27/28 April 2021
Since the early 1990s, the subject of cleaning validation is present. In the regulations relevant to validation (Annex 15, PIC/S PI 006, FDA Guide to Inspection of) at least one chapter is dedicated exclusively to this topic. For years, deficiencies regarding cleaning have been ranking among the top five of the FDA warning letters statistics (see our GMP News of 5 March 2008 on the GMP Warning Letters Report 2007).
But what is new in the field of cleaning validation? How can one keep up to date?
Within the last few months, a number of publications dealt with the topic of cleaning validation in completely different ways. In the following we have compiled a selection:
In February and March 2008, the journal Biopharm International (www.biopharminternational.com) published a two-part series on "Cleaning Validation for Biopharmaceutical at Gentech". It deals with the whole range of cleaning validation in a very comprehensive way with the focus on biotechnological manufacture from the history to the topics of change control and revalidation.
A bit more wide-ranging is an article on "European Regulatory Scene Sees Many Changes in 2007" of January 2008, Volume 13, of the journal BioQuality (http://www.bioquality.biz/). This article presents among other things a comparison of GMP deficiencies between the EU and the USA over a period of 11 years and explains the top 3 among the 483 observations. "Validation Catecories" ranks third in the list of 483 observations. Here, with a share of 30 %, "Cleaning Validation" is in the lead of the various "Categories".
Quite recently, an article titled "A Risk-Based Approach to Cleaning Validation using Visible Residue Limits" (VRL) appeared in the May/June 2008 issue of journal Pharmaceutical Engineering (http://www.ispe.org/cs/publications_section/pharmaceutical_engineering). The interesting thing about this article is the fact that the risk-based approach is reduced to the "visibly clean" criterion, which had not been mentioned so explicitly in previous articles on this topic. The tests described in the article lead to a table "VRL Application and risk assessment", which represents the application of the "visibly clean" criterion to pilot plants and routine production with regard to process risk and risk mitigation. A highly interesting concept.
Not quite as recent, but nonetheless very interesting, too, is an article in the journal "Regulatory Toxicology and Pharmacology (www.elsevier.com/locate/yrtph), 43 (2005), 1-9: "Application of the treshold of toxicological concern concept to pharmaceutical manufacturing operations". The special thing about this article is that it attempts to provide a scientific rationale for the calculation of acceptable-daily-intake (ADI) values in case only few toxicological data are known of a substance. This could be interesting above all for the topic of cleaning validation in the field of research and development.
On behalf of the European Compliance Academy (ECA)