International GMPs

Validation

All GMP codes discuss the need for validation, but it is the US authorities, among all national GMP inspectorates who investigate, to a minute level, the extent and correctness of validation activities performed.

Validation is required in all the GMP codes for five areas of activity:

a.      Analytical Method Validation
b.      Computer Systems Validation
c.      Utilities (Services) Validation
d.      Process Validation
e.      Cleaning Validation

All GMP codes agree that validation is defined as “The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes”. The European GMPs add the caveat that validation needs to be performed within the framework of GMPs.

Much talk is currently on-going in the United States and European industry on competency testing of personnel, or Training Validation, and it seems that this might be the next big push in the validation world. It is an axiom in the world of training, not just training in the pharmaceutical industry that if the student pays full attention and the teacher is a great teacher, then two weeks after the training the student will only have retained 10% of the material that was taught. This is such a concern in the USA that a 1993 court decision as part of a consent decree between the US FDA and Warner Lambert required all laboratory analysts to be competency tested in their analytical capability on a 6-monthly basis. In the United Kingdom, there is a growing requirement for technical staff to be certified as meeting National Vocational Qualification (NVQ) standards. GMP authorities world-wide are looking deeply into the question of assuring the effectiveness of training.

Although the US GMPs from 1976 never defined what validation means, the US FDA has published a series of guidelines outlining their expectations on validation. Key among these guidelines has been a series of guidelines that heavily discuss validation, published in 1993:

Guide To Inspections of Validation Of Cleaning Processes
Guide To Inspections of Pharmaceutical Quality Control Laboratories
Guide To Inspections of High Purity Water Systems
Guide To Inspections of Topical Drug Products

All of these guidance documents (which can be found at FDA’s website at http://www.fda.gov/ora/inspect_ref/igs/iglist.html#DRUGS) follow on from FDA’s seminal guide on validation – “Guideline on General Principles of Process Validation”, issued in 1987.

A highly informative, and very pragmatic, series of validation guidelines has been issued since 2002 by the Canadian HPFB Inspectorate (and are available on their website at http://www.hc-sc.gc.ca/hpfb-dgpsa/inspectorate/gmp_e.html), and include among others:

Cleaning Validation Guidelines
Process Validation: Aseptic Processes For Pharmaceuticals
Process Validation: Form - Fill - Seal For Drugs
Process Validation: Irradiation Sterilization For Pharmaceuticals
Process Validation: Moist Heat Sterilization For Pharmaceuticals
Validation Guidelines For Pharmaceutical Dosage Forms

These guides update the equivalent FDA guides by about 10 years, are prescriptive and far easier to comprehend than the original FDA documents on the same subjects (this is especially true of the Canadian Cleaning Validation Guidlines).



	Introduction

	Drug Quality - Pharmacopoeal Testing

	The Advent of GMPs

	GMPs: Codes, Directives, Guidelines, Points to Consider, or Regulations; and INspection Severity

	Drug Quality – GMP Implementation

	The GMPs

	Quality Management and the Qualified Person

	Validation

	Self Inspection

	Contract Manufacture and Contract Analysis

	Future Trends

	Afterthought

	References