ANALYTICAL METHOD TRANSFER

What is an Analytical Method Transfer?

According to United States Pharmacopeia (USP), Chapter 〈1224〉, “transfer of analytical procedures (TAP), also referred to as method transfer, is the documented process that qualifies a laboratory (the receiving unit) to use an analytical test procedure”. This transfer is performed in conjunction with a transferring unit that ensures that the receiving unit is qualified and can execute the analytical method transferred.

Transferring unit is the laboratory from where the analytical method is being transferred and the receiving unit is the Laboratory which the analytical method is being transferred to. The receiving unit could be Quality control laboratory, another intracompany facility or a Contract research organization.

Why does an Analytical Method Transfer need to be Done?

The ultimate use of a newly developed and validated method is to be able to produce results in the Quality control laboratory for the release of APIs and Finished products. Transfer of any type of analytical method is required by the regulatory agencies. It is done as part of the sustainability of the product. Once the analytical method is validated, it is shared as needed through a documented process to an appropriate accountable and certified area. Analytical method transfer is normally performed generating a transfer protocol, which contains parameters to be evaluated and acceptance criteria that will be applied to the results generated by the receiving area. After protocol execution is completed, a transfer report is generated to compile and document the activity in question.

Methodology

Prior to transferring the method transferring site should verify that the method complies with those as described in the marketing authorization or the relevant technical dossier. It should be ensured that the method validation is complete at the transferring unit before initiating the transfer activity.

It is well understood that any analytical methods transfer can be audited by regulatory agencies, to ensure that procedures were followed by both areas during this process. It is clear, that there are some challenges during a transfer of an analytical method and that it can be very time consuming and stressful. Planning tools need to be used to avoid delays in this process. Although pharmaceutical companies have standard operational procedures (SOP) in place to be followed, these do not contemplate how long it will take and what tools should be used to ensure a flawless transfer. According to the article “The transfer of analytical procedures” written in the Journal of Pharmaceutical and Biomedical Analysis, the key to accomplishing successful analytical method transfers is to have an opened communication among the transferring and receiving units. This should be enabled by written communication, SOP, flow charts, clear definition of roles and responsibilities, what are the type of transfer categories, technical documents such as the transfer plan and report. Another element important to mention is what will be the strategies in case of failed transfer. Potential drawbacks must define such that they can be escalated on time. The transfer activities target is to prove the receiving area’s ability to execute the analytical methods transferred effectively. According to the article mentioned above, “it has to be pointed out that the performance and ability of a receiving area is always the sum of the ability of the staff and the performance characteristics of their equipment and should not depend on the properties or quality of the samples”.

Analytical Method Transfer Planning and Execution

The transfer of an analytical method can happen in different ways and circumstances: from transferring only a method to a whole product specification test requirement, which contains several test methods. Figure contains the process flowchart of an analytical method transfer. To ensure a flawless activity, these nine (9) steps process should be taken into consideration and will be discussed as part of the transfer methodology.

Openness and Transparency

For the success of an analytical method transfer, an open and reliable communication between transfer and receiving areas is crucial. A full risk assessment should be performed, taking into consideration the receiving area capability. Once it is understood, timelines, roles, and responsibilities need to define and agree on. Having all the key elements in place, such as the method to be transferred is valid and fit for use, equipment required to perform the tests are qualified and fulfil in compliance with regulatory and company requirements, planning for transfer activities can be set. Face to face meetings is crucial, and these should be scheduled at least once a week. A project manager can be hired to track the transfer activities, or a timeline tracking tools can be used, managed by either area. Normally is the transferring area that performs this task. Nonetheless, it will depend on the necessity of the areas to complete the task. Roles and responsibilities will be discussed further on.

Documentation Requirement

Written documentations are one of the most important parts of any analytical method transfer. It is where the transfer activities are perpetuated and are used for future reference in case a doubt roused, and/or troubleshooting is needed. As well, these documentations can be audited by any regulatory agencies. Before the start of an analytical method transfer, documents needs to be shared with the receiving area. Some companies call this the transfer documentation package. Before starting any validation, activity these are shared, to ensure that the receiving area gains all the knowledge needed ahead of time.

Transfer types

How many Analytical Method Transfer Types Exist?

Based on the General Chapter 〈1224〉 of the USP, there are four analytical method transfer types:

? Comparative Testing, which normally involves the analysis of a predetermined number of samples of the same lot by both the transferring and the receiving units. This is the most common approach.

? Co-validation between two or more laboratories or areas, in this case, both the transferring and the receiving units participate as part of the analytical method validation, where in the receiving unit performs intermediate precision parameter.

? Revalidation, is another approach for transfer of a validated procedure where in the receiving laboratory can repeat some of the validation parameters like Specificity, Accuracy and Precision.

? Transfer Waiver, in this case, an analytical method transfer can be omitted under the following circumstances.

1. When the product composition is equal or comparable to an existing product that is already analysed by the receiving unit.
2. The analytical testing is described in a compendial methodology, (USP, BP, EP, Japanese Pharmacopeia) is unchanged, in such case method verification can be performed at the receiving unit.
3. The analytical method is the same as or similar to a method already in use in the receiving area.
4. The personnel involved in development, validation, analysis at the transferring unit is relocated to the receiving unit.

What are the Parts of the Analytical Method Transfer?

?According to WHO, guidelines on transfer of technology in pharmaceutical manufacturing to achieve a successful analytical method transfer, coordination, and planning of several activities need to occur. The following general principles and requirements should be met:

?? Transfer Plan must include the quality aspects of the project and be built upon the standards of quality risk management approach. This plan must define the transfer strategies, such as roles and responsibilities, transfer elements (sample type, acceptance criteria), significance tests (accuracy and precision), training requirements, and documentation (transfer protocol and report) that need to be generated in order to support the transfer activities.

? The capabilities of the receiving area should be similar to the transferring area and facilities and equipment should operate according to similar operating principles. A technical gap assessment between both areas (transferring and receiving) including risk assessment and potential regulatory gaps, should be performed.

?? Knowledge transfer to the receiving personnel must be facilitated. Training of the personnel at the receiving unit is highly recommended.

? When transferring to another country or region, requirements from regulatory agencies of both transferring and receiving areas should be considered and interpreted consistently throughout any transfer program project. Any lack of transparency can cause having an ineffective analytical method transfer process. This activity must be a well-document one, where all elements aforementioned are synchronized to ensure having a receiving area capable of generated reproducible and accurate results that complies the requirements of the company and regulatory agencies.?

Transfer Protocol

The method transfer protocol is where is established the strategy of the activity. To ensure a successful transfer, it should be discussed before approval with the receiving area. This document must contain all aspects recommended in the company and appropriate regulatory guidelines and/or procedures. The experimental studies’ strategy and acceptance criteria should be defined.

A Typical AMT protocols should include:

Execution:

?After approving the transfer protocol and having both areas participants trained in the strategy, only the execution of the document remains. Being this one a critical part of the transfer activity. Any deviation of the approved protocol must be addressed and documented. After performing and reporting the tests described in the transfer protocol, results must be verified and approved by the corresponding personnel. Once the data is verified and results are approved, these should be shared with the responsible area that will generate the transfer report.

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Data Analysis

Parameters to be considered for AMT Activity

Transfer Report

Once results from both areas are received, they are tabulated and evaluated against the transfer protocol acceptance criteria. Any deviation should be documented as part of the transfer report. The document will summarize all activities performed and should determine the effectiveness of the execution. It should conclude if the receiving area is qualified to execute the method in question. Table summarized transfer report sections; nonetheless, these can vary according to the company’s procedure.

A Typical AMT Report should include: