An excellent article on Best practices for analytical method transfers from Pauli Laiho, our Pharmaceutical Chemical Expert. Pauli and all our experts in our CMC expert team are happy to help in analytical projects, other CMC projects and in regulatory filing projects requiring CMC expertise. For further information please contact Ulla Orava, email@example.com
The need for technology transfers in the global pharmaceutical industry is constant. Change of drug substance or product production sites and analytical testing sites are some of the most common types of technology transfers, and analytical method transfers are a crucial part of site transfers. In an analytical method transfer, the receiving laboratory becomes qualified to perform the methods being transferred. One of the most important things in this process is the transfer of the technical and scientific knowledge of the method from the sending laboratory to the receiving laboratory. Communication between the laboratories is vital for a successful method transfer.
There are different ways to perform analytical method transfers:
Comparative transfer is used often and is particularly useful in cases where the method has already been validated at the transferring site or by a third party. The results can be compared between the sending and the receiving units using criteria from method validation (intermediate precision/reproducibility).
Covalidation is suitable in cases where the analytical methods are transferred from e.g. a development site to a commercial manufacturing site before the analytical methods have been validated. The receiving site can participate in reproducibility testing. Criteria are defined based on product specifications and purpose of the method.
Revalidation or partial revalidation is useful when the sending laboratory is not involved in the testing, or the original method validation has not been performed according to ICH requirements and therefore needs to be supplemented.
In some situations, however, a method transfer is not needed if it is justified and documented in the protocol.
These situations include:
Pharmacopoeial methods are verified if needed but do not need to be formally transferred.
In case the transfer concerns e.g. an analytical method for a new strength of a product, the transfer can be waived if the analytical methods are the same and the differences include only minor changes, such as different volumes of volumetric flasks used.
Although technical and scientific understanding of the analytical method to be transferred is a key factor to a successful method transfer, the most important thing is often good communication between the sending and receiving laboratory. Quality of communication between the sending and the receiving laboratory sites can make or break the method transfer.
Communication starts by introducing the teams to each other. Analytical experts from each laboratory should have a direct line of communication. It is also good to agree on how documentation will be shared safely and to set up regular follow-up meetings to make sure that any issues can be dealt with in a timely manner.
Introductions are followed by sharing all the relevant data and experiences of the method by the sending laboratory to the receiving laboratory. The data includes e.g. method description, validation report, quality of reference standards and reagents and information for safe handling. Any additional experience, such as risk assessment performed by the sending laboratory, is also shared. Risk analysis is based on the experience and knowledge of the sending laboratory, as well on the complexity and specifications of the method and the product. Assurance that the transferred method complies with the MA and is in compliance with the current regulatory requirements is given. This is also called gap analysis for the method validation and is a requirement in the EU1. The EU GMP guideline requires that the original validation of the test methods 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. If gaps are detected, supplementary validation is conducted. Receiving laboratory will evaluate this data provided by the sending laboratory.
1 Eudralex: Volume 4 EU Guidelines for Medicinal Products for Human and Veterinary Use, Part 1 Chapter 6: Quality Control, chapters 6.37-6.40
At this point, it may be smart to organise a kick-off meeting between the laboratories to further discuss the method and the need for training. If the method is complex and not familiar to the receiving laboratory, on-site training might be a good idea. All the details, including the estimated timetable, materials needed and work safety, are discussed in the meeting. It is also important to discuss the practical tips and the ‘silent’, tacit knowledge not included in the method description. Furthermore, it is important to understand the differences in local practices, e.g. how equipment is calibrated or how peaks are quantified in the HPLC or GC analysis.
After the specifics of the method transfer have been agreed, the transfer protocol is written. This is usually done by the transferring laboratory but can also be created by the receiving laboratory.
The method transfer protocol should preferably include the following:
After the transfer work, a transfer report is usually written by the receiving laboratory.
The method transfer report should include:
To sum up
Analytical methods are a crucial part of pharmaceutical manufacturing. When methods are transferred to a new laboratory, it is therefore very important to ensure that the receiving laboratory has the technical knowledge and the ability to perform the analytical method. This procedure starts by sharing all the relevant data of the method to the receiving laboratory, and usually a meeting between laboratories is held. Based on all the data and discussions, method transfer protocol is written, and the transfer is executed accordingly. Results are reported in a method transfer report, where it is concluded whether the method transfer has been successful or if extra work is needed. Thorough planning and open discussion between the laboratories involved in the method transfer are key factors for a successful analytical method transfer. They also help to prevent laboratory errors at the receiving site in the future. Carefully planned transfer criteria help to ensure that the analytical results are reliable at the new analysis site. In the case of analytical method transfers, the saying ‘Well begun is half done’ certainly applies.