How Does the Update to Chapter 6 of the EU GMP Guidelines Affect You? - Part 2

In a previous blog post I summarised the proposed changes relating to method transfer in the public consultation document for Chapter 6 of the EU GMP Guidelines. Although the inclusion of the section on method transfer is the biggest revision to chapter 6, there are number of other proposed updates. In this blog post I will take a look at some of these.

Since the reason given for the changes is: ‘Inclusion of a new section on Technical transfer of testing methods and other items such as out of specification results’, and I have already dealt with method transfer, I will start with out of specification results. Under the section heading ‘Documentation’, there is a new requirement for: ‘a procedure for the investigation of Out Of Specification and anomalous results and Out Of Trend results’ (6.7)

The expectation that a QC laboratory will have a procedure detailing how they will deal with OOS results is long standing and most labs will already have this in place. The wording makes it clear that this procedure also needs to detail investigation of anomalous results and OOT results. These are typically investigated in the same way as OOS results.

Also under the Documentation heading, the recommendation that records are kept in a manner permitting trend evaluation has been updated to ‘should be recorded in a manner permitting trend evaluation’ with the additional sentence, ‘Any out of trend or out of specification data should be addressed and subject to investigation.’ (6.9)

Sampling is another area which has updates. In 6.11, referring to sample taking, there is an additional requirement that it ‘should be done and recorded in accordance with approved procedures.’ Therefore, if the sampling operation is not currently documented each time, it will need to be in future. In 6.12 there is an extra sentence: ‘the sampling plan used should be appropriately justified.’ It may be that the plan was devised sometime in the past and reasons which were so apparent then are no longer so clear. The requirement to justify the plan ensures that it is scientifically sound.

Under the Testing heading the paragraph regarding method validation (6.15) has been extended to include the following ‘A laboratory that is using a testing method and which did not perform the original validation (e.g. the use of a compendial method), should verify the appropriateness of the testing method.’ So even if a method is taken from a pharmacopeia its use in a particular laboratory needs to be shown to be suitable for the purpose for which it is being used. This assessment may conclude that no actual experimental work needs to be performed but some type of documentation should support this finding.

A new paragraph (6.20) has been inserted which reflects the importance of reference standards, making it clear that ‘Reference standards should be certified, qualified and verified as suitable for its intended use.’

The shelf life of analytical solutions, etc. is addressed in section 6.22. The requirement to mark with the date of preparation has been extended to opening date. Additionally: ‘Their in-use shelf life should be established/documented and scientifically justified.’

Finally, there are two new sections relating to the microbiological laboratory, these are:

‘6.21 Culture media should be prepared in accordance with the manufacturer’s requirements unless scientifically justified. The performance of all culture media should be verified prior to use.’

‘6.25 Microbiological media and strains should be decontaminated and disposed of in a manner to prevent the cross-contamination and retention of residues. The in-use shelf life of microbiological media should be established, documented and scientifically justified.’

In general, the emphasis of the updates is on scientific understanding and justification of the analytical methodology being used in the QC laboratory.

  Tweet