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This article provides a historical review of computer validation in the pharmaceutical industry within the last three decades, evolving from the early years' initial concept and approach to today's current practices. Also included is how the regulations and industry have progressed in addressing the topic of computer validation.
PMA also published other computer validation related articles, mainly in Pharmaceutical Technology, which has published more than 40 articles about computer validation. Historically, this publication played a key role in
shaping and spreading understanding of computer validation in our industry. Even individuals from FDA published articles in
the journal back then (17). Sadly, this is no longer the case because, for better or worse, FDA is now stricter about allowing
its employees to publish. (A list of computer validation–related articles is online at
http://pharmtech.com/.)
The PMA CSVC was dissolved in the mid 1990s, and the US Parenteral Drug Association (PDA) became the industry's main forum.
Part of PDA's computer-validation committee efforts focused on software-supplier audit and the creation of an audit repository
center (ARC) (18). The ARC concept, however, has had varying success. Currently, the repository is managed by Syntegra. Since
the late 1990s, the main industry forum for computerized systems validation has been the ISPE good automated manufacturing
practice (GAMP ) group. The GAMP guideline is widely considered to be the de facto pharmaceutical-industry standard in computer validation. The current GAMP 4 version introduced the risk-management concept
into computer validation in 2001, aligning with FDA's effort on GMPs for the 21st century. Currently, GAMP is working on version
5, which is slated for publication in late 2007 or early 2008. It is important to note that GAMP 4 explicitly excludes 21
CFR Part 11, although a separate guideline has been produced.
The healthcare industry has actively addressed Part 11 regulations. ISPE/GAMP and PDA both have published guidelines on Part
11, hoping to help clarify the implementation and compliance to the regulation. As discussed previously, there was much confusion
about the implementation of Part 11 when it was initially introduced. Accordingly, PDA arranged a public FDA conference about
Part 11 in June 2000 (19). The conference reinforced the public's concerns about Part 11, and based on industry's reaction,
FDA issued the final guidance on Part 11 in August 2003 (15). FDA also scheduled a Part 11 public hearing in June 2004, again
allowing the public to voice concerns and suggestions about Part 11. Unfortunately, President Ronald Reagan's funeral fell
on the same day as the scheduled public hearing date, and the day was declared a federal holiday. The meeting was therefore
cancelled and never rescheduled, prompting industry, as a "21 CFR Part 11 Coalition" to file a public petition letter in September 2004 (20). Since then, there has been a semblance of calm
on the topic as FDA considers rewriting Part 11 and industry adjusts to a risk-based approach. The resulting decline in the
number of Part 11 483s may be related to the fact that FDA is citing the predicate rule directly, rather than Part 11. Until
the new amendment is issued, FDA is indeed showing enforcement discretion regarding the implementation of Part 11. It should
be noted, however, that Warning Letters with severe consequences were sent to Able Labs, MDS Pharma, and Ranbaxy, and the
warnings related to electronic records, even though Part 11 was not mentioned.
Rory Budihandojo is a computer validation manager at Boehinger-Ingelheim, 2820 N. Normandy Dr., Petersburg, VA 23805, tel. 804.504.8373, fax 804.504.8637, rbudihandojo@bichemicals.com.
He is also a member of Pharmaceutical Technology's Editorial Advisory Board.
Articles by Rory Budihandojo
Steve Coates
Steve Coates is the director of computer system quality assurance at Wyeth.
Articles by Steve Coates
Ludwig Huber is worldwide product manager for pharmaceutical solutions at Agilent Technologies GmbH, PO Box 1280 D-76337, Waldbronn, Germany, tel. +49 7243 602 209, fax +49 7243 602 501.
Articles by Ludwig Huber
Jose E. Matos
Jose E. Matos is manager of manufacturing systems and process automation at Bristol-Myers Squibb.
Articles by Jose E. Matos
