, International Regulatory and Health Authorities Inspections Maria Santaella Sr. Quality Director Janssen Ortho LLC Jansen Cilag Manufacturing LLC Gurabo, Puerto Rico FDA-PIA Discussion Session-December 3, 2009

International Regulatory and Health Authorities Inspections Korean Food and Drug Administration (KFDA) Agencia Nacional de Vigilancia Sanitaria (ANVISA-Brazil) Ugandan Health Authority (Uganda) Pharmaceutical and Medical Devices Agency (PMDA-Japan)

General Highlights: Objective: Ensure facilities, systems and procedural controls are in place to protect product safety, integrity, quality and strength Inspection Report:  No report is issued at end of inspection  Report issued to affiliate company requesting the inspection.  Inspection report is issued within 30 days of inspection date Inspection Observations are classified  Critical, Major, Minor  Recommendations or General Comments Frequency for re-inspection will vary International Regulatory and Health Authorities Inspections

Korean Food and Drug Administration (KFDA) Regulation: Good Manufacturing Standard for Medicinal Products (2008) Inspection Language: Korean (translators are required) No of inspectors: 2 Duration of the inspection: 1-3 days Frequency of Inspection: Per product type and compliance profile Areas inspected:  Warehouse (Receiving, Storage and Shipping)  Incoming Sampling  Manufacturing Areas and Rooms  HVAC and Water Systems  Analytical and Microbiology Laboratories International Regulatory and Health Authorities Inspections

Korean Food and Drug Administration (KFDA) Regulation released on 2008 and is being enforced for new products Inspection initiated with an extensive facility tour (all day) Emphasis on controls to avoid cross contamination (viable & non-viable)  Facilities (Solid Dosage):  Gowning and de gowning areas required to be physically separated  Manufacturing rooms must be accessed through an ante room  Differential Pressure must comply with >0.05 inches of water  Environmental Controls (Solid Dosage):  Routine viable and non viable (at rest) monitoring is required for manufacturing rooms, halls, gowning/de gowning areas, sampling rooms and microbiology laboratories  Extensive review of data generated for manufacturing and microbiology laboratory International Regulatory and Health Authorities Inspections

Korean Food and Drug Administration (KFDA) (cont.) Raw materials retain samples are required to be stored in the same container type/material used by manufacturer Quality Agreements are expected to be very detailed GMP Certificate or equivalent document is issued with observations report. Non approval decision is issued if any critical observation is found. International Regulatory and Health Authorities Inspections

Agencia Nacional de Vigilancia Sanitaria (Brazil) Regulation: Technical Regulation of Good Manufacturing Practices to the Production of Drugs Inspection Language: English/Spanish Note: Communication challenges due to language barrier could be expected No of inspectors: 2 Duration of the inspection: 1 week Frequency of Inspection: Every two years Areas inspected:  Materials System (1 day)  HVAC/Water Systems (1 day)  Manufacturing Controls (1 day)  Laboratory Systems (1 day)  Quality Systems (1 day) International Regulatory and Health Authorities Inspections

Agencia Nacional de Vigilancia Sanitaria (Brazil) Inspection strategy:  Documents review in the morning at inspection room  Challenge of actual practices in the afternoon (touring of operational areas) System Based Inspection concept Main focus in HVAC and Water Systems Validation Master Plan with detailed timeline of validation activities is a requirement Process capability evaluation (annual) for products marketed at Brazil is a requirement GMP certificate is issued after inspection to authorize firm for marketing product in Brazil International Regulatory and Health Authorities Inspections

Ugandan Health Authority Regulation: World Health Organization (WHO) Inspection Language: English No of inspectors: 2 Duration of the inspection: 2 days Frequency of Inspection: Unknown Areas inspected:  Warehouse (Receiving, Storage and Shipping)  Incoming Sampling  Manufacturing Areas and Rooms  HVAC and Water Systems  Analytical and Microbiology Laboratories  Environmental, Safety and Health (including Employee Surveillance Program) International Regulatory and Health Authorities Inspections

Ugandan Health Authority Inspection initiated with short facility tour (1/2 day) Focus in documents review Quality Agreement between site and African country is required. Environmental Health and Safety areas were covered during the inspection including but not limited to: Water Treatment Plant, Safety Program, Employee Surveillance Program) Budget restriction could be expected (inspectors requested a hotel less than 80 US /night) International Regulatory and Health Authorities Inspections

Pharmaceutical and Medical Devices Agency Regulation: GQP.GMP 2005 (Ministerial Ordinances on GQP and GMP) Ministry of Health, Labor and Welfare (MHLW) Inspection Language: Japanese (translators are required) No of inspectors: 2 Duration of the inspection: 2 days Frequency of Inspection: Per compliance profile Areas inspected:  Warehouse (Receiving, Storage and Shipping)  Incoming Sampling  Manufacturing Areas and Rooms  HVAC and Water Systems  Analytical and Microbiology Laboratories International Regulatory and Health Authorities Inspections

Pharmaceutical and Medical Devices Agency Inspection initiated with extensive facility tour (1 ½ days) Emphasis on controls to avoid cross contamination (viable & non-viable) Emphasis in manufacturing operations and rooms  Housekeeping, cleanliness and appearance Acceptance Quality Levels for product defects are tighter Quality Agreement between Japan affiliate company and Manufacturing Operation is a regulatory requirement Inspection activities were conducted in a very formal manner International Regulatory and Health Authorities Inspections

The opinions expressed in this presentation are solely those of the presenter and should not reflect the views of Johnson & Johnson 13