A Seminar on
Validation Of Sterilizing filter, Capsule filling
machine & Integrated Lines
Prepared By Guided By:
DAVE JAY Mr.RajeshParmar sir
M. Pharm QA, Sem – III
APMC COLLEGE OF PHARMACEUTICAL EDUCATION
AND RESEARCH. (QA Department)
Equipment qualification / validation includes following things User requirements specification (URS)
Design qualification (DQ)
Installation qualification (IQ)
Operational qualification (OQ)
Performance qualification (PQ)
Validation of sterilizing filters
Sterile filtration processes are employed to sterile-filter a product prior to filling it aseptically into its final containers. Bulk drug solutions are sterile- filtered prior to aseptic crystallization, thus eliminating the possibility of having organisms within the bulk drug crystals. The bulk drug can then be processed into a dosage form aseptically or further processed to be terminally sterilized. Other filtrative operations reduce the organism content of a final product prior to terminal sterilizations.
Filter media consist of a matrix of pores held in a fixed spatial relationship by a solid continuum. The pores allow the product solution to pass through the medium while retaining the unwanted solid particles and micro-organisms. The size of filter medium pores to retain micro-organisms must be quite small. The 0.20- or 0.22-µm pore size filter media are considered to be capable of producing sterile filtrates.
The important aspect of filtration sterilization, the membrane filter medium its pore size, pore size distribution, integrity, and capacity.
Nondestructive Physical Tests for Pore Size Characterization
The bubble point test is a popular single-point physical integrity test for disc filter membranes.
A filter medium is wetted with a liquid, and test gas pressure is slowly raised until a steady stream of bubbles appears from a tube or hose attached to the downstream side of the filter and immersed in water . The pressure at which the bubbles first appear is recorded as the bubble point and is related to the largest pores in the filter medium. Filter Qualification
Following factors that should be part of selecting and qualifying a filter for use as a product sterilizing filter:
1. Particle-shedding characteristics
3. Chemical compatibility
5. Thermal stress resistance
6. Hydraulic stress resistance
7. Toxicity testing
8. Bacterial challenge testing
9. Physical integrity testing
Bacterial Challenge Test
Microbiological challenging of a filter is the only true means of determining the bacterial retention properties of the system. Such a test is sensitive because of the large number of organisms used and because the organism self-replicate and allow even low numbers of bacteria that might pass through a filter system to make themselves known.
The level of sensitivity of the challenged test is dependent on the chal- lenge organism, culture environment of the organism, challenge level of the organism, test volume filtered, challenge rate or the duration of the challenge test, and pressure used during the challenge test. FDA published its guideline on validation of aseptic processing specifying requirements for challenging filters with 107 cells of Pseudomonas (now Brevundimonas) diminuta per cm2 of filter surface and for validating aseptic processes using sterile media fills. Because filtration is a removal process, the most resistant organism to filtration would be the smallest known bacterium.
The microbial challenge test can be performed on a particular filtration medium, whether disk or cartridge type, by following these general steps:
Sterilize the filter system.
Integrity test the filter medium using a...
References: 1. www.usvalidation.com
2. Berry I.R., and Nash R.A., ”Pharmaceutical Process validation” second edition, revised and expanded; Marcel Dekker series; 83-110
4. Media fill test by WHO
5. Syed Imtiaz Haider, “ Validation Standard Operating Procedures ” 314-321
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