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Rules and Regulations Federal Register

8825 

Vol. 79, No. 31 

Friday, February 14, 2014 

CONSUMER PRODUCT SAFETY 

COMMISSION 

[CPSC Docket No. CPSC–2013–0010] 

16 CFR Part 1500 

Hazardous Substances and Articles; 

Administration and Enforcement 

Regulations: Final Rule; Revisions to 

Supplemental Definition of ‘‘Strong 

Sensitizer’’ 

AGENCY: Consumer Product Safety 

Commission. 

ACTION: Final rule. 

SUMMARY: The U.S. Consumer Product 

Safety Commission (CPSC or 

Commission) amends it regulations to 

revise the supplemental definition of 

‘‘strong sensitizer’’ under the Federal 

Hazardous Substances Act (FHSA). The 

revised definition of ‘‘strong sensitizer’’ 

eliminates redundancy, removes certain 

subjective factors, incorporates new and 

anticipated technology, places the 

criteria for classification of strong 

sensitizers in the order of importance, 

defines criteria for ‘‘severity of 

reaction,’’ and provides for the use of a 

weight-of-evidence approach to 

determine whether a substance is a 

strong sensitizer. 

DATES: The rule will become effective 

on March 17, 2014. 

FOR FURTHER INFORMATION CONTACT: 

Carol Afflerbach, Compliance Officer, 

Office of Compliance and Field 

Operations, U.S. Consumer Product 

Safety Commission, 4330 East-West 

Highway, Bethesda, MD 20814; email: 

cafflerbach@cpsc.gov. 

SUPPLEMENTARY INFORMATION: 

A. Background 

The FHSA, 15 U.S.C. 1261–1278, 

requires appropriate cautionary labeling 

on certain hazardous household 

products to alert consumers to the 

potential hazards that a product may 

present. Among the hazards addressed 

by the FHSA are products containing 

substances that are toxic, corrosive, an 

irritant, flammable or combustible, 

generate pressure through 

decomposition, heat or other means, or 

are strong sensitizers. 

Included within the FHSA’s 

definition of ‘‘hazardous substance’’ is 

‘‘any substance or mixture of 

substances’’ that ‘‘is a strong sensitizer,’’ 

15 U.S.C. 1261(f)1(iv). Section 2(k) of 

the FHSA, 15 U.S.C. 1261(k), defines 

‘‘strong sensitizer’’ as a substance which 

will cause on normal living tissue 

through an allergic or photodynamic 

process a hypersensitivity which 

becomes evident on reapplication of the 

same substance and which is designated 

as such by the Commission. Before 

designating any substance a strong 

sensitizer, the Commission, upon 

consideration of the frequency of 

occurrence and severity of the reaction, 

shall find that the substance has a 

significant potential for causing 

hypersensitivity. 

On August 12, 1961, the U.S. Food 

and Drug Administration (FDA) (which 

at that time administered the FHSA), 

issued regulations under the FHSA that 

supplemented the statutory definition of 

‘‘strong sensitizer’’ by explaining that a 

‘‘ ‘strong allergic sensitizer’ is a 

substance that produces an allergenic 

sensitization in a substantial number of 

persons that come into contact with it’’ 

and specifying that ‘‘[a]n allergic 

sensitization develops by means of an 

‘antibody mechanism’ in 

contradistinction to a primary irritant 

reaction which does not arise because of 

the participation of an ‘antibody 

mechanism.’ ’’ 26 FR 7333, 7334. The 

regulation (the 1961 supplemental 

definition) listed five substances that 

the FDA had determined met the 

statutory definition for ‘‘strong 

sensitizer’’: (1) Paraphenylenediamine 

and products containing it; (2) 

powdered orris root and products 

containing it; (3) epoxy resins systems 

containing in any concentration 

ethylenediamine, diethylenetriamine, 

and diglycidyl ethers of molecular 

weight less than 200; (4) formaldehyde 

and products containing 1 percent or 

more of formaldehyde; and (5) oil of 

bergamot and products containing 2 

percent or more of oil of bergamot. Id. 

at 7335. Neither the FDA nor the CPSC 

has added any strong sensitizers to this 

list in the 1961 supplemental definition. 

In 1973, Congress transferred the 

responsibility for the administration of 

the FHSA to the Commission. On May 

30, 1984, the Commission revoked the 

1961supplemental definition because 

the 1961 supplemental definition did 

not account for more recent scientific 

theories and was narrower than the 

statutory definition. 49 FR 22464. 

On August 14, 1986, the Commission 

issued a rule supplementing the 

statutory definition of ‘‘strong 

sensitizer’’ (1986 supplemental 

definition). 51 FR 29094. The 1986 

supplemental definition clarified how 

the statutory definition should be 

interpreted and explained the factors 

the Commission would consider in 

determining whether a substance is a 

strong sensitizer. The 1986 

supplemental definition stated that an 

‘‘allergic’’ response is one that is 

directed by the immune system, such 

that a sensitization reaction could not be 

caused by an irritant or other 

nonallergenic qualities of the substance. 

The 1986 supplemental definition also 

clarified that active sensitizers— 

substances that produce a sensitivity 

reaction solely as the result of a person’s 

first exposure to the substance as 

opposed to a reaction after reapplication 

of the same substance—are included in 

the class of substances that can be 

determined to be strong sensitizers. The 

1986 supplemental definition did not 

address strong sensitizers that cause 

hypersensitivity by a photodynamic 

process, principally because 

Commission staff was unaware of any 

household product subject to the FHSA 

that would cause significant exposure of 

consumers to a photodynamic chemical. 

In 2005, recognizing that the science 

on sensitization had changed since 

promulgation of the 1986 supplemental 

definition, the CPSC convened a panel 

of scientific experts from academia, 

industry, and the federal government to 

examine the available scientific and 

medical information concerning 

sensitizers, and if appropriate, propose 

revisions to the supplemental definition 

of ‘‘strong sensitizer.’’ Based on the 

panel’s input, CPSC staff developed a 

draft technical report on proposed 

revisions to the supplemental 

definition. In 2007, the draft technical 

report underwent federal agency and 

external scientific peer review. In 2008, 


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CPSC staff revised the draft technical 

report based on the input received from 

federal agency and external scientific 

peer reviewers. Subsequently, CPSC 

staff drafted a revision of the ‘‘strong 

sensitizer’’ supplemental definition, 

based on the peer reviewed technical 

report. 

The Commission approved 

publication of a notice of proposed 

rulemaking (NPR) to revise the 

supplemental definition of ‘‘strong 

sensitizer’’ (proposed definition or 

proposed rule). 78 FR 15660 (March 12, 

2013). The proposed definition of 

‘‘strong sensitizer’’ eliminates 

redundancy, removes certain subjective 

factors, incorporates new and 

anticipated technology, ranks the 

criteria for classification of strong 

sensitizers in the order of importance, 

defines criteria for ‘‘severity of 

reaction,’’ and provides for the use of a 

weight-of-evidence approach to 

determine whether a substance is a 

strong sensitizer. 

In addition, the Commission 

approved publication of a notice of 

availability for a document prepared by 

CPSC staff titled, ‘‘Strong Sensitizer 

Guidance.’’ 78 FR 15710 (March 12, 

2013). This guidance document was 

intended to clarify each component of 

the revised ‘‘strong sensitizer’’ 

definition and assist manufacturers in 

understanding how CPSC staff would 

assess whether a substance or product 

containing that substance should be 

considered a strong sensitizer and how 

the Commission would make such a 

determination. 

B. Response to Comments on the 

Proposed Rule 

We received five comments on the 

NPR. The following individuals or 

entities submitted comments: a 

consulting toxicologist; the International 

Fragrance Association of North 

America; the People for the Ethical 

Treatment of Animals (PETA); the 

International Science Consortium and 

the Physicians Committee for 

Responsible Medicine; the American 

Chemistry Council; and the 

Diisocyanates Panel of the American 

Chemistry Council. 

Several commenters expressed 

general support for the proposed rule 

and made statements supporting 

specific aspects of the rule. For 

example, several commenters supported 

deleting the reference to sensitizers that 

occasionally induce an allergic response 

on first exposure so that substances that 

merely cause irritation upon initial 

exposure will not be considered strong 

sensitizers. Similarly, a commenter 

agreed with the proposal’s emphasis 

that sensitization is an immunologically 

mediated, multi-stage process that 

occurs over a period of time. Several 

commenters raised issues that resulted 

in minor organizational and terminology 

changes to the proposed rule. All of the 

comments can be viewed at: 

www.regulations.gov, by searching 

under the docket number of the 

rulemaking, CPSC–2013–0010. 

Following is a summary of, and 

responses to, the comments. 

Harmonization with International 

Criteria 

Comment: Two commenters 

recommended that the CPSC take action 

to align the agency’s chemical 

classification regulations and practices 

with internationally harmonized 

criteria, encouraging the Commission to 

implement the Globally Harmonized 

System of Classification and Labeling of 

Chemicals (GHS). One of the 

commenters argued that harmonization 

of chemical classification and labeling 

will promote regulatory efficiency and 

facilitate trade without lowering the 

level of health and environmental 

protection afforded by current U.S. laws 

and regulations. One of the commenters 

recommended that the Commission use 

the GHS cut-off value criteria for 

determining whether a substance is a 

sensitizer, unless there has been 

sensitization testing on the substance or 

product containing the substance. 

Response: The GHS is a system for 

standardizing and harmonizing the 

classification and labeling of chemicals, 

but the GHS is not a regulation or a 

standard. The intent of the GHS is to 

provide an internationally 

comprehensible system for 

communicating chemical hazards to all 

sectors (e.g., consumers, workers, 

emergency responders, and the public) 

along the entire life cycle of the 

chemical. The GHS establishes agreedupon hazard classification and 

communication criteria with 

explanatory information on how to 

apply the system. Implementation of the 

GHS by the Commission would be 

broad-reaching, with potential impact 

beyond the FHSA, possibly involving 

the revision of existing CPSC statutes 

and regulations. The request that the 

Commission implement the GHS, 

therefore, goes well beyond the limited 

scope of this rulemaking proceeding. 

Description of Strong Sensitizer 

Determination Process 

Comment: Two commenters requested 

a description of the administrative 

process that would be used to make a 

determination that a substance or 

product containing a substance is a 

strong sensitizer so that stakeholders 

will be aware of opportunities for 

participation in the process. 

Response: Under the FHSA, the 

Commission must first designate a 

substance a ‘‘strong sensitizer’’ for the 

substance to be considered a ‘‘strong 

sensitizer.’’ (15 U.S.C 1261(k)). Such a 

designation would occur in a separate 

proceeding that is outside the scope of 

this action. The current action relates 

only to the regulatory definition of a 

‘‘strong sensitizer,’’ not to the 

designation of a particular substance as 

a strong sensitizer. 

Labeling Requirement for Strong 

Sensitizers 

Comment: One commenter requested 

that the Commission set forth the 

circumstances under which a substance 

or product containing a substance that 

has been designated a strong sensitizer 

would not require labeling under 

Section 2(p) of the FHSA (15 U.S.C. 

1261(p). 

Response: A substance that is a strong 

sensitizer or a product containing a 

strong sensitizer would not require 

labeling, unless the substance met the 

FHSA definition of ‘‘hazardous 

substance.’’ A ‘‘hazardous substance’’ is 

one that is a strong sensitizer (or has 

another of the specified ‘‘hazardous 

substance’’ characteristics) and ‘‘may 

cause substantial personal injury or 

substantial illness during or as a 

proximate result of any customary or 

reasonably foreseeable handling or use, 

including reasonably foreseeable 

ingestion by children.’’ 15 U.S.C. 

1261(f). Thus, manufacturers of 

products containing a strong sensitizer 

would have to determine whether the 

concentrations and availability of the 

substance in their products could cause 

substantial injury or illness as a result 

of reasonably foreseeable handling or 

use. Labeling under section 2(p) of the 

FHSA would only be required if the 

product containing a strong sensitizer 

would cause substantial injury or illness 

as a result of reasonably foreseeable 

handling or use. 

The Commission would also have the 

option of issuing a rule under Section 

3(a) of the FHSA to designate a strong 

sensitizer as a hazardous substance to 

reduce uncertainty about which 

products would be considered a 

hazardous substance. Id. 15 U.S.C. 

1262(a)(1). A hazardous substance that 

is not labeled properly with appropriate 

cautionary statements in accordance 

with section 2(p) of the FHSA is 

considered a ‘‘misbranded hazardous 

substance.’’ Id. 15 U.S.C. 1261(p). 

Introducing, delivering for introduction, 

or receiving in interstate commerce a 


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misbranded hazardous substance is a 

prohibited act. Id. 15 U.S.C. 1263(a) and 

(c). 

Effect of Rule on Regulation of Products 

and Risk Management Actions 

Comment: One commenter asserted 

that replacing the 1986 supplemental 

definition with the proposed definition 

could have far-reaching effects on the 

regulation of products at a broader level 

and stated that classifying substances as 

strong sensitizers may prompt risk 

management actions by the CPSC or 

other regulatory bodies. The commenter 

encouraged the CPSC to see that 

classification determinations fully 

reflect a science- and risk-based 

approach that considers the degree of 

hazard and extent of exposure potential. 

Response: The Commission does not 

believe that replacing the 1986 

supplemental definition with the final 

rule definition will have ‘‘far-reaching 

effects.’’ The rule does not designate any 

particular substance as a strong 

sensitizer, but the rule revises the 

regulatory definition of ‘‘strong 

sensitizer.’’ A separate proceeding 

involving a specific substance would be 

required before the agency could declare 

a substance to be a strong sensitizer. 

This rule simply provides guidance 

about the information and data that 

CPSC would consider and the relative 

importance of the information in 

making a strong sensitizer 

determination. 

Moreover, the determination that a 

substance is a strong sensitizer does not, 

by itself, require any action by a 

manufacturer. Under the FHSA, labeling 

or other regulatory action implicating 

risk management factors is required 

only when a substance meets the 

definition of ‘‘hazardous substance.’’ (15 

U.S.C. 1261(f)). A substance that the 

Commission designates as a strong 

sensitizer could be a ‘‘hazardous 

substance’’ under the FHSA, ‘‘if such 

substance or mixture of substances may 

cause substantial personal injury or 

substantial illness during or as a 

proximate result of any customary or 

reasonably foreseeable handling or use, 

including reasonably foreseeable 

ingestion by children.’’ Therefore, by 

definition, the FHSA considers 

exposure and requires a case-by-case 

hazard assessment. The final rule 

definition reflects both a science- and 

risk-based approach so that the decision 

for classification is not based solely on 

a product’s ingredients. 

Separate Treatment of Type I and Type 

IV Allergies in Sensitizer Definition 

Comment: One commenter 

recommended that Type I and Type IV 

allergies be addressed separately in the 

final rule definition because these types 

of allergies have different potential for 

causing illness, discomfort, and chronic 

morbidity; and consideration of 

different types of data would be 

necessary to evaluate the potential of 

substances that trigger these two 

different types of reactions to cause 

substantial illness. 

Response: A Type I allergy or 

immediate hypersensitivity is an 

allergic reaction provoked by 

reexposure to a specific type of allergen 

due to the production of specific 

antibodies. A Type IV allergy or delayed 

hypersensitivity is an allergic reaction 

that typically arises 1 to 3 days after 

exposure to an allergen and is not an 

antibody-mediated response. We agree 

that evaluating whether a substance is a 

strong sensitizer will depend on the 

substance and the allergic response the 

substance induces. However, we believe 

that the final rule definition would be 

significantly and unnecessarily more 

complex if these two types of allergies 

were separated into different categories. 

The criteria contained in the 

supplemental definition allow for 

flexibility in assessing all types of 

allergic reactions to sensitizers. In 

addition, the final rule definition 

includes the various potential routes of 

exposure for sensitizers, as well as 

anatomic sites of an allergic response. 

The outcome of exposure, whether a 

dermal or respiratory response, likely 

will require the analysis of different 

data for evaluation. Evaluating whether 

a substance is a strong sensitizer 

requires a case-by-case inquiry, based 

on high-quality relevant data. The 

Strong Sensitizer Guidance document 

explains the approach CPSC staff would 

take in evaluating the potential causal 

link between exposure to strong 

sensitizers and these two types of 

hypersensitivity. We believe that the 

final rule definition provides the 

flexibility for assessing these two types 

of allergic reactions to sensitizers 

without the need for specifically 

differentiating them. 

Acceptance of Data From Certain QSAR 

Models 

Comment: One commenter requested 

that the Commission revise the 

proposed definition to provide for the 

acceptance of data from Quantitative 

Structure-Activity Relationship (QSAR) 

models (mathematical models that relate 

a quantitative measure of chemical 

structure to biological activity) that the 

Organisation for Economic Co-operation 

and Development (OECD) has evaluated 

and approved for specific applicability 

domains. 

Response: The final rule definition 

specifically states that in determining 

whether a substance has a significant 

potential for causing hypersensitivity, 

chemical or functional properties of the 

substance of interest, in addition to 

QSAR data, can be considered. The 

panel of experts and external peer 

reviewers determined that QSAR data 

are not sufficient as stand-alone 

analyses for determining potency of a 

sensitizer but that QSAR analysis could 

be used in a weight-of-evidence 

approach. 

The OECD Council Act relating to the 

Mutual Acceptance of Data (MAD), 

which was agreed to by all OECD 

member countries, established that 

safety data developed in one member 

country will be accepted for use by the 

relevant registration authorities in 

assessing the chemical or product in 

another OECD country (i.e., the data do 

not have to be generated a second time 

for the purposes of safety assessment), 

under the assurance that the data were 

developed in compliance with the 

Principles of Good Laboratory Practice. 

Therefore, if a manufacturer submitted 

QSAR data to the Commission when the 

Commission was determining whether a 

substance is a strong sensitizer, the 

Commission would take the QSAR data 

into consideration. However, this QSAR 

data would not take precedence over 

high-quality human and animal data. 

The Commission believes that 

modifying the proposed definition in 

response to this comment is not 

warranted. 

Ordering of Factors To Be Considered in 

Determining Whether a Substance Is a 

Strong Sensitizer 

Comment: One commenter suggested 

revising the order of the factors that 

would be taken into consideration to 

determine whether a substance is a 

‘‘strong’’ sensitizer and including a 

reference in that paragraph to unranked 

data that appears elsewhere in the 

proposed definition. The commenter 

requests: (1) Shifting the order of factors 

as they appear in the paragraph listing 

the factors to be considered in 

determining whether a sensitizer is 

‘‘strong’’—for example moving ‘‘wellconducted animal studies’’ to the end of 

the list; (2) moving two of the unranked 

factors listed in the proposed 

supplemental definition (quantitative 

structure-activity relationship 

information and bioavailability data) 

into the list of ranked factors as the 

third and fourth priority position; and 

(3) separating existing versus new in 

vitro and in vivo studies into different 

factor categories. 


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Response: CPSC based the order of 

ranked data criteria in the proposed 

definition on extensive input from the 

international panel of scientific experts 

from academia, industry, and the federal 

government. We concurred with the 

panelists’ suggestion to rank and list the 

qualifying factors in order of importance 

in the final rule definition, instead of 

‘‘any or all,’’ which is how the factors 

appear in the 1986 supplemental 

definition. 

The Commission believes that the 

ranked list of criteria for determining 

whether a substance or product 

containing a substance is a ‘‘strong’’ 

sensitizer should remain as stated in the 

proposed definition but that the 

reference to unranked factors, such as 

quantitative structure-activity 

relationship information, in silico data 

and bioavailability data, should be 

moved to the end of the list of ranked 

factors so that the order is more logical. 

The list of criteria reflects Commission 

policy that human data take precedence 

over animal data and takes into 

consideration the value and relevance 

that the particular data would provide 

in making a determination of sensitizing 

strength, and therefore, the potential to 

cause hypersensitivity. The criteria list 

is consistent with the CPSC Animal 

Testing Policy, the FHSA Chronic 

Hazard Guidelines, and Commission 

policy that strongly encourage the use of 

scientifically validated alternatives to 

animal testing and the use of existing 

information, including expert opinion, 

prior human experience, and prior 

animal testing results. 

Consistency of Order of Factors Listed 

Throughout the Rule 

Comment: One commenter pointed 

out that the factors to be considered in 

determining whether a substance has a 

‘‘significant potential for causing 

hypersensitivity’’ were not listed in the 

same order when listed as factors to be 

considered in determining whether a 

substance is a ‘‘strong’’ sensitizer. The 

commenter requested that the 

Commission be consistent when listing 

the types of data in these two 

paragraphs. 

Response: We agree that the order of 

factors should be consistent in these 

paragraphs. Therefore, we have 

modified the proposed definition by: (1) 

moving ‘‘chemical or functional 

properties of the substance’’ to the end 

of the last sentence in the first 

paragraph of section (ii); and (2) in the 

same sentence reversing the positions of 

in vitro and in vivo. 

Use of Existing Animal Testing Data 

Comment: One commenter 

recommended that we specify that 

existing animal testing data be 

submitted to the CPSC for consideration 

in making a strong sensitizer 

determination before additional animal 

testing data is generated. 

Response: As stated in the CPSC 

Animal Testing Policy, codified at 16 

CFR 1500.232, neither the FHSA, nor 

the regulations issued under the FHSA, 

require animal testing to determine 

whether a hazard exists. The 

Commission’s regulations under the 

FHSA concerning toxicity and irritancy 

allow the use of animal tests to 

determine the presence of the hazard 

when human data or existing animal 

data are not available. However, the 

Commission’s policy encourages 

manufacturers subject to the FHSA to 

use existing alternatives to animal 

testing wherever possible; supports 

limiting animal testing to a minimum 

number of animals; and advocates 

measures that eliminate or reduce the 

pain or discomfort to animals that can 

be associated with such tests. The 

Commission’s animal testing policy 

encourages manufacturers of products 

subject to the FHSA to use existing 

alternatives to animal testing, whenever 

possible, such as: prior human 

experience (e.g., published case 

studies); in vitro or in silico test 

methods that have been approved by the 

Commission; literature resources 

containing the results of prior animal 

testing or limited human tests; and 

expert opinion. We believe that the 

animal testing policy codified at 16 CFR 

1500.232, sufficiently communicates the 

preference for alternatives to animal 

testing, whenever possible, including 

the submission of relevant existing data 

resulting from prior animal testing. 

Consideration of in Vitro Studies in 

Making Strong Sensitizer 

Determinations 

Comment: One commenter asked why 

in vitro studies were added to the list of 

factors to consider in determining 

whether a substance is a strong 

sensitizer when such studies are not 

validated to determine potency. Another 

commenter requested that data from 

well-conducted in vitro assays be 

considered by the Commission in 

making this determination. 

Response: The 1986 supplemental 

definition and the final rule definition 

both list in vitro data as a factor to be 

considered in determining whether a 

substance is a strong sensitizer. We 

agree that currently, there are no 

validated in vitro assays for sensitizer 

potency determination. However, a large 

number of in vitro assays are in 

development, undergoing validation, or 

have completed validation for the 

determination of sensitization. The 

European Union Reference Laboratory 

for Alternatives to Animal Testing 

(EURL–ECVAM) completed validation 

of an in vitro assay and an in chemico 

assay this year. EURL–ECVAM 

recommended that neither assay could 

be used as a stand-alone test; although 

EURL–ECVAM determined that the 

assays could be included in a weight-ofevidence approach or integrated testing 

strategy. Although the assays have some 

limitations, EURL–ECVAM concluded 

that with further work, these assays 

might be able to contribute to the 

assessment of sensitizer potency. As 

stated in the strong sensitizer guidance 

document, the CPSC would follow a 

weight-of-evidence approach, using all 

available validated tools (including both 

positive and negative data), in 

determining whether a substance is a 

strong sensitizer. 

Consideration of Reports of Consumer 

Incidents 

Comment: One commenter 

recommended including in the list of 

factors to be considered in determining 

whether a substance is a strong 

sensitizer, the CPSC’s and 

manufacturers’ records of incidents of 

consumer hypersensitivity to a 

substance or product containing a 

substance. 

Response: We agree that incident 

reports are an important consideration 

in determining a substance’s ability to 

cause hypersensitivity. The final rule 

definition lists ‘‘case histories’’ as 

information that the Commission may 

consider in determining whether a 

substance has a significant potential for 

causing hypersensitivity. The term 

‘‘case histories’’ includes reports of 

incidents of consumer hypersensitivity 

to a substance or product containing the 

substance that are received by 

manufacturers or the CPSC. Commission 

staff will consider revising the Strong 

Sensitizer Guidance document to 

provide additional clarification 

regarding the types and sources of 

incident reports that CPSC should 

consider when determining whether a 

substance is a strong sensitizer. 

Description of ‘‘Clinically Important 

Reaction’’ 

Comment: The proposed definition 

provides that in determining whether a 

substance is a strong sensitizer, the 

Commission must consider the severity 

of the reaction to the substance and only 

designate substances as strong 


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Federal Register / Vol. 79, No. 31 / Friday, February 14, 2014 / Rules and Regulations 8829 

1An ‘‘irritant response’’ is a nonimmune 

mediated response and one that results from direct 

injury to the tissue. An irritant is any agent that is 

capable of producing cell damage in any individual 

if applied for sufficient time and concentration. 

sensitizers that cause a ‘‘clinically 

important reaction.’’ The proposed 

definition includes a list of four 

potential reactions to strong sensitizer 

exposure that would be characterized as 

‘‘clinically important’’ or manifestations 

of ‘‘substantial illness.’’ One of the 

clinically important reactions listed in 

the proposed definition is ‘‘substantial 

physical discomfort or distress.’’ One 

commenter noted that ‘‘discomfort and 

distress are actually perceptual (mental), 

although they may be caused by various 

agents (e.g., physical, chemical agent, 

biological).’’ The commenter suggested 

replacing the phrase ‘‘substantial 

physical discomfort and distress’’ with 

the phrase ‘‘physiological stress 

resulting in discomfort or distress.’’ 

Response: We agree that the phrase 

‘‘substantial physical discomfort or 

distress’’ may not be clear, but we 

believe that ‘‘physiological stress 

resulting in discomfort or distress,’’ as 

suggested by the commenter, may also 

be too vague. We have replaced 

‘‘substantial physical discomfort or 

distress’’ with ‘‘substantial 

physiological effects, such as discomfort 

and distress,’’ as a factor to be 

considered in determining whether a 

strong sensitizer produces ‘‘substantial 

illness.’’ We believe that this phrase 

reflects better a scenario such as a 

systemic allergic contact dermatitis 

rash. 

Meaning of ‘‘Chronic Morbidity’’ 

Comment: One commenter asked 

whether the reference to ‘‘chronic 

morbidity’’ as a factor in determining 

whether a strong sensitizer produces 

‘‘substantial illness’’ was associated 

with a specific length of time, such as 

90 days. 

Response: The proposed definition 

includes a list of four potential reactions 

to strong sensitizer exposure that would 

be characterized as ‘‘clinically 

important’’ or manifestations of 

‘‘substantial illness.’’ One of the 

clinically important reactions listed in 

the proposed definition is ‘‘chronic 

morbidity.’’ The Commission does not 

view the use of the term ‘‘chronic’’ as 

referring to a specific length of time. 

Under the FHSA Chronic Hazard 

Guidelines (16 CFR 1500.135), which 

are broad guidelines containing a 

number of assumptions, methodologies, 

and procedures for determining chronic 

hazard and risk, the Commission does 

not set a length of time for ‘‘chronic,’’ 

but instead, the Commission leaves the 

determination open to expert judgment. 

We have replaced the phrase ‘‘chronic 

morbidity’’ with ‘‘persistent morbidity’’ 

in the final rule definition to clarify that 

a ‘‘clinically important reaction’’ is a 

substantial illness that occurs over an 

extended period of time. 

Addition of ‘‘Mortality’’ to ‘‘Substantial 

Illness’’ Factors 

Comment: One commenter suggested 

that ‘‘mortality’’ be added to the list of 

factors to be considered in determining 

whether a strong sensitizer produces 

substantial illness. 

Response: Mortality (i.e., death) is not 

an illness but is a distinct endpoint that 

in rare cases could result from 

substantial uncontrolled anaphylaxis. 

We have revised the definition to 

include: ‘‘or in rare cases, mortality’’ at 

the end of the section that lists the types 

of reactions to substances that may be 

considered ‘‘substantial illness.’’ 

Removal of Oil of Bergamot From List of 

Strong Sensitizer Substances 

Comment: One commenter requested 

that oil of bergamot (and products 

containing 2 percent or more of oil of 

bergamot) be removed from the list of 

‘‘strong sensitizer’’ substances. 

Response: Oil of bergamot is a 

phototoxin that FDA listed as a ‘‘strong 

sensitizer’’ (the list appears in 16 CFR 

1500.13). The current rulemaking 

proceeding only addresses revisions to 

the supplemental definition of ‘‘strong 

sensitizer.’’ To make any changes to the 

existing list of substances currently 

considered to be strong sensitizers, the 

Commission would need to conduct a 

separate proceeding. 

C. Revisions to the Strong Sensitizer 

Supplemental Definition 

As discussed in Section B, above, the 

comments received in response to the 

NPR generally supported the 

Commission’s replacement of the 1986 

supplemental definition of ‘‘strong 

sensitizer’’ with the proposed 

definition. However, several 

commenters recommended additional 

changes that we have determined 

should be incorporated into the 

supplemental definition of strong 

sensitizer. Below, we discuss the 

differences between the 1986 

supplemental definition and the 

proposed definition, along with the 

changes we have made to the proposed 

definition, based on comments and that 

have been incorporated into the final 

rule. 

1. Definition of ‘‘Sensitizer’’ 

(§ 1500.3(c)(5)(i)) 

The 1986 supplemental definition 

specified that a ‘‘sensitizer’’ will 

‘‘induce an immunologically-mediated 

(allergic) response, including allergic 

photosensitivity,’’ that will become 

evident upon reexposure to the same 

substance, or occasionally, on first 

exposure, by virtue of active 

sensitization. 

The final rule reflects the traditional 

definition for ‘‘sensitization’’; 

sensitization is a multi-stage immunemediated process that occurs over a 

period of time. Replacing the phrase 

‘‘immunologically-mediated (allergic) 

response’’ with ‘‘immunologicallymediated hypersensitivity,’’ captures 

those substances that sensitize through 

atypical mechanisms, rather than by 

inducing an obvious ‘‘immunologicallymediated response.’’ The final rule also 

eliminates the last sentence of the 

current definition based on concerns 

that the sentence could be 

misinterpreted to include substances 

that cause an irritant response only 1

(the response that is noted after the first 

exposure to a substance is more 

frequently an irritant response and not 

an allergic response). Typically, allergic 

responses are the result of a two-step 

process: (1) induction (sensitization), 

which requires sufficient or cumulative 

exposure to induce an immune response 

with few or no symptoms; and (2) 

elicitation when an individual who has 

been sensitized demonstrates symptoms 

upon subsequent exposures. The final 

rule includes the phrase ‘‘variable 

period of exposure’’ to reflect the 

latency period that is a characteristic in 

the development of sensitization. This 

section of the final rule is the same as 

proposed. 

2. Determination of Significant Potential 

for Causing Hypersensitivity 

(§ 500.3(c)(5)((ii)) 

The statutory definition of ‘‘strong 

sensitizer’’ requires that, before 

designating a substance as a strong 

sensitizer, the Commission ‘‘upon 

consideration of the frequency of 

occurrence and severity of reaction, 

shall find that the substance has a 

significant potential for causing 

hypersensitivity.’’ 15 U.S.C. 1261(k). 

As discussed in the NPR, the 

proposed definition added qualifiers for 

susceptibility profiles—genetics, age, 

gender, and atopic status— to the 

information and data listed in the 1986 

supplemental definition that may be 

considered in determining whether a 

substance has a significant potential for 

causing hypersensitivity. These 

characteristics are well-known 

modifiers in the development and 

exacerbation of allergic responses to 

chemical sensitizers. In response to a 


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8830 Federal Register / Vol. 79, No. 31 / Friday, February 14, 2014 / Rules and Regulations 

2QSARs are mathematical models that relate a 

quantitative measure of chemical structure to 

biological activity. In silico data is a computational 

approach using sophisticated computer models for 

the determination of a sensitizing potential. Both of 

these approaches are evolving methodologies that 

have not yet been validated, but are being pursued 

as testing options that would reduce the numbers 

of expensive laboratory and animal experiments 

being carried out. 

comment, for the final rule, we have 

reordered the list as it appeared in the 

proposed definition so that the final 

definition presents the factors to be 

considered in determining whether a 

substance has a significant potential for 

causing hypersensitivity. This 

represents the same order as the factors 

to be considered in determining 

whether a substance is a ‘‘strong’’ 

sensitizer. This reordering results in 

‘‘chemical or functional properties of 

the substance’’ becoming the last 

category on the list, and the references 

to in vitro and in vivo experimental 

studies are reversed. 

As discussed in the NPR, the 

proposed definition also replaced the 

term ‘‘normal’’ with ‘‘non-sensitized,’’ 

which describes more accurately the 

general control population. This 

remains the same in the final rule. 

As discussed in the NPR, the 

proposed definition incorporated the 

factors to be considered in determining 

whether a substance is a ‘‘strong’’ 

sensitizer into the subsection explaining 

‘‘significant potential for causing 

hypersensitivity.’’ The 1986 

supplemental definition of ‘‘strong 

sensitizer’’ contains a separate 

subsection that sets forth factors that 

should be considered in determining the 

strength of a sensitizer. (16 CFR 

1500.3(c)(5)(ii)). This section of the 1986 

supplemental definition includes 

several factors that are subjective rather 

than quantitative (i.e., physical 

discomfort, distress, hardship) and 

allows for risk assessment 

considerations in connection with an 

analysis that should only be a hazard 

characterization step. 

As discussed in the NPR, the 

proposed definition eliminated the 

‘‘quantitative or qualitative risk 

assessment factor. ’’ We believe this 

terminology is confusing because the 

language places a risk assessment step 

within the hazard identification step of 

the process of determining whether a 

product containing a strong sensitizer is 

a hazardous substance that requires 

labeling. The NPR proposed definition 

remains the same in the final rule, 

except for the reordering of certain 

factors in response to a comment. 

As discussed in the NPR, the 

proposed definition makes clear that a 

weight-of-the-evidence approach is to be 

used in determining the strength of a 

sensitizer because of the imprecise 

nature of some of the current factors and 

the potential lack of information or data 

available to permit useful consideration 

of certain factors. Rather than allow an 

‘‘any or all’’ approach to the factors that 

would be considered by the 

Commission in determining whether a 

sensitizer is strong, the revision ranks 

data sources in order of importance 

following the FHSA preference for 

human data over animal data and takes 

into consideration the value and 

relevance that certain data would 

provide in evaluating the potential of a 

substance to cause hypersensitivity. For 

example, the proposed definition 

expressed a preference for general 

population epidemiological studies over 

occupational studies because the degree 

of sensitization in the workplace is 

likely to be greater than that of the 

general population, due to greater 

exposure (both in time and 

concentration) to the sensitizing agent. 

The ranking of data sources remains the 

same in the final rule. 

As discussed in the NPR, the 

proposed definition listed additional 

factors that the Commission can 

consider in determining a substance’s 

sensitizing potential, for which 

validated methods currently do not exist 

but are in development, such as: 

Quantitative Structure-Activity 

Relationships (QSARs), and in silico 2

data, along with the caveat that using 

these techniques would be in addition 

to consideration of human and animal 

data. We have revised the definition in 

the final rule to reposition these factors 

from the end of Section 1500.3(c)(5)(ii) 

to follow immediately the listing of 

ranked factors that are to be considered 

in determining whether a substance is a 

‘‘strong’’ sensitizer. 

As discussed in the NPR, the 

proposed definition provided that for a 

substance to be considered a ‘‘strong’’ 

sensitizer, the substance must be found 

to produce a ‘‘clinically important 

reaction,’’ which is defined as a reaction 

with a significant impact on the quality 

of life. The Commission has revised the 

proposed definition in response to a 

comment to replace ‘‘substantial 

physical effects’’ with ‘‘substantial 

physiological effects’’ as a factor to be 

considered in determining whether a 

strong sensitizer produces ‘‘substantial 

illness’’; to replace ‘‘chronic morbidity’’ 

with ‘‘persistent morbidity’’; and to add 

‘‘or in rare cases, mortality’’ to the end 

of section 1500.3(c)(5)(ii). The change 

from ‘‘physical’’ to ‘‘physiological’’ is 

intended to describe more accurately 

and broadly the body’s response to 

exposure to a substance that could rise 

to the level of a clinically important 

reaction. The change from ‘‘chronic’’ to 

‘‘persistent,’’ also made in response to a 

comment, is intended to convey more 

clearly that a substantial illness may be 

one that endures for an extended period 

of time. 

As discussed in the NPR, the 

proposed definition also directed the 

Commission to consider the location of 

the hypersensitivity response, such as 

the face, hands, and feet, and the 

persistence of clinical manifestations in 

determining whether the substance 

produces a ‘‘clinically important 

reaction.’’ This aspect of the NPR 

remains the same in the final rule. 

3. Definition of Normal Living Tissue 

(§ 1500.3(c)(5)(iii)) 

The statutory definition of ‘‘strong 

sensitizer’’ specifies that a strong 

sensitizer is a substance that will cause 

hypersensitivity on ‘‘normal living 

tissue.’’ The 1986 supplemental 

definition identifies skin and other 

organ systems, such as the respiratory or 

gastrointestinal tract, as types of 

‘‘normal living tissue’’ in which the 

allergic hypersensitivity reaction can 

occur. The proposed definition adds a 

specific reference to mucous 

membranes, such as ocular and oral 

systems, as additional types of normal 

living tissue upon which a substance 

can cause a hypersensitivity that 

warrants a determination that a 

substance is a ‘‘strong sensitizer.’’ This 

remains the same in the final rule. 

D. Staff Guidance and Notice of 

Availability 

Commission staff developed a 

guidance document that is intended to 

clarify the ‘‘strong sensitizer’’ definition 

and assist manufacturers in 

understanding how CPSC staff would 

assess whether a substance and/or 

product containing that substance 

should be considered a ‘‘strong 

sensitizer.’’ A Notice of Availability was 

published in the Federal Register on 

March 12, 2013 (78 FR 15710), which 

provided a link to the location on the 

Commission’s Web site where the staff 

guidance document can be found. 

Several commenters included questions 

and observations regarding the guidance 

document in their submissions 

addressing the proposed revision to the 

definition of ‘‘strong sensitizer.’’ 

Commission staff will review these 

comments, and where appropriate, will 

revise the guidance document. 

E. Impact on Small Businesses 

The Commission certifies that this 

rule will not a have a significant impact 

on a substantial number of small entities 


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Federal Register / Vol. 79, No. 31 / Friday, February 14, 2014 / Rules and Regulations 8831 

under section 605(b) of the Regulatory 

Flexibility Act (RFA), 5 U.S.C. 605(b). 

For the NPR, the Commission’s 

Directorate for Economic Analysis 

prepared an assessment of the impact of 

the proposed definition of ‘‘strong 

sensitizer.’’ That assessment found that 

there would be little or no effect on 

small businesses and other entities 

because the amendment, which simply 

modifies the existing supplemental 

definition of ‘‘strong sensitizer,’’ will 

not result in compliance actions. 

Products will not need to be modified 

to comply with the revised 

supplemental definition, nor will the 

revised supplemental definition impose 

any additional testing or recordkeeping 

burdens. The obligation to label a 

product as a strong sensitizer and any 

costs associated with that obligation 

will not arise until the Commission has 

designated a particular substance 

contained in the product as a strong 

sensitizer, which would occur only in 

connection with a separate process. 

Thereafter, we would assess the 

potential small business impact of 

designating the particular substance as a 

strong sensitizer. Whether the final rule 

would impose any indirect burden on 

small businesses or other entities is 

unknown because the impact of the 

changes to the supplemental definition 

of strong sensitizer on future strong 

sensitizer designation proceedings is not 

known. The Commission did not receive 

any comments concerning the impact 

the rule would have on small businesses 

and is not aware of any information that 

would alter the assessment stated in the 

NPR. 

F. Environmental Considerations 

Generally, CPSC rules are considered 

to ‘‘have little or no potential for 

affecting the human environment,’’ and 

environmental assessments and 

environmental impact statements are 

not usually prepared for these rules (see 

16 CFR 1021.5(c)(1)). The Commission 

does not expect the rule to have any 

adverse impact on the environment 

under this categorical exclusion. 

G. Executive Orders 

According to Executive Order 12988 

(February 5, 1996), agencies must state 

in clear language the preemptive effect, 

if any, of new regulations. Section 18 of 

the FHSA addresses the preemptive 

effect of certain rules issued under the 

FHSA. 15 U.S.C. 1261n. Because this 

rulemaking would revise a regulatory 

definition, rather than issue a labeling 

or banning requirement, section 18 of 

the FHSA does not provide for the rule 

to have preemptive effect. 

H. Paperwork Reduction Act 

This rule would not impose any 

information collection requirements. 

Accordingly, this rule is not subject to 

the Paperwork Reduction Act, 44 U.S.C. 

3501–3520. 

I. Effective Date 

The Administrative Procedure Act 

generally requires that a substantive rule 

be published not less than 30 days 

before its effective date, unless the 

agency finds, for good cause shown, that 

a lesser time period is required. 5 U.S.C. 

553(d)(3). The final rule will take effect 

March 17, 2014. 

List of Subjects in 16 CFR Part 1500 

Consumer protection, Hazardous 

substances, Imports, Infants and 

children, Labeling, Law enforcement, 

Reporting and recordkeeping 

requirements, and Toys. 

Accordingly, 16 CFR part 1500 is 

amended as follows: 

PART 1500—[AMENDED] 

■ 1. The authority citation for part 1500 

continues to read as follows: 

Authority: 15 U.S.C. 1261–1278. 

■ 2. Revise paragraph (c)(5) of § 1500.3 

to read as follows: 

§ 1500.3 Definitions 

* * * * * 

(c) * * * 

(5) The definition of strong sensitizer 

in section 2(k) of the Federal Hazardous 

Substances Act (restated in paragraph 

(b)(9) of this section) is supplemented 

by the following definitions: 

(i) Sensitizer. A sensitizer is a 

substance that is capable of inducing a 

state of immunologically mediated 

hypersensitivity (including allergic 

photosensitivity) following a variable 

period of exposure to that substance. 

Hypersensitivity to a substance will 

become evident by an allergic reaction 

elicited upon reexposure to the same 

substance. 

(ii) Significant potential for causing 

hypersensitivity. (A) Before designating 

any substance a ‘‘strong sensitizer,’’ the 

Commission shall find that the 

substance has significant potential for 

causing hypersensitivity. Significant 

potential for causing hypersensitivity is 

a relative determination that must be 

made separately for each substance. The 

determination may be based on 

documented medical evidence of 

hypersensitivity reactions upon 

subsequent exposure to the same 

substance obtained from 

epidemiological surveys or case 

histories; controlled in vivo or in vitro 

experimental studies; susceptibility 

profiles (e.g., genetics, age, gender, 

atopic status) in non-sensitized or 

allergic subjects; and chemical or 

functional properties of the substance. 

(B) In determining whether a 

substance is a ‘‘strong’’ sensitizer, the 

Commission shall consider the available 

data for a number of factors, following 

a weight-of-evidence approach. The 

following factors (if available), ranked in 

descending order of importance, should 

be considered: well-conducted clinical 

and diagnostic studies, epidemiological 

studies, with a preference for general 

population studies over occupational 

studies, well-conducted animal studies, 

well-conducted in vitro test studies, 

cross-reactivity data, and case histories. 

(C) Additional consideration may be 

given to Quantitative Structure-Activity 

Relationships (QSARs), in silico data, 

specific human sensitization threshold 

values, other data on potency and 

sensitizer bioavailability, if data are 

available and the methods validated. 

Bioavailability is the dose of the 

allergen available to interact with a 

tissue. Bioavailability is a reflection of 

how well the skin or another organ can 

absorb the allergen and the actual 

penetrating ability of the allergen, 

including factors such as size and 

composition of the chemical. 

(D) Criteria for a ‘‘well-conducted’’ 

study would include: validated 

outcomes, relevant dosing, route of 

administration, and use of appropriate 

controls. Studies should be carried out 

according to national and/or 

international test guidelines and 

according to good laboratory practice 

(GLP), compliance with good clinical 

practice (GCP), and good 

epidemiological practice (GEP). 

(E) Before the Commission designates 

any substance as a ‘‘strong’’ sensitizer, 

frequency of occurrence and range of 

severity of reactions in exposed 

subpopulations having average or high 

susceptibility will be considered. The 

minimal severity of a reaction for the 

purpose of designating a material as a 

‘‘strong sensitizer’’ is a clinically 

important reaction. A clinically 

important reaction would be considered 

one with a significant impact on quality 

of life. Consideration should be given to 

the location of the hypersensitivity 

response, such as the face, hands, and 

feet as well as persistence of clinical 

manifestations. For example, strong 

sensitizers may produce substantial 

illness, including any or all of the 

following: substantial physiological 

effects, such as discomfort and distress, 

substantial hardship, functional or 

structural impairment, persistent 

morbidity, or in rare cases, mortality. 


tkelley on DSK3SPTVN1PROD with RULES
8832 Federal Register / Vol. 79, No. 31 / Friday, February 14, 2014 / Rules and Regulations 

1See 49 FR 36644, September 19, 1984 

(correcting the effective date). 

(iii) Normal living tissue. The allergic 

hypersensitivity reaction occurs in 

normal living tissues, including the 

skin, mucous membranes (e.g., ocular, 

oral), and other organ systems, such as 

the respiratory tract and gastrointestinal 

tract, either singularly or in 

combination, following sensitization by 

contact, ingestion, or inhalation. 

* * * * * 

Dated: February 11, 2014. 

Todd A. Stevenson, 

Secretary, U.S. Consumer Product Safety 

Commission. 

[FR Doc. 2014–03260 Filed 2–13–14; 8:45 am] 

BILLING CODE 6355–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 803 

[Docket No. FDA–2008–N–0393] 

RIN 0910–AF86 

Medical Device Reporting: Electronic 

Submission Requirements 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final rule. 

SUMMARY: The Food and Drug 

Administration (FDA) is revising its 

postmarket medical device reporting 

regulation and making technical 

corrections. This final rule requires 

device manufacturers and importers to 

submit mandatory reports of individual 

medical device adverse events, also 

known as medical device reports 

(MDRs), to the Agency in an electronic 

format that FDA can process, review, 

and archive. Mandatory electronic 

reporting will improve the Agency’s 

process for collecting and analyzing 

postmarket medical device adverse 

event information. Electronic reporting 

is also available to user facilities, but 

this rule permits user facilities to 

continue to submit written reports to 

FDA. This final rule also identifies 

changes to the content of required MDRs 

to reflect reprocessor information 

collected on the Form FDA 3500A as 

required by the Medical Device User Fee 

and Modernization Act of 2002 

(MDUFMA). 

DATES: This final rule is effective August 

14, 2015 (see also section IX of this 

document). 

FOR FURTHER INFORMATION CONTACT: 

Sharon E. Kapsch, Center for Devices 

and Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 3208, Silver Spring, 

MD 20993–0002, 301–796–6104. 

SUPPLEMENTARY INFORMATION: 

Table of Contents 

I. History of the Medical Device Reporting 

Regulation 

II. Overview of the Final Rule 

A. Changes to the 2009 Proposed Rule 

B. Highlights of the Final Rule 

C. How do I submit MDRs in electronic 

format? 

D. How have the MDR requirements 

changed? 

III. Comments on the Proposed Rule 

A. General 

B. Submitting Initial and Supplemental or 

Followup Reports (§ 803.12(a)) 

C. Establishing and Maintaining MDR 

Records (§ 803.18) 

D. Copies Kept in MDR Files of All Reports 

Submitted (§ 803.18(b)(1)(ii)) 

E. Copies of All Electronic 

Acknowledgments (§ 803.18(b)(1)(iii)) 

F. Manufacturer Reporting Requirements 

(§ 803.50(a)) 

G. Report Date (§ 803.52(b)(4)) 

H. Product Code and Common Device 

Name (§ 803.52(c)(2)) 

I. Name and Address of the Reprocessor 

(Revised § 803.52(c)(8) and (c)(9)) 

J. Premarket Approval Application (PMA)/ 

Section 510(k) Number and Combination 

Product Status (§ 803.52(e)(5)) 

K. New, Changed, or Corrected Information 

(§ 803.56(c)) 

L. Paper Responses to Requests for 

Additional Information 

M. Analysis of Impact 

N. Common Errors 

O. Effective Date 

P. General Comment Concerning Numeric 

Data Fields 

Q. Receipt Date 

R. Software Changes 

S. System Outages 

IV. What is the legal authority for this rule? 

V. What is the environmental impact of this 

rule? 

VI. What is the economic impact of this rule? 

A. Benefits 

B. Costs 

C. Summary of Benefits and Costs 

D. Regulatory Alternatives to the Final 

Rule 

E. Regulatory Flexibility Analysis 

VII. How does this rule comply with the 

Paperwork Reduction Act (PRA) of 1995? 

A. Reporting Requirements 

B. Recordkeeping Requirements 

C. Changes From the Proposed Rule 

D. Total Annual Cost Burden 

VIII. Does this final rule have federalism 

implications? 

IX. What is the effective date? 

X. What references are on display? 

XI. Stayed CFR Text 

I. History of the Medical Device 

Reporting Regulation 

The MDR regulation was first 

published on September 14, 1984 (49 FR 

36326), with requirements for 

manufacturer and importer reporting of 

deaths, serious injuries, and 

malfunctions effective December 13, 

1984.1 FDA’s regulations governing 

medical device adverse event reporting 

implement section 519 of the Federal 

Food, Drug, and Cosmetic Act (the 

FD&C Act) (21 U.S.C. 360i). Section 519 

of the FD&C Act has undergone several 

changes since its enactment as part of 

the Medical Device Amendments of 

1976 (Pub. L. 94–295). As a result, 

FDA’s regulations at part 803 (21 CFR 

part 803) have also undergone multiple 

revisions. The Safe Medical Devices Act 

of 1990 (SMDA) (Pub. L. 101–629) 

amended the FD&C Act to require 

mandatory reporting of device adverse 

events by user facilities (deaths reported 

to FDA and the manufacturer, and 

serious injuries or illnesses reported to 

the manufacturer) and domestic 

distributors (deaths and serious injuries 

or illnesses reported to FDA and the 

manufacturer, and certain malfunctions 

reported to the manufacturer). The 

SMDA also amended the FD&C Act to 

require manufacturers and distributors 

(including importers) to certify the 

number of MDRs submitted to the 

Agency each year and to require user 

facilities to submit a semiannual report 

summarizing reportable events. FDA 

published a tentative final rule on 

November 26, 1991 (56 FR 60024), to 

implement the SMDA requirements for 

reporting for device manufacturers, user 

facilities, and distributors, including 

importers (the 1991 tentative final rule). 

By statute, user facility reporting 

became effective on November 28, 1991, 

and distributor reporting became 

effective on May 28, 1992. 

On June 16, 1992, the Medical Device 

Amendments of 1992 (the 1992 

amendments) (Pub. L. 102–300) further 

amended certain provisions of section 

519 of the FD&C Act relating to 

reporting of adverse device events. The 

amendments adopted a single reporting 

standard and definition for serious 

injury/serious illness for manufacturers, 

importers, distributors, and user 

facilities. The changes under the 1992 

amendments were effective on June 16, 

1993. 

On September 1, 1993, FDA 

published a final rule (58 FR 46514) that 

collected the requirements for all 

wholesale distributors, importers as 

well as domestic, under a new part 804 

(21 CFR part 804). 

On December 11, 1995 (60 FR 63578), 

FDA published a final rule for 

manufacturers and user facilities (the 

1995 final rule), with changes from the 

1991 tentative final rule, including a 

requirement for the use of the Form 


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