What is validation?

Validation is proving that a piece of equipment, a computer program, or a test process does what it is designed to do on a consistent and predictable basis. eg

• Proving a fridge can maintain temperature within a specified range for as long as required with minimal impact from differences in load or accessing of items in fridge an antibiotic assay can consistently yield the same result from the same test sample
• Media expiry dates are valid
• a total aerobic count test is capable of recovering microbes that may be present within a sample
• a computer program will run as predicted without crashing or yielding unexpected outputs

If you buy a fridge, then there is no point using it if it maintains temperature at a range that is not intended. The same goes for freezers/ovens/incubators. With scientific equipment, you need to prove the equipment does what it is purchased to do.

When an antibiotic assay is validated you can be confidant that the results you get are reliable and consistent through the range of samples tested. Minor variations in sample weights and preparations should be shown to not affect the final result.

An unvalidated TMC test that recovers no growth may be producing this result due to toxicity of the product. Validation is meant to show that microbes where present, can be recovered using the test method used.

Computer programs need to work as intended and be able to cope with data input errors without crashing or hanging.

Why do we need validation?

It is a basic requirement of quality control is to ensure that test methods are validated. This is stated in documentation from the BP/EP, USP and TGA.

From a functional perspective, it is unwise to incubate samples in an incubator that has not been proven to maintain the temperatures required, or to conduct an assay on a product where the test cannot produce a valid result. Having a validated process makes life easier. Though the initial validation may be tricky, it potentially saves much angst later.

Why is this so? If a manufacturer cannot support the results they obtain, then the product they are selling cannot be purported to be or do what it is supposed to do. Eg, a product is free from microbes, or a stability study was at a certain temp for a certain period.

Summary: what is the impact of not having validated processes?

• Unable to prove equipment is suitable for intended use or that it does what the vendor said it is capable of
• Unable to prove test results are valid/accurate
• Can result in difficulties in audits if validation records are not available
• May lead to products being declared to be adulterated

Stages of Validation

• DQ – design qualification (Details what you want the test or equipment to do. May incorporate a User Requirement Spec)
• IQ – installation qualification (Confirms you have what you paid for)
• OQ – operational qualification (Tests that while fallow, the unit does what the DQ/URS requires)
• PQ – performance qualification (Test that in operation, the unit does what the DQ/URS requires)

Alternately, for testing:

• Validation protocol (comparable to DQ)
• Validation report (comparable to IQ, OQ, PQ)

Types of Validation:

• Prospective (preferred)
• Concurrent (for exceptional circumstances)
• Retrospective (for well established, historical methods)

How will knowing about validation assist you?

Day to day, knowing equipment has been validated gives you confidence it will work as expected. For tests, you have confidence in the results produced.

Knowing how an item of equipment or test was validated allows you to determine solutions when validated equipment and processes begin to yield unexpected results. This aids your problems solving skills. Once you have successfully conducted one validation, you are in a good position to conduct further validation.

Temperature mapping on a fridge will allow you to make judgements on temperature excursions where the correct type of mapping has taken place during OQ/PQ.

Validation of TMC tests may allow the microbiologist to determine which products are toxic to microbes. This is helpful in the event of an alert or action level count. Eg, if a validation could not recover Staphylococcus aureus, and a test sample recovered this microbe, it could be argued that the recovery was due to a testing error.

Some companies have dedicated validation departments so being knowledgeable about validation can expand your career opportunities. Validation aids your problem solving, experimental design and report writing skills.

Appendix:

• PIC/S Recommendations on Validation Master Plan Installation and Operational Qualification Non-Sterile Process Validation Cleaning Validation.
• Validating a Refrigerator-Freezer, BioPharm article, November 1998.
• The Development and Application of Guidance on Equipment Qualification of Analytical Instruments, Journal of Accreditation and Quality Assurance (1996) 1:265-274
• Therapeutic Goods Administration – Australian Code of Good Manufacturing Practice for Medicinal Products, 16 August 2002.
• Guidance for Industry – Process Validation: General Principles and Practices, FDA January 2011
• Ten Golden Rules of GMP, Pharmout 2013