Bioresearch Monitoring General Information
The objectives of the bioresearch monitoring program are twofold: (I) to ensure the quality and integrity of data and information submitted in support of investigational and marketing clearance applications or submissions [IDEs, PMAs, and 510(k)s]; and (ii) to ensure that human subjects taking part in investigations are protected from undue hazard or risk. The Division is also charged with the implementation of the FDA's Application Integrity Policy (AIP) for medical devices and radiological health products.
The program objectives are achieved by several means which are discussed in the program functions and inspection program sections below.
The Division of Bioresearch Monitoring's (DBM) operations are directed toward several program areas. These include (1) audits of clinical data contained in PMA and some 510(k) submissions, ordinarily prior to approval; (2) audits of IDE sponsor submissions; (3) inspections of nonclinical laboratories that perform medical device-related safety testing; (4) inspections of Institutional Review Boards that monitor investigational device studies; (5) enforcement of the prohibition against commercialization of investigational devices; (6) providing education, training and guidance to regulated industry and (7) implementation of the FDA's Application Integrity Policy (AIP). Descriptions of some of these activities are summarized below:
The regulations enforced by the bioresearch monitoring program for medical devices are found in four sections of the CFR:
A directed inspection is requested when some specific problem has been identified within one or all entities of the program. The problem may be observed during the review of sponsor submissions related to ongoing IDE investigations or following evaluation of clinical data submitted in a PMA or 510(k) application. Verbal or written complaints from patients, physicians, or competitors may also result in a directed inspection. Inspections issued for PMA data audits also fall into this category.
Deviations revealed during inspections are presented in writing and discussed with the responsible individual at the close of the inspection. Once an inspection has been completed, an establishment inspection report (EIR) is prepared and submitted by the district office. This report is then reviewed and classified by the Division of Bioresearch Monitoring.
Classifications assigned to inspections indicate whether or not the establishment is operating in compliance with the regulations. The classification scheme used by FDA is as follows:
Depending upon the assigned classification, the Division may issue an untitled letter or warning letter based upon the severity of the deviations. These letters are intended to communicate the FDA's position on a matter, but do not commit the FDA to take further enforcement action. They are issued for the purpose of achieving voluntary compliance with the expectation that a majority of firms and individuals will comply with the regulations and implement corrective actions to prevent recurrence of the deviations.
When deviations are flagrant or significantly impact the quality and/or integrity of the research data, various actions have been used by the Division to achieve compliance in the bioresearch monitoring program area. Data audits have resulted in the Division's recommendation to invoke the Application Integrity Policy against the sponsor or reject clinical research data used to support a PMA. Data audits for 510(k)s that disclosed improprieties have led the sponsor to withdraw submissions. Monitoring efforts of IDE studies have led to the Division's recommendation for withdrawal of IDEs. Inspections of violative IRBs have resulted in administrative sanctions that suspend the institution's authority to approve new studies and/or add new subjects to existing studies.