Page 130 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Regulatory Considerations in Veterinary Toxicology Chapter | 6 97

VetBooks.ir interactions, factors specific to certain patient populations, distributors of FDA-approved animal drugs are contained
in 21 CFR y514.80, “Records and reports concerning
individual patient factors, medication errors, product
experience with new animal drugs for which an approved
defects, or other factors, such as the reaction being too
uncommon to be identified in the small number of ani- application is in effect.” ADE reports are classified into
mals in which the drug is tested in preapproval studies essentially four categories: (1) 3-day field alerts, (2) 15-
(CIOMS, 2010). Spontaneous reports of ADEs, medica- day alert initial reports, (3) follow-up reports, and (4)
tion errors and product defects comprise the primary data periodic reports. As defined in 21 CFR y514.80(b)(1),
source upon which the CVM’s postapproval pharmacov- 3-day field alert reports contain information regarding
igilance efforts depend. Also, data from postapproval clin- product and manufacturing defects that may result in seri-
ical studies and from the scientific literature may be ous ADEs. Reports of serious, unexpected ADEs are sub-
utilized. Limitations of utilizing spontaneous ADE report- mitted as 15-day alert or “expedited” reports. As required
ing databases for pharmacovigilance activities include the in 21 CFR y514.80(b)(2), these reports must be submitted
significant underreporting of ADEs, limited detail in sub- on Form FDA 1932 to FDA by the applicant within 15
mitted reports, and reporting bias. Given the variability in working days of first receiving the information. Follow-
reporting and the many factors that affect reporting, ADE up reports are submitted on Form FDA 1932 by the appli-
reporting rates cannot be used to reliably estimate inci- cant if significant new information is revealed during their
dence rates of ADEs in the exposed population. Despite investigation of ADEs that are the subject of 15-day alert
these limitations, the monitoring and evaluation of ADE reports. Reports of ADEs that are not serious and unex-
reports is very important to help ensure that the overall pected and reports of product defects that are not expected
balance of risks and benefits of a particular drug remain to result in serious ADEs are submitted in the periodic
acceptable. Additionally, it allows for communication of drug experience report, which is submitted every 6
essential drug safety information to veterinarians and months for the first 2 years after approval and annually
others involved in the treatment of animals. thereafter.
Most mandatory ADE reports (from manufacturers)
Adverse Drug Experience: Definition are submitted electronically and transmitted via the
Electronic Submissions System (ESS), which is integrated
An ADE, as currently defined by regulation in 21 CFR
with the FDA Electronic Submissions Gateway (ESG)
y514.3, is any adverse event associated with the use of a
and allows for individual or batched reports. Individual
new animal drug, whether or not considered to be drug
reports can also be submitted by manufacturers via a
related, and whether or not the new animal drug was used
Rational Questionnaire (RQ) in the Safety Reporting
in accordance with the approved labeling (i.e., used
Portal, or SRP. At this time, the SRP is not configured to
according to label directions, or used in an extra-label
accept adverse drug event reports from veterinarians or
manner, including but not limited to different route of
consumers. More information about voluntary reporting
administration, different species, different indications, or
of adverse events is available on the CVM website (FDA/
other than labeled dosage). ADE includes, but is not lim-
CVM, 2016b). All reports, mandatory and voluntary,
ited to: an adverse event occurring in animals in the
enter the CVM ADE database for analysis and archiving.
course of the use of an animal drug product by a veteri-
ADE reporting to the CVM has increased dramatically
narian or by a livestock producer or other animal owner
over the last decade. The CVM received 28,825 ADE
or caretaker; failure of a new animal drug to produce its
reports for the fiscal year 2004 and 91,592 for the fiscal
expected pharmacological or clinical effect (lack of
year 2015. Some of the reasons for the significant
expected effectiveness); or an adverse event occurring in
increase may include an increase in number of drug
humans from exposure during manufacture, testing, han-
approvals, label information that provides contact num-
dling or use of a new animal drug.
bers for drug companies, and the interest of the public in
reporting perceived product problems. In addition, wide
Adverse Drug Experience Reporting access to the media and Internet has increased the public’s
In the United States, ADE reporting by veterinarians and general awareness about drug safety.
consumers is voluntary. However, manufacturers and dis-
tributors of FDA-approved animal drugs may be subject
to mandatory ADE reporting requirements as described Unapproved Drugs and Veterinary Devices
by regulation (21 CFR y514.80). All unsolicited reports ADE submission is mandatory only for companies mar-
from veterinarians or consumers, received by the FDA via keting FDA-approved and conditionally approved animal
either the voluntary or mandatory route, are called sponta- drugs. Currently there are no requirements for submitting
neous reports. The regulations that address the spontane- ADEs for unapproved animal drugs (animal drugs which
ous reporting obligations for manufacturers and have not gone through the FDA’s approval process) or