May unvalidated Methods also be accepted to test Drug Products? - The FDA answers

On the FDA homepage, you can find a rubric dedicated to Questions and Answers on cGMP (Current Good Manufacturing Practices) which is updated in irregular intervals. This rubric is structured like 21 CFR Part 211, i.e. with 11 chapters called after the 11 respective subparts of Part 211. Each chapter (excepted "Organization and Personnel", "Packaging and Labelling Control" and "Returned and Salvaged Drug Products") is linked to a page presenting the respective Questions and Answers.

The FDA has recently updated the webpage. Questions and Answers on the topics "Control of Components and Drug Product Containers and Closures" (CFR 211 Subpart E) and "Laboratory Controls" (CFR 211 Subpart I) have been added.

The question below is an example taken from the subpart on Laboratory Controls:

"Is it ever appropriate to use an unvalidated method to test a drug component or product?"

The FDA's detailed answer can be interpreted as a "Yes, under certain circumstances". Analytical methods which are not fully validated may be suitable for use, for example, during an investigation of a quality problem in connection with an atypical impurity for which no validated method is available yet.

Since the investigation and clarification of such quality defects is a priority which mostly needs to be corrected promptly, such methods are appropriate. In its answer, the FDA gives the example of OSCS (oversulfated chrondroitinsulfate) in impure heparin, which caused 3 years ago serious damages on patients and cases of death. At that time, no established validated routine control was available to detect the impurity.

In its statement, the FDA expressively points out that the use of such methods which are either incomplete or not fully validated involves greater risks of analytical uncertainties which need to be taken into account in the data interpretation.

Follow this

link to reach the Q&A webpage which presents a number of questions and FDA's statements on cGMP or use our GMP Newsreader Page.

Note: The lectures and workshops during the "

Validation of Analytical Test Procedures and Measurement Uncertainty" course in Berlin, Germany, from 13-15 April 2011 will deal with the approach on methods validation.

Dr Gerhard Becker
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)

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