Surveillance and Compliance Actions 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 elsewhere in this report, e.g., in the sections entitled, “Ensuring Feed Safety” and “Avoiding Unsafe Drug Residues in Human Food”. We describe a number of other actions in this section.
In November 2010, CVM’s Office of Surveillance and Compliance created the Division of Veterinary Product Safety. Safety reviewers in this new division monitor CVM’s database of adverse events reported for approved and unapproved animal drugs, pet food, and animal devices. Using the information in the database, the safety reviewers identify safety and effectiveness concerns about products marketed for animals. Specifically, the Division of Veterinary Product Safety:
- Monitors the adverse drug event database to identify safety signals and effectiveness issues of concern.
- Evaluates adverse event reports to ensure that the product labeling contains a current accurate safety profile, and identifies unsafe products and unsafe product uses.
- Provides surveillance for adverse events involving consumption of pet food.
- Coordinates with FDA District Offices to receive and evaluate product defect reports for the identification of product safety issues.
For FY 2011, CVM received 54,348 ADE reports. As noted in the section of this report entitled, “Electronic Submission of Adverse Drug Experience Reports” (page xx), an increasing number of these ADE reports were received electronically. With ongoing support from data entry contractors, CVM reviewers have continued to make significant progress on ADE paper backlog reduction. CVM staff reviewed a total of 63,449 ADEs in FY 2011.
The Division of Veterinary Product Safety continued to interact during the year with FDA centers outside of CVM to explore their existing data mining methods. Data mining involves the use of computer algorithms to analyze data in large, complex databases such as our ADE database with the goal of discovering unexpected occurrences of adverse event signals. We anticipate that data mining technologies will be incorporated into our pharmacovigilance program to assist with adverse event safety signal detection to strengthen the Center’s ability to actively monitor the safety of animal drug products.
During the year, the Division of Veterinary Product Safety enhanced the Web site report “Cumulative ADE Summaries Report” to provide the number of times each clinical sign associated with an adverse event was reported alongside the listing of clinical signs. The purpose of the enhancement was to provide the public with a better overall perspective of the ADEs reported for each product. Prior to the change, the signs were listed in decreasing order of frequency, but the public had no information about how many times each clinical sign had been reported. Providing the actual numbers next to each sign gives a better perspective of how many times one sign is reported compared to the other reported signs. For more information please see the FDA’s Web site at the following URL: http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm262670.htm
The Division of Veterinary Product Safety staff drafted VICH Guideline (GL) 35 (Guidance for Industry #214), “Proposed Draft Guidance for Industry on Pharmacovigilance of Veterinary Medicinal Products: Electronic Standards for Transfer of Data,” which was published for comment. The objective of the draft guidance is to provide recommended standards to construct a single electronic message to transmit data elements for submission of adverse event reports to all VICH member regions.
A drug shortage may involve either an actual or a potential shortage of a drug product. When drug shortages involve medically necessary veterinary products, it is CVM’s policy to help prevent or alleviate the shortages. CVM works with drug manufacturers in the United States and, when necessary, other countries, to find ways to resolve shortages of medically necessary veterinary products.
As an example, during FY 2011 CVM announced an anticipated shortage of the injectable drug iron dextran, which is indicated for the prevention and treatment of iron deficiency in baby pigs. CVM considers iron dextran a medically necessary drug and, in order to address and alleviate the inadequate supply, CVM did not object to the temporary importation of iron dextran for a limited period until an adequate U.S. domestically manufactured supply was available. On March 29, 2011, CVM announced the approval of Uniferon (injectable iron), for the prevention and treatment of iron deficiency anemia in baby pigs. The approval of Uniferon provided an adequate U.S. domestically manufactured supply of injectable iron and therefore effectively ended the shortage.
In FY 2011, the Division of Veterinary Product Safety assisted the communications office with several CVM Updates, including:
- “FDA is Warning Pet Owners on the Dangers of Xylitol Ingestion in Dogs and Ferrets”
- “FDA Advises Veterinarians of Recent Recall of Human Drug, Phenobarbital”
- “FDA Warns of Possible Danger with Animal Vaccine Device”
The Office of Surveillance and Compliance has established coordination and communication with the Coordinated Outbreak Response and Evaluation Network, established in August 2011 and located within the Center for Food Safety and Applied Nutrition. The agency created the Coordinated Outbreak Response and Evaluation Network to manage outbreak response and post-response activities related to incidents involving multiple illnesses linked to FDA-regulated human and animal food and cosmetic products. The goal is to strengthen FDA’s efforts to prevent, detect, investigate, respond to, and learn from incidents and outbreaks.
During FY 2011, there were 410 recalls, involving 60 firms/manufacturers, of products regulated by CVM. This included pet food, animal feed, animal drugs, and animal devices. This is more than twice the number in FY 2010. We believe that the increased reporting was due to several actions taken in the past several years. The 2007 FDA Amendments Act authorized the Reportable Food Registry, which requires firms to report Class I recall issues. In addition, CVM’s Division of Compliance has implemented the Pet Food Early Warning Surveillance System which includes several surveillance tools such as a consumer complaint system that allows the public to enter pet food reports through a portal. Also, the Division of Compliance has focused on outreach programs for veterinarians and animal health technicians. During the year, representatives from the Division have made a presentation entitled, “Pet Food Early Warning Surveillance System: The Practitioner’s Role in Pet Food Safety,” to eight of the largest and most prominent veterinary meetings in the United States.
The recalls included:
- 351 Class I recalls (for situations in which there is a reasonable probability that the use of or exposure to a violative product will cause serious adverse health consequences or death). This number compares with 40 the previous year.
- 27 Class II recalls (for situations in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote).
- 32 Class III recalls (for situations in which use of or exposure to a violative product is not likely to cause adverse health consequences).
A significant number (102) of recalled products for FY 2011 were Salmonella related.
CVM officials reviewed labels, labeling, and Web sites of several commercially available pet foods during FY 2011. The Federal Food, Drug, and Cosmetic Act permits pet food manufacturers to make appropriate structure/function claims. However, some structure/function claims imply that the product is intended to diagnose, cure, mitigate, treat, or prevent disease. In that case, the product is regulated as a drug. CVM’s reviews resulted in the issuance of a Warning Letter to a pet food manufacturer whose product is an unapproved new animal drug based on its claims.
CVM officials also issued a Warning Letter to a low-acid canned food manufacturing facility that manufactures pet food. Inspection and testing determined that several pet foods manufactured at the site were adulterated in that valuable constituents listed on the labels were not present in the product. Other ingredients, not listed on the labels, had been substituted.
During FY 2011, FDA conducted 112 domestic and 7 foreign animal drug-related inspections. The agency also conducted 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, 2 seizure actions, and 23 untitled letters. (These numbers include the actions reported in the section of this report entitled, “Unsafe Residues in Human Food,” on page XX)
CVM continued to be actively involved with enforcement activities related to drugs that are manufactured, packaged and shipped by compounding pharmacies. The objective of the FDA pharmacy inspections is to determine whether a firm is engaged in illegal compounding activities including, but not limited to, the importation, manufacturing, and marketing of unapproved new animal drugs. The firm’s activities are of particular concern if it is suspected of compounding drugs for use in food-producing animals and is selling these drug products outside the scope of a valid veterinarian-client-patient relationship.
Traditionally, “compounding” has been defined as the preparation of a drug by a pharmacist to meet the individual or unique needs of a particular patient, as determined by that patient’s veterinarian within the context of a valid veterinarian-client-patient relationship. Over time, compounding of dosage-form drugs for animal use has developed into large-scale manufacturing of drugs by various “compounding pharmacies” operating as manufacturers under the guise of pharmacies. Such pharmacies provide little or no assurance as to the safety and efficacy of these animal drugs, an assurance that is provided through the drug approval process and enforcement of the current Good Manufacturing Practices regulations.