Thursday 17 January 2013

How does the Update to Chapter 6 of the EU GMP Guidelines Affect Your Lab?

The European Commission has launched the public consultation of several revised GMP guidelines including Chapter 6: Quality Control (click here to view the document). The reason for change given is: "Inclusion of a new section on Technical transfer of testing methods and other items such as out of specification results." Since we specialise in method transfer at MTS (and offer a training course on the topic), we have put together a summary of the proposed updates. 
Although up to now the GMP guidelines did not explicitly refer to method transfer activities, for some time it has been an expectation that method transfer activities will both be performed and documented.  The updated guidance provides detail regarding the regulatory expectations for these activities. The new method transfer section is at the end of chapter 6 under the heading ‘Technical transfer of testing methods’.
The first part defines the expected pre-transfer activities: Prior to transferring a test method, the transferring site should verify that the test method(s) comply with those as described in the Marketing Authorisation or the relevant technical dossier.” - It makes sense to check the method against the one submitted in the MA/technical dossier prior to transfer since you want to be sure that you are working on the right method version from the beginning.
It goes on: “The original validation of the test method(s) should be reviewed to ensure compliance with current ICH/VICH requirements.  A gap analysis should be performed and documented to identify any supplementary validation that should be performed, prior to commencing the technical transfer process.” - The original validation data should demonstrate that the method is fit for purpose, a key requirement before you start using it in another laboratory. The data will also provide information on the method capability, essential for evaluation of the success of the method transfer. My interpretation of the second sentence is that the gap analysis and identification of supplementary validation work is performed prior to the technical transfer process, which leaves open the possibility of using a co-validation approach for the actual transfer. 
The next part confirms that a written protocol is required for transfer (fairly standard in most laboratories) and provides guidance on what should be included: 
The transfer of test methodology from one laboratory (transferring laboratory) to another laboratory (receiving laboratory) should be described in a written protocol. 
The protocol should include, but not be limited to, the following parameters: 
  • identification of the relevant test method(s) undergoing transfer 
  • identification of the additional training requirements 
  • identification of standards and samples to be tested by both laboratories 
  • identification of any special transport and storage conditions of test items 
  • identification of the testing to be performed 
  • the acceptance criteria which should be based upon the current validation study of the methodology and with respect to ICH/VICH requirements” 
These protocol requirements are straightforward. Points to note are: 
  1. The requirement for documentation of the training requirements is formalised. 
  2. Attention is drawn to transport and storage of samples, the purpose is to ensure that the same materials is analysed at both laboratories. This implies a comparative testing approach. 
  3. The acceptance criteria should be based on the validation data. Whatever acceptance criteria were felt to be acceptable during validation may also be applied during transfer. My advice is to look at the actual data obtained when setting the transfer acceptance criteria, rather than just using the same values. This is particularly important when criteria are defined in a generic procedure.
The actual transfer is mentioned in terms of dealing with deviations and the requirements for the report are defined: “Deviations from the protocol should be investigated prior to closure of the technical transfer process. The technical transfer report should document the comparative outcome of the process and should identify areas requiring further test method revalidation, if applicable.”

Finally, it is recognised that some methods do not conform to the validation approach outlined in ICH, the particular example of NIR is quoted: “Where appropriate, specific requirements described in others European Guidelines, should be addressed for the transfer of particular testing methods (e.g. Near Infrared Spectroscopy)."

The other updates in Chapter 6 will be summarised in an additional blog very soon.