1. Introductory Validation and the Cleanroom

2. What we see FDA regulations require Documentation These regulations do not provide Guidelines on how specifically to product the documentation It is left up to the specific companies to design their own documentation system. This includes the process of validation

3. Validation and Qualification Validation contains premises from which a conclusion can be logically derived Qualification is a condition or circumstance that must be met or complied with

4. Can anyone give examples of validation?

5. Validation organization As a department validation should cover Process Equipment Facilities Computer Cleaning

6. Steps in developing Validation are

7. Setup a validation dep. Write a validation plan Write policies, sops and admin procedures Establish change control board Establish document reviewers and approvers Establish document distribution Identify equipment to validate and make a list Assign protocols to all functions Validate most critical equipment first

8. Assign equipment numbers Assign protocol numbers Assign change control numbers Change protocols Perform commissioning at the original equipment manufacturer Write and execute qualification protocols Deficiencies Deviations Addendums Archiving Requalifiction Internal audits FDA audits

9. Qualification Testing Written qualification protocols are prepared that specify the tests to be conducted and the data to be collected. Observations are documented.

10. What needs to be tested? Almost everything needs to be tested How does one know? –Observe the equipment in operation –Major components are typical.

11. What level of testing is required A standard for equipment testing has not been made in the pharmaceutical industry Object is to gain confidence that the equipment is operating under a state of control. Some include –Minimum/maximum operating ranges –Worst case

12. How much testing is Enough? The number of repetitions of a process step during qualification should be based on statistical significance. Conventional wisdom –Once is chance –Twice is nice –Three times is validation Sorry but we need to use Statistics.

13. The Cleanroom A room that is clean

14. ISO standard 14644-1 A room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimize the introduction, generation, and retention of particles inside the room and in which other relevant parameters, e.g. temperature, humidity, and pressure, are controlled as necessary.

15. Who uses clean rooms Electronics Semiconductor Optics Biotechnology Pharmacy Medical Devices Food and Drink

16. 2 major types of cleanrooms Turbulently ventilated room –(diffuses) –20 changes per hr min Unidirectional flow –Air sweeps across the room (80ft/min) Both have clean air on top, moving to the bottom.

17. Particles Human Hair (100um) Visible particle (50um) E. coli (A bacteria) 1um Particles we typically measure 0.5um

18. Some Numbers of ISO classes limits (particles/m3 of air) Class 1 10 Class 2100 Class 31000 Class 410,000 Class 5100,000

19. Also limits on microbe contam GradeAir sampleSettle plates A<1 B105 C10050 D20050

20. Some Cleanroom Disciplines A walking person generates 1,000,000 particles permin (0.5um) Some conditions will preclude work in a cleanroom –Skin conditions (dermatitis) –Respiratory conditions –Microfloura –Allergies

21. Other Conditions Good personal hygiene Cosmetics Jewelery Smokers particles and out gassing

22. Control of air transfer Enter and exit through change areas Do not leave doors open Open and close doors quickly Doors usually open inward in production facilities Respect the airlocks

23. Behavior Sitting 100k, moving 1milK, walking 5milk Positioning so do not drip on product Use no touch techniques Do not support materials on body Do not talk over product

24. Entry and Exit of Personnel Hygiene Cloths, makeup and jewlery Wash before and after Check yourself and check others Are you protecting product or yourself.