Pharmaceutical Manufacturing Handbook: Production and

TABLE 4 FDA Center Regulatory Responsibility for Therapeutic Biological Products
CDER
CBER
Monoclonal antibodies (in vivo use)
Cellular product, including products
Proteins intended for therapeutic use:
composed of human, bacterial, or
Cytokines (e.g., interferons)
animal cells
Enzymes (e.g., thrombolytics)
Vaccines
other novel proteins except those assigned to Allergenic extracts
CBER
Antitoxins, antivenoms, venoms
Immunomodulators (nonvaccine, nonallergenic) Blood, blood components, plasma -
Growth factors, cytokines, some hormones and derived products (e.g., albumin,
monoclonal antibodies intended to mobilize, immunoglobulins, clotting factors,
stimulate, decrease, or otherwise alter the fi brin sealants, proteinase inhibitors),
production of hematopoietic cells in vivo recombinant and transgenic versions
of plasma derivatives
As other recombinant proteins and monoclonal antibodies came under development,
the CBER held primary responsibility for this review, with the CDER retaining
responsibility for hormones such as insulin and HGH. However, in 2003 all
therapeutic proteins were transferred from the CBER to the CDER. This reassignment
of review responsibility did not impact the legal classifi cation of these protein
products, such that the Center for Drug Evaluation and Research assumed responsibility
for the review and approval of biologics approved under Section 351 of the
PHSA.
The basic distribution of these therapeutic biologics to the respective FDA center
is refl ected in Table 4 ; however, many of the current complex biotechnology - derived
products do not fi t neatly into accepted defi nitions and require case - by - case classifi
cation [13] .
1.2.3.3 Regulatory Approval Path for Proteins
The relevance of the preceding discussion becomes important with the understanding
that therapeutic proteins classifi ed as drugs are governed under a different set
of laws than those classifi ed as biologics. Drugs are approved via submission of
NDAs under Section 505 of the FD & C Act, while biologics are supported by BLAs
under the PHSA. These two approval paths are similar in terms of application
content, that is, requirement of complete reports of clinical safety and effi cacy data
to support approval. However, only the drug regulation, that is, Section 505 of the
FD & C Act, has been amended to outline an abbreviated approval mechanism for
generic products.
1.2.4
REGULATION OF GENERIC DRUGS
REGULATION OF GENERIC DRUGS 41
1.2.4.1 History of Generic Drug Legislation in United States
In 1984, Congress responded to America ’ s need for safe, affordable medicines by
passing a pivotal piece of legislation, The Drug Price Competition and Patent Term