FDA’s Dunham delves into drug issues

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Dr. Dunham
Dr. Bernadette Dunham (Photo by R. Scott Nolen)

In February, JAVMA News talked with the director of the Food and Drug Administration’s Center for Veterinary Medicine, Dr. Bernadette Dunham, about drug issues and the investigation into adverse health effects associated with jerky pet treats.

Dr. Dunham became CVM director in 2008. She served as an adjunct professor in the Department of Biomedical Sciences and Pathobiology at the Virginia-Maryland Regional College of Veterinary Medicine from 1996-2012. Prior to joining the FDA staff in 2002, she was acting director of the AVMA Governmental Relations Division. She received her DVM degree in 1975 from the Ontario Veterinary College and her doctorate in cardio­vascular physiology in 1984 from Boston University.

In December 2013, FDA rolled out Guidance for Industry No. 213 asking drug sponsors to align with GFI No. 209, FDA’s judicious use principles for antimicrobials. At the same time, the agency published proposed changes to the rules governing veterinary feed directives. What is your central message to veterinarians about these actions?

FDA believes it is important to include veterinary oversight in the use of medically important antimicrobial drugs to ensure their appropriate and judicious use. Veterinarians play a critical role in the diagnosis of disease and in the decision-making process related to instituting measures to treat, control, or prevent disease. FDA believes that the judicious use of medically important antimicrobial drugs in the feed or water of food-producing animals needs the scientific and clinical training of a licensed veterinarian. This is because judicious use involves accurately identifying bacterial disease that is present or likely to be present and selecting the suitable antimicrobial drug.

In the case of prevention, judicious use includes a consideration by the veterinarian of relevant factors for determining the risk of a specific bacterial disease and for determining whether the use of medically important antimicrobials for prevention purposes is appropriate in a particular situation. The decision by the veterinarian to use a specific approved drug or combination drug is based on factors such as the mode of antibacterial action, drug distribution in specific tissues, and the duration of effective drug levels at the site of infection.

Other important factors veterinarians consider when determining the appropriateness of preventive use include whether there is evidence of effectiveness, the preventive use is consistent with accepted veterinary practice, the use is linked to a specific etiologic agent, the use is appropriately targeted to animals at risk of developing a specific disease, and no reasonable alternatives for intervention exist.

It is also important to note that any extralabel use of medicated feed is not permitted by law, and we have very specific sections of our Federal Food, Drug, and Cosmetic Act that address that. Neither veterinarians nor their clients may use, or direct the use of, a medicated feed in an extralabel manner. Therefore, when production claims for medically important antimicrobials are voluntarily removed from the approved labeling of these drugs, any further use of these drugs in medicated feed for production purposes will be considered an extralabel use and, thus, illegal. We realize that these steps represent changes for veterinarians and animal producers, and we have been working—and will continue to work—to make this transition as seamless as possible.

What is the FDA doing to increase the number of legally marketed animal drugs, including New Animal Drug Applications?

Center for Veterinary MedicineCVM’s Office of New Animal Drug Evaluation has been proactive in helping pharmaceutical sponsors meet the statutory and regulatory standards that provide safe, effective, quality-manufactured, and properly labeled animal drugs. An approved New Animal Drug Application ensures the veterinarian is providing quality medicine to patients. Unapproved and compounded drugs do not provide that assurance.

Over the last 10 years, the number of original NADA approvals has remained stable at 11 original NADA approvals and nine supplemental approvals per year. Over this period, 46 new chemical entities were approved. A new chemical entity is a drug that contains no active moiety that has been approved by the FDA in any other application submitted under the Federal Food, Drug, and Cosmetic Act. In addition, CVM approved supplemental applications for 21 new species indications and 55 new disease indications. In fiscal year 2013, CVM completed over 10,000 sponsor submissions at an on-time rate of greater than 99.8 percent.

CVM is working with sponsors to use multiple scientifically valid sources of data, including literature, data from foreign countries, pharmacokinetic models, and epidemiologic designs, in addition to traditional randomized controlled trials to fulfill requirements for demonstrating safety and effectiveness. CVM is working very early in the drug development process to ensure a predictable regulatory path to approval. Sponsors are encouraged to contact CVM’s Office of New Animal Drug Evaluation to discuss any of their drug development plans.

What steps does CVM intend to take with regard to rule making or guidance development on bulk compounding of drugs for use in animals?

As you know, the recently passed Drug Quality and Safety Act does not cover animal drug compounding. Existing law makes no distinction between compounding of drugs for use in animals from bulk drug substances and the manufacturing of new animal drugs. Since the mid-1990s, the agency has addressed this issue through compliance policy guides that set out factors the FDA intends to consider in determining whether to initiate enforcement action for these activities. The agency’s last update to the CPG was in 2003, and FDA believes this CPG needs to be updated to address the evolving nature of the issue. Therefore, as noted on the list of guidances under development posted on CVM’s Web page, we intend to complete a draft of a revised CPG this calendar year. When we put out any guidance for public comment, we really do look forward to the AVMA Council on Biologic and Therapeutic Agents and everyone else providing us constructive feedback.

How confident can veterinarians be in the quality of drug products that are fully prepared overseas?

Animal drugs that are approved by the FDA, regardless of whether they are manufactured domestically or internationally, are required to be manufactured under the same good manufacturing practices; we call them GMPs. Foreign sites that manufacture FDA-approved drugs are routinely inspected to ensure the continued safety and effectiveness of the drug products they produce.

Is there a backup plan in the event a country were to stop delivering supplies?

In terms of drug products, CVM works closely with sponsors to identify and prevent drug shortages and to mitigate the effects of such shortages in the event they occur. CVM may take action to ensure critical or medically necessary animal drugs are available, if a country has an approved product and we have a shortage here in the States.

In terms of animal feed, CVM has limited authority to ensure the supply of feed. However, under certain situations, we may choose to exercise enforcement discretion to provide access to feed ingredients.

Where is the FDA in its investigation into illnesses associated with jerky-type pet treats, and what have been some of the challenges?

First of all, we want to thank veterinarians for their response to our request for information and data. It’s been incredibly helpful in aiding our investigation.

FDA continues to investigate the cause of illnesses associated with the ingestion of jerky pet treats. Since the update released on October 22, 2013, FDA has received over 1,500 reports and valuable information from pet owners and veterinarians.

We are currently following up on many of these cases in hopes of them leading us to the root cause. We have not completed entering all the particulars from those 1,500 case reports into our database and do not yet have updated numbers to share.

While we typically receive excellent diagnostic and patient history information, we are working to obtain better exposure data that will help us document brands, other foods, and concomitant medications from veterinarians and pet owners.

Veterinarians who have read our 21-page report on the investigation have found it very helpful and an assurance that we are actively engaged. The report was current with everything we had done through October 2013. The direct link is fda.gov/downloads/AnimalVeterinary/SafetyHealth/ProductSafetyInformation/UCM371485.pdf. As we do more, we will be putting more information up. Until we can figure this all out, we are continuing to reach out to experts in a variety of areas.