Regulatory Compliant Performance Improvement for Pharmaceutical Plants AIChE New Jersey Section 01/13/2004 Murugan Govin

1. Regulatory Compliant Performance Improvement for Pharmaceutical Plants AIChE New Jersey Section 01/13/2004 Murugan Govindasamy Pfizer Inc.

2. Overview: • Introduction • Significance of Regulatory compliance and guidelines • Automation Project – How to make it successful? • Downtime Monitoring • Conclusion • Discussion

3. Significance of Regulatory Compliance and Guidelines

4. Regulatory Basis Food, Drug & Cosmetic Act Section 501(a)(2)(B) of the Food, Drug & Cosmetic Act deems a drug product to be adulterated if : “the methods used in, or the facilities or controls used for, its manufacture, processing, packaging, or holding do not conform to or are not operated or administered in conformity with current Good Manufacturing Practiceto assure that such drug meets the requirements of this Act as to safety and has the identity and strength and meets quality and purity characteristics, which it purports or is represented to possess.”

5. The Code of Federal Regulations (CFR) is a codification of the general and permanent rules published in the Federal Register by the Executive departments and agencies of the Federal Government. Title 21 of the CFR is reserved for rules of the Food and Drug Administration. Each title (or volume) of the CFR is revised once each calendar year. PART 211 - Current Good Manufacturing Practice for Finished Pharmaceuticals – ‘the regulations in this part contain the minimum current good manufacturing practice for preparation of drug products for administration to humans or animals.’ CGMP - Current Good Manufacturing Practice

6. REGULATORY BASIS FD&C ACT 1962 21 CFR 21CFR 21 CFR 21CFR PART 320 PART11 PART 211 PART 820 QUALITY 21 CFR 211 21 CFR 21 CFR CLINICAL SYSTEM PROPOSED 11.10 211.68 STUDIES REGULATIONS AMMENDMENTS MEDICAL COMPUTER AUTOMATED DEVICES SYSTEMS SYSTEMS QC PROCESS ANALYTICAL RESPONSIBILITIES VALIDATION CONTAMINATION TESTING METHOD VALIDATION

7. Regulatory Guidelines: Code of Regulation - General: 21CFR210 -Current Good Manufacturing Practice in Manufacturing, Processing, Packing or Holding of Drugs: General 21CFR211 - Current Good Manufacturing Practice for Finished Pharmaceutical Automation specific: 21CFR211 - 68 - Automatic, mechanical, and electronic equipment 21CFR211 - 11 - Electronic Records; Electronic Signatures --------------------------- Guidelines: GAMP4 - Good Automated Manufacturing Practice Guidelines

8. GAMP: • Excellent tool for a project • Streamlines the requirements • Value adding activities • Common Language

9. Definitions Validation “Validation is defined as establishing documented evidence that provides a high degree of assurance that a process, system, equipment or assay will consistently produce the desired results according to predetermined specifications and quality attributes.” Qualification “Qualification is defined as the documented evidence that the equipment and systems will work correctly and consistently, leading to expected results.”

10. V Model

11. Validation Project Plan • - A Life Cycle Approach • Pre-Qualification Process • Qualification/Validation Process – IQ, OQ & PQ • Commissioning/Implementation • System Maintenance • Change Control • Re-Validation Criteria • Retirement of the System

12. What to follow? • GMP • Regulatory Documents • Regulatory Guidance • Industry Guidance • Internal Policies and Procedures

13. Quality People + Quality Process = Quality Product

14. Automation Project - How to make it successful?

15. Automation Projects • - Requirements for a successful project • Clear Business Objective • Root Cause Analyzed, better than alternatives • Justified Investment • Well defined project plan • Champion to lead - from start to finish • Management Support

16. Major Objectives: • (Objectives which directly relates to the efficient Manufacturing) • Throughput Increase – Cycle time reduction, Capacity Increase, High-speed • Quality Control / Improvement – Product Quality, Compliance Requirement, Info. for decision making • Cost Control – Asset utilization, Efficiency Improvement, Waste Reduction, COGS • Inventory Control – JIT, Scheduling, Push to Pull • EHS – Safety Requirement, Ergonomics • Specific – Product Launch, Process Optimization, Information for Management

17. Automation Projects • - always good to… • Avoid purchasing Serial #1 – Look for history • Know the alternatives and the consequences • Know the bottlenecks and pitfalls • Plan phased approach - if applicable • Enforce company standards and specifications wherever possible. Alternate standards can be used if justified. • Select the suitable vendors who can establish long term partnership • Select the most suitable hardware & software. They may not be the best in the market

18. Automation Projects • - Watch out for… • Scope creep – not a surprise in any automation project • Validation Issues – Good planning in the beginning will avoid this • No user buy in - forced automation (typically an automation engineer carries the project on his/her shoulder). • No major objective (project - just for a sake of automation) • Right solution or just a band aid? • "Do it right or do it twice."

19. Automation Projects • - Challenges… • Return On Investment • Keeping up with technology • Validation Scope • Risk Assessment • Adopting to change (Automation)

20. Efficiency Improvement through Downtime Monitoring – a brief discussion

21. Downtime Monitoring • Automatically capturing machine downtime and the reasons for analysis • Key Performance Indicators (KPI) • Downtime monitoring – Excellent tool, good opportunity for automation, success is measured on the use • Use: Problem solving through Root Cause Analysis • Can be scaled to fit

22. Utilization and Efficiency Improvement - Business Model for performance tracking

23. Conclusion • Understand the regulations • Follow the guidelines and Procedures • Plan Automation as a tool to improve a process • Design and qualification are key to success • Automation project is a success only when it ‘produces’

24. Discussion