Inspections, Compliance, Enforcement, and Criminal Investigations
PART I - BACKGROUND
Since the Investigational New Drug (IND) Regulations went into effect in 1963, the Food and Drug Administration (FDA) has exercised oversight of the conduct of clinical studies involving FDA-regulated products. The BIMO Program was established in 1977 by a task force that included representatives from the drug, biologic, device, animal drug, and food areas.
Compliance programs (CP) were developed to provide uniform guidance and specific instructions for inspections of Clinical Investigators (CP 7348.811), Sponsors (CP 7348.810), In-Vivo Bioequivalence facilities (CP 7348.001), Institutional Review Boards (CP 7348.809), and Nonclinical Laboratories (CP 7348.808).
Regulations addressing requirements of clinical investigators, sponsors and monitors of human drugs and biologics studies (21 CFR Parts 312 and 314) were published on March 19, 1987, and became effective on June 17, 1987. The animal drug regulations (21 CFR Parts 511 and 514) were published on May 27, 1975. Regulations for clinical investigations of devices (21 CFR Part 812) were published on January 18, 1980, and for premarket approval of medical devices (21 CFR Part 814) on July 22, 1986.
These regulations establish specific responsibilities of sponsors for ensuring (1) the proper conduct of clinical studies for submission to FDA and (2) the protection of the rights and welfare of subjects involved in clinical studies. The specific responsibilities of sponsors of clinical studies include obligations to:
1) Obtain agency approval, where necessary, before studies begin.
2) Manufacture and label investigational products appropriately.
3) Initiate, withhold, or discontinue clinical trials as required.
4) Refrain from commercialization of investigational products.
5) Control the distribution and return of investigational products.
6) Select qualified investigators to conduct studies.
7) Disseminate appropriate information to investigators.
8) Select qualified persons to monitor the conduct of studies.
9) Adequately monitor clinical investigations.
10) Evaluate and report adverse experiences.
11) Maintain adequate records of studies.
12) Submit progress reports and the final results of studies.
Sponsors may transfer responsibility for any or all of these obligations to Contract Research Organizations (CROs). [Note: The medical device regulations (21 CFR Part 812) do not define or delineate responsibilities for CROs. Device study sponsors are therefore held responsible for any regulatory noncompliance by a CRO.] Under the regulations such transfers of responsibility are permitted by written agreement. Responsibilities that are not specified in a written agreement are not considered to be transferred. When operating under written agreements, the CROs are subject to the same regulatory actions as sponsors for any failure to perform any of the obligations assumed.
Monitors are employed by sponsors or CROs to oversee the progress of an investigation.
A sponsor-investigator is an individual who both initiates and conducts an investigation, and under whose immediate direction the investigational article is administered, dispensed or implanted. The requirements applicable to a sponsor-investigator include both those applicable to an investigator and a sponsor. See CP 7348.811 for Clinical Investigators and Sponsor-Investigators.