Fed reg 1&2 COMBINE

Clinical Trials and FDA Regulations

• In all 3 phases of clinical trials, the FDCA requires independent investigators to secure informed consent from patients for the administration of an experimental drug.

Informed Consent and Postmarketing Surveillance

• Informed consent is required from patients for the administration of an experimental drug.
• Under postmarketing surveillance, the manufacturer must submit 5 things to the FDA, including:
  • Reports of serious adverse events (AEs)
  • New information related to the drug's safety and efficacy
  • Information about current clinical studies
  • Quantity of drug distributed
  • Information about labeling and advertising

FDA Monitoring of Approved Drugs

• The FDA monitors drugs after approval through postmarketing surveillance.
• The FDA has the authority to require phase 4 testing for any prescription drug under the FDAAA (FDA Amendments Act of 2007).

Access to Investigational Drugs

• Widespread access allows the provision of investigational drugs outside controlled clinical trials to treat patients with serious or immediately life-threatening diseases for which no comparable or satisfactory therapy is available.
• An individual patient, acting through a physician, may request an investigational drug from the manufacturer under certain circumstances, including:
  • The physician determines that the patient has no comparable or satisfactory alternative therapy and that the risk to the patient from the drug is no greater than the risk from the disease or condition.
  • The FDA determines that there is enough evidence of safety and efficacy to support use and that the use of the drug will not interfere with clinical investigations in support of marketing approval.

Emergency Use Authorization (EUA)

• An EUA is a mechanism to facilitate the availability and use of medical countermeasures, including vaccines, during public health emergencies.
• An EUA does not constitute the approval of the drug in the full statutory meaning of the term but instead authorizes the FDA to facilitate the availability of an unapproved product.

FDA Expectations Following EUAs

• The FDA has certain expectations of manufacturers following EUAs, including the submission of all data from phase 1 and 2 trials, and phase 3 data with a median follow-up of at least 2 months after completion of the full regimen.

Types of NDA Submissions

• An Abbreviated New Drug Application (ANDA) must demonstrate bioequivalence and acceptable manufacturing methods and controls.
• A Type 1 chemical classification of a new drug indicates a new molecular entity.
• A Type 6 chemical classification of a new drug indicates a new therapeutic indication for a drug already approved.
• A Type P (Priority) indicates that the drug represents a major therapeutic gain because there are no other effective drugs available for treating a particular illness or because it has significant advantages compared to currently marketed drugs.
• A Type S (Standard) indicates that the drug is similar to other drugs on the market.

Advertising and Labeling Regulations

• Nonprescription drug product advertising is regulated by the Federal Trade Commission (FTC).
• There are no federal regulations that address direct-to-consumer prescription drug advertising.
• The National Drug Code (NDC) is a numbering system that aids in identifying a drug product, and is required for prescription and OTC drugs.
• The FDA is responsible for administering the Food, Drug, and Cosmetic Act (FDCA).

History of FDA Regulations

• The Pure Food and Drug Act of 1906 prohibited adulteration and misbranding of food and drugs in interstate commerce.
• The Food, Drug, and Cosmetic Act of 1938 (FDCA) was prompted by the sulfanilamide tragedy and stated that no new drug could be marketed until proven safe for use.
• The Durham-Humphrey Amendment of 1951 established two classes of drugs (OTC vs. Prescription).
• The Kefauver-Harris Amendment of 1962 strengthened the new drug approval process by requiring that drugs be proven safe and effective.
• The Orphan Drug Act of 1983 qualified drugs for rare diseases or conditions affecting fewer than 200,000 Americans.
• The Drug Price Competition and Patent Term Restoration Act of 1984 (Waxman-Hatch Amendment) allowed companies to submit an ANDA for approval of generic products and established patent-term extensions or market exclusivity for 2-5 years, depending on the regulatory review of the drug.

FDA Modernization Act of 1997

• The FDAMA created provisions for pharmacy compounding, expediting study and approval of fast-track drugs, elimination of certain labeling requirements, dissemination of off-label treatment information, and encouragement of pediatric studies.
• The act eliminated the " Rx only" label, replacing it with "Caution: Federal law prohibits dispensing without a prescription."