Documentation method transfer process

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. 

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. 

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. 

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. 

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. 

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. 

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. 

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. 

Individual protocols and reports can be written for each test to facilitate transfer of specific mefhods. This approach allows a discrepancy fo be investigated while not holding up unaffected method transfer activities. To facilitate internal and regulatory inspections, the method transfer protocols and reports should be compiled for easy review at the receiving site. The raw data should be readily accessible. Transfer of any relevant documentation such as methods, specifications, validation reports, reference standard information should be completed. From this point on, the change control process should assure that methods and specifications remain the same at the qualified fesfing sifes except perhaps for document format. 

Tod, CEN and ISO cooperate according to the so-called Vienna Agreement of 1991 in order to save resources and to avoid duplication of work or contradictory standard methods in CEN and ISO. Both organizations agreed on basic principles, for example, on synchronized approval procedures or simultaneous publication. Standardization projects started in ISO can be transferred to CEN, if necessary, and vice versa. The transfer process can be started either by the so-called unique acceptance procedure (UAP, see Section 1.3.5) on a finalized ISO or CEN standard or by the parallel voting procedure (PVP, see Section 1.3.5) on a document qualified for an enquiry process (ISO/CEN, 2001). 

The trityl carbonium ion is well documented as a hydride-ion acceptor indeed it can be reduced by aldehyde acetals in an intramolecular hydride-transfer process. This is pivotal in a new method for the deacetaliza-tion of ketone acetals by oxidative hydride transfer trityl fluoroborate is used as reagent, and the glycol moiety is oxidized to an a-ketol, as is shown in Scheme 79. This novel procedure is successful also with hemithioacetals, but fails with thioacetals. 

The importance of master plans in the technology transfer process is described by MacLennon Troll. While the master plan is specifically described for the technology transfer process as a whole, it is also applicable to the transfer of analytical methods and its use is becoming more prevalent within the industry. The technology transfer master plan describes the transfer strategy for all of the testing methods described in the specifications for the test article(s) of interest. The master plan is an auditable document that will help the health authorities during the preapproval inspection (PAI) to understand the overall transfer process and make... 

This chapter highlights the important aspects of the analytical transfer processes as they relate to process, compliance, analytical data, and documentation. Types of method transfers and the timeline of transfer activities are discussed. The risk assessment prior to initiation of transfer activities is also described. The chapter describes content and utility of the transfer protocol and final report, as well as documents that govern analytical method transfers (i.e., SOPs and master plan). The importance of selecting appropriate method transfer acceptance criteria and use of statistical methods to evaluate results are described. The significance of the inclusion of an adequate level of detail in the methods, protocol(s), and other documents cannot be overly stressed. Last of all, the process for transfer of technical ownership of the analytical methods is discussed. 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. 

A pilot production is at about a lOOx level in general, the full scale-batch and the technology transfer at this stage should comprise preformulation information, product development report, and product stability and analytical methods reports. This is the time to finalize the batch production documentation for the lOOx level. The objectives of prevalidation trials at this stage are to qualify and optimize the process in full-scale production equipment and facilities. 

Earlier I discussed a method of planning for PV, in particular the overall development function leading up to it. It appears that the development group has a number of avenues that will lead to the appropriate validation approach it takes. In one approach, the critical process parameters would be measured to monitor the process and document the fact that the process is validated. Many validation programs use this approach, but they are usually undertaken right after or as part of the technology transfer effort. 

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