Method transfer process

Raska et al. (2010) introduced the concept of a risk based method transfer process (which is similar to USP transfer waiver approach). This involves assessing the risk that the sites involved in method transfer could generate non-comparable data either at transfer or subsequently thereafter and assessing the probability of that risk occurring. Thus with constrained resource it is more sensible to focus that resource on either avoidance or mitigation of high risk transfers, whilst accepting the limited risk inherent with a low probability risk scenario. 

Experience with CE method transfer in the biotech/pharmaceutical industry over the past 10—20 years has demonstrated that training is a key element that requires special attention for CE methods. A training video with troubleshooting examples can be very useful. Tips and hints should also be shared during the method transfer process. Other key elements for a successful transfer include selection of the proper testing strategy and assay acceptance criteria. 

When identifying suitable testing labs, the main emphasis should be on the method application requirements, for example, sample analysis for preclinical or clinical studies, testing in conformance with GLP guidelines and, last but not least, the extent and philosophy of method validation between the laboratories. The selection of a compatible laboratory as the receiving laboratory is pivotal to the success of the method transfer process. 

The method transfer process can represent a full gamut of scenarios. Method transfers can be straightforward if the method is robust, fully validated, and being transferred between experienced labs. At the other end of the range, transfer may occur between inexperienced labs with a method that is neither robust nor fully characterized or validated. Here, we present a set of recommendations that should help streamline and simplify such transfers and increase their success rate. 

The number of experiments and the required time frame need to be determined early on in the method transfer process. Since CROs serve many clients in parallel, it is important to understand the time and resource demands on both sides. It is also important to set expectations for communication of anticipated delays from either side. Frequency of project updates need to be agreed upon. The level of review by the sending lab should be aligned with the expertise of the receiving lab and may require compromises to allow efficient progress on the project. To cover all aspects of the project, it is best to document scope of work and expectations before initiating the transfer. 

Both method validation and transfer are important pieces in the drug development puzzle. Without reliable analytical data it is not possible to make informed decisions during product development, and it complicates batch disposition decisions whether for the clinic or the market. Ultimately it is clear that the effort spent on developing and validating robust methods will be time well spent, especially as a product moves through the pipeline toward commercialization. Similarly, the method transfer process should not be seen as a check-the-box activity but rather the transfer of knowledge from a laboratory perspective and an extension of the method development/validation process since the better a method is designed the easier it will likely be for new analysts to perform it well. 

Once a receiving site has been identified, the expert laboratory should perform a risk assessment to identify variables that may pose a problem during the transfer. The following questions are examples of items that the expert laboratory should consider prior to initiating the method transfer process ... 

The overall method transfer process is summarized in Figure 3. In many companies this process is governed by a hierarchical set of controls or standardized procedures. These documents describing the process include, in order of hierarchy ... 

The old adage if it isn t written, it isn t done certainly applies to analytical transfer. The expectation of the health authorities is that a final report will be issued documenting the analytical method transfer process and associated results. Two types of records are subject to PAI Primary records that demonstrate safety, purity, and efficacy of the drug (e.g., batch records, test data) and supporting documentation such as equipment verification records, change control and development and validation reports that demonstrate the cGMP compliance status of the facility. The method transfer report is categorized vmder the latter set of documentation. 

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