09/03/2014

A new FDA investigator warning letter was distributed and can be found at http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2014/ucm411894.htm.

These always include good learning lessons:

In this case the requirements of 21 CFR 312.62(c) related to record retention were not followed.
- The letter includes a good Reminder of the Investigator Record Retention Requirements: You are required to retain these records for a period of two years following the date a marketing application is approved for the drug for the indication for which it is being investigated; or, if no application is to be filed or the application is not approved for such indication, until two years after the investigation is discontinued and FDA is notified. You failed to adhere to these requirements.

The agency looked across multiple protocols; at least two were linked to recently filed Sponsor NDAs with the FDA!
- Specifically, for Protocols (b)(4) and (b)(4): You failed to retain records of the disposition of the drug, including dates, quantity, and use by subjects. You failed to retain adequate and accurate case histories, including signed and dated informed consent forms, case report forms, and all supporting data.
- You were required to retain the study records for both protocols because a New Drug Application (NDA) had been filed for the indication under study, and the application had not yet been decided on (that is, approved or not approved) before you discarded the study records.
- During the inspection, you stated that all original study records related to Protocols (b)(4) and (b)(4) were shredded on January 24, 2014. You stated that your study coordinator “mistakenly included the study files for (b)(4) and (b)(4), along with business documents intended for shredding, and provided them to a mobile shredding company ….”
- In addition, you indicated that (b)(4) notified you on February 11, 2014, that the company had filed an NDA with the FDA and had included the data from Protocol (b)(4) in this submission.

Obviously, the corrective actions were not adequate and are discussed in the letter.
- The letter further discloses: You further stated that you and your staff were “well aware of regulatory record retention requirements having been involved in clinical research since 2001.”
- During the inspection, you stated: “[A]ll study related records and source data pertaining to protocol (b)(4) at our site were shredded . . ." This data is not retrievable and was not available for inspection.
- Due to the destroyed study records, [the FDA investigator] was not able to verify the study data for protocol (b)(4), or the existence of signed informed consent forms during the inspection.
- During the inspection, your study coordinator provided a copy of a Standard Operating Procedure (SOP), signed by you and with an effective date of October 30, 2008, for study-record retention. [The agency found the SOP to be insufficiently detailed to prevent similar violations in future studies] Your SOP for study-record retention does not address how you will ensure that boxes of study records that are appropriately labeled will not be shredded erroneously in the future.
- Failure to retain study records as required by FDA regulations compromises the validity and integrity of data significantly. Because you failed to retain drug accountability records and case histories for both studies, we consider the data generated at your site for Protocols (b)(4) and (b)(4) unreliable in support of a research or marketing application.
- You should address these deficiencies and establish procedures to ensure that any ongoing or future studies will be in compliance with FDA regulations.

Lessons Learned and Questions post read:
- Investigators / Research Institutions:
  - Why wait until an inspection to have procedures for conducting clinical trials?
  - Ensure you have procedures that include preventive measures.
  - Ensure corresctive actions include the elements of an adequate plan: ID noncompliance, root cause / investigate, act, preventive actions, evaluate effectiveness and improvement.
- Sponsors: This impacts the applications to the agency. Could this have been prevented?

What are your thoughts?