Analytical methods transfer
Testing the medicinal products prior their release to the market, throughout their life-cycle, during their routine manufacturing, but also during their development is fundamental for pharmaceutical industry. The analysis of e.g., starting materials, reagents, intermediates, active substances and finished dosage forms plays a significant role in achieving and confirming the quality, efficiency and safety of medicinal products. Each product undergoes analytical control based on analytical methods demonstrated to be suitable for the intended purpose. This is why analytical methods are an inherent part of pharmaceutical industry. The European Pharmacopeia (Ph.Eur.) provides a scientific basis for quality control and contains general methods of analysis. However, in some cases e.g., where no monograph for a particular medicinal product is provided, it is necessary to develop an in-house method. The analytical procedures given in the monographs are considered to be validated, but in-house developed procedures require validation. The appropriate analytical method might be developed, validated and used in several different laboratory sites, but moving it between sites should be done via means of an analytical method transfer. It should also be kept in mind that each pharmacopoeial method must be properly implemented, therefore, when transferring analytical methods from one laboratory to another, also pharmacopoeial methods are often subject to method transfer (this is assessed in detail during the risk analysis included in the protocol).
Analytical Method Transfer: For Whom and When?
Transfer of analytical methods may be a part of the product development process e.g., when the analytical method developed in the R&D department is transferred to Quality Control laboratory. It may also be needed for business-related reasons e.g., when a new (commercially better) testing site is introduced, or any other reasons, e.g. transfer of a method from a third country to the lab located in Europe to be able to release the product into the EU market. The transfer can be performed within the same company structure or between two different companies. The analytical method transfer is not only an internal matter – it may also be a crucial aspect investigated during GMP inspection. Moreover, in some cases the transfer documentation might be required by some registration agencies. Therefore, it is important to perform a well-organized, document-supported and current requirements-compliant transfer.
Transfer And Its Modes
The general idea of method transfer is covered by Annex 7, WHO [1] and GMP Chapter 6 [2]. Some helpful details can be found also in United States Pharmacopeia (USP) [3]. Essentially, the aim is to bring a given method from one laboratory to another, without harm to its performance.
USP defines transfer of analytical methods as a documented process that qualifies a laboratory (the receiving unit, RU) to use an analytical test method that originated in another laboratory (the transferring or sending unit, SU), thus ensuring that the RU has the procedural knowledge and ability to perform the transferred analytical procedure as intended. The following four types of transfers are recognized: comparative testing, covalidation, revalidation and transfer waiver.
1. COMPARATIVE TESTING
The most common variant of method transfer. It requires analysis of predetermined number of samples of the same lot by both the SU and the RU followed by a comparison of the results. The testing is based on a previously approved transfer protocol in which the acceptance criteria and the acceptable variability are pre-defined. The method of interest should be validated in the SU prior to its transfer. A transfer report should be prepared with confirmation that the pre-defined acceptance criteria were met.
2. COVALIDATON
If the method is yet to be validated, covalidation seems like a suitable choice. In that case the SU can involve the RU in an interlaboratory covalidation. This approach is often chosen when the method is transferred from R&D to Quality Control laboratory. Similar to the comparative testing, covalidation also requires a preapproved protocol and a final report. However, the transfer documentation will also include method validation elements as per ICH Q2 [4].
3. REVALIDATION
If the method was validated, but significant adjustments were made in the RU (e.g., to equipment/reagent or to conditions of analysis), the RU is required to perform a complete or partial method validation. This should ensure that the method is still suitable for its intended purpose. Revalidation strategy is also often chosen when other types of transfer are inviable or not available for any other reason (e.g. the SU at which the method was initially validated is unable to take part in the transfer). According to the ICH Q2, the extent of revalidation depends on the analytical performance characteristics impacted by the applied change(s) [4]. Revalidation approach requires preparation of respective protocol (including justification of the scope of revalidation necessary) and report.
4. TRANSFER WAIVER
There are certain circumstances that allow to omit the formal method transfer, which include:
- The RU is already familiar with the product (or is experienced with the similar one) and the testing procedure
- The concerned analytical method is pharmacopeial
- Transferred method (or a very similar one) is already in use in the RU
- The SU personnel in charge of the development, validation or routine analysis are moved to the RU
Although the method is actually transferred, generally no generation or comparison of interlaboratory comparative data is required. In the waiver approach, transfer might be limited to verification of the method or transfer of knowledge. However, in case of verification the results obtained in the RU are often compared with the results with the data generated previously by the SU e.g. stability studies or CoA. The RU is considered to be qualified to use the respective analytical method. Appropriate justification is of course required.
Justification Of Choice
The choice of type of transfer should be based on appropriate risk analysis that takes into account several factors, such as validation status, complexity of the method and the previous experience and knowledge of the RU. Justification of the decision should be presented in the above-mentioned transfer protocol, which is an essential document stipulating all the details of the transfer procedure. A well-designed protocol is a key factor in a successful method transfer – it should be thoroughly discussed, agreed on and documented before the start of the transfer.
Final Remarks
Several aspects are needed in order to conduct a successful transfer. Lion’s share of many transfer challenges is caused by lack of coordination or misinterpretation of shared information. Therefore, clear and frequent communication between the SU and the RU is the key. Topics such as method-specific details, instrument equivalency and essential trainings should be discussed and verified to avoid any variation in the analytical results and to prevent transfer failure. Both the SU and the RU should fully execute the protocol and then complete the transfer report. The report should include transfer results in relation to the established acceptance criteria, along with conclusions that confirm, if the acceptance criteria are met. Only then, the RU is qualified to run the procedure. Moreover, any deviations or a failure to achieve the criteria should be identified, documented and justified. Finally, the report should be reviewed and approved by the SU, as well as the RU.
SciencePharma A Synonym For A Seamless Transfer
We have been involved in many transfers of analytical methods in all of the above listed configurations. These transfers concerned broad range of methods, from relatively simple to more complex, including biological ones. Although analytical method transfer is generally challenging, we find ourselves in the position to always find a tailored solution for our clients. Our Experts have broad scientific background and experience which allows us to understand the scientific principles behind the methods concerned, but also makes us aware of the common challenges and potential risks involved in the transfer. We are able to work proactively to resolve any issues that arise.
Let’s face it together
We will guide you throughout the whole process of the method transfer* to make it well-organized and both, cost and time efficient.
We may help you to (the list is not exhaustive):
- Select the most suitable model of the method transfer
- Provide a risk assessment based justification for the above choice
- Acquire offers from various laboratories in order to find the most suitable one
- Organize a trial testing in the RU (helpful for very complex methods)
- Prepare a transfer protocol in line with the current requirements
- Coordinate transportation of samples, standards and other materials required for the transfer process
- Oversee all transfer activities
- Ensure efficient collaboration between both units (RU, SU) and provide guidance to them
- Prepare a transfer report
- Gather all other necessary transfer documentation.
*Understood as per USP definitions: comparative testing, covalidation, revalidation or transfer waiver.
If you wonder whether you can cope with transfer of analytical method, if you are interested in cooperation in the area described above, please contact us. Our Experts are happy to answer your questions.
References:
[1] WHO guidelines on transfer of technology in pharmaceutical manufacturing, Annex 7 (2011) in Technical Report Series 961
[2] EU GMP Chapter 6 (Oct. 2014): Quality Control
[3] USP General Chapter <1224> Transfer of Analytical Procedures
[4] ICH Q2(R2) Validation of analytical procedures, CPMP/ICH/381/95