Method transfer documentation

With a quality assurance program in place and a qualified instrument ready for analysis, the method development lab is ready to develop, validate, and transfer analytical methods to the end user. McGonigle [27] discusses five essential principles to ensime successful method transfer documentation, communication, acceptance criteria, implementation, and method modification and revalidation. 

The responsibihties of the quahty assurance unit generally fall into two categories support for or improvement of the existing quahty system (31). The support activities of QA often include employee training, quahty system documentation, method vahdation and method transfer, audit, and customer complaints. 

Method Transfer. Method transfer involves the implementation of a method developed at another laboratory. Typically the method is prepared in an analytical R D department and then transferred to quahty control at the plant. Method transfer demonstrates that the test method, as mn at the plant, provides results equivalent to that reported in R D. A vaUdated method containing documentation eases the transfer process by providing the recipient lab with detailed method instmctions, accuracy and precision, limits of detection, quantitation, and linearity. 

Partial or complete re-validation is another precedented approach to method transfer. Those variables described in method validation guidance documents (ICH Q2B, 1996 USP, 2012c) that are likely to be impacted by method transfer, should be assessed and documented (transfer or validation protocol). Agut et al. (2011) indicated that, in the changing industry model with the increased outsourcing of R and D activities (alliances, outsourcing, etc.), method re-validation may constitute, in some cases, an efficient approach when the transfer is performed from the Analytical Development Laboratory of an external partner who does not share exactly the same environment (validation standards, analytical culture or traditions , equipment, etc.). ... 

The pilot-production program is generally a result of cooperation between the development laboratories and the manufacturing department. Technology transfer documentation applies to processes as well as to the systems being qualified and validated and their testing standards and testing methods. This documentation is important, particularly where an NDA is involved. 

The term method transfer does not formally appear in the current FDA regulations or guidance documents. The ICH requirement of reproducibility , however, is intended to demonstrate the precision of analyses between laboratories. As a successful part of the total method validation, this ana-lyst-to-analyst comparison at different laboratory sites serves to prove the method validity. Also, this portion of validation can occur during the original validation experiments or at a future date. As an example, a method is developed in an analytical R D group to be eventually transferred to QC labs, production facilities, or contract laboratories worldwide. These reproducibility experiments would be performed as method-transfer exercises. 

Formal documentation of the method-transfer results as addenda to the original validation report would further substantiate the overall validation process. Thus, each new laboratory setting would either confirm the original method validation, or indicate a possible need for method modification with revalidation. 

The validation report should be a living document that reflects the dynamic validation process. Therefore, it should be updated using addenda to report method transfer results, ongoing system suitability and any revalidation efforts. 

Where the tasks will be performed How the tasks will be defined as successful Documentation criteria Approval criteria Method transfer Definition of method(s)... 

The decision to develop a pharmaceutical product transfers an active principle or compound from the resource-limited research laboratory into a new environment. In a multi-disciplinary approach the compound is subject to a variety of analytical, pharmacological, toxicological, and clinical tests and trials. From now on methods, results, documentation and the materials created are under strict scrutiny exerted by the developing organization itself and finally by several authorities. Research activities are hardly ever subject to such surveillance and control, concerning, for example the precision and consistency of methods and results. It usually takes time for a researcher to fully acknowlewdge and accept this fact. 

Difficulties in using HPLC methods frequently arise when a method is developed in one laboratory and is then transferred for use in another laboratory. To overcome this problem, there is a current trend towards developing method transfer protocols to facilitate a smoother transition. These protocols not only involve additional testing but also may even involve visits (for observation and supervised introduction to carrying out the method) of staff between sites. This seems over elaborate and it remains to be seen whether this trend will continue given that it should not be necessary if a method has been rigorously documented and validated. 

Method Transfer. Method transfer is the process of collecting documented evidence that the receiving laboratories (customers) are capable of running the method. This is based on analytical experiments showing the equivalence of the analytical results obtained in the development and receiving laboratories. These experiments are set up according to the transfer protocol that should contain preapproved acceptance criteria. 

Before the planning of any transfer, an approved document that describes both the general transfer process as well as the specific acceptance criteria necessary for the method(s) being transferred needs to be in place. In many companies, it is common for both the R D and quality units to have general standard operating procedures (SOPs) that govern the transfer process. These SOPs describe the details of a method transfer protocol that is specific to the product and methods. The contents of such a protocol were described in various chapters earlier in this text however, they are important and bear repeating here. 

Many companies have developed the practice of composing what is termed the transfer file as a means of ensuring that all key documents and relevant information are imparted to operations or the receiving laboratory. This file is merely a collection of important reports. For analytical methods, such documents include the method development and validation reports, impurity profiling report, stability reports and tables, and specification archive. The power of such an approach is that it ensures that all information is conveyed to the receiving laboratory. This strategy is useful if operations will be relied on to continue the development process. Examples include development for... 

This chapter highlights the important aspects of the analytical transfer process as they relate to compliance, analytical data, and documentation. Other chapters in this text should be consulted for elaboration on the various important facets of technical transfer, including method development, method validation, documentation, and stability. 

With such a method transfer it is usually not necessary to perform a re-validation as described in Section 20.3 (e.g., a re-determination of linearity is not needed). A documentation which shows that the Performance Qualification (Section 20.6) ist still fulfilled and that the chromatographic numbers of merit did not deteriorate will do the job. 

Method transfers are typically done between laboratories, where a method has been validated at one laboratory and is being transferred to another laboratory. This requires at least a partial validation that is documented and agreed upon by both parties. It is highly recommended that blinded spiked samples as well as incurred samples be tested during a method transfer to compare the performance of both laboratories. Method transfer studies should employ appropriate statistical design and data analysis. 

Very little regulatory documentation directly relates to method transfer and usually where it is mentioned, it refers to cross-validation of the method between two laboratories. It is mentioned in the FDA s Bioanalytical Methods Validation Guidance [1] page 3 under Cross-Validation, When sample analyses within a single study are conducted at more than one site or more than one laboratory, cross-validation with spiked matrix standards and subject samples should be conducted at each site or laboratory to establish inter-laboratory reliability. It is also mentioned in the Appendix of the same guidance that defines reproducibility as the precision between two laboratories. ... 

In the case of method transfer, contracts should include specific milestones defining successful completion of parts as well as the whole project. As a minimum, the contract should contain the number of experiments and documentation requirements for the method transfer results. In addition, early definition of criteria for success and failure of experiments and responsibilities for repeating failed experiments, sets the stage for a smoother process throughout the project. The contract should also state, as part of the deliverables, the level of documentation of method protocols and content of the final report. 

In the case that qualification is included in the method transfer, the contract should contain an agreed list of all analytical characteristics to be addressed. Specific criteria for success and failure of qualification experiments should be agreed upon and described in a protocol. Responsibility for the cost of experimental repeats that are caused by suspicious Vaberrant/anomalous results should be clarified. The criteria for defining anomalous results and how they would trigger repeat analysis should be well documented. 

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. 

A lot of effort is invested at the beginning of the project in defining the scope of work and expectations for transfer completion. This is best covered in a document defining the scope and goal of the method transfer, the regulatory standard to be applied (e.g., following GLP or not), experimental outline, acceptance criteria for assay performance, and transfer or development summary or report. It is useful to spend some time on such a protocol to reduce the risk of misunderstanding and to assure that expectations from both sides match. 

The transfer protocol should be approved by both sides. If changes to the protocol or plan occur, they should be noted and be approved by both sides. For the purpose of the method transfer and development, such a protocol should be seen as a living document that should be used as guidance and not set in stone. Any summary or report written afterward should address changes to the original protocol and reasons for such changes. 

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