Increasing Drug Availability for Minor Use and Minor Species
The Minor Use and Minor Species Animal Health Act of 2004 authorized CVM to establish programs to provide incentives to sponsors to encourage approval of new animal drugs for minor uses in major species and for minor species. It established Conditional Approval to allow sponsors to recover some development costs through earlier access to the market. It also established an alternate legal marketing status for some minor species through the Index of Legally Marketed Unapproved New Animal Drugs for Minor Species. Minor use refers to disease conditions that are rare in major species (cattle, horses, swine, chickens, turkeys, dogs, and cats). Minor species encompasses all other animal species and includes pet animals such as ornamental fish, parrots, ferrets, guinea pigs, and iguanas; zoo animals; and species of agricultural importance, such as sheep, goats, commercially-produced fish such as salmon, catfish and tilapia, and honey bees.
The provisions of the Act accommodate a range of needs for a variety of species and those uses that have not been supported through approvals because of a lack of economic incentive. The incentive provisions include designation and conditional approval.
Designation of a MUMS drug makes the sponsoring pharmaceutical company eligible for incentives to help bring the product to market. These incentives include seven years of exclusive marketing rights beginning on the date of a drug approval or conditional approval, and eligibility to apply for grants to defray the costs of qualified safety and effectiveness studies. The Office of Minor Use and Minor Species Animal Drug Development (OMUMS) granted ten new drug designations during FY 2012, including five for minor species and five for minor uses in dogs, swine, and horses. The following is a brief description of each of these designations:
- Luteinizing Hormone-Releasing Hormone analog (LHRHa) is an injectable product for use as a spawning aid for female channel catfish (Ictalurus punctatus).
- Luteinizing Hormone-Releasing Hormone analog (LHRHa) is an implant product for use as a spawning aid for female channel catfish (Ictalurus punctatus).
- Paclitaxel (PACCAL VET) is an injectable product for the treatment of non-resectable stage III, IV or V mammary carcinoma in dogs.
- Decoquinate/Levamisole (OROGIN) is an oral product for the treatment of equine protozoal myeloencephalitis caused by Sarcocystis neurona in horses.
- Doxorubicin (DOXOPHOS VET) is an injectable product for the treatment of lymphoma in dogs.
- Monepantel (ZOLVIX) is an oral product for the treatment and control of gastrointestinal nematodes in sheep at the adult stage, including Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus colubriformis, Trichostrongylus axei, and Cooperia curticei.
- Monepantel (ZOLVIX) is an oral product for the treatment and control of gastrointestinal nematodes in goats at the adult stage, including Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus colubriformis, Trichostrongylus axei, and Cooperia curticei.
- Gonadotropin Releasing Factor Analog-Diphtheria Toxoid conjugate (IMPROVEST) is an injectable product for the immunological castration and reduction of male aggressive and sexual behavior in cull adult breeding boars intended for slaughter.
- Imidacloprid/Moxidectin (ADVANTAGE MULTI for Cats) is a currently approved topical product with new intended uses for the prevention of heartworm disease in ferrets caused by Dirofilaria immitis, and for the treatment of flea infestations in ferrets.
- 2- methyl sorbinil (KINOSTAT) is a topical ophthalmic product for the prevention of diabetic cataracts in dogs with diabetes mellitus.
The following seven grants were awarded for studies to support approval or conditional approval of the following designated indications:
- Determining exposure parameters that maximize eugenol residues in the fillet tissue and determining the sample times that will adequately characterize the depletion of eugenol residues from the fillet tissue of rainbow trout exposed to AQUI-S 20E.
- Eugenol total residue depletion from the skin-on fillet tissue of rainbow trout exposed to 14C labeled AQUI-S 20E.
- Field effectiveness of 35% PEROX-AID (hydrogen peroxide) to reduce Gyrodactylus sp. infestation density on coolwater and warmwater finfish- Trial 3.
- Field effectiveness of 35% PEROX-AID (hydrogen peroxide) to reduce Gyrodactylus sp. infestation density on coolwater and warmwater finfish- Trial 4.
- Identification of motile aeromonads isolated from Study NumberAEH-090MAS-02 [effectiveness of florfenicol (AQUAFLOR) and oxytetracycline (TERRAMYCIN 200 for Fish) to control mortality in coolwater and warmwater finfish due to Motile Aeromonad infections].
- Target Animal Safety of AQUI-S 20E to rainbow trout (Oncorhynchus mykiss).
- Target Animal Safety of AQUI-S 20E to channel catfish (Ictalurus punctatus).
Conditional approval allows drug sponsors to market products after completing all safety requirements for approval and demonstrating a reasonable expectation of effectiveness. This includes showing safety in the target study animal, the environment, and, if appropriate, safety of any food derived from the animals. Sponsors can use the revenue they obtain from the marketing the product under the conditional approval to fund the pivotal efficacy studies.
Although CVM did not grant any conditional approvals during FY 2012, ONADE gave full approval to the first conditional approval granted under the authority of the MUMS Act (in April 2007). The conditional approval was for AQUAFLOR-CA1 (florfenicol) Type A medicated for the control of mortality in catfish due to columnaris disease associated with Flavobacterium columnare. In FY 2012, CVM granted a supplemental approval for AQUAFLOR (florfenicol) for the control of mortality due to columnaris disease associated with Flavobacterium columnare in all freshwater-reared finfish, which includes catfish. This was the first conditional approval to have the effectiveness technical section completed and to be granted full NADA approval. The first conditional approval granted for a companion animal under the MUMS Act, Kinavet-CA1, remains conditionally-approved for the treatment of nonresectable Grade II or III cutaneous mast cell tumors in dogs that have not previously received radiotherapy or chemotherapy except corticosteroids.
Indexing allows a sponsor to legally market a product that has been evaluated through a new process that differs from the approval process for an NADA. This provision is limited to minor species that are unlikely to be used as human food. It is designed to accommodate uses that are unlikely to be approved because the numbers of animals in the species group are too few or too precious to use in field trials and/or the intended uses and species involved will not support conventional approvals because of a lack of economic incentive. OMUMS added two drugs to the Index of Legally Marketed Unapproved New Animal Drugs for Minor Species (Index) during FY 2012:
- Poly (acetyl arginyl) glucosamine (SYNOPLEX) is a topical product for the treatment of foot and dermal lesions infected with aerobic or facultative anaerobic Gram-positive and/or Gram-negative bacteria, and for the treatment of sterile chronic foot and dermal lesions in elephants and rhinoceroses.
- Deslorelin acetate (SUPRELORIN F) is an implant used to manage adrenal gland cortical disease in domestic ferrets.
The addition of these products to the Index represents the first time legally marketed new animal drugs have been labeled for elephants, rhinoceroses or ferrets.
Liaison to the U.S. Department of Agriculture (USDA) Minor Use Animal Drug Program
CVM’s OMUMS performs a liaison function for the USDA’s Minor Use Animal Drug Program (MUADP), also known as the National Research Support Project # 7 (NRSP-7). MUADP conducts the safety and effectiveness studies required to support approval or conditional approval by CVM. The OMUMS liaison performs a regulatory affairs function to assist in the compilation and submission of the necessary data and information. These data are placed in Public Master Files to be used by pharmaceutical sponsors to support NADAs.
With CVM’s assistance, MDUAP accomplished the following during fiscal year 2012:
- Lincomycin was approved for the treatment of American foulbrood in honey bees using a Public Master File compiled by NRSP-7 to support the effectiveness, target animal safety, human food safety, and environmental technical sections.
- Tulathromycin for the treatment of respiratory disease in goats – the tissue residue depletion study was completed and was under CVM review at the end of the fiscal year.
- Erythromycin for the treatment of bacterial kidney disease in salmonid fish – CVM accepted the data in the effectiveness technical section of the NADA. A revised environmental assessment was under review at the close of the fiscal year.
- Fenbendazole for the treatment of gapeworm in pheasants – a target animal safety study was completed, and was under CVM review at the end of the year.
- Lasalocid for the prevention of coccidiosis in pheasants – the method validation study and tissue residue depletion study protocol, and a completed target animal safety study, were under CVM review at the end of the fiscal year.
- MDUAP and CVM’s OMUMS liaison continued to work in cooperation with the USDA’s Agricultural Research Service and the Tick Eradication Program to investigate the use of mineral blocks containing ivermectin to control cattle fever ticks in the quarantine zone in Texas.
Guidance for Industry
The CVM Office of Minor Use and Minor Species Animal Drug Development continued to work on important revisions to Guidance for Industry #61, FDA New Animal Drug Applications - Special Considerations for Minor Uses and for Minor Species.