1694 Federal Register / Vol. 74, No. 8 / Tuesday, January 13, 2009 / Notices 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2008–D–0053] 

Guidance for Industry on Good Reprint 

Practices for the Distribution of 

Medical Journal Articles and Medical 

or Scientific Reference Publications on 

Unapproved New Uses of Approved 

Drugs and Approved or Cleared 

Medical Devices; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a guidance for industry 

entitled ‘‘Good Reprint Practices for the 

Distribution of Medical Journal Articles 

and Medical or Scientific Reference 

Publications on Unapproved New Uses 

of Approved Drugs and Approved or 

Cleared Medical Devices.’’ The guidance 

provides drug, biologics, and device 

manufacturers with the agency’s views 

on the distribution of medical journal 

articles and scientific or medical 

reference publications that discuss 

unapproved new uses for FDA-approved 

drugs or biologics or FDA-approved or 

cleared medical devices to healthcare 

professionals and healthcare entities. 

DATES: Submit written or electronic 

comments on agency guidances at any 

time. 

ADDRESSES: Submit written requests for 

single copies of the guidance to the 

Office of Policy, Office of the 

Commissioner, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 1, rm. 4305, Silver Spring, 

MD, 20993–0002. Send one selfaddressed adhesive label to assist that 

office in processing your requests. See 

the SUPPLEMENTARY INFORMATION section 

for electronic access to the guidance 

document. 

Submit written comments to the 

Division of Dockets Management (HFA– 

305), Food and Drug Administration, 

5630 Fishers Lane, rm.1061, Rockville, 

MD 20852. Submit electronic comments 

to http://www.regulations.gov. 

FOR FURTHER INFORMATION CONTACT: 

Jarilyn Dupont, Office of Policy, Office 

of the Commissioner, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 1, rm. 4305, Silver Spring, 

MD, 20993–0002, 301–796–4830. 

SUPPLEMENTARY INFORMATION: 

I. Background 

The guidance provides drug, 

biologics, and device manufacturers 

with the agency’s views on the 

distribution of medical journal articles 

and scientific or medical reference 

publications that discuss unapproved 

new uses for FDA-approved drugs 

(including biologics) or FDA-approved 

or cleared medical devices to healthcare 

professionals and healthcare entities. In 

the Federal Register of February 20, 

2008 (73 FR 9342), FDA announced the 

availability of a draft guidance for 

industry entitled ‘‘Good Reprint 

Practices for the Distribution of Medical 

Journal Articles and Medical or 

Scientific Reference Publications on 

Unapproved New Uses of Approved 

Drugs and Approved or Cleared Medical 

Devices.’’ FDA received several 

comments on the draft guidance and 

those comments were considered as the 

guidance was finalized. 

On September 30, 2006, section 401 of 

the Food and Drug Administration 

Modernization Act (FDAMA) (section 

551 of the Federal Food, Drug, and 

Cosmetic Act (21 U.S.C. 360aaa)) ceased 

to be in effect. The provision described 

certain conditions under which a drug 

or medical device manufacturer could 

disseminate medical and scientific 

information discussing unapproved uses 

of approved drugs and cleared or 

approved medical devices to healthcare 

professionals and certain entities 

(including pharmacy benefits managers, 

health insurance issuers, group health 

plans, and Federal or State 

governmental agencies). Section 401 of 

FDAMA provided that, if the described 

conditions were met, dissemination of 

such journal articles or reference 

publications would not be considered as 

evidence of the manufacturer’s intent 

that the product be used for an 

unapproved new use. FDAimplementing regulations were codified 

at 21 CFR part 99. In light of the sunset 

of section 401 of FDAMA and in 

recognition of the public health value to 

healthcare professionals of receiving 

scientific and medical information, FDA 

determined that its current views and 

recommendations concerning ‘‘Good 

Reprint Practices’’ for the dissemination 

of medical journal articles and medical 

or scientific reference publications on 

unapproved uses of drugs and medical 

devices were important. The sunset of 

the statutory provision eliminated the 

authority of FDA to require submission 

of articles for the agency’s review before 

dissemination by the manufacturers in 

instances where the manufacturer chose 

to disseminate information under these 

provisions. In the absence of that ability 

to require such submissions and the fact 

that the implementing regulations are 

no longer applicable, the agency 

determined that guidance to 

manufacturers was appropriate because 

the agency no longer reviews individual 

articles. 

With this guidance, FDA is providing 

its current views on the dissemination 

of medical journal articles and medical 

or scientific reference publications on 

unapproved uses of approved drugs and 

approved or cleared medical devices to 

healthcare professionals and healthcare 

entities. FDA’s legal authority to 

determine whether certain distributions 

of medical or scientific information 

constitutes promotion of an unapproved 

‘‘new use,’’ or whether such activities 

cause a product to be misbranded or 

adulterated has not changed. 

Some of the changes made to the 

guidance based on comments received, 

and on FDA’s own initiative, include a 

specific reference encouraging 

manufacturers to seek approvals and 

clearance for new indications and 

intended uses for medical products. 

FDA recognizes the value of new 

indications and uses for approved 

products and wants these to be studied 

so that patients and healthcare 

professionals receive safe and effective 

treatments. Many comments suggested 

that FDA continue to require presubmission of the articles and suggested 

other mandatory review practices. 

However, given the sunset of section 

401 of FDAMA these were not within 

FDA’s authority and thus outside the 

scope of this guidance. Section IV of the 

guidance clarifies a number of bullet 

points to address comments expressing 

confusion as to some of the terms and 

practices expressed. Additional 

information was provided to distinguish 

the dissemination of these types of 

articles from other industry practices. 

This guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents the agency’s 

current thinking on the dissemination of 

medical journal articles and medical or 

scientific reference publications on 

unapproved uses of approved drugs and 

approved or cleared medical devices to 

healthcare professionals and healthcare 

entities. 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 

requirements of applicable statutes and 

regulations. 

II. Comments 

Interested persons may, at any time, 

submit to the Division of Dockets 

Management (see ADDRESSES) written or 

electronic comments regarding the 

guidance. Submit a single copy of 

Federal Register / Vol. 74, No. 8 / Tuesday, January 13, 2009 / Notices 1695 

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. A copy of the guidance and 

received comments are available for 

public examination in the Division of 

Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

Please note that on January 15, 2008, 

the FDA Division of Dockets 

Management Web site transitioned to 

the Federal Dockets Management 

System (FDMS). FDMS is a 

Government-wide, electronic docket 

management system. Electronic 

comments or submissions will be 

accepted by FDA only through FDMS at 

http://www.regulations.gov. 

III. Electronic Access 

Persons with access to the Internet 

may obtain the document at either 

http://www.fda.gov/oc/op/ 

goodreprint.html or http:// 

www.regulations.gov. 

Dated: January 6, 2009. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E9–452 Filed 1–12–09; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2009–N–0674] 

Participation of Certain Population 

Subsets in Clinical Drug Trials; 

Request for Comment 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice; request for comments. 

SUMMARY: The Food and Drug 

Administration (FDA) is seeking 

information and comments on issues 

related to the enrollment of certain 

populations in clinical drug trials. 

Particularly, we are requesting 

information and comments from 

medical product manufacturers, 

institutional review boards (IRBs), 

patient groups, universities, researchers, 

community groups, and other interested 

parties. This request is related to FDA’s 

implementation of the Food and Drug 

Administration Amendments Act of 

2007 (FDAAA) section 901, which 

requires recommendations be included 

in a report to Congress addressing best 

practice approaches on increasing the 

participation of elderly populations, 

children, racially and ethnically diverse 

communities, and medically 

underserved populations in clinical 

drug trials. FDA requests that those with 

information on possible approaches to 

increase participation of these groups in 

clinical drug trials submit comments. 

DATES: Submit written or electronic 

comments by February 27, 2009. 

ADDRESSES: Submit electronic 

comments to http:// 

www.regulations.gov. 

Submit written comments to the 

Division of Dockets Management (HFA– 

305), Food and Drug Administration, 

5630 Fishers Lane, rm. 1061, Rockville, 

MD 20852. 

FOR FURTHER INFORMATION CONTACT: 

Brenda Evelyn, Office of Special Health 

Issues, Office of the Commissioner, 

Food and Drug Administration, 5600 

Fishers Lane, Rockville, MD 20857, 

301–827–4460. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Section 901 of FDAAA requires that 

FDA submit a report to Congress that 

includes ‘‘recommendations regarding 

impediments to the participation of 

elderly populations, children, racially 

and ethnically diverse communities and 

medically underserved populations in 

clinical drug trials’’ and 

recommendations that address ‘‘best 

practice approaches for increasing the 

inclusion of such subsets of the general 

population’’ in clinical drug trials 

(FDAAA, section 901(d)(5)). In 

developing this report, FDA seeks 

comments that may help to develop 

these recommendations. 

Participation of all segments of the 

population in medical research is 

critical to public health. The ability to 

develop drugs that are safe and effective 

for diverse groups hinges on the 

availability of clinical drug trial 

participants from these same groups. 

Some researchers and public health 

experts argue that inconsistent 

representation of certain communities 

can potentially lead to health disparities 

and insufficient data for risk 

assessment. FDA has previously 

identified the need for inclusion of 

children, both sexes, the elderly, 

racially and ethnically diverse 

communities, and other populations in 

clinical trials so that data are available 

to evaluate the potential differences 

among these subgroups (63 FR 6854, 

February 11, 1998). According to the 

Department of Health and Human 

Services (HHS) Office of Minority 

Health, in a recent prostate cancer 

study, only 8 percent of the 18,000 

participants were minorities 

(www.omhrc.gov/templates/ 

content.aspx?ID=5147). Increased 

participation from all of these subgroups may help assure that data 

relevant to the entire treatment 

population are obtained. 

In addition, statutory mandates and 

incentives such as the Pediatric 

Research Equity Act (PREA) (Public Law 

No. 108–155 as amended by FDAAA) 

and the Best Pharmaceuticals for 

Children Act (BPCA) (Public Law No. 

107–109 as amended by FDAAA) 

require and encourage medical research 

to consider implications for pediatric 

populations. 

For over 20 years, FDA has worked to 

encourage broad participation of all 

groups in clinical drug trials. Under 

FDA regulations (21 CFR 312.33), all 

investigational new drug (IND) 

applications must include in annual 

reports the number of patients tabulated 

by age, gender, and race, and under 21 

CFR 314.50(d)(5)(v) and (d)(5)(vi), new 

drug applications (NDA) are required to 

include analyses of efficacy and safety 

by demographic subgroups. Biologics 

license applications typically include 

analyses of efficacy and safety by 

demographic subgroups. The 

International Conference on 

Harmonization (ICH) guidance on the 

common technical document also calls 

for such analyses (see M4E: The CTD— 

Efficacy (August 2001) available at 

http://www.fda.gov/cber/gdlns/ 

m4ectd.pdf.). 

FDA has issued labeling 

recommendations for specific subpopulations (Guidance for Industry: 

Content and Format of the Adverse 

Reactions Section of Labeling for 

Human Prescription Drugs and 

Biological Products, January 2006, 

available at http://www.fda.gov/cber/ 

gdlns/cfadvers.htm) and guidelines for 

studying gender differences in clinical 

drug studies (Guideline for the Study 

and Evaluation of Gender, July 1993, 

available at http://www.fda.gov/cder/ 

Guidance/old036fn.pdf). FDA has made 

recommendations for minimum 

standards for the collection and use of 

race and ethnicity information to assist 

in the reporting of the summary of 

safety and effectiveness data by 

demographic subgroups (age, gender, 

race), as well as an analysis of whether 

modifications of dose or dosage 

intervals are needed for specific 

subgroups. (Guidance for Industry: 

Collection of Race and Ethnicity Data in 

Clinical Trials, September 2005, 

available at http://www.fda.gov/CBER/ 

gdlns/racethclin.htm; see, also ICH E–7 

Guideline for Industry, Studies in 

Support of Special Populations: 

Geriatrics (August 1994) available at