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biopharmaceuticals biochemistry and biotecnology - Walsh G.

Walsh G. biopharmaceuticals biochemistry and biotecnology - John Wiley & Sons, 2003. - 572 p.
ISBN 0-470-84327-6
Download (direct link): biochemistryandbiotechnology2003.pdf
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Validation studies
Validation can be defined as ‘the act of proving that any procedure, process, equipment, material, activity or system leads to the expected results’. Routine and adequate validation studies form a core principle of GMP as applied to (bio)pharmaceutical manufacture, as such studies help assure the overall safety of the finished product (Box 3.1).
All validation procedures must be carefully designed and fully documented in written format (Box 3.1). The results of all validation studies undertaken must also be documented, and retained in the plant files. As part of their routine inspection of manufacturing facilities, regulatory personnel will usually inspect a sample of these records, to ensure conformance to GMP.
Validation studies encompass all aspects of (bio)pharmaceutical manufacture. All new items of equipment must be validated before being routinely used. Initial validation studies should be comprehensive, with follow-up validation studies being undertaken at appropriate time intervals (e.g. daily, weekly or monthly). It is considered judicious to validate older items of equipment with increased frequency. Such studies can forewarn the manufacturer of impending equipment failure. Some validatory studies are straightforward, e.g. validation of weighing equipment simply entails weighing standardized weights. Autoclaves may be validated by placing external temperature probes at various points in the autoclave chamber during a routine autoclave run. Validation studies should confirm that all areas within the chamber reach the required temperature for the required time.
Periodic validation of clean room HEPA filters is also an essential part of GMP. After their installation, HEPA filters are subjected to a leak test. Particle counters are also used to validate clean room conditions. A particle counter is a vacuum cleaner-like machine capable of sucking air from its surroundings at constant velocity, and passing it through a counting chamber. The number of particles per m3 of air tested can easily be determined. Furthermore, passage of the air through a 0.2 mm filter housed in the counter will trap all airborne microorganisms. By placing the filter on the surface of a nutrient agar-containing Petri dish, trapped microorganisms will grow as colonies, allowing determination of the microbial load per m3 of air.
In addition to equipment, many processes/procedures undertaken during pharmaceutical manufacture are also subject to periodic validation studies. Validation of biopharmaceutical
184 BIOPHARMACEUTICALS
Box 3.1. Validation studies: a glossary of some important terms
Validation master plan: document that serves as an overall guide for a facility’s validation programme. It identifies all items/procedures etc. which must be subjected to validation studies, describes the nature of testing in each instance and defines the responsibilities of those engaged in validation activities.
Validation protocol: document describing the specific item to be validated, the specific validation protocol to be carried out and acceptable results, as per acceptance criteria.
Prospective validation: validation undertaken prior to commencement of routine product manufacture.
Concurrent validation: validation undertaken while routine manufacture of product is also taking place.
Retrospective validation: validation carried out by review of historical records.
Qualification: how an individual element of an overall validation programme performs. When validation of that specific element is complete, it is ‘qualified’. When all elements are (satisfactorily) completed, the system is validated.
Design qualification: auditing the design of a facility (or element of a facility, such as a clean room) to ensure that it is compliant with the specifications laid down and that it is therefore capable of meeting GMP requirements.
Installation qualification: auditing/testing to ensure that specific items of equipment have been correctly installed in accordance with the design specifications laid down.
Operational qualification: auditing/testing process which elevates the system being tested to make sure it is fully operational and will perform within operating specifications.
Performance qualification: demonstration that equipment/processes operate satisfactorily and consistently during the manufacture of actual product.
aseptic filling procedures is amongst the most critical. The aim is to prove that the aseptic procedures devised are capable of delivering a sterile finished product, as intended.
Aseptic filling validation entails substituting a batch of final product with nutrient broth. The broth is subject to sterile filtration and aseptic processing. After sealing the final product containers, they are incubated at 30-37°C, which encourages growth of any contaminant microorganisms (growth can be easily monitored by subsequently measuring the absorbance at 600 nm). Absence of growth validates the aseptic procedures developed.
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