Inspections, Compliance, Enforcement, and Criminal Investigations
Auburn University 16-Aug-04
Department of Health and Human Services
Rockville, MD 20857
August 16, 2004
Certified Mail - Restricted Delivery
Return Receipt -Requested
Edward Richardson, EdD
202 Samford Hall
Auburn University, Alabama 36649
Dear Dr. Richardson:
An inspection of Auburn University was conducted between April 7-16, 2004 by Ms. Patricia S. Smith and Ms. Carmen M. Chan from the Food and Drug Administration (FDA), New Orleans District Office. The inspection was conducted to evaluate the performance of the University as a sponsor of Investigational New Animal Drugs (INADs) and focused on [redacted]. The final study report for INADC [redacted] was requested from [redacted] the University's representative. The report indicated a lack of current monitoring and included documents with missing and unexplained data. FDA records indicate that Auburn University is the sponsor [redacted] INADs.
We have reviewed the inspection report along with the documents collected during the inspection, and the observations listed in the Form FDA 483 which was presented to and discussed with Dr. C. Michael Moriarty, Associate Provost and Vice President for Research, at the conclusion of the inspection.
Based on our evaluation of the information provided in the documents, we conclude that the drug [redacted] sponsored by the University is unsafe under section 512 of the Federal Food, Drug, and Cosmetic Act (the Act) and adulterated under section 501 (a)(5) because the University did not operate in accordance with the regulations promulgated pursuant to section 512(j) of the Act.
The violations include, but are not limited to:
1. The University did not assure that the new animal drug is shipped only to investigators who: 1) are qualified by scientific training and/experience to evaluate the safety and/or effectiveness of the new animal drug; 2) maintain complete records of the investigations, including complete records of the receipt and disposition, of each shipment or delivery of the new animal drug under investigation; and 3) furnish adequate and timely reports of the investigation to the sponsor. [Title 21, Code of Federal Regulations (21 CFR), sections 511.1(b)(7)(i), (ii), and (iii).]
For example, with regard to INADC [redacted] some sites failed to maintain raw data/source documents and failed to submit adequate and timely reports required by the protocol. During the preparation of the final study report in the fall of 2003, a request was made September 9, 2003 by the INAD Coordinator, [redacted] to the investigators to submit forms to "represent activities conducted in 2002 or 2003 as well as [redacted] samples from that period"; The request further stated that the Coordinator had not recently received information from several investigators and that several investigators did not respond to his April 2003 request. Sites/investigators then submitted reports that were signed/dated in 2003; yet the reports/entries appeared to have been generated retrospectively (rather than as observations were made) with data going back to 1997.
2. As sponsor of INAD [redacted] you failed to provide current monitoring. The sponsor is required to provide current monitoring of studies. [21 CFR 511.1 (b)(8)(ii)]. Since the start of the study in 1996 at least [redacted] of the [redacted] investigator sites were never visited, according to Monitor Reports and the final study report. The remaining [redacted] sites were visited once. [redacted] of the [redacted] were visited in 1996 or 1997. One site [redacted] was visited in March 2004--the only monitoring visit conducted since 1997.
The inspection of [redacted], conducted on [redacted] revealed various observations including a lack of current monitoring by the University. [redacted] the coinvestigator and facility manager of [redacted] indicated that the sponsor's representative made telephone contacts with the site. [redacted] had a telephone log to show these contacts, however, [redacted] did not have a log.
3. As a sponsor you are required to submit in triplicate to the Food and Drug Administration a "Notice of Claimed Investigational Exemption for a New Animal Drug"; (NCIE) prior to shipment of the new animal drug for clinical tests in animals [21 CFR 511.1(b)(4)]. The University was allowed to use a Notice of Drug Shipment (NODS) for INAD [redacted]
For INAD [redacted] no NCIE, or NODS, was observed to have been submitted to FDA for the shipment of the test article/feed containing the new animal drug from a [redacted] investigator site to [redacted] no NClEs were observed for shipments to [redacted] and [redacted] These sites were not associated with INAD [redacted] and CVM was not notified of these shipments.
The study drug, [redacted] is a Drug Enforcement Agency (DEA) controlled substance. This is another reason why the product must only be shipped to clinical investigators/sites identified with INAD.
In addition, the University was not aware that it is listed as the sponsor for INADs issued by CVM. 21 CFR Part 511 contains the requirements for the use of a new animal drug for investigational use under an exemption (INAD). The sponsor of the INAD is responsible for adhering to the regulations in 21 CFR Part 511. A copy of this section is enclosed and can also be found on-line at http://frwebgate3.access.gpo.gov/cgi-bin/waisgate.cgi?WAISdocID=65862813198+1+0+0&WAISaction=retrieve.
[redacted] was issued a letter from FDA's Center for Veterinary Medicine (CVM) dated June 28, 2004 [redacted] letter stating that the technical sections for animal safety and effectiveness of INAD [redacted] remain incomplete. This decision was based on a review of the final study report submitted by [redacted] and the report of the inspection covered by this letter. The numerous data integrity problems listed in the [redacted] letter were of such concern that the data cannot be used to determine safety or efficacy. A copy of the[redacted] letter is enclosed.
This letter serves to remind you that FDA expects that any study under an INAD must meet requirements for current sponsor monitoring and that the studies must be adequate and well-controlled. One or more adequate and well-controlled studies are required to establish, by substantial evidence, that a new animal drug is effective. It is imperative that all safety regulations be followed scrupulously to help assure the highest level of confidence possible in the conduct of this type of research.
This letter is not intended to be an all-inclusive list of violations at the University. It is your responsibility to ensure adherence to each requirement of the Act and its regulations. The specific violations noted in this letter may be symptomatic of serious underlying problems. You are responsible for Investigating and determining the causes of the violations identified above and to prevent recurrence of similar violations for any INAD sponsored by the University.
You should take prompt action to correct these violations. Failure to promptly correct these violations may result in regulatory action without further notice. Such actions include seizure and/or injunction. Federal agencies are advised of the issuance of all Warning Letters regarding drugs so that they may take this information into account when considering the award of contracts.
We request that you respond in writing within fifteen (15) working days of receiving this letter and describe the corrective actions you have implemented or are planning to implement to prevent a recurrence of the violations noted above. Please direct your written response and any pertinent documentation to:
Vernon D. Toelle, Ph.D., Team Leader
BIMO and Administrative Actions Team (HFV-234)
Division of Compliance
Office of Surveillance and Compliance
Center for Veterinary Medicine
7500 Standish Place, Suite E469
Rockville, MD 20855-2773
If you have any questions, please feel free to contact either Dr. Vernon D. Toelle at 301-827-0312 or Mr. George A. Prager at 301-827-7791.
Gloria J. Dunnavan
Division of Compliance (HFV-230)
Office of Surveillance and Compliance
Center for Veterinary Medicine