Analytical method transfer examples

For any new excipients, APIs or drug products (where new does not necessarily mean novel, but new to the receiving site) there are additional testing criteria, e.g. supplier audits, third-party contract laboratory audits, analytical method transfers, sample management/tracking, etc. For those key excipients, where there is on-site historical experience, it still behoves both parties to check whether the local grade/supplier used by the CMO is equivalent to that used by the supplier (Worsham, 2010). There are many examples of differences in excipient physical properties, e.g. particle size, which have been attributed to different excipient sources that could ultimately impact on the performance of those excipients in formulated products (Frattini and Simioni, 1984 Dansereau and Peck, 1987 Phadke et al., 1994 Lin and Peck, 1994). 

Since the aim of the protocol is to ensure the mitigation of problems, the essential elements of the protocol consists of sections that include (a) an Introduction, (b) treatment and disposition of data, (c) types of methods being transferred, (d) materials, reference standards, and reagents being used, (e) recommended type of equipment, (f) sample handling, (g) predetermined acceptance criteria, and (h) an Acknowledgment section. An example of a typical table of contents (TOC) of an analytical methods transfer protocol is discussed in Table 16-2. 

Charge-transfer absorption is important because it produces very large absorbances, providing for a much more sensitive analytical method. One important example of a charge-transfer complex is that of o-phenanthroline with Fe +, the UV/Vis spectrum for which is shown in Figure 10.17. Charge-transfer absorption in which the electron moves from the ligand to the metal also is possible. 

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. 

The process of method transfer must follow a method-transfer protocol which defines the experiments and acceptance criteria necessary to demonstrate the analysts proficiency, equipment s suitability, and true ruggedness of the analytical method. If we assume that any quality analytical laboratory has proficient analysts who operate suitable equipment, then the method transfer stands as an ongoing means to substantiate the suitability of the original method validation. Example 5 contains an example of a method-transfer protocol for a chromatographic procedure. 

Table 6.4 lists some categories of improved and future dosimetry systems, their analytical methods, and several examples of each. This list includes both reference and routine dosimeters, as well as some of those suitable for transfer dosimeters, all three of these being defined in Chapter 5 of McLaughlin et al. (1989). 

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 first example presents a typical process from our research environment, where a chemical synthesis is transferred from development to production. In this situation validation of the chemical process is performed throughout, including variations of process parameters for intermediates that are not isolated. For these intermediates a pre-selected analytical method is normally... 

Verification or revalidation should be performed when relevant, for example, when there are changes in the process for synthesis of the drug substance changes in the composition of the finished product changes in the analytical procedure when analytical methods are transferred from one laboratory to another or when major pieces of equipment instruments change. 

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... 

Let s discuss now some possible statistical approaches for evaluating the data obtained from development or scale-up activities, to learn all there is about the process prior to transfer to manufacturing. In addition, let s see how this data can be used to establish practical and reasonable in-process requirements and acceptance criteria for the process and product as we enter the process validation phase. The examples used in the following sections are of solid dosage forms, although the techniques are certainly applicable to other dosage forms and also analytical method development. 

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