Abstract

The Minor Use and Minor Species Animal Health Act of 2004 (MUMS; Public Law 108-282)¹ was signed into law on August 2, 2004 by President Bush after many years of work by House and Senate sponsors of the bill, and with assistance, input and guidance of the Food and Drug Administration (FDA) and a MUMS Coalition of more than 43 entities. Many of the elements of MUMS are similar to the program created in 1983 by the Human Orphan Drug Act that increased the availability of drugs for rare and uncommon human diseases. Regulations promulgated as a result of MUMS legislation will offer pharmaceutical companies incentives to develop drugs for uncommon diseases in major animal species, and diseases in minor species. This paper and presentation is intended to provide a brief overview of the MUMS legislation and its elements to be considered in the future promulgation of regulations^2,3, with an emphasis on drugs for aquatic animal diseases.

Introduction

In general, the full FDA approval of veterinary drugs costs $8-10 million and takes 8-10 years. For many drug sponsors, because of limited sales opportunities, low profit margins, and the high capital investment necessary for bringing a drug to market, it was untenable to consider drugs for rare animal conditions and many minor species.

Recognizing the resulting critical shortage of approved animal drugs for minor uses and minor species, Congress passed the Animal Drug Availability Act in 1996 (ADAA; Public Law 104-250)⁴ that, in part, recognized particular problems relating to the availability of approved MUMS drugs. The ADAA directed the Secretary of Health and Human Services to consider and announce proposals for legislative or regulatory change to the approval process for such drugs. After public comments through 1998 FDA concluded in report entitled Proposals to Increase the Legal Availability of Animal Drugs for Minor Species and Minor Uses⁵ that federal statutes should be amended. In 1999 legislation, using FDA proposals and technical assistance, and input from the MUMS Coalition, was drafted. House and Senate bills were introduced into the 106th (1999-2000) and 107th (2001-2002), and finally passed in the 108th (2003-2004) Congress.

Passage of the MUMS legislation allowed Section 360b of the Federal Food, Drug and Cosmetic Act (FFDCA; 21 U.S.C.)⁶ to be amended to incorporate the elements of MUMS that were approved by Congress. Specifically, the MUMS legislation provided authority to FDA to establish a new MUMS Office within the FDA Center for Veterinary Medicine (CVM) and promulgate regulations concerning designating certain drugs to be designated as MUMS drugs that may be "conditionally approved" or "indexed", and may be accompanied by financial incentives.

Minor species include all aquatic animals and those not legally defined as "major species" (cats, dogs, horses, cattle, swine, turkey, chickens). The minor uses provisions of MUMS address drug needs for animal diseases that occur infrequently or in limited geographic areas in any animals, including major species.

Office of Minor Use and Minor Species Animal Drug Development

Directed by the new law, FDA established an Office for Minor Use and Minor Species at CVM in late 2004 and is initially staffed by two individuals. The new Office will handle designation requests, indexing, and will liaise with other minor use and minor species groups involved in aquatic animal drug development such as the USDA's National Research Support Project No. 7 (NRSP-7) Program⁷, the Aquatic Animal Drug Approval Partnership (AADAP) Program⁸ and other entities. The Office is also tasked for writing and implementing MUMS regulations.

MUMS Designation Designating a drug as applicable for MUMS parallels the human Orphan Drug Program. Sponsors will need to apply to FDA/CVM to get their specific products "designated." After being reviewed by FDA, a MUMS designation will make the drug eligible for conditional approval or indexing, and for the sponsor to apply for grants to support drug development for minor use and minor species. Funds for grants will not be appropriated until the final designation regulations are published.

Incentives for MUMS Drugs

Once designated as a MUMS drug, a sponsor may elect, depending on the nature of the drug, its proposed use and other conditions, to request the drug be eligible for conditional approval or indexing. In addition, the drug sponsor will enjoy seven years of marketing exclusivity (protection against generic copying and other pioneers for the same drug, dosage form, and intended use). Drugs designated for MUMS are also excluded from user fees, a fee initiated with the passage of the Animal Drug User Fee Act of 2003 (ADUFA; Public Law 108-130)⁹ to enable FDA to expedite the review process for animal drugs. Tax advantages that were included in earlier versions of the MUMS bill, but excluded in the 2004 version, may be added to these incentives, but will require future Congressional legislation and modification of the Internal Revenue Service regulations.

Conditional Approval of MUMS Drugs Conditional approval is intended for early marketing of a new drug before it receives full approval from FDA to allow a sponsor to recoup some investment through early marketing. Once FDA accepts all safety and the manufacturing components of a New Animal Drug Application (NADA), a conditional approval to market the drug may be granted for those products for which there is a "reasonable expectation of effectiveness" (MUMS; Public Law 108-282.)¹ Sponsors have up to five years to complete the technical requirements to produce the data that demonstrates full efficacy for the disease conditions claimed, to gain a full FDA approval for the drug. For drugs not demonstrated to be fully effective within this 5-year period, their NADA will be withdrawn.

MUMS Drug Indexing Drug indexing is a completely new process. Indexing is intended for use of sponsors who want to market drugs for non-food, minor animal species for which the potential market is just too small to ever support the costs of the drug approval process, even under a conditional approval. Examples include drugs for endangered species, ornamental fish, pocket pets, zoo animals, etc. Technically, FDA indexed drugs will not be "approved" (a legal definition), but they will be allowed to be marketed with FDA oversight. Drugs included in the "Legally-Marketed Unapproved New Animal Drug Index" will provide legal status for products that have traditionally been unable to go through the full FDA approval process to demonstrate good manufacturing practice, safety and efficacy sufficient to get a regular FDA approval. This option will be limited to non-food minor species provided there is "reasonable certainty that the animal or edible products from the animal will not be consumed by humans or food-producing animals; and [is a] new animal drugs intended for use only in a hatchery, tank, pond, or other similar contained man-made structure in an early, non-food life stage of a food-producing minor species, where safety for humans is demonstrated ..." (including, for an antimicrobial new animal drug, with respect to antimicrobial resistance). The index shall not include a new animal drug that is contained in or a product of a transgenic animal" (MUMS; Public Law 108-282).¹ The Secretary of Heath and Human Services will approve drugs to be included on the Index based on FDA/CVM's determination that the product is eligible for indexing and a report of a review all safety and efficacy data available for the product by an outside expert panel.

Implementation Timeframe Dates for implementation of these provisions were included in the new legislation. The ability for FDA to designate MUMS drugs and for conditional approval went into effect with the signing of the bill. Processes and policies are being developed as the first requests/applications are being submitted. The grants portion of designated MUMS drugs cannot be initiated until funds are appropriated which cannot occur until after publication of final regulations for designation. Indexing also requires final regulations to be published before it can go into effect.

The statute sets the following dates for promulgation of regulations:

Sponsors of drugs that may be applicable to minor uses and minor species are encouraged to contact the U.S. Food and Drug Administration, Center for Veterinary Medicine, Office for Minor Use and Minor Species.¹⁰

References

1.  MUMS; Public Law 108-282. Minor Use and Minor Species Animal Health Act of 2004. The full text of the MUMS Act can be found at http://www.gpoaccess.gov/plaws/108publ.html.

2.  Oeller M, J Scheid. 2004. New "MUMS" Legislation to Help Make Animal Drugs Available for Limited Uses, Minor Species. FDA Veterinarian, 10 (14): 1-2. (July/August 2004)

3.  Scheid J, A Beaulieu, M Oeller. 2004. What Does the MUMS Legislation Mean? FDA Veterinarian, 10 (14): 2-4. (July/August 2004).

4.  ADAA; Public Law 104-250. Animal Drug Availability Act of 1996.

5.  FDA, 1997. Proposals to Increase the Availability of Approved Animal Drugs for Minor Species and Minor Uses-Discussion draft. ADAA Minor Use/Minor Species Working Group Report, CVM 97132. Food and Drug Administration, Center for Veterinary Medicine, Rockville, MD 20855

6.  FFDCA; 21 U.S.C. Federal Food, Drug and Cosmetic Act. The full text of the FFDCA, as amended, can be found at http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm.

7.  NSRP-7. National Research Support Project No. 7. Information available at http://www.nrsp-7.org/.

8.  AADAP. Aquatic Animal Drug Approval Partnership (AADAP) Program. Information available at http://fisheries.fws.gov/aadap.

9.  ADUFA; Public Law 108-130. Animal Drug User Fee Act of 2003. The full text of the ADUFA can be found at http://www.gpoaccess.gov/plaws/108publ.html.

10. Office for Minor Use and Minor Species (Dr. Andrew Beaulieu, Office Director (301-827-2954; abeaulie@cvm.fda.gov); Dr. Meg Oeller (301-827-3067;moeller@cvm.fda.gov), FDA/CVM/HFV-50, 7519 Standish Place, Rockville, MD 20855.