Analytical method transfer report

The designated laboratory is responsible for issuing and following SOPs that define their criteria for accepting an analytical method. The method transfer report includes data generated in accordance with those SOPs. 

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. 

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. 

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. 

Setting An established analytical method consisting of the extraction of a drag and its major metabolite from blood plasma and the subsequent HPLC quantitation was precisely described in a R D report, and was to be transferred to three new labs across international boundaries. (Cf. Section 4.32.) The originator supplied a small amount of drug standard and a number of vials containing frozen blood plasma with the two components in a fixed ratio, at concentrations termed lo, mid, and hi. The report provided for evaluations both in the untransformed (linear/linear depiction)... 

To demonstrate the validity of an analytical method, data regarding working range/ calibration, recovery, repeatability, specificity and LOQ have to be provided for each relevant sample matrix. Most often these data have to be collected from several studies, e.g., from several validation reports of the developer of the method, the independent laboratory validation or the confirmatory method trials. If the intended use of a pesticide is not restricted to one matrix type and if residues are transferred via feedstuffs to animals and finally to foodstuffs of animal origin, up to 30 sets of the quality parameters described above are necessary for each analyte of the residue definition. Table 2 can be used as a checklist to monitor the completeness of required data. 

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. 

Eventually the point will be reached at which the development of a product is complete the formulation is finalized, the equipment has been selected, the analytical methods are validated, the development transfer report has been issued, and the Preapproval Inspection (PAI) is anticipated. Now is the time to consider validation of both the manufacturing and cleaning processes. Although some process validation may have also been completed or a process validation protocol may have been prepared and approved, it is likely that very little has been finished that would enable us to state that the cleaning process is fully validated. 

A common industry practice is to list the actual equipment used during the original validation in the validation report and analytical method. Quite frequently or equivalent will follow the listing. Since certain instrumental parameters can differ between manufacturers of basically the same equipment (e.g., UVdetectors for HPLC), it is essential to include experiments in the method-transfer exercise that are specifically designed to qualify the equipment as equivalent or suitable. 

Numerous extraction methods and techniques have been developed and reported, especially if one takes into account the variety of modifications. The most common and simple general classification of these methods is similar to that introduced in chromatography and based on the kind of phase to which the analyte is transferred. One can distinguish the extractions as liquid, solid, gas, and supercritical fluid phase extractions. More precise description specifies the two phases between which the analyte is distributed (e.g., liquid-liquid or solid-liquid [leaching] extractions). The latter methods are all called solvent extraction. 

In cases where a general QL is required, as in pharmaceutical analysis, it is essential to define a realistic QL (or DL) for the analytical procedure, independently from the equipment used, because this limit has important consequences (e.g., for the consistent reporting of impurities or for method transfer). They may be derived by taking QL (or DL) from various instruments into account ( intermediate QL, during the development process) or can be defined taking the requirements of the control test (specification limits imposed by toxicology or by a qualified impurity profile) into consideration. For example, a QL which... 

The on-line coupling between TLC and mass spectrometry provides a powerful combination for the detection and identification of substances separated by a planar chromatographic method. The on-line coupling between these two methods has to overcome the problem of vaporizing and introducing the sample into the mass spectrometer. Different methods are reported in the literature, but the analytical principle is the same the sample is ionized from the layer surface by means of a laser beam, under vacuum, and in the presence of an energy-buffering matrix. Once the ions are transferred into the mass spectrometer, more sophisticated methods can be applied for data analysis and interpretation, e.g., MS-MS. 

However, the (undisclosed) proprietary immobilization process appears to modify the enantiomer separation characteristics as compared to the coated versions [145, 146]. Ghanem et al. compared the chiral recognition profile of a coated CHIRALPAK AD CSPs with that of the immobilized version, employing hexane/ 2-propanol containing TEA (0.1%) as mobile phase [145]. They reported superior enantiomer separation for the coated CSP, with some analytes failing to resolve on the immobilized version. These differences in the enantiomer separation capacity of coated and immobilized polysaccharide-type CSPs may complicate attempts at direct method transfer. 

It is extremely beneficial to have a comprehensive analytical development report that provides the scope of each analytical method, chronology, rationale for changes, and equivalency or superiority of the optimized methods. Usually, the analytical development report for each method, along with the validation report, facilitates the technology transfer process. 

Analytical methods validation and technology transfer reports for drug substance and drug product... 

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... 

The analytical procedure that is used by this laboratory for the analysis of simple Fusarium mycotoxins will be reported separately. However, the analytical scheme is outlined in Figure 2. The method is very arduous due to several sample clean-up steps which necessitates transfer of the sample between containers. The trichothecenes and their derivatives have a tendency to adhere to glass and can be quantitatively transferred only with numerous methanol washes. While the analytical method is both sufficiently sensitive and definitive for the program requirements, the sheer amount of human manipulation required for the completion of this analysis makes it somewhat unreliable if implemented without a responsible quality assurance and quality control program. 

Transfers of analytical methods are also evaluated very critically, and analytical transfer plans with defined acceptance criteria are expected, as well as related transfer reports. On this topic, the USP <1224> Transfer of Analytical Procedures offers some guidance. For assistance on the confirmation of pharmacopoeia methods, the chapter USP <1226> Verification of Compendial Methods can be looked up. 

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