Guideline No. 117
Guidance for Industry: Pharmacovigilance of Veterinary Medicinal Products: Management of Adverse Event Reports (AER's) - VICH GL24 - DRAFT GUIDANCE
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
CENTER FOR VETERINARY MEDICINE
Guidance for Industry
Pharmacovigilance of Veterinary Medicinal
Products: Management of Adverse Event Reports
(AER's) - VICH GL24
DRAFT GUIDANCE...
This guidance document is being distributed for comments only
This draft guidance document describes a system for the management of adverse drug event reports following the use of marketed veterinary medicinal products.
Comments and suggestions regarding the document should be submitted to Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments. All comments should be identified with the Docket No. 2000D-1632.
For questions regarding this document, contact Lynn Post, Center for Veterinary Medicine, (HFV-210), Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, 240-276-9062; e-mail: lynn.post@fda.hhs.gov.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Veterinary Medicine
May 1, 2006
VICH GL 24 (PHARMACOVIGILANCE)
November 2005
For consultation at Step 4
PHARMACOVIGILANCE OF
VETERINARY MEDICINAL PRODUCTS:
MANAGEMENT OF
ADVERSE EVENT REPORTS
Recommended for Consultation
at Step 4 of the VICH Process
on 2 November 2005
by the VICH Steering Committee
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THIS GUIDANCE HAS BEEN DEVELOPED BY THE APPROPRIATE VICH EXPERT WORKING GROUP AND IS SUBJECT TO CONSULTATION BY THE PARTIES, IN ACCORDANCE WITH THE VICH PROCESS. AT STEP 7 OF THE PROCESS THE FINAL DRAFT WILL BE RECOMMENDED FOR ADOPTION TO THE REGULATORY BODIES OF THE EUROPEAN UNION, JAPAN AND USA. |
Pharmacovigilance of Veterinary Medicinal Products:
Management of Adverse Event Reports
I. Introduction
II. Scope
III. Definitions
III.1 Veterinary Medicinal Product (VMP)
III.2 Adverse event (AE)
III.3 Serious adverse event
III.4 Unexpected adverse event
III.5 Adverse Event Report (AER)
III.6 Marketing Authorization Holder (MAH)
III.7 Regulatory Authority (RA)
III.8 Periodic Summary Update (PSU)
III. 9 International Birth Date
IV.1 Information flow in the Pharmacovigilance System.
IV.2 Informational unit
IV.3 Recording AER's
IV.4 Submitting AER's
IV.5 Expedited AER submissions
IV.6 Periodic AER submissions
IV.7 Reporting source
This draft guidance, when finalized, will represent the Food and Drug Administration’s (FDA’s) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of
I. Introduction
Pharmacovigilance of veterinary medicinal products (VMPs) can be defined as the detection and investigation of the effects of the use of these products, mainly aimed at safety and efficacy in animals and safety in people exposed to the products. This document will only deal with the spontaneous reporting system for identification of possible adverse events following the use of marketed VMPs.
Within all regions involved in the VICH process there are certain legal obligations for the pharmaceutical industry, the commercial party responsible for the products, with regard to adverse events reported to them. Those legal obligations relate to the acceptance of adverse event reports and the storage and submission of those reports to the authorities.
It is of importance for all parties, the Marketing Authorization Holders (MAHs), the Regulatory Authorities (RA) and the users of VMPs to develop harmonized and common systems, common definitions and standardized terminology within pharmacovigilance. Harmonization of those elements between the regions facilitates the reporting responsibilities for the MAHs, many with worldwide activities. At the same time harmonization of systems and requirements facilitates the inter-regional comparison of data and exchange of information, thereby increasing the general knowledge of a product`s general performance and safety profile.
FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word “should” in Agency guidances means that something is suggested or recommended, but not required.
II. Scope
The scope of pharmacovigilance in this VICH document is defined as the management of the detection and investigation of the clinical effects of marketed VMPs mainly concerned with the safety and efficacy in animals and the safety in people exposed to these products. While pharmacovigilance in its broadest sense may entail a wide range of activities, this document only deals with the spontaneous reporting system for the identification of possible adverse events following the use of marketed VMPs.
III. Definitions
The terms and definitions in this document are intended to harmonize other previously used terms referring to similar concepts. Within the scope of this document the following definitions of items or actions have been developed.
III.1 Veterinary Medicinal Product (VMP)
Any medicinal product with approved claim(s) to having a protective, therapeutic or diagnostic effect or to alter physiological functions when administered to or applied to an animal. The term applies to therapeutics, biologicals, diagnostics and modifiers of physiological function. (For the definitions of "drug" and "new animal drug" in the U.S., see 21 U.S.C. 321(g)(1) and (v).)
The “same biological VMP” is defined as originating from the same MAH being responsible for pharmacovigilance of this/these VMPs with same manufacturing specifications.
The “same pharmaceutical VMP” is defined as originating from the same MAH being responsible for pharmacovigilance of this/these VMPs with same formulations.
A “similar pharmaceutical VMP” is defined as:
originating from the same MAH being responsible for pharmacovigilance of this/these VMPs,
the same active ingredients,
major excipients with the same or similar pharmaceutical function,
at least one common registered species.
III.2 Adverse event (AE)
An adverse event is any observation in animals, whether or not considered to be product-related, that is unfavorable and unintended and that occurs after any use of VMP (off-label and on-label uses). Included are events related to a suspected lack of expected efficacy according to approved labeling or noxious reactions in humans after being exposed to VMP(s). (See 21 C.F.R. 514.3 for the definition of an adverse drug experience in the U.S.)
An AE may at some point be concluded by a RA to be an adverse reaction when there is at least a reasonable possibility (i.e., relationship cannot be ruled out) that harmful and unintended observations were a response to a VMP administered at doses normally used in animals for prophylaxis, diagnosis or therapy of disease or for modification of physiological function.
III.3 Serious adverse event
A serious adverse event is any adverse event which results in death, is life-threatening, results in persistent or significant disability/incapacity, or a congenital anomaly or birth defect. (See 21 C.F.R. 514.3 for the definition of a serious adverse drug experience in the U.S.)
For animals managed and treated as a group, only an increased incidence of serious adverse events as defined above exceeding the rates normally expected in that particular group is considered a serious adverse event.
III.4 Unexpected adverse event
An unexpected adverse event is an adverse event of which the nature, severity or outcome is not consistent with approved labeling or approved documents describing expected adverse events for a VMP. (See 21 C.F.R. 514.3 for the definition of an unexpected adverse drug experience in the U.S.)
III.5 Adverse Event Report (AER)
An adverse event report is a direct communication from an identifiable first-hand reporter (see IV.7) that includes at least the following information:
an identifiable reporter
an identifiable animal(s) or human(s)
an identifiable VMP
one or more adverse events
One animal or one human being, or a medically appropriate group exhibiting similar clinical signs should be included in a single report.
III.6 Marketing Authorization Holder (MAH)
The Marketing Authorization Holder is the commercial party who, according to the RA is responsible for the pharmacovigilance of the VMP. (See 21 CFR 514.80 for requirements on establishing, maintaining, and reporting required information relating to experiences with a new animal drug, defined in 21 U.S.C 321(v).)
III.7 Regulatory Authority (RA)
The Regulatory Authority is the national or regional authority which, according to the legislation, is responsible for the issuing, adaptation or withdrawal of marketing authorizations/licences of VMPs and for pharmacovigilance activities. (See 21 U.S.C 360b.)
III.8 Periodic Summary Update (PSU)
The document submitted to the RA at set intervals to support the continued marketing and the adequacy of the approved labeling of the VMP and will include an analysis of all AERs received during the interval. (See 21 C.F.R. 514.80 for periodic drug experience report requirements in the U.S.)
III.9 International Birth Date
International Birth Date (IBD) is the date of the first marketing authorization for same or similar product granted in any VICH region.
IV. The Pharmacovigilance Process
IV.1 Information flow in the Pharmacovigilance System.
The flow of information is illustrated below:
Information flow in the pharmacovigilance system.
Data preferably flows as shown in the upper half of the figure, where the reporter communicates with the MAH and the MAH submits AERs it has received to the RA. An alternate path is shown in the lower half, where the reporter communicates with the RA and the RA notifies the MAH of AERs it has received.
IV.2 Informational unit
The basic unit of information in the pharmacovigilance system covered by this document is the AER.
IV.3 Recording AER's
The MAH should record each AER received and store it in a manner which allows easy access to the data. The receipt, acknowledgement or recording of an AER by the MAH or the RA does not necessarily have any implication regarding the veracity or authenticity of the AER nor implies any degree of causality. See 21 C.F.R. 514.80 for recordkeeping requirements in the U.S.
IV.4 Submitting AER's
The MAH must submit an AER to regional authorities as provided by relevant laws or legislation either as an expedited submission or as a periodic submission. See 21 C.F.R. 514.80 for reporting requirements. The submission of an AER does not necessarily imply an endorsement or agreement with its content, unless regional or national regulations require differently.
IV.5 Expedited AER submissions
Expedited submission of certain AERs may be required (see 21 CFR 514.80), related to the seriousness or unexpectedness of the reported event or because of the urgency of its implications regarding the safety of animals or man.
Expedited submission to RAs in other VICH regions/observer countries will occur when:
an AER is an expedited submission in the country where the AER occurs and
the same VMP is approved in other VICH regions/observer countries and
the species of animal involved in the AER is a species approved in the other VICH regions/observer countries or
there are serious implications regarding human safety
The timeclock for the expedited submission to RAs in other VICH regions/observer countries begins when the AER becomes the knowledge of the MAH within the other region. A follow-up submission will occur when the investigation of the AER is completed by the MAH in the country where the AER occurred.
If, based on these expedited submissions, the RA decides on a regulatory action, the MAH will immediately inform all VICH regions/observer country RAs where the same VMP is approved about this action.
In addition, when the MAH determines that it is likely that actions will be implemented based on the AERs it has received, the MAH will contact all VICH regions/observer RAs where the same VMP is approved to inform them of the MAH concerns and its likely actions.
IV.6 Periodic AER submissions
At regular intervals, the MAH must submit all AERs not previously submitted. See 21 C.F.R. 514.80 for periodic drug experience report requirements in the U.S.
IV.7 Reporting source
Although reporting via the attending veterinarian is encouraged, an AER may be initiated by anyone directly involved with the purported adverse event. Preferably, an AER is communicated by the reporter directly to the MAH, but the AER may also have been routed through an agent or the RA. A communication through an intermediate agent should be considered an AER only if the agent has been authorized by the reporter and provides sufficient information to allow direct contact between the reporter and the MAH.
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