Global Regulatory Framework

Global Regulatory Framework

UNITED STATES FEDERAL STATUTES RELEVANT TO PHARMACEUTICALS

The Administrative Procedure Act

The Administrative Procedure Act (APA) of 1946 is the United States federal law governing how administrative agencies (for example, the Food and Drug Administration [FDA]) within the federal government of the United States of America propose and establish regulation. The APA sets up a process for the United States federal courts to review directly (that is, judicial review) any agency decisions/regulations. The difference between federal statutory law and federal administrative law (agency regulation) is explained as follows: Congress finalizes the content and approves (legislates) a federal bill that, when signed by the president, becomes federal statutory law. Federal executive departments (that is, the president’s cabinet) such as the Department of Health and Human Services (HHS) and subordinate administrative agencies (for example FDA, the National Institutes of Health [NIH]) declare and publish (promulgate) regulations/administrative law to codify and put into practical motion the governing federal statutory laws. The verb “promulgate” is interchangeable with the verb “codify,” the verb associated with the Code (that is, collection) of Federal Regulations. The United States Justice Department indicts and prosecutes based on alleged violation of one or more specific regulations/administrative laws promulgated by a federal agency (which has its basis in a federal statutory law). A federal court verdict or injunction references the prevailing federal statutory law, while prosecutors present to the court evidence that is shown to violate one or more specific administrative laws/regulations.

United States Federal Food, Drug, and Cosmetic Act

The Food, Drug, and Cosmetic Act (FDCA) of 1938 is the United States federal statute governing the marketing, manufacture, and distribution of finished pharmaceuticals, medical devices, foods, dietary supplements, and cosmetics. It has never been replaced or renamed, but rather supplemented or amended through subsequent acts. The FDCA replaced the 1906 Federal Safe Food and Drugs Act after revelations in Upton Sinclair’s book The Jungle of intentional inclusion of filth by the United States meat packing industry. The 1938 FDCA improvements over the 1906 Act included the following:

• Extending control to cosmetics and therapeutic devices

• Requiring new drugs to be shown safe before marketing

• Providing that safe tolerances be set for unavoidable poisonous substances

• Authorizing standards of identity, quality, and fill-of-container for foods

• Authorizing factory inspections

• Adding the remedy of court injunctions (to the previous Act’s seizures and prosecutions)

Table 1.1 provides some FDA website listings for amendments to the FDCA. 

United States Public Health Service Act

The United States Public Health Service (PHS) originated in name in 1798; however, the PHS Act of 1944 consolidated many previous federal laws relating to public health services and newly mandated the licensing of human biologic products, or their suspension if they endangered public health. The PHS Act is codified and enforced by several federal agencies under the Department of HHS.

The Virus-Serum-Toxin Act

The Virus-Serum-Toxin Act (VSTA) (as amended) requires licensing of animal vaccine products and establishments, and requires permits for the importation of animal biologic products. The Veterinary Biologics Program of the United States Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) enforces the VSTA by codifying regulations in 9 CFR 101–118.

It should be noted that the term “pharmaceuticals” is interchangeable with “drugs” in the United States and with the term “medicinal products” in the rest of the world. It is an umbrella term that includes biologics (usually large-molecule therapeutic entities greater than 5 kDaltons) and nonbiologic drugs (usually small-molecule entities less than 5 kDaltons). Biologics, like other drugs, are used for the treatment, prevention, or cure of disease in humans; however, they are generally derived from living material and are complex in structure and often less definitively characterized than nonbiologic drugs. Biologics are not characterized down to every element, ionic state, water of hydration, three-dimensional structure, including disulfide bond, hydrogen bond, or protein quaternary subunit.

EUROPEAN UNION LEGAL SYSTEM RELEVANT TO PHARMACEUTICALS

Within the member countries of the European Union (EU), regulations, directives, and decisions are the principal forms of legislation governing pharmaceutical manufacturing and pharmaceutical marketing. Specifically, a “regulation” is a binding legislative act that must be applied in its entirety across the EU. A “directive” is a legislative act that sets out a goal that all EU countries must achieve; however, it is up to the individual countries to decide how to achieve that goal. A “decision” only deals with a particular issue and specifically mentioned persons or organizations.

Member states of the EU enact national laws to enforce the provisions of EU directives. Directive 2001/83/EC (similar to the United States FDCA) continues to be amended over time but maintains its original structure and general content (comprising Articles and Annexes). This directive requires each holder of a medicinal product manufacturing authorization to have “permanently and continuously at his disposal the services of at least one qualified person [QP].” The specific duties of the QP, as well as the guidelines for pharmaceutical good manufacturing practices (GMP), are detailed in the Eudralex Volume 4, Part I.

JAPAN LEGAL SYSTEM RELEVANT TO PHARMACEUTICALS

The Ministry of Health, Labour, and Welfare (MHLW) (the Koseirodosho) was established by a merger of the Ministry of Health and Welfare and the Ministry of Labour on January 6, 2001, as part of the government program for reorganizing government ministries. The MHLW, which was originally established in 1938, was in charge of the improvement and promotion of social welfare, social security, and public health, and the new organization has the same tasks. The department consists of the ministry proper, affiliated institutions, councils, local branches, and an external organization. The MHLW is in charge of pharmaceutical regulatory affairs in Japan (veterinary drugs are under the jurisdiction of the Ministry of Agriculture, Forestry and Fisheries). The Pharmaceutical and Food Safety Bureau (PFSB) undertakes the main duties and functions of the Ministry: it handles clinical studies, approval reviews, and post-marketing safety measures, that is approvals and licensing for ensuring food and drug safety.