Method development report transfer

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. 

Research reports—Research reports such as stability reports, method validation and transfer reports, and pharmaceutical development reports are key documents used for NDA/MAA filings. These documents are strictly version controlled. 

The final step of method development is validation of the HPLC method. Optimisation of chromatographic selectivity [110], performance verification testing of HPLC equipment [591], validation of computerised LC systems [592] and validation of analysis results using HPLC-PDA [34] were reported. The feasibility of automated validation of HPLC methods has been demonstrated [593]. Interlaboratory transfer of HPLC methods has been described [594]. 

In order to solve the mathematical model for the emulsion hquid membrane, the model parameters, i. e., external mass transfer coefficient (Km), effective diffu-sivity (D ff), and rate constant of the forward reaction (kj) can be estimated by well known procedures reported in the Hterature [72 - 74]. The external phase mass transfer coefficient can be calculated by the correlation of Calderback and Moo-Young [72] with reasonable accuracy. The value of the solute diffusivity (Da) required in the correlation can be calculated by the well-known Wilke-Chang correlation [73]. The value of the diffusivity of the complex involved in the procedure can also be estimated by Wilke-Chang correlation [73] and the internal phase mass transfer co-efficient (surfactant resistance) by the method developed by Gu et al. [75]. 

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. 

This article will avoid, as far as possible, duplication of these earlier reports and will emphasize the use of DMSO as an inert solvent in mechanistic investigations of heterolytic reactions. Studies where such use has led to interesting results will of course be highlighted, but others have been selected which illustrate the methods developed for mechanistic study in dipolar aprotic media. Discussion has not been restricted to reactions which give the characteristic rate variations on transfer to dipolar aprotic solvents the effect of DMSO on product distributions is discussed, and we have also speculated on possible future uses of DMSO in mechanistic investigations. 

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. 

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... 

Method transfer for ore-Studv validation Method development summary report Data table showing acceptable method performance Method is ready for pre-study validation... 

In addition to calcium phosphate transfection, methods for DNA transfer into mammalian cells by electroporation [31, 32] and by transfection mediated through cationic lipids, liposome [33-35], biohstics [36] and polymers [37, 38] have been developed. Most of these techniques have been reported to mediate higher transfection efficiencies as compared to calcium phosphate-mediated DNA transfer. Such claims must be regarded with some caution, as all DNA transfer techniques estabhshed so far suffer from high variabihty due to technical difficulties. Other factors to cause major variations in transfection efficiency are the type of cells used and the condition of the cells prior to transfection. 

Method validation and method transfer are distinct processes. Method validation certifies that the method performs in the manner for which it was developed and is the responsibility of the method development laboratory. Method transfer, on the other hand, is the introduction of a validated method into a designated laboratory so that it can be used in the same capacity for which it was originally developed. Accordingly, method transfer criteria should be based on the SOPs which are unique to the designated laboratory. For the essential principles of method transfer, cfr. ref. [69]. Interlaboratory transfer of HPLC methods has been reported [70]. Inter technique validation is equally important. Both in R D and in a production environment, the change from one technology to another must be totally transparent. A sample concentration obtained by a method in one laboratory must be the same as that obtained by another method in another laboratory. 

The timeline and essential tasks of a typical method transfer are described in Eigure 3. This timeline does not include the Risk Assessment, which could take place as much as 1 year prior to the required transfer completion date to provide time for any additional method development activities. A typical transfer may take approximately 6 months from the start of transfer activities to the final approval of the report however, transfer activities for countries that require import permits for supplies may need to be initiated as much as 6 months prior to the expected testing dates. Likewise, some countries will require marketing valuation of supplies to enable excise collection on the imported materials. Close coordination with the commercialization group is required as this valuation may need to occur... 

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