Guideline for Adverse Experience Reporting
for Licensed Biological Products
- Adverse experience
- any undesirable event reported to or known by the licensed manufacturer
that is associated with the use of the product in humans, whether
or not considered product-related by the licensed manufacturer.
Reporting an adverse experience does not necessarily reflect a
conclusion by the licensed manufacturer or FDA that the event
is causally related to the product. An adverse experience may
occur in professional practice, as a result of self-medication,
from overdose, whether accidental or intentional, from withdrawal,
or when a product fails to produce the expected pharmacological
action (failure of effect).
- Any corporate entity related to the licensed manufacturer, including
all subsidiaries, licensors, etc.
- Causality assessment
- Determination of whether there is reasonable possibility that
the product is etiologically related to the adverse event. Causality
assessment includes, for example, assessment of temporal relationships,
dechallenge/ rechallenge information, association with (or lack
of association with) underlying disease, presence (or absence)
of a more likely cause, plausibility, etc.
- administration of a suspect product by any route.
- withdrawal of a product
from the patient's therapeutic regimen.
- Negative dechallenge
presence of an adverse experience after withdrawal of the drug.
- Positive dechallenge
- partial or complete disappearance of an adverse event after withdrawal of
- reintroduction of a
product suspected of having caused an adverse event following
a positive dechallenge.
- Negative rechallenge
- failure of
the product, when reintroduced, to produce signs or symptoms similar
to those observed when the product was previously introduced.
- Positive rechallenge
of similar signs and symptoms upon reintroduction of product.
- CIOMS form
- An adverse reaction reporting form developed by the Council for
International Organizations of Medical Sciences (CIOMS), intended
for notifying the regulatory authorities of countries
other than the country where the report originated.
- Expected experience
- an adverse experience described in the ADVERSE REACTIONS, WARNINGS
or PRECAUTIONS section of the current labeling. Also referred
to as a labeled experience.
- The International Classification of Diseases, ninth revision,
Clinical Modification. This coding system, in the context of this
Guideline, is used to assign standardized numerical coding and
nomenclature for underlying medical conditions and indications.
- Increased frequency
- an increase in the reported rate of occurrence of a particular
adverse biological product experience after appropriate adjustment
for biological product exposure.
- an investigational new drug application for a new biological
product that is used in a clinical investigation. The term also
includes a biological product that is used in vitro for diagnostic
- Licensed manufacturer
establishment issued a product license under 21 CFR 601.20.
- an adverse experience that is fatal or life-threatening, is permanently
disabling, requires inpatient hospitalization, or is a congenital
anomaly, cancer or overdose.
- a person who takes responsibility for and initiates a clinical
investigation. The sponsor may be an individual or pharmaceutical
company, governmental agency, academic institution, private organization,
or other organization.
- A postmarketing, clinical or surveillance investigation with a
protocol identifying specific objectives and a scientific methodology
for collecting and analyzing adverse experience data. Adverse
events incidental to other types of studies should be treated
as spontaneous reports.
- a human who participates in an investigation, either as a recipient
of the investigational new drug or as a control. A subject may
be a healthy human or a patient with a disease.
- a product associated with the adverse experience as determined
by the initial reporter, regardless of the opinion of the licensed
- Unexpected Experience
- an adverse experience that is not listed in the current labeling
for the product; this includes an event that may be symptomatically
and pathophysiologically related to an event listed in the labeling,
but differs from the event because of greater severity or specificity.
In some cases, it may be difficult to decide whether the reported
experience is expected. In these situations, the event should
be considered unexpected. An unexpected
experience is also referred to as an unlabeled
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