7612 Federal Register / Vol. 80, No. 28 / Wednesday, February 11, 2015 / Notices 

to assemble supporting scientific 

information when the claim is novel or 

when the claim is pre-existing but the 

scientific underpinnings of the claim are 

not widely established. These are claims 

that may be based on emerging science, 

where conducting literature searches 

and understanding the literature takes 

time. It is also possible that references 

for claims made for some dietary 

ingredients or dietary supplements may 

primarily be found in foreign journals 

and in foreign languages or in the older, 

classical literature where it is not 

available on computerized literature 

databases or in the major scientific 

reference databases, such as the 

National Library of Medicine’s literature 

database, all of which increases the time 

of obtaining substantiation. 

In the Federal Register of January 6, 

2000 (65 FR 1000), we published a final 

rule on statements made for dietary 

supplements concerning the effect of the 

product on the structure or function of 

the body. In that final rule, we estimated 

that there were 29,000 dietary 

supplement products marketed in the 

United States (65 FR 1000 at 1045). 

Assuming that the flow of new products 

is 10 percent per year, then 2,900 new 

dietary supplement products will come 

on the market each year. The structure/ 

function final rule estimated that about 

69 percent of dietary supplements have 

a claim on their labels, most probably a 

structure/function claim (65 FR 1000 at 

1046). Therefore, we assume that 

supplement manufacturers will need 

time to assemble the evidence to 

substantiate each of the 2,001 claims 

(2,900 × 69 percent) made each year. If 

we assume that the 2,001 claims are 

equally likely to be pre-existing widely 

established claims, novel claims, or preexisting claims that are not widely 

established, then we can expect 667 of 

each of these types of claims to be 

substantiated per year. Table 1 of this 

document shows that the annual burden 

hours associated with assembling 

evidence for claims is 189,428 (the sum 

of 667 × 44 hours, 667 × 120 hours, and 

667 × 120 hours). 

Dated: February 5, 2015. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2015–02787 Filed 2–10–15; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2012–D–0630] 

Safety Considerations To Mitigate the 

Risks of Misconnections With SmallBore Connectors Intended for Enteral 

Applications; 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 

‘‘Safety Considerations to Mitigate the 

Risks of Misconnections with SmallBore Connectors Intended for Enteral 

Applications.’’ The use of common 

connector designs, such as Luer 

connectors, has led to unintended 

connections between devices that have 

different intended uses and has resulted 

in serious and sometimes fatal 

consequences to patients. This guidance 

provides recommendations to 

manufacturers regarding the 

expectations for design and testing of 

small-bore connectors intended for 

enteral applications (‘‘enteral devices’’). 

FDA is making these recommendations 

to reduce the risk of unintended 

connections between enteral and nonenteral devices. 

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 ‘‘Safety 

Considerations to Mitigate the Risks of 

Misconnections with Small-Bore 

Connectors Intended for Enteral 

Applications’’ 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. Send one selfaddressed 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: 

Priya Venkataraman-Rao, Center for 

Devices and Radiological Health, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 66, Rm. G222, 

Silver Spring, MD 20993–0002, 301– 

796–6243. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Numerous publications regarding 

patient injury and death from tubing 

and catheter misconnections indicate 

that reports of misconnections have 

increased in frequency over the past 

several years. On July 9, 2010, FDA 

issued a letter to healthcare 

professionals, hospital purchasing 

departments, and manufacturers of 

enteral feeding tubes regarding Luer 

lock misconnections (Ref. 1). FDA 

advised manufacturers to assess the 

risks of misconnections for their devices 

and provide proposed solutions with 

validation for premarket review. At that 

time, some manufacturers were using 

color-coding and labeling to reduce the 

risk of misconnections; others were 

creating proprietary connectors 

designed to be incompatible with 

devices for non-enteral applications 

(‘‘non-enteral devices’’). However, 

recent reports of adverse events have 

demonstrated that reliance on colorcoding and tagging of enteral devices 

alone cannot adequately mitigate the 

risk of misconnections, especially with 

similarly color-coded intravenous PICC 

(percutaneously inserted central 

catheter) lines with Luer connectors. 

This guidance provides updated 

recommendations to manufacturers of 

small-bore connectors intended for 

enteral applications. The guidance 

recommends that manufacturers: (1) 

Design and test enteral connectors based 

upon Association for the Advancement 

of Medical Instrumentation (AAMI)/

CN3:2014 (PS), ‘‘Small-bore connectors 

for liquids and gases in healthcare 

applications—Part 3: Connectors for 

enteral applications’’ and AAMI/

CN20:2014 (PS), ‘‘Small-bore connectors 

for liquids and gases in healthcare 

applications—Part 20: Common test 

methods’’; (2) for connectors that do not 

meet AAMI/CN3:2014 (PS), design and 

test connectors based upon the AAMI/ 

American National Standards Institute 

(ANSI)/International Organization for 

Standardization (ISO) 80369–1 standard 

‘‘Small-bore connectors for liquids and 

gases in healthcare applications—Part 1: 


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Federal Register / Vol. 80, No. 28 / Wednesday, February 11, 2015 / Notices 7613 

General requirements’’; (3) no longer 

rely solely on color-coding, labeling, 

and tagging to prevent misconnections; 

and (4) perform and document risk 

assessments to demonstrate that the 

proposed design and testing have 

effectively mitigated the risk of the 

enteral connector misconnecting to nonenteral devices. 

Elsewhere in this issue of the Federal 

Register, we are announcing a 

publication containing modifications to 

the list of standards that FDA recognizes 

for use in premarket reviews (‘‘FDA 

Recognized Consensus Standards’’). 

Specifically, this publication announces 

the addition of a list of recognized 

standards that are relevant to safety 

considerations to mitigate the risks of 

misconnections with small-bore 

connectors intended for enteral 

applications. This publication, entitled 

‘‘Modifications to the List of Recognized 

Standards, Recognition List Number: 

039’’ (‘‘Recognition List Number: 039’’), 

will assist manufacturers who elect to 

declare conformity with consensus 

standards to meet certain requirements 

for medical devices, specifically smallbore connectors for enteral applications. 

In the Federal Register of July 27, 

2012 (77 FR 44256), FDA announced the 

availability of the draft guidance 

document. We invited interested 

persons to comment by October 25, 

2012. Seven sets of comments were 

received and offered strong support for 

the finalization of this guidance as part 

of a continued effort to reduce the 

likelihood of incidents involving 

unintended connections between 

connectors with different intended uses. 

Multiple comments also applauded FDA 

for collaborating with the standards 

organizations to address this issue. 

The comments also noted the 

potential drawbacks of aligning the 

recommended testing with the current 

version of the AAMI/ANSI/ISO 80369– 

1 standard. Its methodologies, 

particularly those in Annex B, seek to 

demonstrate that each proposed enteral 

connector is physically incompatible 

with non-enteral devices. However, ISO 

is proposing substantial changes for 

future versions that could affect the 

recommended testing. FDA 

acknowledges this potential drawback; 

however, the current version of 80369– 

1 was the available reference at the time. 

As noted above, additional consensus 

standards relating to the design and 

testing of small-bore connectors 

intended for enteral applications have 

been published and recognized. 

Therefore, the guidance has been 

modified accordingly to reference and 

align with these recognized standards. 

Multiple comments also suggested 

that the description of included and 

excluded devices be modified and 

clarified, and gave examples for 

consideration. The guidance has been 

modified accordingly. Several 

comments requested language and 

definition changes to provide more 

clarity and consistency with the 

published standard, which FDA has 

considered and incorporated as 

appropriate. Lastly, due primarily to 

space considerations on the label affixed 

to a device, multiple comments 

expressed concern regarding FDA’s 

recommendation to eliminate the use of 

shortened terms such as ‘‘enteral-only’’ 

or ‘‘non-IV’’ in favor of more descriptive 

labeling. FDA has considered these 

comments and recommends that the 

device’s instructions for use, as opposed 

to its affixed label, fully describe the 

subject connector’s interconnectability. 

The instructions for use will afford 

adequate space for the recommended 

longer phrases describing the devices to 

which the subject connector can and 

cannot connect. However, for 

connectors for which noninterconnectability has been 

demonstrated, the product design could 

also incorporate color-coding, labeling, 

and tagging or imprinting on the 

connector. 

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 mitigating the risks 

of misconnections with small-bore 

connectors intended for enteral 

applications. 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. Persons 

unable to download an electronic copy 

of ‘‘Safety Considerations to Mitigate the 

Risks of Misconnections with SmallBore Connectors Intended for Enteral 

Applications’’ may send an email 

request to CDRH-Guidance@fda.hhs.gov 

to receive an electronic copy of the 

document. Please use the document 

number 1784 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 (the PRA) (44 

U.S.C. 3501–3520). The collections of 

information in 21 CFR part 820 have 

been approved under OMB control 

number 0910–0073; the collections of 

information in 21 CFR part 812 have 

been approved under OMB control 

number 0910–0078; 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 

56.115 have been approved under OMB 

control number 0910–0130; the 

collections of information found in 21 

CFR part 814 have been approved under 

OMB control number 0910–0231; 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 have been approved under 

OMB control number 0910–0485. 

The labeling provisions of this 

guidance are not subject to review by 

OMB because they do not constitute a 

‘‘collection of information’’ under the 

PRA. Rather, the recommended enteral 

connector labeling is a public disclosure 

of information originally supplied by 

the Federal Government to the recipient 

for the purpose of disclosure to the 

public (see 5 CFR 1320.3(c)(2)). 

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. 

VI. References 

The following reference has 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, and is available 


tkelley on DSK3SPTVN1PROD with NOTICES
7614 Federal Register / Vol. 80, No. 28 / Wednesday, February 11, 2015 / Notices 

electronically at http://

www.regulations.gov. (FDA has verified 

the Web site addresses in this reference 

section, but FDA is not responsible for 

any subsequent changes to the Web sites 

after this document publishes in the 

Federal Register.) 

1. FDA Center for Devices and Radiological 

Health, Letters to Industry Page, ‘‘Letter to 

Manufacturers of Enteral Feeding Tubes,’’ 

(http://www.fda.gov/downloads/

MedicalDevices/ResourcesforYou/Industry/

UCM218631.pdf). 

Dated: February 5, 2015. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2015–02802 Filed 2–10–15; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2015–D–0288] 

Premarket Studies of Implantable 

Minimally Invasive Glaucoma Surgical 

Devices; Draft 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 draft guidance 

entitled ‘‘Premarket Studies of 

Implantable Minimally Invasive 

Glaucoma Surgical (MIGS) Devices.’’ 

This leap frog guidance document was 

developed to notify manufacturers of 

the recommended non-clinical and 

clinical studies to support a premarket 

approval application (PMA) for 

implantable MIGS devices. This draft 

guidance is not final nor is it in effect 

at this time. 

DATES: Although you can comment on 

any guidance at any time (see 21 CFR 

10.115(g)(5)), to ensure that the Agency 

considers your comment of this draft 

guidance before it begins work on the 

final version of the guidance, submit 

either electronic or written comments 

on the draft guidance by May 12, 2015. 

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 draft guidance 

document entitled ‘‘Premarket Studies 

of Implantable Minimally Invasive 

Glaucoma Surgical (MIGS) Devices’’ 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. Send one self-addressed adhesive 

label to assist that office in processing 

your request. 

Submit electronic comments on the 

draft 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: 

Michelle Tarver, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave. Bldg. 66, Rm. 2504, Silver Spring, 

MD 20993–0002, 301–796–5620. 

SUPPLEMENTARY INFORMATION: 

I. Background 

When finalized, this draft guidance 

document will recommend non-clinical 

and clinical studies to support a PMA 

for implantable MIGS devices. 

Glaucoma is a progressive condition 

that damages the optic nerve of the eye, 

is associated with elevated intraocular 

pressure, and leads to irreversible vision 

loss. It is the second leading cause of 

visual disability and blindness in the 

world, with 1 in 40 adults over 40 years 

of age suffering from glaucoma having 

some visual loss. Current surgical 

treatments are aimed at reducing 

intraocular pressure (IOP) and often 

reserved for moderate to severe disease. 

During the past decade, novel medical 

devices, called MIGS devices, have 

emerged. These devices are designed to 

treat less severe glaucoma by enhancing 

physiological aqueous outflow with an 

approach that causes minimal ocular 

trauma. 

This draft guidance is a leap-frog 

guidance; leap frog guidances are 

intended to serve as a mechanism by 

which the Agency can share initial 

thoughts regarding the content of 

premarket submissions for emerging 

technologies and new clinical 

applications that are likely to be of 

public health importance very early in 

product development, generally before 

FDA has even received any such 

submissions. This leap-frog guidance 

represents the Agency’s initial thinking 

and our recommendations may change 

as more information becomes available. 

The Agency strongly encourages 

manufacturers to engage with the Center 

for Devices and Radiological Health 

(CDRH) through the Pre-Submission 

process to obtain more detailed 

feedback for implantable MIGS devices. 

For more information on PreSubmissions, please see ‘‘Requests for 

Feedback on Medical Device 

Submissions: The Pre-Submission 

Program and Meetings with Food and 

Drug Administration Staff’’ (http://

www.fda.gov/downloads/

MedicalDevices/

DeviceRegulationandGuidance/

GuidanceDocuments/UCM311176.pdf). 

II. Significance of Guidance 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the Agency’s current thinking 

on implantable MIGS devices. 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 draft guidance may do so by 

downloading an electronic copy from 

the Internet. A search capability for all 

CDRH guidance documents is available 

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

DeviceRegulationandGuidance/ 

GuidanceDocuments/default.htm. 

Guidance documents are also available 

at http://www.regulations.gov. Persons 

unable to download an electronic copy 

of ‘‘Premarket Studies of Implantable 

Minimally Invasive Glaucoma Surgical 

(MIGS) Devices’’ may send an email 

request to CDRH-Guidance@fda.hhs.gov 

to receive an electronic copy of the 

document. Please use the document 

number 1400049 to identify the 

guidance you are requesting. 

IV. Paperwork Reduction Act of 1995 

The guidance document ‘‘Premarket 

Studies of Implantable Minimally 

Invasive Glaucoma Surgical (MIGS) 

Devices’’ refers to previously approved 

information collections found in FDA 

regulations and guidance. 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 814, subparts B and E are 

approved under OMB control number 

0910–0231 and the collections of 

information in the guidance document 

entitled ‘‘Requests for Feedback on 

Medical Device Submissions: The PreSubmission Program and Meetings with 


tkelley on DSK3SPTVN1PROD with NOTICES