Regulatory Requirements for Vaccines: A Short Note

Corresponding Author:

Sashy Paul Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania E-mail: s_paul@psm.edu

Abstract

Introduction

Historically, biologics regulation has been undertaken in reaction to safety concerns. Legislative authorities have changed throughout time to improve and modernise vaccination and other biologics regulation. Prior to 1902, there were no legally required manufacturing and product standards for biologics. Following the deaths of 20 children who received contaminated products, the United States Congress approved an act in 1902 to govern the sale of viruses, serums, toxins, and related items (later known as the Biologics Control Act). This Act empowered the Public Health and Marine Hospital Service’s Hygienic Laboratory to issue regulations governing all areas of commercial vaccine, serum, toxin, and antitoxins manufacture, as well as related products, with the goal of assuring their safety and purity. The 1902 Biologics Control Act was re-enacted by Congress in 1944 as part of the Public Health Service Act (PHS Act) of 1944. 4 The 1902 Biologics Control Act was incorporated into Section 351 of the PHS Act (42 U.S.C. 262). The 1944 PHS Act, like the 1902 Act, was primarily concerned with ensuring the safety and purity of manufacturing procedures. The specific addition of the need that biologics makers demonstrate potency as a measure of therapeutic utility was unique to the 1944 PHS Act. The Laboratory of Biologics Control was established under the Public Health Service Act to make testing and licencing of biological goods and manufacturing facilities easier.

The Consumer Safety Act of 1972 gave the FDA regulatory jurisdiction over the 1944 PHS Act, which was previously held by the National Institutes of Health. The Secretary of Health, Education, and Welfare transferred the Division of Biologics Standards, which was responsible for administering and enforcing Section 351 of the PHS Act, to the FDA in 1972, and it became the Bureau of Biologics. Following the transfer of administrative responsibility for biologicals regulation from the NIH to the FDA, the FDA declared its plan to require that all new biologicals meet the higher safety and efficacy standards specified by the Drug Amendments Act of 1962. Regardless of the technology used to manufacture vaccines, a single set of basic regulatory standards applies to all of them. Vaccines must meet the regulatory approval standards outlined in Title 21 CFR, regardless of their indication or intended target group. A BLA can be approved if “the biological product that is the subject of the application is safe, pure, and potent; and (b) the facility in which the biological product is manufactured, processed, packed, or held meets standards designed to assure that the biological product continues to be safe, pure, and potent,” according to Section 351 of the PHS Act (42 USC 262).

A substantial safety database for vaccines assessed in clinical end point efficacy trials will most likely come from a double-blind, randomised, well-controlled efficacy research. Additional studies will likely be required for vaccines evaluated in immunogenicity end point studies to create an acceptable safety database. When the number of patients included in effectiveness studies is deemed insufficient to give relevant safety data, further controlled safety studies are frequently requested. If the number of injections, route of administration, or schedule vary across groups, especially when infants and young children are involved, safety studies may be unblinded. Phase II safety trials should offer information on the vaccine’s most common local and systemic responses.

Acknowledgement

None

Conflicts of Interest

The authors declare no conflict of interest.