Unit 3: Japan drug approval and safety monitoring

Unit 3: Japan drug approval and safety monitoring

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  SAROJINI NAIDU VANITAPHARMACY MAHA VIDYALAYA (CO – ED) (Sponsored By The Exhibition Society) (UGC AUTONOMOUS INSTITUTION) Affiliated To Osmania University Approved By PCI, NBAAccredited, Accredited A+ Grade By NAAC Presented By: Byti Rahul 1704-25-867-003 II semester 1st year M Pharmacy Regulatory Affairs SUB: Regulatory Aspects of Drugs & Cosmetics UNIT:III Japan: Drug Approval & Safety Monitoring The step-by- step drug regulatory approval process and Post-Marketing Surveillance (PMS) requirements in Japan.
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  Contents • Introduction toJapan's Drug Regulatory System • Drug development and Approval • Post-Marketing Surveillance (PMS) in Japan • Conclusion • Reference
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  Japan: Drug Approval& Safety Monitoring • Introduction to Japan's Drug Regulatory System • Japan has a structured regulatory system designed to ensure that medicines meet appropriate standards of: Quality , Efficacy , Safety. • PMDA evaluates the scientific evidence and conducts regulatory inspections, while the MHLW is responsible for regulatory decisions and policy. • The system covers the entire product lifecycle: • Research → Development → Clinical Trials → Approval → Marketing → PMS → Re-examination/Re-evaluation
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  Major Regulatory Authorities •1. MHLW • Ministry of Health, Labour and Welfare • Main responsibilities: • Pharmaceutical policy • Regulatory decision-making • Final approval of drugs • Safety measures • Regulatory standards
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  • 2. PMDA Pharmaceuticalsand Medical Devices Agency • Main responsibilities: • Scientific review • Clinical trial consultations • GCP/GMP/GPSP inspections • Safety monitoring • Post-marketing activities • Re-examination/re-evaluation support
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  Legal Framework • Theprincipal legislation is the: • Pharmaceuticals and Medical Devices Act (PMD Act): It regulates: • Pharmaceuticals • Medical devices • In-vitro diagnostic products • The Act establishes requirements concerning: • Manufacturing • Marketing authorization • Quality • Efficacy • Safety • Post-marketing safety monitoring
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  DRUG DEVELOPMENT ANDAPPROVAL • Drug discovery ↓ Non-clinical studies ↓ Clinical trial consultation / preparation ↓ Clinical trials ↓ New Drug Application (NDA) ↓ PMDA review ↓ GMP inspection ↓ Expert discussion ↓ PMDA review report ↓ MHLW / Pharmaceutical Affairs Council review ↓ Approval
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  • PMDA confirmsthat new-drug review evaluates quality, pharmacology, pharmacokinetics, toxicology, clinical aspects and biostatistics, with expert discussions during the review. • 1. Step-by-step drug approval process in Japan • 1. Regulatory consultation and development planning • The sponsor develops the drug's quality, non-clinical and clinical program. • PMDA provides consultations during development, including advice on clinical-trial plans and the data required for a marketing application. • A Japanese regulatory strategy should address the planned indication, dosage, target population, clinical endpoints, manufacturing process and post-marketing risk-management strategy.
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  2. Non-clinical development •Pharmacology, pharmacokinetics and toxicology studies are conducted according to applicable standards. • Safety studies supporting the application must comply with GLP where applicable. • PMDA can inspect non-clinical facilities and assess the reliability of GLP data. • 3. Clinical development • Clinical trials are conducted under Japan's GCP requirements. • The clinical package generally progresses through early-phase studies and confirmatory trials to establish safety and efficacy for the proposed indication.
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  • PMDA canconduct GCP inspections and document-based compliance assessments of the clinical-trial data. • 4. Preparation of the Marketing Authorization Application (MAA) The sponsor compiles the application dossier, including, broadly: • Quality/CMC information • Non-clinical pharmacology and toxicology • Clinical efficacy and safety • Statistical analyses • Proposed labeling/package insert
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  • Manufacturing information •Risk-management and post-marketing plans • The application must meet Japan's requirements for the reliability of submitted data. PMDA assesses whether the underlying studies and submitted materials comply with GLP, GCP and other applicable standards. • 5. Submission to MHLW/PMDA • The marketing authorization application is submitted through the Japanese regulatory framework. • PMDA performs the scientific review and associated compliance inspections.
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  • Manufacturing facilities/processesare subject to GMP conformity assessment as applicable. PMDA specifically performs GMP inspections to assess manufacturing quality systems. • 6. PMDA scientific review PMDA evaluates the product's: Quality, Efficacy ,Safety • The review can include questions/requests for clarification and additional analyses or information from the applicant. • 7. Expert and regulatory review The regulatory review proceeds through the Japanese approval framework, including the relevant expert/committee processes where applicable.
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  • 8. MHLWmarketing approval If the product satisfies the applicable requirements, MHLW grants marketing approval. The approved indication, dosage and administration, labeling and other conditions form the basis for subsequent commercialization and safety monitoring.
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  2. Post-Marketing Surveillance(PMS) in Japan • PMS is not simply an optional observational program after approval. Japan has a structured post-marketing framework under GPSP (Good Post-Marketing Study Practice), together with pharmacovigilance and the Risk Management Plan (RMP). • Main PMS components PMS activity Main purpose Post-marketing safety reporting Detect and evaluate adverse drug reactions and other safety information Use-results survey Collect real-world information on safety and appropriate use
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  PMS activity Mainpurpose Specified use-results survey Evaluate particular populations, conditions or risk factors Post-marketing database study Analyse existing healthcare/real-world databases Post-marketing clinical trial Generate additional clinical evidence when necessary Re-examination Regulatory reassessment of newly approved drugs after the specified post- approval period
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  • PMDA's GPSPframework covers post-marketing surveys and studies, and PMDA can inspect their conduct and assess the reliability of the resulting data. • 3. Risk Management Plan (RMP) • An important feature of the Japanese system is the Risk Management Plan. • The RMP links risk management from development through regulatory review and the post-marketing period. It identifies, among other things: • Important identified risks • Important potential risks • Important missing information
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  • Pharmacovigilance activities •Risk-minimization measures • The RMP is intended to be updated/evaluated as safety information accumulates and is used to support appropriate risk management after approval. • 4. Post-marketing safety reporting • After commercialization, the Japanese Marketing Authorization Holder (MAH) has a central responsibility for post-marketing safety reporting.
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  • Safety informationcan originate from: • Healthcare professionals • Patients • Literature • Clinical studies • PMS activities • Other sources of safety information • PMDA states that post-marketing safety reports from the MAH are submitted by the Japanese MAH distributing the product in Japan.
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  • 5. Re-examination:an important Japanese PMS feature • Japan has a specific re-examination ( 再審査 ) system for newly approved drugs. • The rationale is that clinical trials have limited patient numbers and controlled conditions, whereas real-world use exposes a drug to: • Much larger patient populations • Concomitant medications • Different doses/use patterns • Less controlled clinical circumstances • Therefore, after a specified post-approval period, real-world data are reviewed to reassess the drug's approved efficacy and safety.
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  • The companysubmits a re-examination application with the required PMS evidence. PMDA assesses the submitted information and can conduct GPSP inspections and document-based assessments. • Possible regulatory outcomes include: • Approval cancellation • Deletion or modification of an indication/approved claim • No regulatory action • Even where no major regulatory action is taken, labeling/package-insert changes may still result from the review.
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  • 6. Re-evaluation •Re-examination should be distinguished from re- evaluation( 再評価 ). • Re-examination primarily concerns newly approved products after their designated post-marketing period. • Re-evaluation can apply to already-approved drugs and reassesses their quality, efficacy and safety against current scientific/medical standards. It can potentially result in cancellation, modification/deletion of indications, or no action.
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  • The MarketingAuthorization Holder (MAH) continuously collects safety information. • Sources • Healthcare professionals • Patients • Clinical studies • PMS studies • Literature • Other safety databases/sources
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  • Process Collect safetyinformation ↓ Validate & assess ↓ Identify safety signals ↓ Report to authorities ↓ Risk-minimization action, if necessary
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  CONCLUSION • MHLW isthe main government authority responsible for marketing approval. • PMDA performs scientific reviews and regulatory inspections. • Drug development must comply with GLP, GCP and GMP requirements. • PMS continues throughout the product's post-approval lifecycle. • GPSP governs post-marketing studies and surveillance. • RMP integrates safety risks and risk-minimization activities. • Re-examination and re-evaluation provide additional regulatory oversight after approval. • Japan therefore uses a lifecycle-based approach to drug safety.
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  References • Ministry ofHealth, Labour and Welfare (MHLW) — Pharmaceuticals and Medical Devices regulatory framework • PMDA – Review and Approval Services • PMDA – GLP/GCP/GPSP • PMDA – Risk Management Plan (RMP)
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  THANK YOU