Animal & Veterinary

Conditional Approval Explained: A Resource for Veterinarians


What animal drugs are eligible for conditional approval?
What's the difference between conditional approval and full approval?
What does FDA's conditional approval allow a drug company to do?
What happens if the drug company can't complete the effectiveness requirements before the conditional approval terminates?
How does conditional approval benefit you and your patients?
Can you use conditionally approved animal drugs in ways that are not described on the label (extra-label use)?
Should you report problems related to a conditionally approved animal drug?
What are the four animal drugs that FDA has conditionally approved and for what uses?
What does the "CA1" mean after each drug name?
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The Minor Use and Minor Species (MUMS) 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 four animal drugs—one to control mortality in catfish due to a bacterial disease and three 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 one of the seven major species: horses, dogs, cats, cattle, pigs, turkeys, and chickens. A drug to treat a disease in sheep or goats, for example, is eligible for conditional approval because both are minor species. A minor use in a major species is the use of a drug in a major species 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.

A drug to control pain in dogs with bone cancer is eligible for conditional approval because fewer than 70,000 dogs typically get bone cancer each year.

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What’s the difference between conditional approval and full approval?

For both conditional approval and full approval, the drug company must prove, among other things, that the animal drug is 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.”

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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 show active progress toward proving “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 collecting the necessary data, the company then submits an application to FDA for full approval. FDA reviews the application and, if appropriate, fully approves the drug.

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What happens if the drug company can’t complete the effectiveness requirement before the conditional approval terminates?

If FDA grants all four annual renewals, the drug company has up to four-and-a-half years to develop and submit the necessary data to complete the effectiveness requirement. If the company does not submit all necessary information to support full approval by this four-and-a-half-year deadline, the conditional approval terminates immediately. The drug company must stop marketing the drug because it is now considered to be unapproved.

If the company submits the necessary information before the four-and-a-half-year deadline, the conditional approval period runs another six months, for a total of five years, while FDA reviews the application for full approval. The conditional approval automatically terminates five years after the date of the initial conditional approval. If FDA does not fully approve the drug before the five-year termination date, the drug company must stop marketing the drug because it is now considered to be unapproved.

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How does conditional approval benefit you and your patients?

Not many MUMS drugs are on the market. This 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.

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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 doesn't allow 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 every 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.

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Should you report problems related to a conditionally approved animal drug?

Yes. FDA encourages veterinarians to report all problems related to any drug—fully approved, conditionally approved, or unapproved. Problems include adverse drug events and product defects. An adverse drug event, also called an adverse drug experience, is an undesired side effect associated with a drug or a lack of effectiveness. Adverse drug events also include unfavorable reactions in people who handle the drug. Product defects are problems such as defective packaging or an abnormal appearance of the drug. Please see How to Report Animal Drug Side Effects and Product Problems.

A drug company that markets a conditionally approved animal drug is required to submit to FDA all reports of adverse drug events and product defects 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.

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What are the four 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. It was eligible for conditional approval because it was intended for catfish, a minor species. 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. It was eligible for conditional approval because FDA determined that the labeled indication fits the “minor use in a major species” category. Mast cell tumors—within the limitations described on the label—occur infrequently and in a small number of dogs each year.

    FDA conditionally approved KINAVET-CA1 on December 15, 2010, but the agency didn’t fully approve the drug by December 15, 2015. Therefore, the conditional approval for KINAVET-CA1 has terminated and the drug is now an unapproved animal drug with no legal marketing status.
     
  • 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.

      PACCAL VET-CA1 was eligible for conditional approval because FDA determined that the labeled indications fit the “minor use in a major species” category. Mammary and squamous cell carcinomas—within the limitations described on the label—occur infrequently and in a small number of dogs each year.

      In February 2017, FDA withdrew the conditional approval for PACCAL VET-CA1 at the request of the drug’s manufacturer. Therefore, the conditional approval for PACCAL VET-CA1 has terminated and the drug is now an unapproved animal drug with no legal marketing status.
  • TANOVEA-CA1 (rabacfosadine for injection) to treat lymphoma in dogs. FDA conditionally approved TANOVEA-CA1 in January 2017. It was eligible for conditional approval because the agency determined that the labeled indication fit the “minor use in a major species” category. Canine lymphoma occurs infrequently and in a small number of dogs each year.

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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.

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For More Information

If you have questions or want more information, please contact CVM’s Education & Outreach Staff at 240-402-7002 or AskCVM@fda.hhs.gov.

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Page Last Updated: 02/16/2017
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