The Food and Drug Administration FDA

The FDA must be assured that the rights and welfare of human subjects are adequately protected through compliance with applicable trial regulations. The results of studies on investigational new drugs will determine whether a drug will be approved by the FDA. Unlawful conduct, such as bribery and false statements pertaining to principal investigators, affects the integrity of the drug approval process.

Since 1977, clinical investigators, sponsors (that is, pharmaceutical companies), and Institutional Review Boards have been subject to inspection by the FDA Bioresearch Monitoring Program. All FDA product areas - drugs, biologics, medical devices, radiological products, foods, and veterinary drugs - are involved in the Bioresearch Monitoring Program. While program procedures differ slightly depending upon product type, all inspections have as their objective ensuring the quality and integrity of data and information submitted to the FDA as well as the protection of human research subjects. The objectives of these FDA audit procedures are to:

1 protect the rights and welfare of research subjects;

2 assure adherence to the regulations; and

3 determine the integrity of scientific testing and the reliability of the data in support of pending product approval by the FDA.

In 1999, the FDA financial disclosure regulations (21 CFR Part 54) were promulgated and became part of the expanded FDA inspectional procedures. The purpose of these regulations is to ensure that financial interests and arrangements of clinical investigators (that could affect the reliability of data) are identified and disclosed by the sponsor of the product. This information is obtained from the investigator before an investigator is allowed to participate. The penalty for not certifying and/or disclosing the financial information might result in the FDA refusing to file the market application (NDA).

Since the Investigational New Drug Regulations went into effect in 1963, the FDA has conducted over 6000 clinical investigator and 2000 institutional review board audits. Currently, the FDA is conducting over 400 inspections in the US (Figure 7.4) and 70 inspections outside of the country per year (Figure 7.5).To date, clinical data from 42 different countries have

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o o 150 100

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Figure 7.4 FDA inspections of US investigators, 1992-99. 70 60

Figure 7.4 FDA inspections of US investigators, 1992-99. 70 60

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1992 1993 1994 1995 1996 1997 1998 1999


Figure 7.5 FDA inspections of non-US investigators, 1992-99.







1997 Year



Figure 7.6 FDA inspections of Institutional Review Boards, 1995-99.

been inspected by the FDA. During the period of 1980-99, 380 non-USA inspections have been assigned in the following global regions: Western hemisphere (104), Europe-Japan-Australia-New Zealand (203), and former Eastern Bloc Countries (17). Non-USA studies may be audited by the FDA, if two USA adequate and well-controlled studies do not exist and international studies provide basis for drug approval. The FDA accepts as a sole basis non-USA studies for drug approval if:

1 the data are applicable to US population;

2 the studies have been performed by investigators of recognised competence; and

3 the studies are audited by the FDA or may be evaluated through appropriate means.

About 250-300 Institutional Review Boards (IRB) from an inventory of 1600 IRBs are inspected annually (Figure 7.6). The IRB inspections are performed to determine the current state of compliance to informed consent (21 Code of Federal Regulations [CFR] Part 50) and institutional review board (21 CFR Part 56) regulations and applicable ICH Good Clinical Practices.

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