MUMS Meeting Summary

On October 2, 2005, Dr. Darryl Styles attended the MUMS (minor use/minor species) meeting hosted by the American Veterinary Medical Association in Chicago.  Below is his report to the AFA summarizing the conclusions regarding the meeting.

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October 5, 2005

Dear Dr. Tully and Dr. Gallaway;

I participated in the MUMS (minor use minor species) meeting at the AVMA headquarters in Schaumburg, IL on Oct. 2, 2005 with FDA representatives, affiliated minor species AVMA groups, and AVMA officials in attendance. This report details the findings and conclusions regarding this meeting.

The other groups represented at the meeting were one member of the association of reptile and amphibian veterinarians, one member of the association of zoo veterinarians, two members representing lab animal organizations, one from the American animal hospital association, six members representing aquatic medicine, and two drug industry veterinarians specializing in aquatic medicine. One FDA member was present and another joined by teleconference. There were officials from the AVMA present and Dr. John Pitts led the meeting.

After a broad overview by FDA veterinarians describing the MUMS initiative, we discussed applications and how each specialty could participate. The aquatic industry has been working on this for several years and is well organized. The reptile and amphibian veterinary group has been discussing the issue for about 2 years, and our group and the zoo vets are newcomers to the field.

First, let me say that the MUMS act does not exceed the authority already given to the clinician under the extra-label usage provisions dictated by the Animal Medicinal Drug Use Clarification Act (AMDUCA). Therefore, avian practitioners will continue to enjoy the same practice latitude and extra-label drug use in non-food animals species already provided for in AMDUCA.

MUMS is a means to approve or make available drugs for use in:
a) non-food animal species (minor species)
b) minor food-animal species (minor species)
c) early life-stages of food animal species (major species)
d) specific rare conditions in major species (minor uses in major species).

MUMS could make drugs available that would normally be unavailable to the clinician, or provide proprietary protection for a manufacturer/sponsor of drugs so that they may be labeled for a specific use in a particular species. Indexing is the primary way MUMS accomplishes this.

Indexing a drug requires that the "sponsor", usually a manufacturer or product distributor, supply minimum data showing safety and some basis for efficacy in treating specific illnesses in particular species. This minimum data would be much less than is required for the usual drug approval process and can consist of empirical observation, anecdotal reporting, and pilot studies. The usual pharmacokinetic/pharmacodynamic data would not be required but is desirable and enhances the drugs ability to be indexed. The application for indexing would be reviewed by a panel of "experts" in the field that functions external to, and completely independent of the FDA. The FDA was very vague about who would compose this expert panel and what credentials would be necessary to qualify a panelist. The panelists may be appropriately compensated for their time reviewing an indexing request providing that there is no direct conflict of interest.

The following list details the actions outlined in MUMS:

(1) Indexing OTC (over the counter) drugs for particular uses in specific species.

This system would remove from the pet store shelf...drugs that were not efficacious or were hazardous, and replace them with preparations shown to have safe application as a specific use in particular species. As you may have surmised by their representation at this meeting, this act would have the greatest impact in the aquatic industry where large quantities of these drugs are sold OTC. The aquatic animal veterinary group has already reviewed the OTC drugs used in their industry and tabulated results regarding their efficacy and safety. In the aquatics industry, there is much less risk of zoonotic infections and the quantity of drugs used is on a much higher scale than those used in avian practice. Therefore, the quantity of drugs used in the aquatics industry could justify the cost of indexing. Apparently, some of these more effective preparations could be subjected to the indexing process and become labeled for use in the fish industry. Others not meeting the criteria set down by FDA in the indexing process would be eliminated....eventually.

Regarding OTC antibiotic use in avian species, I informed the FDA officials that the AAV would likely be opposed to indexing ANY avian OTC antibiotic due to the peculiarities of disease in avian patients and the risks involved with psittacosis. These were my reasons: (a) even if an OTC antibiotic was labeled for "mild" bacterial infections, its use may be inappropriate because sub-therapeutic dosing or inappropriate antibiotic class selection for that infection which could prolong the infection or induce subclinical Chlamydophila infection and potentially threaten the health of both bird and owner, (b) such usage of OTC antibiotic could possibly make pet stores and distributors/manufacturers liable, (c) psittacosis is a reportable disease in many states and the use of an OTC antibiotic would remove the clinician from the process and technically be in abeyance of state law, (d) usage of OTC antibiotic requires the unqualified consumer to become the "diagnostician"; if resolution does not result from medication, this could seriously impair efforts to diagnose disease by a qualified clinician and may predispose the bird to more serious illness or death.

Regarding non-antibiotic OTC avian drugs which are primarily neutriceuticals, the FDA was unclear of whether these neutriceuticals would qualify to be covered by the MUMS act.

Conclusion, indexing of OTC antibiotics for avian use is not recommended and may be hazardous to both patient and owner.

(2) Indexing prescription drugs.

This may have some application in our field. If the appropriate "sponsor" can be identified, drugs previously unavailable domestically can be indexed and used by clinicians in the industry. Experimental drugs may also qualify for this type of indexing. For example, pharmaceuticals that are available to our colleagues in Europe could be made legally available here via the indexing process. However, FDA officials were again very vague about the cost of indexing such drugs and who might qualify as a sponsor. For example, Vibravenous (injectible doxycycline from Janssen Pharmaceutics) may be one preparation that could be indexed. However, who would serve as a sponsor (obviously, Janssen is not going to expend the funds to pursue such a small market) and what the cost would be to index the drug have yet to be determined. Nevertheless, indexing may have some utility if a highly desirable drug candidate and sponsor can be identified.

Conclusion, indexing of prescription drugs may be useful when drugs not normally available to the practitioner can be indexed and be legally marketed in this country.

The next more stringent step in the MUMS process above indexing is conditional approval leading to full approval. This process affords the sponsor greater proprietary protection and relaxed rules under MUMS facilitates the full approval process:

(3) Conditional approval of prescription drugs leading to full approval.

The process for conditional approval under MUMS has been relaxed to use primarily safety data with some minimal efficacy data. The expert panels would review the conditional approval application and forward that to the FDA for final approval. The drug would be approved on a renewable annual basis providing that the "sponsor" shows progress in getting the preparation approved by collecting the appropriate pharmacodynamic/kinetic data while efficacy data was being collected via "field trials". Again, drugs undergoing conditional approval via the MUMS process would be held to less stringent standards than those being examined by the traditional avenues of approval. For example, there may already be sufficient data for Bayer to get approval of Baytril (enrofloxacin) for use in non-food bird species, but whether Bayer would serve as a sponsor and whether it is cost effective for Bayer to pursue approval is highly questionable (Baytril already enjoys wide use without the need for conditional approval). Where conditional approval may be helpful is that Bayer could be provided some proprietary protection for use in birds. If another antibiotic were to compete with Baytril, and if Bayer decided to get the drug approved for birds, then approval could provide Bayer with some market advantage over the competitor. However, because approval does not exceed the latitude for extra-label usage provided for under AMDUCA, I seen no reason as why Bayer would seek to approve Baytril because practitioners would still be free to use both Baytril and the competitor equally. One could argue that because Baytril would be labeled for specific uses in birds, then in a liability suit the clinician would have more legal standing because he or she used the drug per label rather than extra-label use.

However, FDA admitted that they currently did not have the resources to monitor and provide the proprietary protection that would serve as the incentive for the sponsor. They were also unclear on when this enforcement aspect of the MUMS regulation would be effective.

Conclusion, it does not appear that there is sufficient incentive for a sponsor to pursue conditional approval leading to full approval of a drug for birds unless future regulations limits the practice latitude granted for extra-label usage under AMDUCA or the sponsor is given a sufficient proprietary advantage to market such a drug.

FDA also wishes to promote the development of novel compounds or the use of known drugs for new applications via a process called designation:

(4) Designation.

Similar to the human "orphan drug act", grants would be made available to assist in the development and approval drugs for minor uses or in minor species. Such funding is subject to congressional approval and the FDA had not comment on when this funding would be made available.

Conclusion, designation status may qualify a drug funding for study and development in minor uses in major species or uses in minor species......considering the country's current economic climate and disasters designation in the foreseeable future is unlikely!

Another problem in the MUMS act is "grouping". This pertains to what acceptable phylogenic category for which a drug can be specifically labeled.

(5) Grouping.

FDA would probably not accept a label stating "for use in birds". It may accept a label stating "for use in psittacine birds". However, again FDA was particularly vague about what phylogenic categorization would suffice for purposes of labeling. The FDA officials did state that they were seeking input from interested groups on where and how to apply the appropriate phylogenic categorization. Again, this is where the AAV would need to provide the necessary information to ensure that future drug applications would be appropriately processed.

Conclusion, AAV should take an active role in making suggestions to the FDA on how phylogenic grouping should be applied for drug labeling in birds.

The formation of an expert panel was referred to above in the indexing and conditional approval process.

(6) Expert panel.

I do feel that it is our responsibility as avian practitioners to identify qualified individuals who would be willing to serve on the "expert panels" used for indexing or conditional approval. I did get FDA to confirm that empanelled reviewers would be immune from liability. Without outright expressing it, the FDA seemed anxious for the affiliated groups to identify qualified individuals to serve on these panels. I feel that it would be prudent to identify a pool of panelists from our group or other credentialed individuals outside our group who may be willing to serve in this capacity. From the discussion at the meeting, it seemed that once selected, these experts would serve in this capacity long-term.

Conclusion, the AAV should identify a pool of eligible candidates based on their areas of interest in drug or related studies to serve on the expert panels.

Summary, considering that our current ability to use drugs in an extra-label fashion is protected under AMDUCA, the utility of MUMS in the avian industry appears to be minimal. Indexing of OTC drugs for birds would not be recommended. Indexing of prescription drugs may be of some utility if the appropriate sponsors and drugs can be identified. Conditional approval of drugs under MUMS seems unlikely because of the reduced cost/benefit ratio and lack of proprietary incentive to the sponsor. Designation for funding of the development of drugs for minor species is unlikely to occur anytime in the near future. The AAV probably does need to take an active role in the outlining the phylogenic grouping of birds for purposes of labeling and establish a pool of experts willing to assist in the drug approval process. The FDA was unclear about whether it would take comment prior to the official proposed rule disclosure that would occur on or about February 2006. I will contact the FDA and ask if it will continue to take comment up until the proposed rule is published or if we must wait to submit official comment after the February 2006 proposed rule publication date. Importantly, we may need to address some of these issues prior to the February 2006 AAV board meeting.

Sincerely,

Darrel K. Styles, DVM, PhD