The first version of Annex 11 been originally published in 1991 as an Annex to the Pharmaceutical Inspection Convention/Cooperation Scheme (PIC/S) GMP. The first EU GMP Annex 11 was published in 1993. A draft of an updated version was published in 2008 and the final update in January 2011. The current version is very much complete and in junction with the updated EU GMP Chapter 4 on Documentation it provides a complete information on managing computerized systems in regulated environments. There is a good chance that the current version will be published by PIC/S again as an official GMP Annex. Considering that now the US FDA is a member of PIC/S and that the FDA does not have an equivalent document (Part 11 is much less complete) it may well be that US field investigators will use the new Annex as some kind of an inspection guide. From recent FDA warning letters with citations about back-up, contingency planning and configuration management it became clear that FDA is looking beyond the requirements of Part 11 with its focus on electronic records and signatures. Attend the new Labcompliance audio seminar to learn everything about the new Annex 11 and receive 10+ best practice for easy implementation.

"Inadequate Performance Qualification" cited in FDA Warning Letter

Laboratory equipment should be checked on a regular basis to verify adequate performance for the intended application. During the inspection of an API manufacturer the FDA found several instruments that either have not been qualified at all or important tests were missing. The letter reads: "Your HPLC calibration lacks a carry over test (sample injection residual test), sample energy (intensity of light source), and lamp use hours determination. You fail to challenge the analytical balances for minimum weight, measurement for uncertainty, and drift value. In addition, you do not calibrate the Karl Fisher syringe used during xxx API water content analysis. In addition the company failed to adequately reprocess API batches, to thoroughly investigate complaints for API, for not using USP acceptance criteria. and for not maintaining equipment re-qualification raw-data. The Warning Letter can be downloaded from the Labcompliance Usersclub. Non members can preview excerpts. Scroll down to W-246. To learn more about recent lab control related warning letters, attend the audio seminar "Learning from Recent Warning Letters Related to GMP Laboratory Controls".

Laboratory Controls #1 Deviations in FDA GMP Inspections

FDA has published a hit list of deviations found in international GMP inspections in fiscal year 2010. With almost 19% (including deviations related to unvalidated lab test methods) laboratory controls ranked as number 1, far ahead to quality systems (9%) and production&process control systems (6%). A further breakdown shows that deviations related to lab controls are highest in China with 28%, Europe is about average with 18% and India below average with 13%. Equivalent numbers are not available from US but based on individual analysis they are expected to be in the same range as Europe. We at Labcompliance are not surprised about this trend. Several times we have reported about FDA's increased focus on GMP lab inspections and also gave several examples for lab related deviations in FDA 483's and warning letters. To learn everything about FDA GMP lab inspections and laboratory inspection findings, attend the audio seminar "Learning from Recent Warning Letters Related to GMP Laboratory Controls" and get access to 20 examples warning letters and to the related full FDA statistics.

USP Publishes the new Chapter <1224> for Analytical Method Transfer

In Oct 2009 USP had published a Stimuli article “Transfer of Analytical Procedures". Based on comments received, USP now proposes a new general information chapter <1224>. The procedure-transfer process focuses on qualifying the receiving laboratory to perform an analytical procedure that was developed and validated in another laboratory within the same or in a different organization. One of the major differences to the stimuli paper chapter is that <1224> suggests a risk based approach for type and extent of transfer activities, e.g., for comparative testing. The intended chapter <1224> has been published as a Pharmacopeial Forum article that can be downloaded free of charge. To learn everything about the new intended chapter, attend the audio seminar "Transfer of Analytical Procedures According to the New USP <1224" and receive SOPs, templates and examples for easy implementation.

FDA Warning Letter for Inadequate Transfer of Analytical Methods

The FDA expects that transfer of analytical methods should follow a documented procedure and chemists in the receiving laboratory should formally trained . This became obvious during a recent FDA inspection which resulted in a 483 with 24 observations. Several observations were related to inadequate method validation and transfer. For example: "The analytical method has not been transferred between the issued laboratory and the two chemists currently working in the QC laboratory. The methods have been transferred before the two chemists were hired. There are no records which document training in the two procedures". The 483 can be downloaded from the Labcompliance Usersclub. Non members can preview excerpts. Scroll down to W-241. To learn everything about FDA requirements for analytical method transfer attend the audio seminar "Transfer of Analytical Procedures According to the New USP <1224".

FDA Publishes the Final Version of the Process Validation Guidance

On the January 25, 2011, the FDA published the final version of the industry guidance: Process Validation: General Principles and Practices. . This guidance outlines the general principles and approaches that FDA considers appropriate elements of process validation for the manufacture of human and animal drug and biological products, including active pharmaceutical ingredients (APIs or drug substances), collectively referred to in this guidance as drugs or products. This guidance incorporates principles and approaches that all manufacturers can use to validate manufacturing processes. There are no big changes in the final version compared to the draft from November 2008. The guidance can be downloaded from the FDA website.

FDA Part 11 Inspections Starting with Delay

Last year in July the FDA has announced to start a specific Part 11 inspection initiative in the 4th quarter of 2010. The main purpose of the program is to check how the industry complies with Part 11. The outcome of the initiative will be used to decide on how to proceed with Part 11. Because of administrative reasons the start of the program has been delayed until beginning of February. Now each routine FDA inspection under CDER includes an evaluation of computer systems and electronic records and specific Part 11 inspections will be set up based on a company's compliance history. Sign up for the audio seminar "How to Prepare Yourself for FDA's New Part 11 Inspection Program to learn what the FDA is looking for and how to avoid 483's and warning letters.

Free Document of the Month

As a 'Thank You' for our visitors Labcompliance offers every month one document for free. This month's document is the SOP "Electronic Audit Trail: Specifications, Implementation and Validation". To download your free copy, go to the Part 11 Compliance Package website. Scroll down and click on the corresponding ICON on the left (offer expires on March 1, 2011). Labcompliance offers more than 120 SOPs that help to comply with FDA and ISO 17025 compliance. For titles and ordering, click here.

Conferences

Analytica Vietnam, Hoh Chi Minh City, Vietnam, April 7-9, 2011
April 8: Full day Workshop by Dr. Ludwig Huber
Validation of Analytical Methods for FDA and EU Compliance