The End of Process Validation As We Know It?

In 1987, when the US Food and Drug Administration issued its Guideline on General Principles of Process Validation, a young FDA reviewer asked her supervisors, "What does this term validation really mean?"

"We don't know," they responded.

Much has changed in the past 18 years. So much has changed, in fact, that the current concept of process validation, once a fresh idea in quality control, and which later became accepted dogma, may now be ready for the trash bin. With companies achieving new levels of process understanding, what does it mean to validate a manufacturing process? Industry leaders and FDA are now examining that question and looking at new models to follow.

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Author(s):

Laura Bush

Journal:

Pharmaceutical Technology, Aug 2, 2005

Essentials of Validation Project Management

All pharmaceutical validation projects are labor and capital intensive, and each must be planned and managed carefully. Numerous tasks and activities must be identified early and then scheduled to support the project completion date. Stakeholders such as the Quality Assurance (QA) and Calibration–Metrology departments must be alerted to impending increased workloads under compressed time frames. Standard operating procedures (SOPs) and protocol formats must be developed, test equipment must be purchased or rented, and contractors must be evaluated and hired. Managers must decide whether the US Food and Drug Administration will participate in the design review process, and if so, what will be the agency's exact involvement and participation. Considering the set of activities and programs that require timely completion, pharmaceutical validation projects must be carefully organized, managed, and monitored.

Part I of this article covered the following four critical components common to all successful validation projects: design review to ensure GMP compliance, project scope definition, project labor and cost estimating, and validation master plan development (1). Part II of this article introduces three additional programs, thereby providing validation project managers and participants the knowledge to plan and execute a project properly, no matter how difficult or complex. This final article also examines activities that are initiated well after project inception and often continue to project completion and operations:

protocol and SOP development, scheduling, and implementation;
turnover package preparation;
deviation and discrepancy management.

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Author(s):

William Garvey

Journal:

Pharmaceutical Technology, Jan 1, 2006

Characterization, Qualification, and Validation of a Disposable Final Filling Process for Parenteral

Many articles describe the growing need for and benefits of the replacement of traditional, reusable technologies with disposable, single-use components in the pharmaceutical and biotechnology industries (1–6). Replacing reusable materials (e.g., stainless steel) with disposable products is cost effective and increases operator and product safety (3–6).

For disposable technologies to be accepted by an industry, vendors must show that disposable systems can have equal or better performance than traditional systems. As vendors begin supplying complete sterile, disposable solutions to the pharmaceutical and biotechnology industries, suppliers will be required to have complete validation packages and an in-depth understanding of their products.

The first decision that must be made when designing and manufacturing a disposable assembly is the choice of materials to be used. The materials typically chosen are polymeric materials that must be sterilized using common sterilization methods. Typically, prepackaged, presterilized disposable assemblies are gamma irradiated at >25 kGy. Therefore, the materials of these assemblies must be nontoxic and resist changes to their physical properties after being irradiated.

Once the materials are chosen, bioburden (i.e., the level of contamination) must be minimized during the assembly process. Low levels of bioburden are required throughout the product fluid path to ensure endotoxin levels are well below accepted levels. Overall bioburden levels for inner and outer material surfaces also must be monitored carefully and maintained during the manufacture of the disposable modules to ensure the validity of the subsequent sterilization process.

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Author(s):

Brett M. Belongia, PhD , James A. Allay, PhD.

Journal:

Pharmaceutical Technology, Mar 2, 2006.

Method Validation Guidelines

"The objective of validation of an analytical procedure is to demonstrate that it is suitable for its intended purpose" (International Conference on Harmonisation Guideline Q2A). 1 "Methods validation is the process of demonstrating that analytical procedures are suitable for their intended use" (US Food and Drug Administration Draft Guidance for Industry, 2000 ). 2

So, is your assay fit for the job ?

Validated analytical test methods are required by good manufacturing practice (GMP) regulations for products that have been authorized for sale and almost certainly for late-stage trial clinical material.3 Also, some methods used during the pre-clinical phase of drug development under good laboratory practice (GLP) regulations may also require validation.4

However, during the development of biopharmaceuticals, methods may be employed that may not need full validation — for example, those used only for process validation or comparability studies. The various terms applied to the "not-quite-validation" of such methods include "test characterization," "qualified method," and "validated for Phase I." Considerable confusion has arisen over this topic, which has been the subject of several articles and numerous presentations at conferences. This article also seeks to explain and clarify the situation.

In basic terms, a suitable method must be based on firm scientific principles; capable of providing the necessary sensitivity, accuracy, precision, etc.; and capable of generating reliable results. During test development, we learn more about the ability of a test to meet these requirements, and we decide whether the test is going to meet suitability standards. The key questions to be answered are:

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Author(s):
Alex D. Kanarek, Ph.D.
Journal:
BioPharm International, September 2005.

Validation of Spectrometry Software: Critique of the GAMP Good Practice Guide for Validation of Labo

In this column over the past few years, I have not mentioned in any great detail guidance documents on computer validation but started the discussion on a specific topic from the regulations themselves. This is due to the fact that most guidance has concentrated to a large extent on manufacturing and corporate computerized systems rather than laboratory systems including spectrometers.

This has changed with the publication of the Good Automated Manufacturing Practice (GAMP) Forum's Good Practice Guide (GPG) on Validation of Laboratory Computerized Systems (1). However, this publication needs to be compared and contrasted with the AAPS publication on Qualification of Analytical Instruments (AIQ) (2). Both publications have been written by a combination of representatives from the pharmaceutical industry, regulators, equipment vendors, and consultants.

Overview of the Guide

Published in 2005, the stated aim of the GPG is to develop a rational approach for computerized system validation in the laboratory and provide guidance for strategic and tactical issues in the area. Section 5 of the GPG also notes that: ". . . the focus should be on the risk to data integrity and the risk to business continuity. The Guide assumes that these two factors are of equal importance" (1).

However, the GPG notes that companies must establish their own policies and procedures based upon their risk own management approaches. Of interest, the inside page of the GPG states that if companies manage their laboratory systems with the principles in the guide there is no guarantee that they will pass an inspection, and therefore: caveat emptor!

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Author(s):

Robert D. McDowall

Journal:

Spectroscopy, Apr 1, 2006