Federal Register / Vol. 72, No. 198 / Monday, October 15, 2007 / Notices 58313 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2007D–0388] 

Draft Guidance for Industry: Questions 

and Answers Regarding Adverse Event 

Reporting and Recordkeeping for 

Dietary Supplements as Required by 

the Dietary Supplement and 

Nonprescription Drug Consumer 

Protection Act; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a draft guidance entitled 

‘‘Questions and Answers Regarding 

Adverse Event Reporting and 

Recordkeeping for Dietary Supplements 

as Required by the Dietary Supplement 

and Nonprescription Drug Consumer 

Protection Act.’’ This draft guidance is 

intended to assist the dietary 

supplement industry in complying with 

the serious adverse events reporting and 

recordkeeping requirements prescribed 

for dietary supplement manufacturers, 

packers, and distributors by the Dietary 

Supplement and Nonprescription Drug 

Consumer Protection Act. Separate 

guidance, issued by the Center for Drug 

Evaluation and Research on reporting 

for nonprescription (over-the-counter 

(OTC)) human drugs marketed without 

an approved application, is announced 

elsewhere in this issue of the Federal 

Register. 

DATES: Submit written or electronic 

comments on the draft guidance 

document, including comments 

regarding proposed collection of 

information, by December 14, 2007. 

ADDRESSES: Submit written requests for 

single copies of the draft guidance to the 

Office of Nutritional Products, Labeling, 

and Dietary Supplements (HFS–800), 

Food and Drug Administration, 5100 

Paint Branch Pkwy., College Park, MD 

20740. Send one self-addressed 

adhesive label to assist the office in 

processing your request, or include a fax 

number to which the draft guidance 

may be sent. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the draft guidance. 

Submit written comments on the draft 

guidance, including comments 

regarding proposed collection of 

information, to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, Rm. 

1061, Rockville, MD 20852. Submit 

electronic comments to either http:// 

www.fda.gov/dockets/ecomments or 

http://www.regulations.gov. 

FOR FURTHER INFORMATION CONTACT: 

Vasilios Frankos, Center for Food Safety 

and Applied Nutrition (HFS–810), Food 

and Drug Administration, 5100 Paint 

Branch Pkwy., College Park, MD 20740, 

301–436–2375. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance entitled ‘‘Questions and 

Answers Regarding Adverse Event 

Reporting and Recordkeeping for 

Dietary Supplements as Required by the 

Dietary Supplement and 

Nonprescription Drug Consumer 

Protection Act.’’ On December 22, 2006, 

the President signed into law the 

Dietary Supplement and 

Nonprescription Drug Consumer 

Protection Act (the DSNDCPA) (Public 

Law 109–462, 120 Stat. 3469). This law 

amends the Federal Food, Drug, and 

Cosmetic Act (the act) with respect to 

serious adverse event reporting for 

dietary supplements and nonprescription drugs marketed without an 

approved application. The draft 

guidance document contains questions 

and answers relating to the new 

requirements under the DSNDCPA, 

concerning the mandatory reporting to 

FDA of serious adverse events 

associated with dietary supplements, 

the minimum data elements to be 

submitted in such reports, and records 

of serious and non-serious adverse 

events reported to a dietary supplement 

manufacturer, packer, or distributor. 

The draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent 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. An 

alternative approach may be used if 

such approach satisfies the requirement 

of the applicable statutes and 

regulations. 

II. Paperwork Reduction Act of 1995 

Under the Paperwork Reduction Act 

of 1995 (the PRA) (44 U.S.C. 3501–

3520), Federal agencies must obtain 

approval from the Office of Management 

and Budget (OMB) for each collection of 

information they conduct or sponsor. 

‘‘Collection of information’’ is defined 

in 44 U.S.C. 3502(3) and 5 CFR 

1320.3(c) and includes agency requests 

or requirements that members of the 

public submit reports, keep records, or 

provide information to a third party. 

Section 3506(c)(2)(A) of the PRA (44 

U.S.C. 3506(c)(2)(A)) requires Federal 

agencies to provide a 60-day notice in 

the Federal Register concerning each 

proposed collection of information 

before submitting the collection to OMB 

for approval. To comply with this 

requirement, FDA is publishing notice 

of the proposed collection of 

information set forth below. 

With respect to the following 

collection of information, FDA invites 

comment on: (1) Whether the proposed 

collection of information is necessary 

for the proper performance of FDA’s 

functions, including whether the 

information will have practical utility; 

(2) the accuracy of FDA’s estimate of the 

burden of the proposed collection of 

information, including the validity of 

the methodology and assumptions used; 

(3) ways to enhance the quality, utility, 

and clarity of the information to be 

collected; and (4) ways to minimize the 

burden of the collection on respondents, 

including through the use of automated 

collection techniques, when 

appropriate, and other forms of 

information technology. 

Title: Adverse Event Reporting and 

Recordkeeping for Dietary Supplements 

as Required by the Dietary Supplement 

and Nonprescription Drug Consumer 

Protection Act. 

Description of Respondents: 

Respondents to this collection of 

information are manufacturers, packers, 

and distributors of dietary supplements 

marketed in the United States. 

The draft guidance presents FDA’s 

recommendations for complying with 

the dietary supplement adverse event 

reporting and recordkeeping 

requirements of the act, as amended by 

the DSNDCPA. These requirements 

become effective on December 22, 2007. 

A. Reporting 

Under section 761(b)(1) of the act (21 

U.S.C. 379aa–1(b)(1)), the manufacturer, 

packer, or distributor whose name 

(under section 403(e)(1) of the act (21 

U.S.C. 343(e)(1))) appears on the label of 

a dietary supplement marketed in the 

United States is required to submit to 

FDA any serious adverse event report it 

receives regarding use of the dietary 

supplement in the United States, 

accompanied by a copy of the product 

label. In addition, under section 

761(c)(2) of the act, the submitter of the 

serious adverse event report (referred to 

in the statute as the ‘‘responsible 

person’’) is required to submit to FDA 

a followup report of any related new 

medical information the responsible 

person receives within 1 year of the 

initial report. 

The draft guidance discusses how, 

when, and where to submit serious 


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58314 Federal Register / Vol. 72, No. 198 / Monday, October 15, 2007 / Notices 

adverse event reports for dietary 

supplements and followup reports of 

new medical information. In accordance 

with the statutory requirements that 

serious adverse event reports for dietary 

supplements be submitted via 

MedWatch (section 761(d) of the act) 

and that FDA consolidate all 

information related to a serious adverse 

event into a single report (section 

761(c)(3) of the act), the draft guidance 

directs the responsible person to submit 

serious adverse event reports on 

MedWatch Form 3500A and to attach a 

copy of the initial serious adverse event 

report on Form 3500A as part of any 

followup report of new medical 

information. 

FDA estimates the burden of this 

collection of information as follows: 

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1

No. of 

respondents 

Annual frequency 

per response 

Total annual 

responses 

Hours per 

response Total hours 

Serious adverse event reports for dietary supplements (21 U.S.C. 379aa–

1(b)(1)) 80 12 960 2 1,920 

Followup reports of new medical information (21 U.S.C. 379aa–1(c)(2)) 20 12 240 1 420 

Total 2,160 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

B. Reporting Burden 

Because mandatory reporting of 

serious adverse events for dietary 

supplements does not become effective 

until December 22, 2007, FDA has no 

data on mandatory dietary supplement 

adverse event reports from past years to 

use in developing a burden estimate. 

However, FDA currently collects 

voluntarily-submitted adverse event 

reports for dietary supplements. 

Industry, health care providers, and 

consumers voluntarily submit several 

thousand reports annually to FDA’s 

Center for Food Safety and Applied 

Nutrition (CFSAN) through the CFSAN 

Adverse Events Reporting System 

(CAERS), which contains reports of 

adverse events associated with 

conventional foods, dietary 

supplements, and cosmetics. According 

to a Congressional Budget Office Cost 

Estimate (Ref. 1), in 2005 CAERS 

received almost 500 reports of adverse 

events suspected to be related to dietary 

supplements. 

Only manufacturers, packers, and 

distributors of dietary supplements are 

required to report adverse events for 

these products to FDA, and only if the 

firm’s name appears on the label of the 

dietary supplement associated with the 

adverse event. Moreover, reporting is 

required only for those adverse events 

defined as ‘‘serious.’’ FDA does not 

know how many of the 500 reports of 

dietary supplement adverse events 

voluntarily submitted in 2005 would 

have been considered serious, nor how 

many of these reports originated from or 

were reported to the manufacturer, 

packer, or distributor whose name 

appears on the label of the dietary 

supplement associated with the adverse 

event. As a rough estimate for planning 

purposes, CAERS staff estimate that 

they will receive about 80 serious 

adverse event reports relating to dietary 

supplements each month. Thus, we 

estimate that the number of dietary 

supplement serious adverse event 

reports submitted to FDA annually will 

total 960 reports (12 x 80 reports per 

month). FDA requests comments on this 

estimate. 

FDA’s Center for Drug Evaluation and 

Research estimates it will take 

respondents a total of 2 hours to collect 

information about a serious adverse 

event associated with an over-thecounter drug marketed without an 

approved application and report the 

information to FDA on MedWatch Form 

3500A. That time burden estimate is 

based on FDA’s knowledge of the 

adverse drug experience reports 

submitted to the agency for 

nonprescription drug products marketed 

under an approved application, 

including knowledge about the time 

needed to prepare the reports. FDA 

believes that the time for a dietary 

supplement firm to collect information 

about a serious adverse event associated 

with a dietary supplement and report 

the information to FDA will be 

approximately the same, as MedWatch 

Form 3500A will be used in both cases; 

therefore, we also estimate this time 

burden at 2 hours per report. The 

estimated total annual burden for 

dietary supplement serious adverse 

event reports is shown in row 1 of table 

1 of this document. 

If a firm that has submitted a serious 

adverse event report receives new 

medical information related to the 

serious adverse event within 1 year of 

submitting the initial report, the firm 

must provide the new medical 

information to FDA in a followup 

report. Given our lack of experience 

with mandatory dietary supplement 

adverse event reporting, we do not have 

any information on the number of 

followup reports of new medical 

information that will be submitted to 

FDA each year. We expect followup 

medical information to be reported for 

some percentage of the 960 serious 

adverse event reports we estimate 

receiving annually. In the absence of 

data that would support a more precise 

estimate, we will assume that 25 percent 

of the 960 serious adverse event reports 

for dietary supplements will have a 

followup report submitted. FDA 

requests comments on this estimate. We 

estimate that each followup report will 

require an hour to assemble and submit, 

including the time needed to copy and 

attach the initial serious adverse event 

report as recommended in the draft 

guidance. We assume the followup 

report will take less time than the initial 

serious adverse event report, as the 

responsible person will not need to fill 

out Form 3500A for the followup report. 

FDA requests comments on whether the 

burden estimate of 1 hour is reasonable 

for this information collection. The 

estimated total annual burden for 

followup reports of new medical 

information is shown in row 2 of table 

1 of this document. 

C. Recordkeeping 

Section 761(e)(1) of the act requires 

that responsible persons maintain 

records related to dietary supplement 

adverse event reports they receive, 

whether or not the adverse event is 

serious. Under the statute, the records 

must be retained for a period of 6 years. 

The draft guidance provides FDA’s 

recommendations as to what records 


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Federal Register / Vol. 72, No. 198 / Monday, October 15, 2007 / Notices 58315 

industry should maintain to satisfy the 

statutory recordkeeping requirement. 

The guidance recommends that the 

responsible person document its 

attempts to obtain the minimum data 

elements for a serious adverse event 

report. Along with these records, the 

guidance recommends that the 

responsible person keep the following 

other records: (1) Communications 

between the responsible person and the 

initial reporter of the adverse event and 

with any other person(s) who provided 

information about the adverse event; (2) 

(for serious adverse events only) the 

responsible person’s serious adverse 

event report to FDA on MedWatch Form 

3500A, with attachments; (3) any new 

medical information about the adverse 

event received by the responsible 

person; (4) (for serious adverse events 

only) any reports to FDA of new 

medical information related to the 

serious adverse event report. We 

estimate that assembling and filing these 

records, including any necessary 

photocopying, will take approximately 

0.5 hours per adverse event report 

received by the responsible person. 

Once the documents pertaining to an 

adverse event report have been 

assembled and filed, FDA expects the 

records retention burden to be minimal, 

as the agency believes most 

establishments would normally keep 

this kind of record for at least several 

years after receiving the report, as a 

matter of usual and customary business 

practice. FDA requests comment on 

current adverse event recordkeeping 

practices in the dietary supplement 

industry, including the length of time 

such records are typically kept. 

According to a 2001 report by the 

Office of the Inspector General, between 

1994–1999 FDA received 2,547 adverse 

event reports involving dietary 

supplements, or about 500 reports per 

year, on average (Ref. 2). According to 

the report, the actual number of adverse 

events relating to dietary supplements is 

likely to be at least 100 times that many, 

or more than 50,000 adverse events per 

year. In the absence of data on how 

many adverse events will be reported 

each year to the responsible person once 

the DSNDCPA becomes effective in 

December 1997, we are using the 50,000 

per year figure as an upper bound 

estimate of reporting. This is almost 

certainly an overestimate of the number 

of reports the firms will receive, as it is 

unlikely that every adverse event that 

occurs will be reported to the 

responsible person. FDA requests 

comments on this estimate. 

We estimated in the economic impact 

analysis of the Dietary Supplement 

Good Manufacturing Practices final rule 

(the GMP final rule) (72 FR 34752, June 

25, 2007) that there are 1,460 

manufacturers, packers, and holders of 

dietary supplements (72 FR 34752 at 

34920). We assume that the estimated 

50,000 adverse event reports related to 

dietary supplements will be spread 

evenly among these firms. The estimate 

of the number of manufacturers, 

packers, and holders of dietary 

supplements from the GMP final rule is 

FDA’s best estimate of the number of 

firms that are ‘‘responsible persons’’

who must comply with the 

recordkeeping requirements of the 

DSNDCPA; however, it is not a precise 

estimate because the number of dietary 

supplement establishments covered by 

the GMP final rule is likely to be larger 

than the number of ‘‘responsible 

persons,’’ where a ‘‘responsible person’’

is a dietary supplement manufacturer, 

packer, or distributor whose name is 

listed on the label of a dietary 

supplement marketed in the United 

States (see section 761(b)(1) of the act). 

Thus, FDA’s estimate for the number of 

respondents in table 2 may be 

overinclusive. FDA requests comments 

on the number of firms that would be 

subject to the recordkeeping 

requirements of the DSNDCPA. 

The estimated total annual 

recordkeeping burden under the statute 

and this guidance is shown in table 2 of 

this document. 

TABLE 2.—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

No. of 

recordkeepers 

Annual frequency 

per recordkeeping 

Total annual 

records 2

Hours per 

record Total hours 

Dietary supplement adverse event 

records (21 U.S.C. 379aa–1(e)(1)) 1,460 4.2465 50,000 0.5 25,000 

Total 25,000 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

2For purposes of estimating the number of records and hours per record, a ‘‘record’’ means all records kept for an individual adverse event report received by the responsible person. 

III. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) written or electronic 

comments regarding the draft guidance, 

including comments regarding proposed 

collection of information. Submit a 

single copy of electronic comments or 

two paper copies of any mailed 

comments, except that individuals may 

submit one paper copy. Comments are 

to be identified with the docket number 

found in brackets in the heading of this 

document. The draft guidance and 

received comments may be seen in the 

Division of Dockets Management 

between 9 a.m. and 4 p.m., Monday 

through Friday. 

IV. References 

The following references have been 

placed on display in the Division of 

Dockets Management (see ADDRESSES) 

and may be seen by interested persons 

between 9 a.m. and 4 p.m., Monday 

through Friday. 

1. S. 3546 Dietary Supplement and 

Nonprescription Drug and Consumer 

Protection Act, Congressional Budget Office 

Cost Estimate, December 27, 2006. 

2. ‘‘Adverse Event Reporting For Dietary 

Supplements: An Inadequate Safety Valve,’’

Office of the Inspector General, Department 

of Health and Human Services, April 2001, 

OEI–01–00–00180. 

V. Electronic Access 

Persons with access to the Internet 

may obtain the draft guidance at http:// 

www.cfsan.fda.gov/guidance.html. 

Dated: October 10, 2007. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. 07–5074 Filed 10–11–07; 11:34 am] 

BILLING CODE 4160–01–S 


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