Potency assay

Vaccine Source materiai Processing Potency assay Safety tests... 

Table 15.3 lists the immimosera for which there is a need, or a potential need, today and indieates the reqnired potencies of these immimosera and the sahent features of the potency assay methods. 

Immunoserum Potency assay methed Potency requirement... 

The quality control of immunoglobuhns includes potency tests and conventional tests of safety and sterihty. The potency tests consist of neutrahzation tests that parallel those used for the potency assay of immunosera, except that in the cases of some immimoglobulins the assays are made in vitro, fit addition to the safety and sterihty tests, total protein is determined by nitrogen estimations, the protein composition by... 

The current potency assay used for human growth hormone (hGH) products is performed with hypo-physectomized rats and measures weight gain over 7 days in response to intact hGH. The assay utilizes many rats, is labor intensive, and the results can be... 

Several in vitro tests are currently employed to assure drug product quality. These include purity, potency, assay, content uniformity, and dissolution specifications. For a pharmaceutical product to be consistently effective, it must meet all of its quality test criteria. When used as a QC test, the in vitro dissolution test provides information for marketing authorization. The dissolution test forms the basis for setting specifications (test, methodology, acceptance criteria) to allow batch release into the market place. Dissolution tests also provides a useful check on a number of physical characteristics, including particle size distribution, crystal form, etc., which may be influenced by the manufacturing procedure. In vitro dissolution tests and QC specifications should be based on the in vitro performance of the test batches used in in vivo studies or on suitable compendial specifications. For conventional-release products, a single-point dissolution... 

Analytical methods are important not only in the development and manufacture of commercial biopharmaceutical drugs, they also play a vital role in the whole drug development life cycle. Drug discovery and preclinical research require development and application of analytical methodologies to support identification, quantitation, and characterization of lead molecules. It is difficult to perform a comparative potency assay on lead molecules if one does not know how much of each is going into the assay or how pure the molecule is. Analytical methods are typically developed, qualified, and validated in step with the clinical... 

Assays Validated methods of analysis (e.g., ELISA for MAb), QPCR for residual DNA, and potency assays for vaccines... 

Liu, L., Osborne, L. M., and Nussbaum, M. A. (1996). Development and validation of a combined potency assay and enantiomeric purity method for a chiral pharmaceutical compound using capillary electrophoresis. J. Chromatogr. A 745(1—2), 45 —52. 

The final, purified bulk product is thoroughly characterized and compared to reference standards established by the manufacturer for new molecular entities or available from the United States Pharmacopoeia (USP) or the World Health Organization s National Institute of Biological Standards and Control. Characterization tests of proteins may include biologic potency assays, chromatographic assays, gel... 

All potency assays, from the simplest designs to the most complex Latin square design, necessitate potency estimation by computer. Low-precision assays employing plotting of zone sizes (response) against concentration of standards must be dealt with using computerized regression analysis, with the potency (standard equivalent) estimation calculated from the computed equation of the line. In this way, all opportunity for operator subjectivity is minimized. 

The most important aspects of data handling for potency assays and low-precision assays are that the data is handled by validated computer programs and that the acceptance and rejection criteria incorporated are clear and based upon statistical or proven (at validation) limits. 

For the determination of potency assay of a drug substance or a drug product, the usual range of linearity should be +20% of the target or nominal concentration. For the determination of content uniformity, it should be 30% of the target or nominal concentration. Figure 3 illustrates the linearity of a sample set of data. 

An example of the minimum requirement for potency assay of the drug substance and drug product is tabulated in Table 4. Note that the postponement of intermediate precision is aligned with previous discussion that the use of early phase analytical method resides mainly in one laboratory and is used only by a very limited number of analysts. Each individual company s phased method validation procedures and processes will vary, but the overall philosophy is the same. The extent of and expectations from early phase method validation are lower than the requirements in the later stages of development. The validation exercise becomes larger and more detailed and collects a larger body of data to ensure that the method is robust and appropriate for use at the commercial site. 

Analytical Development of API and Drug Products. Early methods to support synthetic and formulation developments are often developed in the form of potency assay, impurities/related substance assay, dissolution, Karl Fischer, identity, chiral method, and content uniformity. These analytical methods are developed and validated in a fast and timely manner to support all phase II studies. 

ICH Q2A [1] proposed the guidelines shown in Table 2.1 for the validation of a potency assay for a drug substance or drug product. 

VALIDATION PRACTICES Table 2.1. Guidelines for Drug Potency Assay... 

Critical separations in chromatography should be investigated at the appropriate level. Specificity can best be demonstrated by the resolution of two chromographic peaks that elute close to each other. In the potency assay, one of the peaks would be the analyte peak. Figure 2.4 illustrates the selectivity of a method to resolve known degradation peaks from the parent peak. Based on the... 

There are various situations during the life cycle of a dissolution test that will require revalidation of the method. These are similar to those described for the potency assay in Chapter 2. 

Meeting the foregoing criterion should not be interpreted to mean that an individual composite potency assay will meet the in-house limits with high assurance. If this is desired, a prediction interval for a single future observation, or better yet, a tolerance interval, should be used. The validation specialist should be cautioned that additional composite assays might need to be tested to meet either one of these criteria with high confidence. 

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