Introduction

An early characterization of biopharmaceuticals (proteins) is needed to evaluate the comparability of materials, which is more complicated due to the inherently heterogeneous nature of many biologicals. This includes factors such as micro-heterogeneity of glycosylation, differential proteolytic processing during cellular production, or variations in post-translational modifications, factors which are not common to small molecule characterization and evaluation for interaction. This requires availability of highly specific discriminating methodologies, such as spectrophotometric, chromatographic, electrophoretic methods, and mass spectroscopy (MS), often combined with liquid chromatography (LC).

Unlike small molecule drugs, there are three-dimensional (3D) and four-dimensional (4D) considerations (aggregates) with almost endless variation of polypeptides and proteins that make them a challenge to develop into products. Whereas in small molecule drugs there can be classes of drugs with common elements, this is not the case with protein drugs as each one of them offers a unique structure requiring techniques of production and purification specific to the protein. The same holds true for the stability profile of these compounds. Specification of biopharmaceutical drugs also includes elements not found in small molecules like virus clearance, aggregate formation, and so on. As a result, the regulatory authorities worldwide treat biopharmaceutical drugs under separate administration wherein a high level of expertise is inducted to evaluate these products.

Marketing authorization approvals for biological products are subject to a similar process as adopted for chemical drugs; however, the nature of these products mandates special evaluation and monitoring techniques. As a result, historically, the United States Food and Drug Administration (U.S. FDA) has established separate sections for these products. Title 21 of the Code of Federal Regulations (CFR) concerns food and drugs. Table 1 lists those parts that particularly pertain to products under the purview of the Center for Biologics Evaluation and Research (CBER) of the U.S. FDA. The CFR (1996-2005) is available for browsing and/or searching (1).

On June 30,2003, FDA transferred some of the therapeutic biological products that had been reviewed and regulated by the CBER to the Center for Drug Evaluation and Research (CDER). CDER now has regulatory responsibility, including premarket review and continuing oversight, over the transferred products. In regulating the products assigned to them, CBER and CDER will consult with each other regularly and whenever necessary (Table 2).

The categories of therapeutic biological products transferred to CDER (2) are as follows.

Table 1 Parts of Title 21 of the Code of Federal Regulations Relevant to Biological Drugs

Parts

Table 1 Parts of Title 21 of the Code of Federal Regulations Relevant to Biological Drugs

Parts

Maintaining The Body

Maintaining The Body

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