Summary of DIA Workshop: Comparability Challenges: Regulatory and Scientific Issues in the Assessment of Biopharmaceutic
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Summary of DIA Workshop: Comparability Challenges: Regulatory and Scientific Issues in the Assessment of Biopharmaceuticals
Ricbard M. Lewis, PLD Access Bio, L C
Mary Ellen Cosemza, PbD Director Of Regulatory Affairs. Amgen, Inc.
On February 3-4, 2009, a DlA Workshop was held to review and discuss comparability challenges and issues fix biotechndogy-derived pharmaceuticals. The workshop was hdd in the Washington, DC, area and was attended by representativesfrom the FDA and biotech and pharmaceutical industries. The expectation was to develop a consensus on which data are
Key Words Comparability; Regulatory; Biological product; Pharmacokinet ics: Pharmacodynamics; Biochemical: Analyses
Correspondence Address Richard M. Lewis (email: rlew is @accessbio.com)
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OVERVIEW During the lifetime of all pharmaceutical products, the need to make a change in production methods will arise. The effects of any change must be evaluated for quality and safety purposes as well as for submission to regulatory authorities (1-3). This is especially important for biotechnology-derived products whose characteristics are closely related to the manufacturing process. Biotechnology-derived molecules are often complex, possessing various posttranslational modifications (4). Their functions depend on higher order structures and are usually defined not only by product characteristics, but also by the manufacturing process. Sequence variants can occur and even minor carbohydrate differences are often important. The FDA requires that a new manufacturing method produce a product comparable to the previous method and offers regulatory guidance in ICH, Q5E (1). Depending on the change, in vitro comparisons, animal data, clinical data, or some combination of these may be necessary to demonstrate comparability. This does not mean that the product is identical before and after the change. From the regulatory perspective, there must be no adverse impact on the quality, safety, or efficacy of the drug product. The degree of testing and extent of similarity often depend on the product's stage of development. For example, changes in the
necessary to provide assurance of comparability fix manufacturing changes made to biotechndogy products during different stages of development or postmarketing. Numerous case studies were reviewed and discussed to build on best practices and recognize successjid approaches to Comparability.
master cell bank during a phase 2 trial might require a more extensive comparison than the same change during phase 1 trials. An important component of comparability is the nature and extent of the change. Recently, there has been an increase in the generation and evaluation of nonclinical animal and clinical data; however, an FDA representative at the workshop stated that the vast majority of comparability decisions are made based on quality data, such as in vitro analytical testing incorporating both physicochemical and functional bioassays (5). Quality testing should include, but may not be limited to, product specificat
