Vaccine Adverse Event Reporting
Background
The National Childhood Vaccine Injury Act (NCVIA) of 1986 mandated the reporting of certain adverse events fol-lowing the vaccination of children to help ensure the safety of vaccines distributed in the United States. The Act led to the establishment of the Vaccine Adverse Event Reporting System (VAERS) in November 1990 by the Department of Health and Human Services. Today, VAERS provides a data-base management system for the collection and analysis of data from reports of adverse events following vaccination of humans. However, there is currently no federal or state man-date for veterinarians to report adverse events associated with animal vaccination. Practitioner reports of known or suspected vaccine adverse events in animals may be volun-tarily submitted to either the vaccine manufacturer, the U.S. Department of Agriculture Center for Veterinary Biologics, or the United States Pharmacopeia (USP) through the Veteri-nary Practitioners’ Reporting Program (VPRP).
At the time of this writing, an amendment 35 to the Virus-Serum- Toxin Act has been proposed by the U.S. Animal and Plant Health Inspection Service to:
1. require veterinary biologics manufacturers (licensees and permittees) to record and submit reports to the APHIS concerning adverse events associated with the use of biological products they produce or distribute,
2. require veterinary biologics manufacturers to report to the APHIS the number of doses of each licensed product they distribute, and
3. provide definitions for adverse event and adverse event report.
NOTE: The definitions and information provided below on vaccine adverse events and adverse event reporting are sub-ject to change if this amendment is approved.
Definition
For purposes of this discussion, a vaccine adverse event is defined as any undesirable side effect or unintended effect (including lack of desired result) associated with the administration of a licensed biological product (vaccine).
For vaccines administered to animals, adverse events are those involving the health of the treated animal and include the apparent failure to protect against a disease.
It is impor-tant to note that an adverse event includes any injury, toxic-ity, or sensitivity reaction associated with the use of a vaccine, whether or not the event can be directly attributed to the vaccine. In other words, it is appropriate to report any known or suspected event associated with vaccination. A vaccine adverse event report may be defined as a source of communication concerning the occurrence of one or more suspected adverse events, which identifies the product(s), animal(s), and person making the report.
Purpose of Reporting
Reporting field observations of unexpected vaccine perform-ance is the most important means through which the manufac-turer and the regulating agency (and the American Veterinary Medical Association) can be made aware of potential vaccine safety or efficacy problems that, if necessary, warrant further investigation. If a particular adverse event is well documented, reporting serves to provide a baseline against which future reports can be compared. In addition, reported adverse events could lead to the detection of previously unrecognized reac-tions, to the detection of increases in known reactions, to the recognition of risk factors associated with reactions, to the identification of vaccine lots with unusual events or unex-pected numbers of adverse events, and to further clinical, epi-demiological, or laboratory studies. Therefore, veterinarians are encouraged to report any clinically significant adverse event occurring during or after administration of any vaccine licensed in the United States. Reporting a vaccine adverse event is not an indictment against a particular vaccine. Report-ing simply facilitates review of temporally associated condi-tions and adds to the safety database of the product.
Reporting a Vaccine Adverse Event
The AVMA Council on Biologic and Therapeutic Agents has reported that the current adverse event reporting system needs significant improvement in the capture, analysis, and reporting of adverse events.36 Veterinarians are encouraged to participate in the vaccine adverse event reporting process by reporting suspected and known adverse events to any of the following three locations:
1. The vaccine manufacturer, usually through telephone communication with technical services [Table 3];
2. the USDA-CVB by toll-free call (800-752-6255); or
3. the United States Pharmacopeia (USP) Veterinary Practi-tioners’ Reporting Program (VPRP) by toll-free call (800-487-7776; press #3), by fax (301-816-8373), or online (
www.usp.org/vprp).
Reports made to the USDA are forwarded directly to the vaccine manufacturer without specific action. Although adverse event reports made to the USP VPRP are collected and maintained in a database, individual vaccine adverse event reports are not necessarily forwarded by USP to the vaccine manufacturer. While still available, the future of the USP VPRP is currently under review.
Event Criteria
Reporting a known or suspected vaccine adverse event should include the:
1. Manufacturer’s name
2. Product brand name, lot/serial number, and expiration date
3. U.S. veterinary license number and product code
4. Signalment (age, species, breed, gender) of patient affected
5.
A description of the clinical signs or diagnosis associ-ated with administration of the vaccine. Although spe-cific reporting criteria are not defined for clinical events, the type of reaction and length of time between adminis-tration of the vaccine and onset of the adverse event should be documented using the following guidelines:
a. Local (injection-site) reactions occur exclusively at or around the site of inoculation. They may occur at the time of injection, or several minutes, hours, or days later and may persist from minutes (e.g., pruritus) to months (e.g., granuloma). Reports should include the route of administration (i.e., subcutaneous, intramus-cular, or topical [oral, conjunctival, or nasal]). Exam-ples of injection-site (local) reactions following vaccination include pain, pruritus, swelling, injection-site alopecia, abscess formation, granuloma forma-tion, and neoplasia. Infection and skin necrosis are rare but have been reported. Vaccines licensed for administration by the topical (conjunctival/intranasal) route have been associated with sneezing (persisting =3 days), nasal and oral ulceration, ocular discharge, and cough (persisting >24 hours).
b. Systemic reactions are events that involve the entire body or a defined location/region other than the injec-tion site. Like injection-site reactions, systemic reac-tions typically don’t occur at the time of injection but can develop within minutes or hours and may persist for hours or days. Examples of systemic reactions fol-lowing vaccination include angioedema, especially involving the face, muzzle, and ears (most often reported in dogs); anaphylaxis and collapse; poly-arthritis (lameness); vomiting with or without diar-rhea (most often reported in cats); respiratory distress; fever; and lethargy. Severe events that may be vaccine associated requiring long-term medical intervention and patient follow-up include immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, icterus, renal failure, and glomerulo-nephritis.
c. Vaccine-associated death, although rare, does occur. In dogs, anaphylactic shock is the most commonly reported adverse event leading to death. There has been no trend to suggest an association between ana-phylaxis and a particular manufacturer’s vaccine. Vet-erinarians are strongly encouraged to report any death suspected or known to be associated with vaccination to the vaccine manufacturer
