March 22, 2003
Kent D. McClure, DVM, JD
Animal Health Institute
1325 G Street, NW, Suite 700
Washington, D.C. 20005-3104
Dear Dr. McClure:
This responds to the Animal Health Institute's Request for Correction of Information dated January 22, 2003, which FDA received on January 23, 2003. Your request concerns the Center for Veterinary Medicine's (CVM's) Campylobacter risk assessment. As explained below, a decision on your request will be made within 60 days of the final decision in the hearing on the proposal to withdraw approval of the new animal drug application (NADA) 140-828 for enrofloxacin (Baytril 3.23% Concentrate Antimicrobial Solution).
Background Regarding the Risk Assessment
In the Federal Register of October 31, 2000 (65 FR 64954), CVM issued a notice of opportunity for a hearing (NOOH) proposing to withdraw approval of NADA 140-828 for enrofloxacin (Baytril 3.23% Concentrate Antimicrobial Solution). Bayer Corp., the sponsor of the NADA, responded by filing a request for a hearing on November 29, 2000. Upon review of Bayer Corp.'s response to the NOOH, the FDA Acting Principal Deputy Commissioner concluded that a hearing was appropriate with respect to CVM's proposal and published a notice of hearing (NOH) in the Federal Register of February 20, 2002 (67 FR 7700).
CVM's proposal to withdraw approval of this NADA is based on its conclusion that the use of fluoroquinolones in poultry is a significant cause of fluoroquinolone-resistant Campylobacter on poultry carcasses and, therefore, a significant cause of fluoroquinolone-resistantCampylobacter infections in humans. This conclusion is based on data from surveillance programs, published literature, and other sources. It is supported by data establishing a temporal association between approval of fluoroquinolones for use in poultry and an increase in fluoroquinolone-resistant Campylobacter infections in humans; by a comparison of fluoroquinolone use in poultry with other possible causes of fluoroquinolone-resistant human infections; and by a risk assessment that determined that in 1999 a mean estimate of 9,261 persons infected with campylobacteriosis and prescribed a fluoroquinolone in the United States would have had a fluoroquinolone-resistant illness due to the use of fluoroquinolones in chickens.
This risk assessment, the Risk Assessment on the Human Health Impact of Fluoroquinolone Resistant Campylobacter Associated with the Consumption of Chicken, was first issued October 18, 2000, and last revised January 5, 2001. CVM developed the risk assessment to assist in establishing the extent of the adverse human health impact of fluoroquinolone use in poultry. Its purpose is to estimate the extent of the risk to human health from resistant Campylobacter pathogens attributed to the use of fluoroquinolones in chickens in the United States. While CVM was developing the risk assessment, it held a two-day public workshop in December 1999, in which it invited experts and others to discuss a first draft of the risk assessment. Following the public workshop, there was an open comment period during which comments could be submitted to Docket 98D-0969. As part of the NOOH, CVM referenced the risk assessment. During the public comment period on the NOOH, CVM received extensive feedback on the risk assessment. In addition, CVM held a public meeting in January 2001. Although the focus of this meeting was the establishment of regulatory thresholds on antimicrobial resistance, CVM received additional public comments about the risk assessment.
The hearing on CVM's proposal to withdraw approval of NADA 140-828 is currently in progress, and is being conducted in accordance with FDA's regulations at 21 CFR Part 12. The hearing is based on all the scientific information listed in the second paragraph of this section. Each piece of information, fluoroquinolone use in poultry, presence of fluoroquinolone-resistant Campylobacter in chickens, human consumption of chicken contaminated with fluoroquinolone-resistant Campylobacter, humans becoming ill with campylobacteriosis caused byCampylobacter that are fluoroquinolone resistant, seeking care and being treated with a fluoroquinolone, is part of the overall evidence that leads to questions about the safety of fluoroquinolone use in poultry. The risk assessment is a process by which one can assimilate this and other information to estimate the number of persons who are put in harm's way because of the use of fluoroquinolones in poultry. The parties to the hearing have disclosed required data and information and submitted their sworn testimony to the hearing record. Cross examination is scheduled to begin April 28, 2003 and briefs will be scheduled and filed after the testimony is all on the record. Judge Daniel J. Davidson will issue a decision as soon as possible after the filing of briefs and oral argument. This initial decision is subject to review by the Commissioner of Food and Drugs, either upon request of any party to the hearing or upon the Commissioner's own initiative. The Commissioner is to issue a final decision as soon as possible after the filing of briefs and any oral argument. If there is no appeal from or review of the initial decision, it becomes the agency's final decision by operation of law.
Your Request for Correction
Your request for correction was made pursuant to Section 515 of the Treasury and General Government Appropriations Act for Fiscal Year 2001 (Public Law 106-554). It asserts that the risk assessment does not meet the applicable OMB, HHS, and FDA guidelines, because it constitutes influential information, as defined by the FDA Guidance, but does not:
- adhere to the National Academy of Sciences paradigm for conducting quantitative risk assessments;
- use the best available science;
- use data collected by accepted methods;
- ensure that the presentation of information is comprehensive; or
- identify alleged additional studies the agency did not use that support or fail to support the findings of the assessment or explain why they were not used.
You request that the risk assessment be corrected by conducting additional review, and you recommend several specific procedural measures for this additional review.
Almost all of the support for your assertions is contained in other documents submitted as part of other processes. These were submitted by AHI or others to the record for the hearing on CVM's proposal to withdrawal approval of NADA 140-828 or were submitted by AHI in support of its Request for Correction of Information Made to the Centers for Disease Control and Prevention (see pages 7, 13, 14, 15, and 16 of your request). The two exceptions are the short discussions asserting that the risk assessment does not use recent data, does not specify each population addressed by the estimates of applicable effects, and does not specify the methodology used to reconcile certain alleged inconsistencies in the data (see pages 14 and 16 of your request). You state that the same assertions made in your request for correction have been previously raised with CVM on numerous occasions by various parties (see pages 1, 9, and 14 of your request).
You explicitly note that the request is being filed with FDA's Office of the Ombudsman rather than CVM. You ask that if the Ombudsman concludes that FDA should not or cannot review your request, whether because of the pendency of the administrative hearing or for some other reason, that either the Office of the Secretary of HHS or OMB consider the request.
FDA's Process for Responding to Requests for Correction
Section 515 of Public Law 106-554 required the Director of the Office of Management and Budget (OMB) to issue guidelines providing policy and procedural guidance to federal agencies regarding the information they disseminate. OMB's guidelines require each federal agency to, among other things, establish administrative mechanisms allowing affected persons to seek and obtain correction of information maintained and disseminated by the agency that does not comply with the OMB guidelines. OMB published its guidelines in the Federal Register on February 22, 2002 (67 FR 8452). The Department of Health and Human Services (HHS) and FDA published their guidance, pursuant to the OMB guidelines, on October 1, 2002, and these are available at www.hhs.gov/infoquality. These are, respectively, the HHSGuidelines for Ensuring and Maximizing the Quality, Objectivity, Utility, and Integrity of Information Disseminated to the Public and FDAGuidance on Ensuring the Quality of Information Disseminated to the Public.
Under the HHS Guidelines, requests for correction of information quality pursuant to Section 515 are to be directed to the relevant agency. The FDA Guidance describes the agency's procedures for processing requests for correction, also known as complaints. It states that the agency intends to address requests for correction using its existing complaint mechanisms, such as the general review mechanism of 21 CFR 10.75 or the agency's more specific procedures for dispute resolution during application review. Once FDA receives a request for correction, it will respond within 60 days. The response will either be a decision or a letter informing the requester that more time is required for a decision, explain why, and provide an estimated decision date. If, however, there is an existing public comment procedure that allows affected persons to raise information quality issues, FDA will use that procedure rather than the procedure described in the guidelines.
Why the CVM Director Is Issuing this Response
You filed your complaint with FDA's Office of the Ombudsman. That office has forwarded your request to CVM for a response. CVM has determined that the appropriate, existing mechanism for addressing your request is the procedure contained in 21 CFR 10.75. This provision allows an interested outside party to seek internal agency review of a staff decision. Since, as Center Director, I initially approved and disseminated the risk assessment at issue, I am responding to your request for correction and will reevaluate that decision based on the information submitted as part of your request as well as other information in the administrative file.
This approach is consistent with the OMB, HHS, and FDA guidelines. As discussed in the preamble to the OMB guidelines:
Recognizing that many agencies already have a process in place to respond to public concerns, it is not necessarily OMB's intent to require these agencies to establish a new or different process. Rather, our intent is to ensure that agency guidelines specify an objective administrative appeal process that, upon further complaint by the affected person, reviews an agency's decision.
67 FR 8458. As provided for by 21 CFR 10.75, the official reviewing any administrative appeal would be different from the official with responsibility for handling the initial request for correction.
Why a Decision on Your Request for Correction Will Not Be Made Within 60 Days
I will take more than 60 days to issue a decision on your request for correction because I will make that decision after the hearing described above is concluded. Therefore, a decision on your request for correction will be made within 60 days of the final decision in the hearing. This time frame is appropriate for several reasons.
First, the hearing was pending at the time AHI submitted its request for correction and the hearing should proceed first to its conclusion. This is consistent with OMB's statement that the correction process should serve to address the genuine and valid needs of outside parties without disrupting agency processes. 67 FR at 8458. This should be particularly true for processes, such as formal evidentiary hearings, that have their own adequate safeguards for ensuring the quality of the decision. Acting on your request for correction while the hearing is in progress could interfere with Judge Davidson's adjudication of the issues that overlap your request for correction.
Second, the Commissioner's decision in the hearing will be binding on the agency. Our sequence for issuing a decision on your request for correction will enable me to ensure that the decision is consistent with the Commissioner's decision at the hearing. Because most of the issues raised in your request for correction have also been raised in the hearing, that will address, inform, and, perhaps, partially or fully resolve those issues.
Third, processing your request for correction while the hearing is being conducted would be an inefficient use of resources. Data from the risk assessment informed CVM's proposal to withdraw approval of NADA 140-828, and the validity and reliability of the risk assessment have been raised as issues in the hearing. Indeed, almost all the support for your request for correction relies on testimony already introduced at the hearing regarding these issues. It is best to take advantage of this existing process, especially since some of the staff members who would be needed to assist with the review of your request for correction are also devoting much of their time to the proceedings of the hearing. Duplicating the processing of these issues in the hearing and in your request for correction, especially when they are so closely related, would go against CVM's duty to use its resources prudently.
Fourth, the fact that CVM will not issue a decision within 60 days will not prejudice AHI. As you note, AHI and others have already used multiple opportunities to raise the same issues for CVM's consideration. These opportunities occurred both while the agency was developing the risk assessment and after the agency disseminated it and the comments are all in the public record. The transcripts of the December 1999 meeting are at www.fda.gov/cvm/antimicrobial/oldmeet.htm, the comments on the risk assessment submitted after that meeting are in docket 98D-0969, the comments on the NOOH , including the risk assessment, are in docket 00N-1571, and the sworn written testimony submitted to the hearing is also in docket 00N-1571. As noted above, almost all the arguments and information you have presented are being actively considered by FDA in the context of the hearing or by CDC in the context of your request for correction submitted to that agency. Thus, the concerns you raise are being actively considered. As a further measure, CVM has added a notice to the risk assessment explaining that AHI has submitted a request for correction.
In sum, this approach will serve the purpose of the OMB, HHS, and FDA guidelines by affording an opportunity for correction of any material that does not comply with the guidelines, without interfering with the orderly progress of FDA's legal obligations or duplicating efforts.
If the circumstances change, for example, if the risk assessment becomes irrelevant to the hearing, the hearing is terminated for some reason before a final decision is issued, or if there is a request for reconsideration of the final decision in the hearing pursuant to 21 CFR 12.139, I will revisit the question of when to respond to your request for correction and notify you of any changes to the above-described time frame.
If you have any questions, please contact Dr. Linda Tollefson at 301-827-2953. You can also direct any questions to the CVM or FDA Ombudsman Offices at 301-827-4535 or 301 827-3390.
Stephen F. Sundlof, DVM, Ph.D.
Center for Veterinary Medicine
Last Revised: April, 2004