1. VALIDATION OF COMPUTERISED SYSTEMS IN THE PHARMACEUTICAL INDUSTRY Matt Safi Product manager

2. What does need validation? l Any drugs manufactured for use by humans and animals needs to be validated. l A satisfactory inspection and approval by a regulatory inspector is required before a drug is released for sale.

3. What is validated? The Process of manufacturing a drug

4. What is Process Validation? “Validation is documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes” FDA

5. Documentary evidence? “If ain’t written, it ain’t done” Sam Clarke (FDA inspector), 1993

6. Principles of validation l Document what is to be done l Document how it is to be done l Do it l Produce documented evidence that it was done in accordance with the “how” l Demonstrate that it remains in a state of control

7. Who is responsible for validation? The manufacturer of a drug is responsible for getting the process validated

8. What is FDA validation? l FDA (Food & Drug Administration) is responsible for granting approval for drugs intended for the use by humans and animals within the US.

9. Does every drug need FDA validation? l No, only drugs which are intended for use within USA. l Generally every country has its own regulatory body l MCA (Medicines Control Agency): regulatory body in the UK. l FDA has the most stringent requirement

10. Can a Computerised system claimed to be FDA validated? l No. Only the process can be validated. l If a system has been used in a validated process then it will help the validation process

11. Regulators requirements Computerised systems installed in pharmaceutical companies are fit for their intended purposes (in the context of relevant GMPs) by considering: v Quality assurance of the development life-cycle v Performance validation v In-use controls v Accuracy and reliability

12. Pharmaceutical Company Requirements Computerised systems requirements: v Quality assured, robust, reliable system delivered on time within budget v Meet functional and business targets v Acceptable to regulatory agencies v Ease of maintenance

13. Cost of poor quality l Denial of product approval l Increased regulatory scrutiny l Seizure of product l Increased cost of implementation and maintenance

14. What is our responsibility? l Ensure that the supplied automation system satisfies the requirement specification l Provide documentary evidence. l Documentary evidence will be integrated with the overall documentation for submission to the inspector

15. Some of the regulators l FDA: Federal Drug Administration (US) l HPB: Health Protection Branch (Canada) l Irish Medicines Board l MCA: Medicines Control Agencies (UK) l TGA: Therapeutic Goods Administration (AUS)

16. Some of the regulations & guidelines l EU 91/EEC/44-356-412 Good Manufacturing Practice l CFR 201/211 Current Good Manufacturing Practice l FDA Guide to Inspection of Computers Systems l FDA Guide to Soft ware development l FDA Compliance Policy Guidelines l FDA Computerised Systems in Clinical Trials (Draft 1998) l APV Interpretation of Annex 11 (1996), 91/EEC/356 l GAMP Guide l PDA Technical Report 18- Computer Validation