Background

BACKGROUND

The legal requirements for the development, approval and marketing of drugs in the United States are contained in the Federal Food, Drug and Cosmetic Act (FDCA) (Pub. L. No. 75-717, 52 Stat. 1040 (1938)), as amended (codified as amended at 21 U.S.C. §§ 301 et seq.). Biological products (e.g. vaccines, blood, cellular derived products and most products derived from biotechnology) are approved (licensed) pursuant to the Public Health Service Act (PHSA) (Ch. 288, 37 Stat. 309 (1912)), as amended (codified as amended at 42 U.S.C. § 262). Biological products are also subject to the legal requirements for drugs during the devel-opmental stage as well as the post-approval marketing stage. For purposes of this chapter, when there is a discussion of drugs, the reader must assume that the same requirements apply to biological products unless specifically identified otherwise.

A pharmaceutical company must look to three sources of information to determine the legal stan-dards for pharmacovigilance in the United States: laws, regulations and guidance documents. If a manu-facturer, sponsor or individual violates standard in the law, then they are subject to the penalties described in such laws. These laws, however, are often rela-tively general (i.e. manufacturers shall keep records and make reports). Often the FDA must publish regulations that further define the more generalized standards in the law. The FDA develops regulations by publishing a proposed rule in the Federal Regis-ter, taking public comment and then publishing a final rule that takes into account comments received. Once a final regulation takes effect, it is published in the US government’s Code of Federal Regulations (CFR). Assuming the FDA regulations are properly developed, they set legally binding standards. If a company violates a regulation, then it is the same as if the company has violated the law itself and the company is subject to the penalties described in the law. Guidances are a third source of information about the FDA’s standards. Guidance documents are informal communications from the FDA that provide the agency’s current thinking about how to comply with various legal requirements. Guidance documents, however, do not have the force and effect of law. Therefore, if a company violates or otherwise does not comply with the conduct described in a guidance, then the company is not automatically violating the law or subject to penalties.

The FDA adds the following disclaimer to all guidance documents it publishes:

This guidance has been prepared by the Center for Drug Evaluation and Research at the Food and Drug Administration (FDA). This guidance represents the Agency’s current thinking on [the topic of the respective guidance]. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes, regulations, or both.

Conduct that is contrary to an FDA guidance represents a risk, however, that the FDA will consider such conduct a violation of law and attempt to bring an enforcement action.