Validation of pharmaceutical process a case study

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SEMINAR ON Validation of pharmaceutical process a case study PRESENTED BY SUBMITTED TO PENDBHAJE VAIBHAV.V Mr.Y.P . SHARMA F.Y.M.PHARM. HOD , DEPT.OF P’CEUTICS DEPT.OF P’CEUTICS SND COLLEGE OF PHARMACY SND COLLEGE OF PHARMACY 1

CONTENT:-: 

CONTENT:- What is Validation ? Importance of Validation Type of Validation Phases of process Validation Type of process Validation Case study 2

What is Validation ?: 

What is Validation ? Establish documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.” This approach will be applied to….. I ndividual pieces of equipment. Manufacturing process as a whole. 3

Importance of Validation : 

Importance of Validation Increased throughput Reduction in rejections and reworking Reduction in utility costs Avoidance of capital expenditures Fewer complaints about process-related failures Reduced testing in-process and in finished goods More rapid and reliable start-up of new equipment Easier scale-up from development work Easier maintenance of equipment Improved employee awareness of processes More rapid automation 4

Type of Validation -: 

Type of Validation - There are four types of validation Process validation . Cleaning validation . Analytical validation . Computer validation . 5

Phases of process Validation - : 

Phases of process Validation - Validation is broken down into four phases: Design Qualification (DQ). Installation Qualification (IQ). Operational Qualification (OQ). Performance Qualification (PQ). These four protocols are used to define tests that will demonstrate that the process consistently and repeatedly produces the desired product . 6

Design Qualification (DQ) : 

Design Qualification (DQ) It contains - 1)Descriptions of equipment. 2)References:- a) specifications. b) Quotation. c) Order number. 3)Machine specifications. 4)Approvals. 5)Manuals. 6) Certificaton 7

Installation Qualification (IQ) -: 

Installation Qualification (IQ) - This protocol insures that the system/equipment and its components are installed correctly and to the original manufacturer’s specifications. Calibration of major equipment, accessory equipment, and/or utilities should be performed in this step as well. 8

Operational Qualification (OQ) - : 

Operational Qualification (OQ ) - This step proceeds after the IQ has been performed. In the OQ, tests are performed on the critical parameters of the system/process. These are usually the independent and manipulated variables associated with the system/equipment. All tests’ data and measurements must be documented in order to set a baseline for the system/equipment. 9

Performance Qualification (PQ)- : 

Performance Qualification (PQ )- This is the final phase of validation. This phase tests the ability of the process to perform over long periods of time within tolerance deemed acceptable. PQ is performed on the manufacturing process as a whole. Individual components of the system are not tested individually. 10

Type of process Validation: 

Type of process Validation Prospective Validation. Retrospective Validation. Concurrent Validation. Revalidation. 11

Prospective Validation: 

Prospective Validation It is a experimental plan also called as validation protocol. Validation conducted prior to distribution either of a new product . A product made under a revised manufacturing process. Validation is completed and the results are approved prior to any product release. 12

Retrospective Validation: 

Retrospective Validation Validation of a process for a product already in distribution, based on ; accumulated production , testing, and control data's. Summary of existing historical data. 13

Concurrent Validation : 

Concurrent Validation Study of concurrent validation under protocol during the course of normal production. A combination of retrospective and prospective validation . Performed against an approved protocol but product is released on a lot-by-lot basis. Usually used on an existing product not previously validated or insufficiently validated. 14

Revalidation: 

Revalidation To validate change in equipment, packaging, formulation operating procedure . process that could impact product safety, efficacy or potency. It is important to establish a revalidation program for critical equipment to maintain validity. 15

Process Validation: 

Process Validation 1. Requalification or revalidation. 2. Calibration, verification, and maintenance of process equipment. 3. Establishing specifications and performance characteristics. 4. Selection of methods, process, and equipment to ensure the product meets specifications. 5. Qualification or validation of process and equipment. 6. Testing the final product, using validated analytical methods, in order to meet specifications. 7. Challenging, auditing, monitoring, or sampling the recognized critical and key steps of the process 16

Case study: 

Case study STEAM STERILIZATION VALIDATION 17

STEAM STERILIZATION: 

STEAM STERILIZATION Various types of steam sterilizers are commercially available :- • Saturated Steam • Water Immersion • Air-Steam Mixtures • Gravity Air Displacement (unpacked materials sterilization ) • Vaccum air Displacement (Packed materials) 18

STEAM STERILIZATION: 

STEAM STERILIZATION Microbiological aspects of Steam Sterilization and Dry Heat Sterilization are basically the same . D- Value is determined in the same way Z- Value :- the z- value is the number of degrees of temperature Change to required to produce a 10-fold change in D- value this is relates to the heat of a microorganism to changes in temperature Lethality (F0 ) can be calculated in the same way . 19

STEAM STERILIZATION : 

STEAM STERILIZATION 1 . Design Qualification : Facility layout. • Utility requirements and specifications. • Required capacity of the sterilizer. • Type of materials to be sterilized ( Liquids, wrapped ,hollow or porous materials ) • Requirement for Gravity and Prevacuum cycles. 20

STEAM STERILIZATION: 

STEAM STERILIZATION 2. Installation Qualification- CALIBRATIONS :- The following pieces of equipment should be calibrated by removing . • Pressure Gauges. Timing Devices. Temperature Recording Devices. Verification of safety Systems and Devices. 21

Steam Sterilization Validation: 

Steam Sterilization Validation 3. Operational Qualification :- The actual operational performance of the Electro/mechanical components and utilities. It Should be verified and documented. Clean Steam Generator. Air Filtration Systems and compressed air Power Source Heat Exchanger, Cooling Water. 22

Steam Sterilization Validation : 

Steam Sterilization Validation 4. Performance Qualification : Temperature Distribution :- External monitoring and recording instruments Shall be calibrated before and after the OQ/PQ Studies (3 point calibration, ± 0.5 0C tolerance). Uniformity of the temperature distribution in Case of Min & Max . loading should be verified by using Thermocouples with 3 replicates. 23

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At least one T/C shall be placed located in the steam exhaust line or adjacent to the equipment temperature controller. Min . 10-12 T/C ‘s shall be used . They should not be inserted in the load . Data should be recorded during the whole cycle at 1 min intervals. Location of the “cold spot” should be determined and documented. 24

Steam Sterilization Validation: 

Steam Sterilization Validation Performance Qualification : Heat Penetration- Acceptance Criteria: Thermocouples should be inserted into the load. At least three biological indicators and T/C’s shall be placed around the cold spot. External T/C readings should comply with manufacturer’s specifications (with Max ± 1 0C difference ) Biological indicator (bacillus stearothermophilus ) results should ensure the 6-log reduction and Lethality calculation should verify the Equivalent F0 (15 min. at 121 0C) value for defined cycle. 25

Bowie-Dick or DART Test :- : 

Bowie-Dick or DART Test :- The Bowie-Dick test verifies the performance of a dynamic air-removal steam sterilizer. The test only verifies the ability of the sterilizer to remove air and replace it with steam . Origins and history:- The first Bowie-Dick Test was created by Dr. J. Bowie and Mr. J. Dick and was first published in the ‘Lancet’ journal in 1963. The Bowie-Dick Test is a Class 2 Chemical Indicator. 26

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purpose of evaluating the efficacy of dynamic air removal sterilizer systems. The Bowie-Dick Test is not to be considered a biological performance test. If the air is not effectively removed, air pockets will occur in the chamber and sterilization conditions will not be attained . Bowie-Dick or DART Test pack, the uniformity of the color change on the indicator sheet should be checked. (3.5 min. at 134 0C ) 27

LEAK RATE TEST:-: 

LEAK RATE TEST:- The presence of air prevents proper penetration of of the load by steam and thus inhibits sterilization. Air leaking from outside into the chamber at the end of sterilization cycle will contaminate the load. A leak rate equivalent to a rate of change in pressure of 1 mm Hg/min. over a period of 10 min . after stabilization is the maximum permitted rate . 28

CHANGE CONTROL AND REVALIDATION: 

CHANGE CONTROL AND REVALIDATION Any changes to the sterilization equipment and/or related utilities should be evaluated by a Change Control Procedure. Typical Changes Requiring Revalidation • Any changes in operating cycle ( i.e:temperature , time , belt speed, chamber pressure) • Change in load configuration. • Change in sterilized materials. • Major maintenance work on critical instruments/elements or utilities. 29

Reference:-: 

Reference:- 1) Pharmaceutical Process Validation, edited by Bernard T Loftus and Robert A Nash. 2) Pharmaceutical Process Validation: Second Edition, Revised and Expanded, edited by Ira R. Berry and Robert A. Nash. 3) Pharmaceutical Process Validation: An International Third Edition, Revised and Expanded, edited by Robert A Nash and Alfred H. Wachter . 4) validation of pharmaceutical process Third Edition , edited by james agalloco Fredrick .Carleton 5) Bowie-Dick Test problem By Charles O. Hancock, JANUARY 2005. 6) Bowie-Dick Test self study by Arthur Henderson, Michael Russell, ; Richard Bancroft; and Heide Ame 7) principles and practice of disinfection preservation and sterilization, third edition edited by A.D.Russell ` et.al .8)Validation of pharmaceutical process,sterile products,second edtion revised and expanded edited by J.Carleton.et.al 30

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