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.
10th & 11th April 2013
Pharmaceuticals
need to be assessed for stability to support the assigned shelf life. Therefore,
when analysing stability samples obtained from these studies analytical methods
are required which are stability indicating, i.e. there is a measureable response
which correlates with degradation, if present. HPLC is a popular technique for
monitoring the decrease in drug and corresponding increase in degradation
products due to its separating abilities. However, the HPLC method must be developed
carefully to ensure that degradation products are both separated and detected
appropriately. 
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