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Support and utilities validation

It includes validation of utilities used in pharmaceutical industry.

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Support and utilities validation

  2. 2. VALIDATION • Validation is the process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in testing and then production maintains the desired level of compliance at all stages. • In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results. • Since a wide variety of procedures, processes, and activities need to be validated, the field of validation is divided into a number of subsections including the following:
  3. 3.  Equipment validation  Facilities validation  HVAC system validation  Cleaning validation  Process Validation  Analytical method validation  Computer system validation  Packaging validation  Cold chain validation Most important part in any industry is the utility available in the industry. Hence its Qualification and Validation are one of the most important parameters.
  4. 4. SUPPORT DOCUMENTS • The User Requirements Specification (URS) • FAT/SAT • Change Management • Design Specifications • Functional Specification • Purchases Requisitions • Turn-Over-Packages • Vendor Manuals • P&IDs • Manuals
  5. 5. CRITICAL UTILITY QUALIFICATION • Construction Qualification During construction, document procurement and verification of construction activities, are critical components of a successful Installation Qualification (IQ). • Installation qualification Full description of equipment capabilities, design features and company's specific intended use in manufacture, Vendor, equipment ID, serial number, etc.
  6. 6. CONT.…. • Operational Qualification Is a documented plan for the performance of inspections and tests to verify specified dynamic attributes of a system. • Performance Qualification (PQ) – Is a documented plan for the execution of tests to demonstrate the effectiveness and reproducibility of a system/process as a fully integrated functional entity.
  7. 7. VALIDATION OF PURIFIED WATER SYSTEMS • Purified Water is used in Aspect of GMP Manufacturing Operations • Water Usage in Pharmaceutical Production –Potable -EPA –USP Purified –different types –USP Water For Injection
  8. 8. VALIDATION OF CRITICAL WATER SYSTEMS • FDA REQUIREMENTS: Phase 1 • All water systems should have documentation containing a system description and accurate drawing. • The drawing needs to show all equipment in the systems from water input to points of use. It should also show all sampling points and their designations. • After all the equipment and piping has been verified as installed correctly and working as specified, the initial phase of the water system validation can begin.
  9. 9. PHASE 1 • During the initial phase the operational parameters and cleaning/sanitation procedures and frequencies will be developed. Sampling should be daily after each step in the purification process and at each point of use for two to four weeks. • The sampling procedures for point of use should reflect how they are taken, e.g. use of hose, and time for flushing. At the end of the two (2) or four (4) weeks the firm should have developed its SOPs for operation and maintenance of the water system.
  10. 10. FDA REQUIREMENTS: PHASE 2 • The second phase of the water system validation is to demonstrate that the system will consistently produce the desired water quality when operated in conformance with SOPs. • The sampling is performed as in the initial phase and for the same period . At the end of this phase the data should demonstrate that the system will consistently produce the desired quality of water.
  11. 11. FDA REQUIREMENTS: PHASE 3 • The third phase of validation is designed to demonstrate that when the water system is operated, in accordance with the SOPs, over a long period of time it will consistently produce water of desired quality. • Any variations in quality of the feedwater, that could affect the operation and ultimately the water quality, will be noticed during this phase of the validation.
  12. 12. • Sampling is performed according to routine procedures and frequencies. • For Water for Injection systems samples should be taken daily from a minimum of one point of use, with all points of use tested weekly. • The validation of the water system is completed when the firm has collected data for a full year. • The FDA states that “while the above validation scheme is not the only way a system can be validated, it contains the necessary elements for validation of a water system.” • First, there must be data to support the SOPs.
  13. 13. • Second, there must be data demonstrating that the SOPs are valid and that the system is capable of consistently producing water that meets the desired specifications. • Finally, there must be data to demonstrate that seasonal variations in the feedwater do not adversely affect the operation of the system or the water quality. This last part of the validation is the compilation of the data, with any conclusions into the final report.
  14. 14. Contaminant Specification Conductivity USP Specifications Endotoxin No Specifications Bacteria 100 cfu/ml pH 5.0 - 7.0 TOC 500 ppb Specifications for purified water system:
  15. 15. VALIDATION OF PURIFIED STEAM SYSTEMS • Clean Steam Usage in Pharmaceutical Production Clean Steam Requirements –Steam-In-Place (SIP) –tanks, transfer lines, bioreactors, etc. –Sterilization Process –autoclaves • Clean Steam Validation Requirements –URS –DQ –IQ, OQ & PQ
  16. 16. • Clean Steam Design –It includes Clean Steam Generator –Distribution System –Points of Use (Traps) –Autoclave, Reactors, etc. • PQ Requirements –Typically 7 –14 days depending on the complexity of the system
  17. 17. CLEAN STEAM SYSTEM ENVIRONMENTAL MONITORING PROGRAM • Sample Site and Frequencies Determination • –For Clean Steam systems samples should be before manufacturing process i.e. SIP, autoclave, etc. and from a minimum of one point of use, with all points of use tested bi-weekly.
  18. 18. VALIDATION OF COMPRESSED AIR SYSTEMS • Compress Gases Usage in Pharmaceutical Production Compress Gases Requirements • –Preserve the Status of product • –Drying after cleaning • –Assist Cell Growth • –Instrument Actuation • –Move Fluid
  19. 19. Types Of Gases –Clean Dry Air –Nitrogen –Carbon Dioxide –Helium –Oxygen –Argon CLEAN STEAM MAJOR COMPONENTS Cylinders •Dryer •Manifold •Automatic/Manual Switchover System •Valves •Pressure Gauges •Filters •Control System (Low Gases, Low Oxygen) •Distribution System (SS or Type L copper)
  20. 20. COMPRESS GAS SYSTEMS ENVIRONMENTAL MONITORING PROGRAM • Sample Site and Frequencies Determination • For compress gas systems samples should be taken daily from a minimum of one point of use, with all points of use tested weekly.
  21. 21. VALIDATION OF HVAC SYSTEMS • HVAC is used in Aspect of GMP Manufacturing Operations • Clean Room Standards This ISO committee produces 10 new standards documents that relate to cleanrooms or clean zones. The nine standards have been published: ISO 14644- 1 and -9.
  22. 22. CLEAN ROOM CERTIFICATION • Clean Room Certification Testing • Differential Air Flow • Humidity/Temperature • Supply Air Volume/Room Air Change Rate • Room Differential Pressures • DOP Test of HEPA Filters • Room Non-Viable Particulate Counts • Light Levels • Noise Levels • Recovery Time • Unidirectional and Parallelism • Enclosure Induction
  23. 23. HVAC SYSTEMS ENVIRONMENTAL MONITORING PROGRAM • Sample Site and Frequencies Determination • Would the act of sampling at a given site disturb the environment sufficiently to cause erroneous data or possibly cause the product to be contaminated? • At which site would the potential of microbial contamination most likely affect product quality adversely? • During the PQ study which sites were highest in microbial contaminates. • What sites would be the most difficult to clean? • Should site selection involve statistical design or should it be based on a grid profile? • How often is a particular area or process used?
  25. 25. Table 2: Airborne particulate classification
  26. 26. Table 3: EU-GMPANNEX 1recommended limits for microbial contamination
  27. 27. REFERENCES 1. Pharmaceutical validation by Chitlange