Number of FDA BIMO Citations Continued to Drop in FY 2018

J.W. Schomisch
September 30, 2019 at 12:27 PM EST
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The FDA issued 216 inspection observations (483s) after bioresearch monitoring inspections in fiscal year (FY) 2018, which was 27 fewer than were issued in FY 2017 (243) and 55 fewer than were issued in FY 2016 (271). There were 283 483s issued in FY 2015, 297 in FY 2014 and 273 in FY 2013.

The FY 2018 bioresearch monitoring (BIMO) 483s contained 397 citations, which was nearly 100 fewer than the 492 citations in FY 2017 but nearly the same as the 392 citations in FY 2016.

By far the most cited regulation in BIMO 483s for FY 2018 was the same as in previous years – 21 C.F.R. §312.60 because the study was not conducted in accordance with the signed statement of the investigator (Form FDA 1572) or the investigational plan. The regulation was cited 118 times in FY 2018, which was 22 times fewer than the 140 times in FY 2017. 21 C.F.R. §312.60 was cited 120 times in FY 2016, 171 times in FY 2015, 164 times in FY 2014 and 129 times in FY 2013 BIMO 483s.

The next most frequently cited (69 times) was 21 C.F.R. §312.62(b) for failure to prepare or maintain adequate or accurate case histories with respect to observations and data pertinent to the investigation or informed consent. 21 C.F.R. §312.62(b) was cited 76 times in FY 2017, 70 times in FY 2016, 92 times in FY 2015, 99 times in FY 2014 and 85 times in FY 2013.

Rounding out the top five were: 21 C.F.R. §115(a)(2) – institutional review board meeting minute problems – 24 citations in FY 2018 (nine times in FY 2017, 20 times in FY 2016, 29 times in FY 2015, 19 times in FY 2014 and 30 times in FY 2013); 21 C.F.R. §312.62(a) – accountability records – 13 citations in FY 2018 (18 times in FY 2017, 26 times in FY 2016, 24 times in FY 2015 and FY 2013 and 38 in FY 2014); and 21 C.F.R. §50.27(a) – consent form not approved/signed/dated – 10 times in FY 2018 (16 times in FY 2017, 12 times in FY 2016 and 15 times in FY 2015).

Concerns with nine citations in FY 2018 were:

  • 21 C.F.R. §56.115(a)(5) for list of IRB members — A list of IRB members was not prepared or maintained, identifying members by name, earned degrees, representative capacity, indications of experience sufficient to describe each member’s chief anticipated contribution to IRB deliberations, or any employment or other relationship between each member and the institution (nine citations in FY 2017, 11 citations in FY 2016 and 14 citations in FY 2015).
  • 21 C.F.R. §312.50 — Failure to select qualified investigators, provide investigators with the information needed to conduct the study properly, ensure proper monitoring of the study, ensure the study is conducted in accordance with the protocol and/or investigational plan, or ensure that FDA and all investigators are promptly informed of significant new adverse effects or risks. (11 citations in FY 2017 and 2016 and 14 citations in FY 2015).

There were seven citations for IRBs either not having or failing to follow written procedures for the conduct of initial or continuing review (21 C.F.R. §56.108(a)(1)). There were eight such citations in FY 2017, one citation in FY 2016 and 13 citations in 2015. In addition, there were six citations in FY 2018 for IRBs not reviewing proposed research at a convened meeting at which a majority of IRB members were present (21 C.F.R. §56.108(c)). There were eight such citations in FY 2017.

Concerns with five citations were:

  • 21 C.F.R. §56.107(e) for conflict of interest – the IRB allowed a member to participate in the IRB’s review of a project in which the member had a conflicting interest (five citations in FY 2017 and two citations in FY 2016).
  • 21 C.F.R. §312.66 for initial and continuing review – failure to assure that an IRB [complying with applicable regulatory requirements] was responsible for the initial and continuing review and approval of a clinical study (seven citations in FY 2017, six citations in FY 2016 and four citations in FY 2015).

Concerns with four citations were:

  • 21 C.F.R. §312.60 for informed consent – failure to obtain informed consent in accordance with 21 C.F.R. Part 50 from each human subject prior to drug administration or conducting study-related tests (10 citations in FY 2017, six citations in FY 2016 and 14 citations in FY 2015).
  • 21 C.F.R. §50.20 for consent not obtained, or exceptions to informed consent do not apply – legally effective informed consent was not obtained from a subject or the subject’s legally authorized representative, and the situation did not meet the criteria in 21 C.F.R. §50.23-24 for exception (one citation in both FY 2016 and 2017).
  • 21 C.F.R. §56.115(a)(6) for written procedures – documentation was not prepared or maintained for IRB written procedures, as required by 21 C.F.R. §56.108(a) and (b) (two citations in FY 2017 and one in FY 2016).
  • 21 C.F.R. §312.64(b) for safety reports –failure to promptly report to the sponsor adverse effects that may reasonably be regarded as caused by, or probably caused by, an investigational drug (seven citations in FY 2017, eight citations in FY 2016 and 13 in FY 2015).
  • 21 C.F.R. §58.63(a) for equipment calibration – not all equipment used for the generation, measurement, or assessment of data was adequately tested, calibrated and/or standardized (one citation in both FY 2016 and 2017).
  • 21 C.F.R. §58.35(a) for quality assurance unit (QAU) monitoring – the QAU did not monitor each study to assure management that the facilities, equipment, personnel, methods, practices, records, and controls were in conformance with FDA good laboratory practice regulations (one citation in FY 2017).
  • 21 C.F.R. §58.35(b)(5) for deviations from protocols or standard operating procedures – the QAU failed to determine whether any deviations from approved protocols SOPs had been made with proper authorization and documentation (three citations in FY 2017 and one citation in FY 2016).

There were nine regulations that were cited three times in FY 2018 and 15 were cited twice. In FY 2017, six regulations were cited three times and 21 were cited twice. In FY 2016, seven regulations were cited three times and 13 were cited twice. In addition, 47 regulations were cited once in FY 2018. There were 54 regulations cited once in FY 2017 and 52 regulations cited only once in FY 2016.

Interestingly, 21 C.F.R. §50.25(a)(2), which is cited because the informed consent document lacked a description of reasonably foreseeable risks or discomforts to the subject, received two citations in FY 2018, the same as in FY 2016 after being cited nine times in FY 2017.

In addition, 21 C.F.R. §56.108(a)(1), which is cited for IRB failure to comply with applicable regulatory requirements to conduct initial and continuing review and approval of a clinical study, was cited only once in FY 2018, after being cited eight times in FY 2017, 12 times in FY 2016, 22 times in FY 2105, 19 times in FY 2014, and 23 times in FY 2013).

The full list of FY 2018 Inspectional Observation Summaries is available at https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-references/inspection-observations.

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