Surveillance and Compliance Actions That Protect Public and Animal Health
CVM conducts a wide range of surveillance and compliance activities designed to ensure post-approval safety of new animal drugs that receive CVM approval, and safety of all other products that are within CVM’s regulatory sphere. Some of those activities are described in Avoiding Unsafe Drug Residues in Human Food and, Ensuring Feed Safety. We describe a number of other significant actions in this section.
Unapproved New Animal Drugs
The marketplace continues to offer many unapproved new animal drug products, including compounded products that do not comply with the extra-label use regulations. Many of these products have had a long history of use but have not gone through the FDA drug approval process to insure safety and effectiveness, including safety to the consumers of edible products from animals that had been administered the products.
In 2010, we launched an initiative to protect human and animal health by reducing the number of unapproved new animal drugs on the market. In FY 2012, we built on the initiative in several ways. One way is to encourage firms marketing unapproved drugs to follow the route to CVM approval. Near the end of the previous fiscal year, CVM approved two such drugs: pergolide for Cushing’s disease in horses, and phenylpropanolamine (PPA) for urinary incontinence in dogs. Both of these drugs had been marketed without approval, although we had permitted compounding of pergolide in recent years through exercise of enforcement discretion with regard to pharmacy compounding of the product.
During FY 2012, we announced that we would no longer exercise enforcement discretion over illegal compounding with pergolide, we publicized the two new approvals to veterinarians and pharmacists, and issued an import alert to restrict the use of bulk active ingredients to manufacture the approved products.
In addition, several CVM staff members conducted a systematic review of the published literature on the safety of potassium bromide (KBr), a product widely used as an anti-seizure medication in dogs. The results of their review were published in the March 15, 2012 edition of the Journal of the American Veterinary Medical Association (JAVMA). These results are now available for anyone to use as part of an application to establish legal marketing status for the new animal drug.
We also developed an external communications strategy to address the manufacture and use of unapproved new animal drugs. We updated the unapproved new animal drug Webpage, created the year before, to provide information about the benefits and availability of FDA-approved new animal drugs. The story of Pill Bottle Pete was created for the CVM internet Kid’s Page to educate children and teachers about the benefits of approved drugs, and we conducted joint webinars jointly with the American Veterinary Medical Association, now posted on CVM’s website.
On a related issue, we established a working group to address the numerous products marketed without approval as devices for animals that may in fact be subject to FDA’s regulatory regime as animal drugs.
Marketing Certain Nutritional Products for Dogs and Cats
In September 2012, FDA announced the availability of a draft compliance policy guide (CPG) entitled, Labeling and Marketing of Nutritional Products Intended for Use to Diagnose, Cure, Mitigate, Treat or Prevent Disease in Dogs and Cats. The CPG provides guidance to FDA staff and industry on how FDA intends to use its enforcement discretion with regard to the labeling and marketing of these products. These nutritional products or therapeutic diets are pet foods that are specially formulated to address specific disease conditions (for example urinary tract disease in cats).
These products were originally sold through and used under the direction of licensed veterinarians. Recently, FDA has observed an increase in marketing directly to pet owners over the Internet and in supermarkets and pet stores. This shift in marketing directly to pet owners, without veterinary direction, concerns FDA because these products are formulated for specific needs and may not be tolerated by all animals. The draft CPG sets out the factors FDA will consider when determining whether or not to initiate enforcement action if the products are sold or marketed inappropriately.
Addressing Human Public Health Issues Related to Reptiles and Amphibians
Salmonella illnesses during the year challenged us to address public health issues related to turtles and other reptiles and amphibians. The Centers for Disease Control and Prevention (CDC) continued to raise concerns about these Salmonella cases, associated with handling small turtles (shell size less than 4 inches) particularly by young children. A lawsuit filed by turtle farmers in 2010, however, seeks revocation of the FDA regulation related to Salmonella and turtles. Among other actions, a CVM team prepared a detailed response to five questions remanded to the agency by the court. In addition, a CVM representative serves as FDA lead on many 50-State phone calls with CDC in which we have encouraged the states to take a greater role in addressing outbreaks caused by pet turtles, other reptiles, and other amphibians, such as water frogs. A growing number of states including North Carolina, Florida, and Texas are working to change their laws to address outbreaks at a local level.
CVM’s work in this area is yielding benefits for public health protection. Through this effort we have been able to shift the paradigm from uncoordinated response by separate federal and state agencies to a coordinated framework maximizing resources and impact. The new model will focus on prevention and education to reduce and possibly eliminate these types of Salmonella outbreaks in the future.
Adverse Drug Experience (ADE) Reporting and Related Accomplishments
Having ADE data available in an easily reviewable form is absolutely vital when we attempt to identify and evaluate significant adverse events through surveillance methods such as data-mining and case series analysis. D`ata-mining involves using computer algorithms to analyze data in large, complex databases such as CVM’s Adverse Drug Event database. The goal is to discover unexpected occurrences of adverse event signals. If a signal is detected, we conduct a case series analysis by reviewing each individual report for common risk factors that could be associated with the illness or adverse event.
The CVM ADE database includes over 200,000 reports and has developed into a useful tool for identifying new safety concerns associated with marketed animal drugs. In addition, the database serves as a resource to CVM for timely response to requests for ADE information. To accommodate the increasing number of ADE reports received each year and to expedite the adverse event review process, we continued to expand the use of electronic ADE reporting that we began in fiscal year 2011.
Achieving our goal of increased electronic reporting was not without challenge. We worked with IT contractors to navigate through the complexities of implementing several specialized IT systems, which together allow CVM to receive mandatory ADE reports directly from manufacturers. Our efforts, continuing into fiscal year 2012, have been successful. For the year, CVM received a total of 73,406 ADE reports. Industry has embraced the electronic reporting option, as shown by the fact that we received 75 percent of these reports electronically through either the Electronic Submissions Gateway or the Safety Reporting Portal.
CVM has monitored the progress of electronic reporting since it began with FDA TRACK, an agency-wide program performance management system. For fiscal year 2012, electronic reporting grew from a first quarter average of 58 percent to a fourth quarter average of 85 percent.
In addition to this success, CVM reviewers have continued to make significant progress on the entry and review of the existing backlog of paper reports with ongoing support from data entry contractors. CVM staff reviewed a total of 44,968 paper ADEs. At the current rate, the paper backlog is projected to be eliminated during fiscal year 2013.
OSC’s Division of Veterinary Product Safety (DVPS) provided continued surveillance of pet food related illness and product problems through FDA’s Field Accomplishments and Compliance Tracking System (FACTS), an Office of Regulatory Affairs consumer complaint system and through the Safety Reporting Portal. DVPS also initiated integration with the Coordinated Outbreak Response and Evaluation Team (CORE) by having regular communication about what we’re seeing in pet foods regarding complaints, illnesses, and outbreaks.
DVPS also participated in numerous outreach presentations to a variety of audiences (Animal Health Institute, veterinary conferences, veterinary schools), with a dual focus on educating audiences about CVM’s ADE reporting program and on avoiding commonly recognized medication errors.
The MNVP program focuses on shortages of products needed to treat serious or life threatening diseases, as well as those shortages that would have the greatest impact on public health. The consolidation within the animal drug industry, reduction in number of manufacturing sites, and shifting manufacturing overseas have resulted in a greatly reduced ability for the system to respond to drug shortages.
During the year, we identified animal drugs that have only one manufacturing site; developed a table listing animal drug shortage status; established a drug shortage information webpage with up-to-date information on potential, current, and resolved shortages of animal drugs (with links to information on human drug shortages that may impact veterinary practice); and changed internal policy and procedures to improve review times and to establish clear responsibility for specific actions.
In FY 12 we received 12 MNVP requests and an additional 30 requests for information on whether proposed regulatory action would impact drug availability. One example of a medical necessity determination involved an anthelmintic for use in cattle and sheep, and another concerned a narcotic immobilization product used for terrestrial wild and exotic animals.
We responded to all requests within the target 15 day timeframe, with an average response time of 11 days. These responses have enabled CVM to be proactive in preventing or mitigating animal drug shortage, and have provided veterinarians and consumers with needed information on shortages. This includes information that a veterinarian can use in deciding whether to change a drug regimen for a patient.
Health Hazard Evaluations (HHEs) and Product Recalls
The Center accomplished a total of 73 HHEs during FY 2012, including 18 for Salmonella and two for BSE. A “health hazard evaluation” is an evaluation by FDA scientists of the threat to health presented by a product, including its labeling and/or promotional materials, that is being recalled from the market or considered for recall. It takes into account factors such as adverse reactions that have already occurred from the use of the product, assessment of the degree of seriousness of the health hazard to the population at greatest risk, and assessment of long range or immediate consequences of the hazard.
There were 212 product recalls, involving 67 firms. A total of 76 recalls were Class 1 (of greatest public health concern), 88 were Class 2, and 48 were Class 3. One of the Class 1 recalls (expanded to three recalls after investigation) involved a very large quantity of pet food that was contaminated with Salmonella and that caused human illness. A second noteworthy event involved four recalls totaling over 62 million pounds of 92 different animal feed products contaminated with aflatoxin. Prompt action in these instances helped limit adverse human and animal health consequences.
During FY 2012, FDA conducted 112 domestic and seven foreign animal drug-related inspections, and 430 medicated feed mill inspections. In addition, the states conducted 5,517 inspections related to the BSE feed ban, and FDA conducted 1,519 such inspections. Also during the year, CVM processed 79 Warning Letters, 11 injunction actions, two seizure actions, and 23 untitled letters. (These numbers include the actions reported in the section of this report entitled, “Avoiding Unsafe Residues in Human Food”.)
CVM leadership focused on adjustments needed to facilitate faster processing of Warning Letters. This action resulted in completion of 37 of 61 Warning Letters in fewer than 15 days, exceeding the goal by 11 percent. This improved FDA’s ability to take timely action to protect human and animal health. This action reflect Office of Surveillance and Compliance support for the operational goal of the FDA Food and Veterinary Medicine Plan of streamlined processes to enable real-time decisions regarding frontline corrective actions, enforcement and other measures to achieve public health and consumer protection.