Japan Drug GMP Requirements and Audits

Contact us today for a free consultation with a Japan regulatory affairs consultant to discuss your specific needs.

When a foreign drug company wants to register its drug in Japan, one of the most important steps is Japan GMP requirements. These GMP requirements are outlined in Japan’s MHLW’s Ministerial Ordinance No. 179, 2004 – “The GMP ordinance”.  GMP standards and requirements cover drug manufacturing control and validity control by drug manufacturers. The Japanese PMDA (under the MHLW) does GMP inspections on foreign manufacturing sites making new drugs, biologics, API, radiopharmaceuticals, etc. There are two types of PMDA audits – 1. a pre-marketing GMP audit and 2. a periodical GMP audit done every 5 years to maintain the drug’s marketing authorization.

Pacific Bridge Medical helps foreign drug companies with Japan GMP audits. We can do a mock audit at your facility to prepare for the official PMDA audit. Below is a typical Japanese GMP mock audit.

Agenda for GMP Gap Audit

Document Review Items (Draft)

The following documents are listed, based on sub-systems to be checked in the GMP inspection by the PMDA. However, due to the time constraints during this on-site visit for the GMP gap assessment, the items marked with * will be prioritized to be reviewed.

  1. Quality Systems
  • GMP Organization and Responsible Person for each Quality System*
  • Site Master File*
  • Management of Blank Format of Master Batch Record*
  • Document Control, including Data Integrity*
  • Product Release, including Storage Operation*
  • Change Control, including validation when changed*

List for Change Controls in the past two (2) years*

  • Deviation Management, including Analytical Testing*

List for Deviations in the past two (2) years*

  • Quality Information and Quality Complaint*
  • Self-Inspection*
  • Product Recall*
  • GMP Training, including Qualification Program for Personnel, including Operator for Visual Inspection*
  • Quality Agreement with Marketing Authorization Holder (MAH) *
  • Quality Policy*
  • Quality Manual*
  • Product Quality Review*
  • CAPA Management*
  • Hygiene Control*
  • Environmental Control*
  • Supplier Control & External Contractor Management*
  • Role and Responsibility of Senior Management*
  • Management Review, including Internal Information transfer, Escalation to Senior Management, and Resource Management*
  • Technology Transfer*
  • Oversight for Quality System Management, including Quality Risk Management & Knowledge Management*
  • Rework/Reprocessing*
  • Validation Master Plan*
  • Risk Control for Contamination of Nitrosamines and Elemental Impurities*
  • Contamination Control Strategy*
  • BSE/TSE control*
  1. Facility/Equipment System
  • Buildings & Facilities (including operating room), equipment, and the qualifications. (Pharmaceutical water, manufacturing facilities, analytical testing equipment) *
  • Facility/Equipment Maintenance for Production, Storage, Packaging & Analytical Testing*
  • Computerized System Management, including qualification/Validation/Security*
  • Calibration*
  • Utilities Controls, including Water System, Air Conditioning System, and Gases for Production*
  • Pest Control*
  • Prevention from Cross-contamination and Mixed-up*
  • Containment Measures*
  • Others (Drawing, Structural Frame Management, Entrance/Exit Management, Lighting (including Shading Management)
  1. Storage System for Finished Products, Intermediates, & Raw Materials
  • Incoming Materials Control*
  • Storage Condition and Status Control, including for Rejected Materials*
  • Inventory Control, including, including FIFO or FEFO*
  • Testing or validation of supplier’s Test Results, Quality Oversight of Material Suppliers*
  • Retest Control*
  • Prevention of foreign materials contamination, and cross-contamination & mixed-up*
  • Good Distribution Practice for raw materials, intermediates, and finished Products
  1. Production & Labeling System
  • Manufacturing Instruction and Records, including data integrity management*
  • Pre-work Check, including line clearance*
  • In-Process Control*
  • Prevention of Foreign Materials, Cross-Contamination & Mixed-up during Manufacturing*
  • Material & Personnel Flow, Zoning, and Clothes Control*
  • Process Validation*
  • Cleaning Control, including Cleaning Procedure and Cleaning Validation
  • Status Control*
  • Yield Control
  • Holding Time during Production*
  • Label Management, including insurance, storage, and disposal of labels*
  1. Analytical Testing System
  • Management for Analytical Testing Instruction and Records, including data integrity management*
  • Sampling Operation and Sample Control*
  • Regents, Test Solutions, and Standard Materials Control*
  • Control of Water Systems for Analytical Testing*
  • Decision of Analytical Testing Results*
  • Approval Label Management and information control (approval information to transfer to storage responsible person) *
  • Reference and Retention Samples Management*
  • Stability Monitoring*
  • Analytical Testing Method Validation*
  • Control of testing by External Contractor, including Quality Agreement*
  • Prevention for Mixed-up*
  • OOS/OOT Investigation*
  1. Consistency between Manufacturing Batch Record and NDA Submission Dossier

Contact us today for a free consultation with a Japan regulatory affairs consultant to discuss your specific needs.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)
Mr. Gross founded PBM in 1988 and has helped hundreds of medical companies with regulatory and business development issues in Asia. He is recognized nationally and internationally as a leader in the Asian medical markets. Mr. Gross has a BA degree, Phi Beta Kappa, from the University of Pennsylvania and an MBA from Columbia University.