Presentation Transcript

1. FDA Overview of Antibiotic Regulatory Activities

   Craig A. Lewis, DVM, MPH, DACVPM Center for Veterinary Medicine (CVM) U.S. Food and Drug Administration (FDA) Presented to NIAA 2014 Annual Conference Antibiotics Council April 1, 2014
2. Topics Background FDA’s ongoing strategy Guidance for industry (GFI) #209 Draft guidance for industry (GFI) #213 Veterinary Feed Directives Next Steps Finalizing VFD Rule Monitoring Progress
3. Antimicrobial Resistance – In Perspective Complex, multi-factorial issue Acquired vs. naturally occurring Use as a driver of resistance All uses (human, animal, horticultural, other) are part of the picture Gaps in our understanding of the issue remain – the science continues to evolve. But, these complexities and uncertainties do not mean that steps can’t be identified to mitigate risk.
4. Antibiotic Use in Animal Agriculture Has been the subject of scientific and policy debate for decades. Consumers, public health advocates, Congress, and others continue to be concerned about public health impacts. While debate continues, identify measures that address public health concern and that continue to assure animal health needs are met.
5. Remaining Concerns A process is in place, with implementation of GFI 152 in 2003, that now evaluates the safety of antimicrobial new animal drugs with regard to their microbiological effects on bacteria of human health concern. However, concerns remain about products that pre-date current assessment process. Focus of recent efforts is on taking steps to assure that existing antibiotics (including those that predate 2003 assessment process) are used as judiciously as possible.
6. Judicious Use of Antimicrobials Guidance 209 – ‘‘The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals’’ Published as draft in June 2010 Finalized April 2012 Describes overall policy direction
7. Judicious Use: Guidance 209 Focus is on initiating steps to assure that medically important antimicrobial drugs are used as judiciously as possible. Antimicrobials must continue to be available to combat disease in animals, including treatment, control, and prevention. Goal: preserve availability of effective drugs (for both humans and animals).
8. Judicious Use: Guidance 209 Two key principles outlined in Guidance 209: Limit use of medically important antimicrobial drugs to those uses considered necessary for assuring animal health (i.e., therapeutic purposes). Increase veterinary involvement/consultation.
9. Guidance 213: Overview Published December 2013 Provides more detailed guidance on implementation of key principles in Guidance 209 Definition of “medically important” Process for updating product labels Data required to obtain approval of new uses Proposed implementation timeline
10. Guidance 213: Medical Importance Proposed definition of medically important: those drugs currently listed in GFI #152, Appendix A regardless of their ranking GFI #152 provides guidance on evaluating the potential effects of antimicrobial new animal drugs on non-target bacteria as part of the new animal drug application process. Appendix A describes a process for ranking antimicrobial drugs with regard to their relative importance in human medicine.
11. Guidance 213: Affected Drugs Medically important antimicrobials Administered in feed/water Approved for production uses Available OTC
12. Guidance 213: Affected Drugs 7 Classes (with some examples): Aminoglycosides (streptomycin, spectinomycin) Lincosamides (lincomycin) Macrolides (tylosin, erythromycin) Penicillins(penicillin G procaine) Streptogramins(virginiamycin) Sulfonamides (sulfamethazine) Tetracyclines (chlortetracycline, oxytetracycline)
13. Guidance 213: New Uses Potential new therapeuticuses Therapeutic = treatment, control, prevention Includes data required to obtain approval of new uses Any new uses are expected to: demonstrate therapeutic effectiveness have defined dosing duration include veterinary oversight
14. Guidance 213: Timeline (3 months) Requested notification from drug sponsors as to their intentions within 3 months (by March 12, 2014) FDA has received responses from all of the sponsors affected by this guidance and is very encouraged by the positive response. The number of affected sponsors is 26. 25 sponsors confirmed their intent to engage in Guidance #213. These 25 sponsors hold 99.6 percent of the applications affected by Guidance #213. These applications represent 99.95 percent of the total sales of products affected by Guidance #213, based on 2011 data.
15. Guidance 213: Timeline (3 years) Target for implementing changes to use conditions of affected products within 3 years (by December 12, 2016) FDA is confident that these changes can be completed within the three-year implementation period. Veterinary Feed Directive (VFD) streamlining To facilitate transition to increased veterinary oversight of medicated feeds, FDA is also updating the VFD regulation. Intent is to implement revised VFD regulation within 3-year timeframe, but will adjust timeframe as necessary if VFD changes not yet in effect.
16. Veterinary Oversight One of two key principles described in Guidance 209: Limit use of medically important antimicrobial drugs to those uses considered necessary for assuring animal health (i.e., therapeutic purposes). Increase veterinary involvement/consultation.
17. Veterinary Oversight Primary objective is to include veterinarian in decision-making process… Does not require direct veterinarian involvement in drug administration. Practically, this means changing marketing status from OTC to Rx or VFD.
18. Veterinary Feed Directive Existing framework for veterinary oversight of feed use drugs is the veterinary feed directive (VFD). In 1996 Congress passed Federal Law stating that medicated feeds which require veterinary oversight are designated VFDs. In 2001 FDA finalized regulations for distribution and use of VFDs.
19. Updating the VFD Process Changes intended to make process more efficient Critically evaluated all current requirements Information required on VFD form Transmitting VFD Recordkeeping requirements Specificity of order
20. Proposed VFD Rule: Major Provisions Replace the explicit “veterinarian-client-patient relationship” (VCPR) provision with the requirement that veterinarians ordering the use of VFD drugs must do so “in compliance with all applicable veterinary licensing and practice requirements” Revise the definition of Category II to eliminate the automatic classification of VFD drugs into Category II. Reduce the recording keeping burden for VFD drugs from 2 years to 1 year.
21. Proposed VFD Rule: Example Current process Requires VFD orders be written for a specific amount of medicated feed for specifically identified animals. Proposed change Allows veterinarians to be this specific, but also provides the flexibility for veterinarians to issue a broader "standing order" For up to 6 months Limited by approximate number of animals specified on the VFD
22. Guidance #213: Next Steps Finalize VFD rule Proposed rule published with final GFI #213 90-day public comment period (closed 3-12-2014) Monitoring Progress of Guidance #213 Notifying Public Assessing Impacts
23. Notifying the Public of Progress Listing all antimicrobial products and sponsors affected by GFI #213 Publishing summary indicating the level of engagement of affected drug sponsors following the 3-month notification period indicated in the guidance Notifying the public of completed changes to affected products through publication of approval of supplemental new animal drug applications Evaluating the rate of adoption of the recommended changes at the end of 3 years
24. Assessing Impacts of Strategy Monitoring trends in antimicrobial resistance among foodborne bacteria from humans, retail meats, and animals through the NARMS program. Enhancing data FDA currently collects on the sales and distribution of antimicrobial drugs intended for use in food-producing animals. Collaborating with other agencies, including USDA and the CDC, to explore approaches for enhancing current data collection efforts in order to measure the effectiveness of the strategy.
25. A Collaborative Approach FDA believes that a collaborative approach is the fastest way to implement the changes outlined in Guidance #213. We have worked with stakeholders, including animal pharmaceutical companies, to encourage their cooperation on this important public health issue, and we are confident in their support.
26. The Role of Animal Producers and Veterinarians Once drug companies voluntarily make these changes, animal producers and veterinarians can no longer use these products for production purposes, and therapeutic use of these products would require veterinary oversight. By law, drugs administered through feed must be used according to the approved labeling. In addition, the extralabel use of approved drugs in animals by or on the lawful order of licensed veterinarians is limited to situations where the health of an animal is threatened or suffering or death may result from failure to treat.
27. Judicious Prevention Use A veterinarian practicing judicious use principles would consider relevant factors to determine: the risk of a specific bacterial disease, whether it would be appropriate in a particular situation to use medically important antimicrobials for prevention purposes. For example, the veterinarian would consider: the way the drug acts against the particular bacteria in question, whether it can effectively reach the site of infection, how long the drug maintains effective levels at the site of infection.
28. Judicious Prevention Use Other important factors veterinarians consider when determining whether a particular drug is appropriate for preventive use include whether: There is evidence that the drug will be effective in treating the particular disease. Such preventive use is consistent with accepted veterinary practice. The use is intended to address particular bacteria. The use is appropriately targeted to animals at risk of developing a specific disease. There are no reasonable alternatives for intervention.
29. Related CVM Websites Judicious Use of Antimicrobials: http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/JudiciousUseofAntimicrobials/default.htm NARMS http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/default.htm ADUFA 105 Reports: http://www.fda.gov/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/ucm042896.htm
30. Thank You