Warning letters.

The following are recent FDA warning letters to clinical investigators, IRBs, sponsor/monitors, CROs and testing labs issued in October 2006. Each letter is $7 plus retrieval. Please order by RECORD-RETRIEVE Number (e.g., 12338W, 12399W, etc.). Copies of responses to the letter, along with any 483s and EIRs, are available from RECORD-RETRIEVE: [phone], or [e-mail].

FDA investigated Wolf's clinical site from April 19 through May 22 to determine whether activities and procedures related to his participation in an investigator-initiated study complied with applicable federal regulations.

Violations included failure to ensure that informed consent was obtained in accordance with the current, IRB-approved version of the informed consent form.

For example, FDA said the original signed informed consent forms for all subjects associated with the study were missing because they had been destroyed by the study coordinator or were considered to be lost. Wolf told the FDA investigator that the subjects were being "re-consented," but the agency found no indication of any such action.

Furthermore, according to an internal audit report dated Feb. 21, 17 of the first subjects enrolled in the study signed an unapproved informed consent form prior to IRB approval.

Additionally, Wolf failed to perform the 30-day visit to assess coagulation status for subjects on anti-coagulants; failed to assess pre-operative supine, sitting and standing blood pressures and heart rates as required by the protocol in order to detect postural hypotension; and, failed to conduct laboratory assessments--white blood cell, hematocrit, hemoglobin and platelet counts--prior to hospital discharge as required by the protocol.

He also failed, within the required 48 hours, to conduct transesophageal echocardiograms to determine whether clots were present in the subjects' left atriums and to evaluate the size of the left atriums.

FDA also noted that Wolf signed two royalty agreements that were in direct conflict with two conflict of interest statements he had signed in 2005.

Finally, Wolf was cited for failure to adequately supervise the conduct of the study. He admitted to FDA investigators that he did not review the CRFs and did not have access to the electronic CRF database.

Moreover, at the close of the FDA inspection, Wolf read a statement to the FDA investigators and provided a signed copy of the statement in which he stated: "I am not, nor ever have been involved with any data collection or entry in any study. If my life depended on it, I could not access data. I do not know how. I do not know which patients are enrolled in the current FDA study." Doc. 13977W

IVF Michigan P.C., Rochester Hills, MI, Sept. 21 (Detroit).

During a June 20-July 10 FDA investigation, serious deviations from the regulations for human cells, tissues, and cellular and tissue-based products were documented.

Violations included, but were not limited to, failure to test specimens from anonymous donors of cells or tissues for evidence of infection due to relevant communicable disease agents by testing for the antibody to HIV, types 1 and/or 2 and/or the antibody to hepatitis C virus, although the donors were determined to be eligible.

IVF also was hit with failure to test specimens from anonymous donors of cells or tissues for evidence of infection due to Chlamydia trachomatis and Neisseria gonorrhea, although the donors were determined to be eligible.

In sum, FDA said IVF had failed to establish procedures for all steps that it performed in testing, screening, determining donor eligibility and complying with all other requirements of 21 CFR Part 1271, Subpart C--"Donor Eligibility"; failed to follow written procedures for completion of the "Screening-Gamete Provider" forms, "Clinical Evidence of Disease-Gamete Provider" forms and the "Summary of FDA Required Communicable Disease Screening/Testing forms"--all of which were missing required signatures, eligibility determinations and dates for donors. Doc. 13978W

Randall Wolf, M.D., University of Cincinnati Medical Center, Cincinnati, Sept. 28 (CDRH).