Federal Register / Vol. 79, No. 218 / Wednesday, November 12, 2014 / Notices 67175 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2013–D–0258] 

Combined Functionality for Molecular 

Diagnostic Instruments; Guidance for 

Industry and Food and Drug 

Administration Staff; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of the guidance entitled 

‘‘Molecular Diagnostic Instruments with 

Combined Functions.’’ This guidance 

document provides industry and 

Agency staff with FDA’s current 

thinking on regulation of molecular 

diagnostic instruments that combine in 

a single instrument both approved/

cleared device functions and device 

functions for which approval/clearance 

is not required, and on the type of 

information that FDA recommends that 

applicants include in a submission for 

a molecular diagnostic instrument that 

measures or characterizes nucleic acid 

analytes and has combined functions. 

DATES: Submit either electronic or 

written comments on this guidance at 

any time. General comments on Agency 

guidance documents are welcome at any 

time. 

ADDRESSES: An electronic copy of the 

guidance document is available for 

download from the Internet. See the 

SUPPLEMENTARY INFORMATION section for 

information on electronic access to the 

guidance. Submit written requests for a 

single hard copy of the guidance 

document entitled ‘‘Molecular 

Diagnostic Instruments With Combined 

Functions’’ to the Office of the Center 

Director, Guidance and Policy 

Development, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 5431, Silver Spring, 

MD 20993–0002; or Office of 

Communication, Outreach and 

Development, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 3128, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

request. 

Submit electronic comments on the 

guidance 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. Identify comments with the 

docket number found in brackets in the 

heading of this document. 

FOR FURTHER INFORMATION CONTACT: 

Andrew Grove, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 5515, Silver Spring, 

MD 20993–0002, 301–796–6198; or 

Stephen Ripley, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 7301, 

Silver Spring, MD 20993–0002, 240– 

402–7911. 

SUPPLEMENTARY INFORMATION: 

I. Background 

This guidance document provides 

industry and Agency staff with FDA’s 

current thinking on regulation of 

molecular diagnostic instruments that 

combine in a single instrument both 

approved/cleared device functions and 

device functions for which approval/

clearance is not required, and on the 

type of information that FDA 

recommends that applicants include in 

a submission for a molecular diagnostic 

instrument that measures or 

characterizes nucleic acid analytes and 

has combined functions. Molecular 

diagnostic instruments, for example, 

real-time thermocyclers, are critical 

components of certain in vitro 

diagnostic devices. They are often used 

to perform multiple unrelated assays, 

such as those that detect methicillin 

resistant Staphylococcus aureus, 

hepatitis C virus, and genetic markers of 

cystic fibrosis. These types of 

instruments cannot generally be 

approved/cleared alone, i.e., without an 

accompanying assay, because their 

safety and effectiveness cannot be 

evaluated without reference to the 

assays that they run and their defined 

performance parameters. However, the 

same instruments may also be used for 

additional purposes that do not require 

FDA approval or clearance, such as for 

basic scientific research. In the past, 

FDA has provided informal advice in 

response to individual inquiries 

regarding the permissibility of having 

functions for which approval/clearance 

is not required on an instrument 

intended to be used with approved/

cleared in vitro diagnostic assays. This 

guidance is meant to communicate 

FDA’s policy regarding molecular 

diagnostic instruments with combined 

functions. 

This guidance applies to molecular 

diagnostic instruments that are medical 

devices used with assays that measure 

or characterize nucleic acid analytes, 

human or microbial, and that combine 

both approved/cleared and nonapproved/non-cleared functions in a 

single instrument. This guidance 

applies to the instrument itself 

(hardware) as well as to any firmware or 

software intended to operate on or to 

control the instrument. This guidance 

also addresses software that is 

distributed as a stand alone device for 

use with an approved/cleared molecular 

diagnostic assay. 

The guidance does not apply to 

instruments approved/cleared for use 

with assays that are intended to screen 

donors of blood and blood components, 

human cells, tissues, and cellular and 

tissue-based products, for 

communicable diseases. The document 

also does not apply to instruments 

approved/cleared for blood grouping. 

We encourage manufacturers wishing to 

market such instruments with combined 

functionality to contact the appropriate 

office in the Center for Biologics 

Evaluation and Research (CBER). 

The recommendations in this 

guidance do not apply to assays and 

reagents. They are also not intended to 

change FDA’s position regarding the 

marketing of Research Use Only and 

Investigational Use Only assays for 

clinical use. 

The draft guidance was announced in 

the Federal Register of April 9, 2013 (78 

FR 21128), and the comment period 

closed on July 8, 2013. Several 

comments were received during the 

comment period. We took the 

suggestions into consideration in 

revising and finalizing this guidance. 

II. Significance of Guidance 

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 molecular 

diagnostic instruments with combined 

functions. 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 the applicable statute 

and regulations. 

III. Electronic Access 

Persons interested in obtaining a copy 

of the guidance may do so by 

downloading an electronic copy from 

the Internet. A search capability for all 

Center for Devices and Radiological 

Health guidance documents is available 

at http://www.fda.gov/MedicalDevices/

DeviceRegulationandGuidance/

GuidanceDocuments/default.htm. 

Guidance documents are also available 

at http://www.regulations.gov or from 


TKELLEY on DSK3SPTVN1PROD with NOTICES
67176 Federal Register / Vol. 79, No. 218 / Wednesday, November 12, 2014 / Notices 

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

BloodVaccines/GuidanceCompliance

RegulatoryInformation/default.htm. 

Persons unable to download an 

electronic copy of ‘‘Molecular 

Diagnostic Instruments With Combined 

Functions’’ may send an email request 

to CDRH-Guidance@fda.hhs.gov to 

receive an electronic copy of the 

document. Please use the document 

number 1763 to identify the guidance 

you are requesting. 

IV. Paperwork Reduction Act of 1995 

This guidance refers to previously 

approved collections of information 

found in FDA regulations. These 

collections of information are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

Reduction Act of 1995 (44 U.S.C. 3501– 

3520). The collections of information in 

21 CFR part 807, subpart E, have been 

approved under OMB control number 

0910–0120; the collections of 

information in 21 CFR part 803 have 

been approved under OMB control 

number 0910–0437; and the collections 

of information in 21 CFR part 801 and 

21 CFR 809.10 have been approved 

under OMB control number 0910–0485. 

V. Comments 

Interested persons may submit either 

electronic comments regarding this 

document to http://www.regulations.gov 

or written comments to the Division of 

Dockets Management (see ADDRESSES). It 

is only necessary to send one set of 

comments. Identify comments with the 

docket number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday, and 

will be posted to the docket at http://

www.regulations.gov. 

Dated: November 5, 2014. 

Leslie Kux, 

Assistant Commissioner for Policy. 

[FR Doc. 2014–26694 Filed 11–10–14; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Submission for OMB Review; 30-Day 

Comment Request; HIV Study in Blood 

Donors From Five Chinese Regions 

(NHLBI) 

SUMMARY: Under the provisions of 

Section 3507(a)(1)(D) of the Paperwork 

Reduction Act of 1995, the National 

Institutes of Health (NIH) has submitted 

to the Office of Management and Budget 

(OMB) a request for review and 

approval of the information collection 

listed below. This proposed information 

collection was previously published in 

the Federal Register in Volume 79, June 

12, 2014 on page 33764 and allowed 60- 

days for public comment. One public 

comment was received that was a 

personal opinion regarding conducting 

research about the Chinese blood 

donation system. The purpose of this 

notice is to allow an additional 30 days 

for public comment. The National 

Institutes of Health (NIH) may not 

conduct or sponsor, and the respondent 

is not required to respond to, an 

information collection that has been 

extended, revised, or implemented on or 

after October 1, 1995, unless it displays 

a currently valid OMB control number. 

Direct Comments to OMB: Written 

comments and/or suggestions regarding 

the item(s) contained in this notice, 

especially regarding the estimated 

public burden and associated response 

time, should be directed to the: Office 

of Management and Budget, Office of 

Regulatory Affairs, OIRA_submission@

omb.eop.gov or by fax to 202–395–6974, 

Attention: NIH Desk Officer. 

Comment Due Date: Comments 

regarding this information collection are 

best assured of having their full effect if 

received within 30-days of the date of 

this publication. 

FOR FURTHER INFORMATION CONTACT: To 

obtain a copy of the data collection 

plans and instruments or request more 

information on the proposed project 

contact: Simone Glynn, MD, Project 

Officer/ICD Contact, Two Rockledge 

Center, Suite 9142, 6701 Rockledge 

Drive, Bethesda, MD 20892, or call 301– 

435–0065, or Email your request, 

including your address to: glynnsa@

nhlbi.nih.gov. Formal requests for 

additional plans and instruments must 

be requested in writing. 

Proposed Collection: HIV Study in 

Blood Donors From Five Chinese 

Regions, 0925–0596 Reinstatement With 

Change, National Heart, Lung and 

Blood Institute (NHLBI) 

Need and Use of Information 

Collection: This Study is a reinstatement 

with change of OMB Number: 0925– 

0596 expiration date, January 31, 2012. 

To better understand the diversifying 

and changing Human 

Immunodeficiency Virus (HIV) 

epidemic, and contemporary HIV risk 

factors, especially those associated with 

recent HIV infections, this HIV risk 

factor study in China is proposed as part 

of the Recipient Epidemiology and 

Donor Evaluation Study–III (REDS–III). 

The major objectives of the study will be 

to evaluate the proportion of blood 

donors in China who test positive for 

HIV and have acquired their infection 

recently or more remotely; the risk of 

releasing a blood product that contains 

HIV (HIV residual risk); and the risk 

factors associated with HIV infection in 

China. The study will also assess the 

frequency of distinct HIV–1 viral 

lineages and drug resistant mutations 

among HIV-positive blood donors. In 

2011, there were 780,000 people 

infected with HIV in China and it is 

estimated that over 300,000 HIV 

infected people in China are not aware 

of their infection status. The large 

migrating population and the 

complexity of HIV transmission routes 

in China make it difficult to implement 

a comprehensive and effective national 

HIV control strategy. Risk factors for 

infections can change over time; thus, 

identifying factors that contribute to the 

recent spread of HIV in a broad crosssection of an otherwise unselected 

general population, such as blood 

donors, is highly important for 

obtaining a complete picture of the 

epidemiology of HIV infection in China. 

Because the pace of globalization means 

infections can cross borders easily, the 

study objectives have direct relevance 

for HIV control in the US and globally. 

Recent years have seen an increase in 

blood donations from repeat donors in 

most Chinese regions. This increase 

permits longer-term follow-up and 

testing of repeat donors which allow for 

calculation of new HIV infection rates 

and residual risks. The HIV data, for 

both recently and remotely acquired 

infections, from the proposed study will 

complement existing data on HIV risks 

obtained from general and high risk 

populations to provide comprehensive 

HIV surveillance data for China. This 

study will also monitor genetic 

characteristics of recently acquired 

infections through genotyping and drug 

resistance testing, thus serving a US and 

global public health imperative to 

monitor the genotypes of HIV that have 

recently been transmitted. For HIV, the 

additional monitoring of drug resistance 

patterns in newly acquired infection is 

critical to determine if currently 

available antiretroviral medicines are 

capable of combating infection. 

Genotyping and host response 

information are scientifically important 

not only to China, but to the US and 

other nations since they provide a 

broader global understanding of how to 

most effectively manage and potentially 

prevent HIV, for example through 

vaccine development. Efforts to develop 

vaccines funded by the National 

Institutes of Health and other US-based 


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