Conditional Approval Explained: A Resource for Veterinarians
FDA Center for Veterinary Medicine, September 2014
The Minor Use and Minor Species Animal Health Act helps FDA ensure that innovative treatments are available for small populations of animals. This law, passed in 2004, amended the Federal Food, Drug, and Cosmetic Act by adding provisions to increase the availability of drugs for minor species, such as ferrets and fish, and for minor uses in a major species, such as to treat certain types of cancer in dogs. Greater access to these “MUMS drugs” gives veterinarians more options in treating unique creatures and uncommon conditions.
One main provision created a new pathway called conditional approval to bring MUMS drugs to the marketplace more quickly. Since 2004, FDA has conditionally approved three animal drugs—one to control mortality in catfish due to a bacterial disease and two to treat specific cancers in dogs.
Conditional approval differs from full approval in several ways, and these key differences have implications for veterinarians who use conditionally-approved animal drugs in their practices.
What animal drugs are eligible for conditional approval?
Only drugs for minor species or minor uses in a major species are eligible for conditional approval. Minor species are all animals that are not major species. A minor use in a major species is the use of a drug in one of the seven major species—horses, dogs, cats, cattle, pigs, turkeys, and chickens—for a condition that occurs:
- Infrequently and in only a small number of animals each year; or
- In a limited geographic area and in only a small number of animals each year.
FDA defines a “small number” as fewer than:
50,000 horses; 70,000 dogs; 120,000 cats; 310,000 cattle; 1,450,000 pigs; 14,000,000 turkeys; and 72,000,000 chickens.
What’s the difference between conditional approval and full approval?
For both conditional approval and full approval, the drug company must prove the animal drug to be safe when used according to the label. The difference lies in the effectiveness requirement.
For full approval, the drug company must provide “substantial evidence of effectiveness.” For conditional approval, the drug company has shown the drug to have a “reasonable expectation of effectiveness,” but not yet proven that it meets the “substantial evidence” standard of effectiveness for full approval.
Conditionally approved animal drugs must state on the labeling: "Conditionally approved by FDA pending a full demonstration of effectiveness under application number XXX-XXX.”
What does FDA’s conditional approval allow a drug company to do?
FDA’s conditional approval allows the drug company to legally sell the animal drug before proving it meets the “substantial evidence” standard of effectiveness for full approval. The company can also legally promote and advertise the conditionally approved drug for the labeled uses (also called the labeled indications).
The conditional approval is valid for one year. The drug company can ask FDA to renew the conditional approval annually for up to four more years, for a total of five years of conditional approval. To receive a renewal from FDA, the company must be actively collecting data to prove “substantial evidence of effectiveness” for full approval.
During the conditional approval period, the company can legally market the animal drug for the labeled indications while collecting the remaining effectiveness data. After the company completes the effectiveness requirement, FDA reviews the data and, if appropriate, fully approves the drug.
What happens if the drug company can’t complete the effectiveness requirement before the conditional approval expires?
The drug company has up to five years, if FDA grants all four annual renewals, to complete the effectiveness requirement and get the drug fully approved. If the company does not do so, the conditional approval automatically expires five years after the date of the initial conditional approval. If this happens, the drug company must stop marketing the drug because FDA now considers it to be unapproved.
How does conditional approval benefit you and your patients?
Not many MUMS drugs are on the market. This lack can be explained by two main reasons. First, it’s very expensive for a drug company to develop a drug and get it approved by FDA. Second, the market for a MUMS drug is too small to generate an adequate financial return for the company. The combination of the expensive drug approval process and the small market often makes drug companies hesitant to spend a lot of resources to develop MUMS drugs when there is so little return on their investment.
By allowing a drug company to legally market a MUMS drug early (before it is fully approved), conditional approval makes the drug available to you faster and gives you more options for treating your exotic patients and patients with uncommon conditions. This early marketing also helps the company recoup some of the investment costs while pursuing full approval.
Can you use conditionally approved animal drugs in ways that are not described on the label (extra-label use)?
No. The Federal Food, Drug, and Cosmetic Act prohibits extra-label (also called “off-label”) use of conditionally approved animal drugs. You can only use these drugs for the labeled indications. To drive this point home, the labeling for a conditionally approved drug explicitly states, “It is a violation of Federal Law to use this product other than as directed in the labeling.” This is different for fully approved drugs which, under certain conditions, you can legally prescribe for extra-label uses in animals.
Should you report an adverse reaction related to a conditionally approved animal drug?
Yes. FDA encourages veterinarians to voluntarily report all adverse reactions (also called adverse drug experiences) related to any drug—fully approved, conditionally approved, or unapproved. Please see How to Report an Adverse Drug Experience.
A drug company that markets a conditionally approved animal drug is required to submit to FDA all reports of adverse drug experiences that the company receives. FDA reviews the reports to identify potential safety and effectiveness concerns that may not have been apparent at the time of conditional approval. FDA conducts this post-marketing monitoring to make sure the drug continues to meet the required standard of safety and “reasonable expectation of effectiveness” established during the conditional approval process.
What are the three animal drugs that FDA has conditionally approved and for what uses?
- AQUAFLOR-CA1 to control mortality in catfish due to columnaris disease associated with Flavobacterium columnare. This drug was FDA’s first conditional approval of an animal drug. (In April 2012, FDA fully approved AQUAFLOR to control mortality due to columnaris disease associated with Flavobacterium columnare in all freshwater finfish, including catfish.)
- KINAVET-CA1 (masitinib mesylate) to treat nonresectable Grade II or III cutaneous mast cell tumors in dogs that have not previously received radiotherapy and/or chemotherapy except corticosteroids.
-
PACCAL VET-CA1 (paclitaxel) to treat:
-Nonresectable stage III, IV, or V mammary carcinoma in dogs that have not received previous chemotherapy or radiotherapy; and
-Resectable and nonresectable squamous cell carcinoma in dogs that have not received previous chemotherapy or radiotherapy.
AQUAFLOR CA-1 was eligible for conditional approval because it was intended for use in catfish, which are minor species. KINAVET-CA1 and PACCAL VET-CA1 were eligible for conditional approval because FDA determined that the labeled indications for the two drugs fit the “minor use in a major species” category. Mast cell tumors, mammary carcinoma, and squamous cell carcinoma—within the limitations described on the label—occur infrequently and in a small number of dogs each year.
Provided that KINAVET-CA1 and PACCAL VET-CA1 receive all four annual renewals, the conditional approval for each drug expires on January 20, 2017, and February 27, 2019, respectively.
What does the “CA1” mean after each drug name?
The “CA1” indicates that FDA conditionally approved (CA) the drug and that it’s the first (1) conditionally approved application for that particular animal drug. If FDA were to conditionally approve a second application for the drug, the suffix would then be “CA2.”
Now that AQUAFLOR is fully approved to control mortality due to columnaris disease associated with Flavobacterium columnare in all freshwater finfish, including catfish, “CA1” is no longer included after the drug name.
For More Information: Contact CVM’s Education & Outreach Staff at 240-276-9300.
PW 12/23/14