Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 67

Legal requirements for drug safety come from multiple areas. There are laws, regulations, and guidances issued by the United States’ federal government. These are the predominant formal requirements governing drug safety. In the US, a “law” is a written statute, requirement, or ordinance that has been passed by a legislature and then signed into law (where required) by the executive. That is, a federal law is passed by Congress in Washington, D.C., and signed by the president. Laws may be created at multiple levels of government (federal, state, and local). Regulation of interstate commerce is the FDA’s main enforcement authority.

The law governing investigational drugs (“New Drugs”) is found in Section 505(i) [21 U.S.C. 355], and the law governing marketed drugs is found in Section 505(k) of the Food Drug and Cosmetic Act (https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/FederalFoodDrugandCosmeticActFDCAct/default.htm).

In addition to laws, the US Food and Drug Administration (FDA) is empowered by Congress to create regulations. Regulations are rules issued by government authorities under the power of laws. Regulations thus have the force of law. To create a regulation, the FDA publishes the proposed version of the new or amended regulation in the Federal Register (https://www.federalregister.gov/). A period is defined during which time the public may send written comments on the proposal to the FDA. After review, a final regulation is published in the Federal Register and in the Code of Federal Regulations (https://www.ecfr.gov/cgi-bin/ECFR?page=browse). A long period may elapse between publishing the draft and the final regulation (e.g., 6 months or more) and FDA is under no obligation to finalize a draft regulation or guidance. Also, a draft regulation may be withdrawn. While a proposed or final regulation may be published and put into force anytime, the Code of Federal Regulations is updated with final regulations once a year, on April 1st.

Finally, the FDA issues guidances that contain the FDA’s preferences on laws and regulations. Guidances are often an offshoot of guidelines that are developed by consensus organizations, e.g., the International Council for Harmonization (ICH) or the Council of International Organizations of Medical Sciences (CIOMS).

As the FDA states on its Center for Drug Evaluation and Research (CDER) Guidance page (https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm): “Guidance documents represent the Agency’s current thinking on a particular subject. They do not create or confer any rights for or on any person and do not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both.” However, it is generally held in practice in the industry to be a wise course of action to follow FDA guidances. Some of the applicable pharmacovigilance (PV) guidances can be found at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064993.htm. Clinical trial guidances may be found at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064981.htm.