified Controlled Devices are subject to Pre-market Approval
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  + Pre-market Approval(Shonin) - CLASS II, III & IV MEDICAL DEVICES + To register and market a “Highly Controlled Medical Device” the MAH needs to file a Pre- market Approval Application with the PMDA and obtain their approval. Class II devices that are not Specified Controlled Devices are also subject to Pre-Market Approval ACCREDITATION OF FOREIGN MANUFACTURERS + A foreign manufacturer (a person/ a company) intending to manufacture drugs, quasi-drugs, or medical devices in foreign countries and export them to Japan, is required to be accredited by the Minister of Health, Labour, and Welfare as an “Accredited Foreign Manufacturer”. + In addition, a foreign manufacturer intending to manufacture only drug substances to be exported to Japan also need to obtain accreditation as an “Accredited Foreign Manufacturer” PHARMACEUTICALS + An “Applicant” is required to submit “Application for Accreditation” (Form No. 18 in the PAL Enforcement Regulations) that is addressed to the Minister, and “Application for Accreditation Examination” [Form No.16- (2)] + Documents to Be Attached to Accreditation Application:- + A medical certificate from a physician which indicates whether or not an “Applicant” has mental disorders or is addicted to narcotics, cannabis, opium or stimulant drugs. + A curriculum vitae of the person who is responsible to the manufacturing establishment QUASI DRUGS + A medical certificate for an “Applicant” from a physician” and “a curriculum vitae of the person who is responsible for the foreign manufacturing establishment. + In this case, the “Applicant” can omit filling out the space of “Address” in the section of “Person who is responsible for manufacturing establishment APPLICATION FOR CHANGE VS RENEWAL CHANGE + must submit a form, “Application for Change/Addition” (Form No. 21 specified in the PAL Enforcement Regulations) + accredited to new categories while cancelling their previously accredited categories. RENEWAL + Unless an “Accredited Foreign Manufacturer” renews their accreditation, using a form of “Application for Renewal of Accreditation” , within its 5 year effective period, their accreditation becomes null and avoid. Form No – 20 is the application for renewal DMF IN JAPAN Drug master file in japan:- Ø A DMF is a system to register confidential data on quality manufacturing methods, etc. of a drug substance used for a drug. Domestic and foreign drug manufacturers register their DMFs to the PMDA on a voluntary basis Ø The manufacturer of the drug substance can be reviewed by the competent Japanese authority without sharing information containing details on its manufacturing methods, production management and quality control with the manufacturers of the drug product. Ø DMF is not a patent and cannot be approved/disapproved but can be registered for regulatory review. Ø Not required registration of MF
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  Ø DMF isreviewed at the time of the approval review for the pharmaceutical products listing Ø DMF. At the time of DMF registration, PMDA checks whether it is written in the correct format, e.g., minimum required items are included (application) and data is attached (CTD M3). Drug approval system in japan:- Ø The entire process of approval review from review related inspections and clinical trial consultation to review works is undertaken by the PMDA. Ø Application forms for approval to market drugs are usually submitted to the PMDA. Ø When application forms for new drugs are received by the PMDA, a compliance review of the application data (certification from source data), GCP on-site inspection, and detailed review are undertaken by review teams of the PMDA and the team prepares a review report. Ø Applicability of DMF in Japan: In Japan DMF can be submitted only for: § Drug Substances or intermediates (For medical use) § Cellular and tissue-based materials used for manufacturing § New and pre-mix excipients with different composition ratios from the existing ones Qualification of MF Holder • The MF holder can only be the actual manufacturer of the API • DMF application cannot be accepted if the company performs only repackaging, packaging, labeling, storage or testing of the AP DMF Content in Japan The name of the API, excipient or other drug substance The manufacturing site General Requirements for DMF Registration in Japan CTD MODULE 3 Application form, Notification and other related documents Combined in a Master File PMDA 5 Application Process for Pharmaceutical Drug Product Without Master File API Manufacturer sends all information including CTD – 3 Disclosed (open) and restricted (closed) part to the Marketing Authorization (MA) Applicant The MA Applicant sends the dossier to the PMDA for approval With Master File API Manufacturer sends Dossier to In- Country Caretaker The In-Country caretaker registers the MF and the Dossier holds a Registration number The API is registered to the PMDA and posted on the website for reference to other companies, keeping confidential all the CTD-3 information 7 Registration Process of DMF in Japan • Foreign Manufacturers had to hire an In- Country caretaker to register an API in Japan • The In-Country Caretaker submits the Master file dossier and gets a MF number • The Master file of the API is submitted to the PMDA with the MF number
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  The ingredients, includingquantity, chemical structure, and general properties Manufacturing method, process controls, process validation, process development and material controls Quality control testing, analytical procedures, validation of analytical procedures, justification of specifications and excipients of human/animal origin information (if applicable) Safety data Non-clinical study data (primarily for new excipients) Test methods, including impurities and description of methods for determining structure Specifications, analytical procedures, validation of these procedures, batch analyses, justification of specifications and reference standards/materials Storage method, stability testing data, post-approval stability protocol and expiration date AFM or domestic manufacturing license category, number and/or date ICC name and add ress PMDA Timeline (Business Days) PMDA Issuance of DMF certificate/form 43 60 business days after approval PMDA Publishing non-confidential DFM update on PMDA homepage 15 days after issuance of Form 43 Changes to the registred DMF 1. Minor changes the MF registrants submit the minor change notification along with application of chnge to the PMDA and MHLW 2. Partial changes The MA holder submit the partial change application to MHLW and PMDA 3. Cancellation of DMF The notification (original 1), statement and an original MF certificate is submitted to the PMDA. • To protect the “know-how” of API manufacturing methods from the marketing authorization applicant (MAA) / holder (MAH) of pharmaceutical products.(* MF is not a patent.) Registration in the MF is optional, not required by law. An MF registration certificate is not a marketing certificate. • In a regulatory review, items registered in the MF are quoted as information necessary for the review. Some of these items will be approval items. PMDA Review Process of Drug Application Referencing DMF Pharmaceutical manufacturer (applicant) Safety, Quality and efficacy data Drug substance manufacturers Quality and Manufacturing methods data PMDA review Application data DMF registration Number Register quality and manufacturing method data Reviewed as complete data Non-disclosure information (excludes public health safety ) 9
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  • Foreign manufacturersapplying for MF registration must appoint an in-country caretaker for drug substances (APIs), etc. Ø Not required by law Ø No fee for MF registration The Application Form, Notification, And Other Related Documents Ø CTD module 3 must in English Ø Application Form, Notification, And Other Related Documents for pharmaceuticals which are submitted to PMDA, written in Japanese Ø an in-country caretaker for drug substances (APIs) etc., who lives in Japan and will undertake clerical work for the relevant registration. Application for Registration of Drug Substances, etc. Application (Original 1, Duplicate 1; Duplicate must not be a Xerox copy of Original) Data of Application for MF Registration(including CTD Module3*) *The CTD M3 submits only electronic data. More in ppt DMF IN Japan POST MARKETING SURVEILANCE IN JAPAN • Post marketing surveillance (PMS), also known as post market surveillance, is the practice of monitoring the safety of a pharmaceutical drug or medical device after it has been released on the market and is an important part of the science of pharmacovigilance. • In JAPAN, Post market surveillance is overseen by both the Pharmaceuticals and Medical Devices Agency (PMDA) and the Ministry of Health, Labor and Welfare (MHLW). GOOD VIGILANCE PRACTICE (GVP) GOOD POST-MARKETING STUDY (GPSP) Collection & Analysis of Safety Information Planning & Execution of Safety Measures FSCA- Report to authority, etc. In-house Inspection Training/ Education of Relevant Staff Preparation of SOPs on the above Post-Marketing clinical study Specified-Use survey Use-Result survey
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  COLLECTION OF SAFETYINFORMATION WHAT INFORMATION IS NECESSARY? 1. Medical Device Information • Brand Name • Device Identification Number • Usage of Device. • Maintenance Condition if there is any problem with the medical device/ equipment. 2. Product Problem Information • Date of Incident • Reporter’s Awareness Date • Details of Incident • Concomitant Medical Products 3. Patient Information • Initials, Age, Sex, Weight, Outcome • Health damage, Patient’s condition at the incident • Medical treatment after the incident 4. Detailed adverse event § Operation/ usage status when it occurred. § Whether the operator checked the package inserts/ manuals or not. § Whether the operator complied with the package inserts/ manuals or not. § Whether the operator checked and complied with other safety information or not. § Was the intended use appropriate? § Was the device within the expiration date? § If it is a controlled medical device requiring special maintenance, were daily inspection and maintenance appropriate? PHARMACOVIGILANCE OPERATION FLOWCHART Health Profession al/ Medical Institution Foreign government/ Foreign company MAH Governme nt Institution Academic society/Lit erature/ Study Other MAH, company
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  JAPAN’S POST-MARKETING ACTIVITIES PMDA Receiptof ADR/ Infection Report Compiling Reports Scientific Objective Research Analysis of Accumulative Information § Expert Consultations § Company Interviews Information Provision System MHLW Keep Tracking Information Extracting Urgent & Significant Information Planning for Safety Measure Safety Measure Implementation Information Provision Real-Time Notification Medical Professionals Public and Companies DATAB ASE Advisory Committee PMS Periodic Re-evaluation Periodic Safety Report Incl. PSUR EPPV Expedited Re-examination Risk minimization Risk Communication Safety Report Quality Ad hoc Periodic Post-Marketing Clinical Trial Drug Use Investigation of Special population Drug Use Investigation
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  EARLY POST-MARKETING PHASEVIGILANCE: EPPV • To ensure necessary information for appropriate use is explained to the medical institutions 2 weeks before delivery. • To request medical institutions to use the drugs carefully and report serious ADRs, if occurred, immediately to pharmaceutical companies. • To request appropriate use and ADR reporting repeatedly to medical institutions for 6 months after delivery. RE-EXAMINATION • The re-examination system is aimed at reconfirmation of the usefulness of drugs by performing GPSP or GVP as one aspect of PMS, through collecting information on the efficacy and safety of the drug during a specified period of time after approval. • The surveillance and studies required for re-examination applications must be performed in compliance with the GPMSP (GPSP), GCP or GLP depending on their objective. • The timing when these drugs should be re-examined is designated by the MHLW at the time of their approval as new drugs. • Re-examination period of drugs containing new active ingredients is 8 years (maximum 10 years). RISK MANAGEMENT OPTIONS IN JAPAN 1. RISK COMMUNICATION q Risk communication Tools q For HCPs § Package Insert § Leaflet § Website q For patients § Medication Guide § Leaflet, Website 2. INFORMED CONSENTS 3. MANAGED DISTRIBUTION Registration of HCPs, Patients etc 4. PRODUCT RECALL Recall, Withdrawal, Suspension of the sale GVP REQUIREMENTS Prescription drugs Drugs other than prescription ones Quasi drugs, cosmetics etc. Organization and personnel Creation of safety management department Qualified safety management supervisor (over 3yrs experience) Not mandatory Safety management supervisor (no qualification required) Same as on left. Sop Preparation of sops Same as on left. Not mandatory Collection of information for safety management Health care professionals Scientific papers MHLW, PMDA, etc. Foreign authorities, etc. Other companies Others Same as on left. Scientific papers Others In-house inspection, education/ training Required Same as on left. Not mandatory
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  ADR REPORTING BYCOMPANIES Electronic reporting ICMR Data input Pharmaceutical Company PMDA Database Paper Documents ADR REPORTING RULES § Reporting time frame depends on seriousness and predictability of the case. § No time frame defined for health care professionals reporting. SERIOUSNESS PREDICABILITY TIME FRAME OF REPORT TO PMDA Serious Predictable 15 days Not Predictable Death etc.*:15 days Others: 30 days Not Serious Predictable Annually (Annual Cumulative Report) Not Predictable - ADR REPORTING BY HEALTH CARE PROFESSIONALS ICSR Data Input ADR Reporting by Company PMDA Feedback MHLW Electronic Reporting Investigation FAX Postal Mail Pharmaceutical Company Medical Institute Paper and Electronic Reports 1 2 3 4 5 Note: * means -Death -ADR caused by new drug ingredient within 2 years after approval. -ADR detected by Early Phase Post Marketing Vigilance (EPPV).
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  Cosmetics regulation inJAPAN cosmetics are regulated by the Ministry of Health, Labour and Welfare (MHLW) under the Pharmaceutical Affairs Law (PAL) beauty products are divided into quasi-drugs and cosmetics. And both regulated differ Cosmetic from a legal point of view defines cosmetics as “articles with mild action on the human body, which are intended to be applied to the human body through rubbing, sprinkling or other method, aiming to clean, beautify and increase the attractiveness, alter the appearance or to keep the skin or hair in good condition. cosmetics are furthermore classified into 6 different categories Quasi-drugs from a legal point of view beauty products are classified into two categories cosmetics and quasi drug difference between cosmetics and quasi-drugs remains ambiguous. In practice, this distinction is made based on differences in the effects assigned to each product the nature and the quantity of ingredients used, application method, dosage, and appearance of the product. The PAL defines “Quasi-drug” (医薬部外品) as an item for the purpose of: 1. Preventing nausea and other discomfort. 2. Preventing heat rash, soreness, etc. 3. Encouraging hair growth or removing hair, or 4. Exterminating and preventing mice, flies, mosquitoes, fleas, etc. Among the quasi-drugs are deodorants, depilatories, hair growth treatments, hair dyes, perm and straightening products, as well as medicated cosmetics, such as whitening products, anti-aging products and oily skin or acne treatment products. the item shall have mild effects on the human body IMPORTING COSMETICS TO JAPAN 1. Importation flow Ø To sell cosmetic products in Japan, importers must ensure they comply with the PAL (Protection of Cosmetics) law. Ø This involves assessing samples by testing and inspection facilities designated by the MHLW, owned or contracted by the importer. Ø The importer must take full responsibility for imported cosmetics through regulation analysis and safety testing, even if they are already legal in their home country. Ø After testing and testing, importers must fill 3 forms: o Manufacture and Sales of Cosmetics Notification, o Cosmetics Import Notification for Manufacture and Sales o manufacturer’s or importer’s brand name Ø These forms contain a record of the testing and inspection results, verifying the product does not contain prohibited combinations. Ø Labeling and advertising for cosmetics are regulated by law, with improper labeling resulting in prohibition. Ø Importers must inspect every item to ensure packaging, add a Japanese label, and possibly repack the product. Ø the container, packaging, or package inserts of cosmetics be specifically labelled to ensure the appropriate use, handling and quality, and liability. Ø Once fully legal, products can be dispatched to the responsible distribution company. 2. Notifications and licenses
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  Ø entirely possiblefor an exporting company o handle the importation or distribution of its products a) primary distribution by product category • all ready approved cosmetics • to prohibition or restriction in cosmetics combinations, • those that are allowed in cosmetics combinations in specific ingredient groups • Antiseptics, ultraviolet ray absorbents and tar coloring are subject to a positive list that indicates the maximum mixture quantities • those covered by a negative list of combinations • all ingredient names must be listed in the labeling. • the provided ingredients do not violate the Cosmetics Standards and all the ingredients are indicated on the labeling, approval for primary distribution by product b) Cosmetics manufacturing and sales license Ø when importing and distributing cosmetics, the importer must obtain a cosmetics manufacturing and sales license. Ø refers to the act of selling, renting, or lending of manufactured or imported cosmetic Ø 3 main incharge : o Marketing supervisor o Quality supervisor o Quality control supervisor Who responsible for checking the compliance of improted cosmetics the sale sections Ø Marketing License holders have to implement a set of standards called o Good Quality Practice (GQP) for maintaining the quality of products, and o Good Vigilance Practice (GVP) for undertaking appropriate actions for safety management. Ø After obtaining a business code number in advance, applicants must include with their submission: • a copy of the corporate registration (in the case of a corporation); • a list of duty specifications; • a medical certificate specifying the applicant; All ready approved prohibition or restriction subject to a positive list negative list of combinations • For new ingredients • exceeding qty • Not disclose – on label must obtain primary distribution approval
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  • documents certifyingthe qualifications of the marketing supervisor-general; • an employment contract of the marketing supervisor-general; • documents disclosing the quality management system; • documents disclosing the post-marketing safety management system; • a floor plan of the business office and storage facility. Ø The validity of these licenses is 5 years. and renewed every 5 years c) Notification After obtaining the cosmetics manufacturing and sales license but before initiating product importation, the importer must, as stated above, fill 3 notifications to the proper administrative agency: I) Manufacturing and sale of cosmetics notification – sample prefecture as that which has granted the cosmetics manufacturing and sale license II) Cosmetics import notification for manufacture and sale - kanto-Shinetsu Regional Bureau of Health and Welfare (Tokyo) or the Kinki Regional Bureau of Health and Welfare (Osaka) III) Manufacturer’s or importer’ s brand name pharmaceutical device agency , Japan (Tokyo) d) Cosmetic manufacturer's license Ø Any importer that engaged with final packaging , labelling in the Japan storage of the imported product, is required this license Ø Application for such a cosmetic manufacturer's license requires: o an outline of the physical facility; o a floor plan of the manufacturing facility; o documents certifying the qualifications of the responsible engineer; o the employment contract of the responsible engineer; a copy of the contract with a testing laboratory (when used) e) GQP And GVP GQP – required to properly evaluate their product management and quality control of cosmetics. - It consists in establishing a procedures manual for the registration of product delivery, collection of information on the quality of products, processing of defective products, products’ withdrawal from the market, etc GVP - a monitoring system that handles customer complaints over product quality and product recalls, as required by the GVP standards. - consists in collecting information relating to the safety of products provided by the competent authorities, professional , organizations, manufacturers, retailers, consumers, researchers, etc. - if the license holder becomes aware of any information indicating that one of the imported cosmetic product may have a harmful effect, they must report that fact to the MHLW within 30 days. - Flow chart for approval of cosmetics
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  (a) Required documentsfor the application of primary distributor’s license and cosmetics manufacturer’s license • a. primary distributor’s license • a copy of the corporate registration (in the case of a corporation) • a list of duty specifications; • a medical certificate specifying the applicant; • documents certifying the qualifications of the marketing supervisor-general; • an employment contract of the marketing supervisor-general; • documents disclosing the quality management system; • documents disclosing the post-marketing safety management system; • a floor plan of the business office and storage facility. (b) cosmetics manufacturer’s license • an outline of the physical facility; • a floor plan of the manufacturing facility; • documents certifying the qualifications of the responsible engineer; • the employment contract of the responsible engineer; • a copy of the contract with a testing laboratory (when used) f) Quasi-drug Ø This require pre-approval is mandatory as they contain active ingredients which give mild effect on body
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  Ø They needapproval of MHLW Ø Having an active ingredient approved by the MHLW allows the product to display its effectiveness for a result that has yet to be recognized. This allows companies to indicate that the product is "Medicated." Ø This process takes approximately six month for the MHLW to carry out the appropriate examination. g) Requirements on sunscreens In Japan, sunscreens are classified as quasi-drugs, therefore, they require approval of their formulations, ingredients, use levels and functionalities, in addition to stability testing and a certificate showing no animal-derived materials were used. Product evaluations should be based on ISO 24442 in vivo testing and labeling. Also, an SPF of 50+, corresponding to PA++++, is the maximum level allowed on the label. h) Labelling requirement the Consumer Affairs Agency (CAA) may require documentation, for labeling that makes claims of superior quality etc. all information must be expressed in Japanese For cosmetics: • Product name by type • Brand name • Name and address of primary distributor • Content (weight or capacity) • Country of origin • Manufacturing number or code • List of ingredients as required by the MHLW • Expiration date, for a cosmetic designated by the MHLW • Precautions on usage or storage
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  • Information contact Forsoaps: o Name and address of primary distributor o Brand name o The word "Soap" o List of ingredients as required by the MHLW o Manufacturing number or code o Expiration date, for a designated cosmetic soap o For those products manufactured by a frame mixing method, a term to that effect o Standard weight per unit o Country of origin