Contains Nonbinding Recommendations 
Safety Considerations to Mitigate the 
Risks of Misconnections with Small-
bore Connectors Intended for Enteral 
Applications  
Guidance for Industry and Food and 
Drug Administration Staff 
Document issued on February 11, 2015. 
 
The draft of this document was issued on July 27, 2012 
 
For questions about this document, contact the Division of Reproductive, Gastro-renal, and 
Urological Devices, 301-796-7030 and Priya Venkataraman-Rao, M.D., 301-796-6243, 
Priya.Venkataraman-Rao@fda.hhs.gov. 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
Office of Device Evaluation 
Division of Reproductive, Gastro-renal, and Urological Devices 
Gastroenterology Devices Branch  Contains Nonbinding Recommendations 
Preface 
 
Public Comment 
 
You may submit electronic comments and suggestions at any time for Agency consideration to 
http://www.regulations.gov. Submit written comments to the Division of Dockets Management, 
Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 
20852. Identify all comments with the docket number FDA-2012-D-0630. Comments may not 
be acted upon by the Agency until the document is next revised or updated. 
 
Additional Copies 
 
Additional copies are available from the Internet. You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please use the document 
number 1784 to identify the guidance you are requesting. 
 
  Contains Nonbinding Recommendations 
Table of Contents
 
 
I.  Introduction .................................................................................................................................. 1 
II.  Definitions ..................................................................................................................................... 2 
III.  Background ................................................................................................................................... 3 
IV.  Scope ............................................................................................................................................. 4 
V.  Recommendations ........................................................................................................................ 5 
A.  Connector materials ..................................................................................................................... 5 
B.  Mechanical testing of enteral connectors to assess incompatibility .......................................... 6 
C.  Enteral connector risk assessment .............................................................................................. 6 
D.  Inadequacy of color-coded and labeled connectors ................................................................... 7 
E.  Side ports, transition connectors, adapters, and syringes .......................................................... 7 
F.  Labeling ........................................................................................................................................ 7 
G.  Usability and human factors testing ............................................................................................ 8 
VI.  Future Considerations ................................................................................................................... 8 
VII.  References .................................................................................................................................. 10 
  Contains Nonbinding Recommendations 
Safety Considerations to Mitigate the 
Risks of Misconnections with Small-
bore Connectors Intended for Enteral 
Applications  
Guidance for Industry and Food and 
Drug Administration Staff 
This guidance represents the Food and Drug Administrations (FDAs) 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. You can use an alternative approach if the approach satisfies 
the requirements of the applicable statutes and regulations. If you want to discuss an 
alternative approach, contact the FDA staff responsible for implementing this guidance. If 
you cannot identify the appropriate FDA staff, call the appropriate number listed on the 
title page of this guidance.  
I.  Introduction 
This guidance provides recommendations to manufacturers, FDA reviewers, and other entities 
involved in manufacturing devices that contain small-bore connectors designed for enteral 
feeding, as well as those submitting or reviewing premarket notification submissions 
[510(k)s] for these devices. Small-bore connectors provide a mechanism for the connection 
between a variety of medical devices including those with enteral and non-enteral (e.g., 
intravenous) 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.1,2,3 
 
This guidance recommends that manufacturers 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 to ensure that 
each proposed enteral connector is physically incompatible with non-enteral devices. For 
enteral connectors that do not meet AAMI/CN3:2014 (PS), also known as proprietary 
connectors or transition connectors, this guidance continues to recommend that manufacturers 
design and test the devices 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: General requirements.  
1  Contains Nonbinding Recommendations 
 
Furthermore, this guidance document serves to notify manufacturers submitting 510(k)s or 
modifying a device already cleared for enteral connectors that color-coding, labeling, and 
tagging attached to the device, by themselves, are no longer sufficient to satisfy safety 
concerns regarding misconnection hazards associated with connectors such as 6% tapered 
Luer connectors.  Lastly, this guidance recommends that when submitting a 510(k) or 
modifying an existing product already cleared via 510(k), a manufacturer should perform a 
risk assessment to assess the risks of the proposed enteral connector misconnecting to non-
enteral devices. 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidances describe the Agencys current thinking on a topic and 
should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited. The use of the word should in Agency guidances means that 
something is suggested or recommended, but not required. 
II.  Definitions 
Adapter: A device, or a component of a device, whose purpose is to form intermediary 
connections between two incompatible medical devices. 
 
Enteral connectors: Connectors that attach to devices involved in administration of fluid 
(liquid) to the gastrointestinal tract or removal of gas or fluids from the gastrointestinal tract. 
These include nasogastric, nasoduodenal, gastrostomy, and gastrojejunal feeding tubes, 
including enteral feeding sets, gravity and pump feeding sets, Y-ports and T-set medication 
ports, enteral pouches, and syringes for feeding and/or administering enteral medication. 
 
Luer: The AAMI/ANSI/ISO 80369-1 standard describes the Luer connector as a small-bore 
conical fitting with a 6% taper for syringes, needles, and certain other medical equipment. 
Luer connectors have a male and a female component that are joined to form a secure, yet 
detachable leak-proof connection. The connection is achieved by use of a push fitting (a Luer 
slip) or a screw-in threaded fitting (a Luer lock) that joins the male and the female tapered 
fittings. 
 
 
 
Luer Lock   Luer Slip 
 
Picture Courtesy of Beaumont Hospitals 
 
 
2  Contains Nonbinding Recommendations 
Misconnection: Inappropriate connections occurring between two connectors that attach 
devices with different intended uses or applications, such as enteral feeding systems and non-
enteral systems. 
 
Non-enteral connectors: Small-bore connectors on devices that are not involved in enteral 
(through the gastrointestinal system) feeding systems. 
 
Non-interconnectable connectors: Connectors that have geometries and other design 
characteristics that prevent secure and unintended connections. 
 
Proprietary connector:  For purposes of this guidance, small-bore connector designed to 
conform to the AAMI/ANSI/ISO 80369-1 standard, but does not meet the design 
requirements of AAMI/CN3:2014 (PS). 
 
Representative market sampling: For purposes of misconnection testing (refer to Section 
V.B), a sampling of small-bore connectors that are commonly marketed in the United 
States, and which are representative of connectors that may be present with an enteral 
connector. These select connectors should include connectors from the medical application 
types that are identified in AAMI/ANSI/ISO 80369-1.   
 
Side port: Connecting attachment to feeding tube which allows for (1) medication 
administration and/or flushing and (2) fluid or air inflation of balloons. 
 
Transition connector: For purposes of this guidance, facilitates enteral-specific 
connections between the AAMI/CN3:2014 (PS), Part 3 compliant connectors and non-
AAMI/ANSI/ISO 80369-1 compliant enteral connectors. 
III.  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.1,2,4-9 Misconnections occur when a connector on a medical device 
performing a specific function is unintentionally or intentionally attached to a connector from 
another medical device that performs a completely different function. Small-bore Luer 
connectors can freely connect to many different medical devices.2-9 Human factor errors 
coupled with widespread use of Luer connectors may promote misconnections of enteral to 
non-enteral devices.4 To reduce the frequency of connector hazards, the FDA is collaborating 
with the International Organization for Standardization to develop the AAMI/ANSI/ISO 
80369 standards. 
 
On July 9, 2010, the FDA issued a letter to healthcare professionals, hospital purchasing 
departments, and manufacturers of enteral feeding tubes regarding Luer lock misconnections. 
The 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 non-enteral 
devices. However, recent reports of adverse events have demonstrated that reliance on color-
3  Contains Nonbinding Recommendations 
coding 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.8,9  
 
AAMI/ANSI/ISO 80369-1 was published on December 15, 2010, and recognized by the FDA 
on March 14, 2011, as noted on the FDAs Recognized Consensus Standards webpage 
(http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfstandards/results.cfm). 
AAMI/ANSI/ISO 80369-1 provides general requirements for small-bore connectors for 
liquids and gases in healthcare applications. It provides a framework for testing connectors of 
different medical applications against each other to ensure non-interconnectability, and also 
establishes specific misconnection testing methods. AAMI/CN3:2014 (PS) Part 3 was 
published on December 2, 2014 and recognized by the FDA on February 11, 2015. 
AAMI/CN3:2014 (PS) Part 3 specifies the dimensions and recommendations for the design 
and functional performance of small-bore connectors intended to be used on medical devices 
and accessories that have an enteral application.  In addition, AAMI/CN20:2014 (PS) Part 20 
was published on December 2, 2014 and recognized by the FDA on February 11, 2015. 
AAMI/CN20:2014 (PS) Part 20 specifies test methods to support the functional requirements 
for the small-bore connectors identified in AAMI/ANSI/ISO 80369-1. The FDAs recognition 
of AAMI/ANSI/ISO 80369-1, AAMI/CN3:2014 (PS) Part 3, and AAMI/CN20:2014 (PS) Part 
20, and the Agencys concern regarding enteral to non-enteral misconnections prompted the 
FDA to publish the current guidance. Through the combined efforts of industry, medical 
device purchasers, healthcare professionals, and the appropriate regulatory authorities, the 
risk of misconnection can be optimally mitigated.  
IV.  Scope 
The recommendations made in this guidance are applicable to connectors that are part of, or 
form connections to, enteral devices intended for administration of fluids (e.g., enteral 
formulas and medications) and other nutritional substances. These products are all regulated 
under 21 CFR 876.5980, and include the following devices:  
 
  Enteral feeding tubes (product code KNT); 
  Enteral specific transition connectors (PIO); 
  Gastrostomy tubes (KNT, KGC, FPD and FHT); 
  Gastrointestinal tubes with enteral specific connectors (PIF); 
  Gastrojejunal tubes (KNT); 
  Nasogastric tubes (KNT, BSS, FEF, FFW and FPD); and 
  Nasoduodenal tubes (KNT).  
 
The recommendations also apply to connections located directly on feeding tubes:  
  Extension/administration sets (KNT); and 
  Feeding reservoirs/spikes, and syringes (KNT, FMF).  
 
This guidance also addresses side ports and adapter connections. Ports for balloon inflation 
are not addressed in this guidance. 
4  Contains Nonbinding Recommendations 
V.  Recommendations 
The FDA recommends that devices with connectors that are part of, or form connections to, 
enteral feeding tubes conform to AAMI/CN3:2014 (PS) Part 3. If such devices with an 
existing 510(k) clearance have been modified in order to conform to this standard, and the 
modifications would trigger the need for a new 510(k), FDA does not intend to object if firms 
submit a declaration of conformity to AAMI/CN3:2014 (PS) Part 3 in an add-to-file to their 
existing 510(k) rather than submitting a new 510(k).10 Please note the devices with such 
connectors remain subject to requirements such as GMP requirements (21 CFR 820), 
including design controls (21 CFR 820.30), and registration and listing (21 CFR 807).11  In 
the event a manufacturer creates or modifies device connectors such that they do not fully 
conform to the AAMI/CN3:2014 (PS) Part 3 standard, e.g., proprietary and transition 
connectors, FDA expects the manufacturer to submit a 510(k) for FDA review when a 510(k) 
submission is required. For more information on when to submit a 510(k), please see FDAs 
guidance, Deciding When to Submit a 510(k) for a Change to an Existing Device 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ 
ucm080235.htm). 
 
Given that AAMI/ANSI/ISO 80369-1 establishes a framework for testing different 
connectors, but does not identify the specific connectors to be evaluated, even if devices with 
proprietary or transition connectors conform to AAMI/ANSI/ISO 80369-1, the FDA 
recommends that full test reports, containing the test protocol, results, any deviations, and 
conclusions, be submitted as part of the 510(k) submission when a 510(k) submission is 
required. 
 
A.  Connector materials 
The FDA recommends that enteral connectors be made of rigid or semi-rigid materials, as 
described in the currently FDA-recognized version of AAMI/ANSI/ISO 80369-1, Clause 4 or 
in AAMI/CN3:2014 (PS) Part 3 as appropriate. In addition, it is recommended that the 
connectors be made of materials with a modulus of elasticity either in flexure or in tension 
greater than 700 MPa, in accordance with AAMI/CN3:2014 (PS) Part 3. Testing verifying the 
materials chosen should be conducted according to ASTM D747 Standard Test Method for 
Apparent Bending Modulus of Plastics by Means of a Cantilever Beam, ASTM D790 
Standard Test Methods for Flexural Properties of Unreinforced and Reinforced Plastics and 
Electrical Insulating Materials, or equivalent method. Use of rigid or semi-rigid materials 
will reduce the likelihood of forced fits between flexible connectors that are not intended to 
connect with each other. 
 
                                                           
10 Any device that is represented to conform to an FDA-recognized standard and does not conform to such 
standard in all respects is adulterated under section 501(e)(2) of the FD&C Act, 21 U.S.C.  351(e)(2). 
11 Manufacturers continuing obligations under the quality system regulations in 21 CFR part 820 require control 
of supply and outgoing product for compliance with design specifications.  Compliance with these obligations 
may be evaluated during routine inspections. 
5  Contains Nonbinding Recommendations 
B.  Mechanical testing of enteral connectors to assess 
incompatibility 
For connectors that do not conform to AAMI/CN3:2014 (PS) Part 3, the FDA recommends 
mechanical force testing of enteral connectors following AAMI/ANSI/ISO 80369-1, Clause 
5.8, Annex B methods, or an equivalent alternative, to demonstrate that enteral connectors are 
non-interconnectable with connectors from other health care applications. The following 
components should be tested: 
  connectors for the following device types: 
o   intravascular devices; 
o   hypodermic applications; 
o   breathing systems and driving gas devices; 
o   urethral/urinary devices; 
o   limb cuff inflation devices; and 
o   neuraxial devices. 
 
For each of the device types listed above, manufacturers should identify in their premarket 
submissions the most commonly sold or used non-enteral connectors found in U.S. markets, 
as determined from a representative sample analysis, against which the subject device should 
be tested. 
 
Regarding testing, to demonstrate non-interconnectable characteristics, the proposed 
connector should not provide a secure connection with a non-enteral connector when 
assembled with moderate force, and should easily disengage. As described in 
AAMI/ANSI/ISO 80369-1, Annex B, and AAMI/CN3:2014 (PS) Part 3, Clause 6, the test 
connectors should be appropriately conditioned and assembled by applying a specified axial 
force and torque for a specified amount of time. Then, without activating any latch or 
disengagement mechanism, an axial force of separation should be applied to the assembled 
connectors to verify that the connectors disengage. Threaded connectors should be tested with 
both clockwise and counterclockwise rotation. 
 
C.  Enteral connector risk assessment 
When submitting a new 510(k) or modifying an existing 510(k)-cleared device, a 
manufacturer should conduct a risk assessment to demonstrate that the risk of misconnection 
has been effectively mitigated with the enteral product. There should be objective evidence to 
demonstrate that the risks have been reduced to acceptable levels according to the currently 
FDA recognized version of ISO 14971 or equivalent. For example, the manufacturer may 
document selection of appropriate material (Section V.A, above) and quantitative mechanical 
testing data to demonstrate that the proposed enteral connector has a reduced risk of forming 
stable attachments to connectors routing into non-enteral devices (Section V.B, above). 
 
6  Contains Nonbinding Recommendations 
D.  Inadequacy of color-coded and labeled connectors 
AAMI/ANSI/ISO 80369-1, Clause 5.8, provides an approach and testing method (Annex B) 
for reducing misconnection hazards by designing enteral connectors physically incapable of 
secure attachment to connectors of non-enteral devices. As supported by AAMI/CN3:2014 
(PS) Part 3, Annex A, color-coding, labeling, and tagging or imprinting (e.g., feeding only, 
medication only) on the device, by themselves, are not sufficient to mitigate health 
concerns from enteral misconnection.8,9 However, for connectors for which non-
interconnectability has been demonstrated (Sections V.A, B, and C, above), color-coding, 
labeling, and tagging or imprinting on the connector could also be incorporated into the 
product design. 
 
E.  Side ports, transition connectors, adapters, and 
syringes 
To reduce the likelihood of misconnections, the FDA recommends that side port connectors 
that are used for flushing and/or drug administration be tested similarly to the enteral 
connectors described in Sections V.A, B, and C of this guidance. This means that the 
connectors should be made of rigid or semi-rigid materials, and mechanical testing should be 
performed according to recommendations outlined in AAMI/ANSI/ISO 80369-1, Clause 5.8 
and Annex B, or an equivalent alternative, to demonstrate that enteral flushing/drug 
administration side ports are non-interconnectable with connectors of non-enteral devices. 
The use of enteral only syringes may also be used as part of the mitigation of this issue.  
 
Side port connectors that are used with inflation devices have different risk profiles, and do 
not  necessarily  need  the  same  testing  as  other  enteral  connectors.  However,  the  FDA 
recommends  that  manufacturers  identify  risks  and  design  mitigations  to  reduce  risks  of 
misconnection. 
 
If the risk of use is acceptable, transition connectors may temporarily be necessary within 
GI applications (e.g., for tubes with both suctioning and feeding functions or for connection 
between proprietary and AAMI/CN3:2014 (PS) Part 3 compliant connectors). In certain 
limited circumstances, use of an adapter can provide for medication delivery until 
connectors meeting the standard are in wide-spread use, in order to avoid deprivation of care.   
 
Syringes are also often used in enteral applications. Syringes used for enteral feeding should 
only attach to enteral connectors. Therefore, the FDA recommends that mechanical testing 
should be performed according to recommendations described in Section V.A, B, and C of 
this guidance. 
 
F.  Labeling 
In considering approaches to labeling of a specific enteral device, the interpretation of the 
device name and/or claims are of high importance. The FDA recommends a simplified 
labeling strategy designed for easy interpretation of connectors to avoid potential confusion. 
Instructions for use might include statements such as: 
 
7  Contains Nonbinding Recommendations 
  The ____ (device) connection is intended to connect to ___________ (compatible 
devices). 
 
The FDA recommends that enteral labeling, including the instructions for use, not include the 
terms enteral-only and Non-IV. Enteral-only may be misleading in that it may be 
interpreted to mean compatibility with all other enteral connectors, but incompatibility with 
non-enteral connectors. Non-IV is not appropriate because the term non-IV does not 
encompass all the testing that is needed to demonstrate non-connectability with connectors 
used in other medical applications. When a device manufacturer wants to provide information 
in the instructions for use regarding the design features of their device that may mitigate the 
risk of misconnections, the FDA recommends statements such as the following: 
 
  The ____ (device) connection is intended to reduce the risk of misconnection 
between the following connectors/applications: ... 
 
  The (device/connector) was tested to demonstrate a reduced likelihood of a 
misconnection in the following device applications: ... 
 
Information regarding the potential to misconnect with other device applications should be 
included as a warning in the instructions for use. Specific connector types that have the 
potential to misconnect, and those that were demonstrated to misconnect, should be 
specified in the instructions for use. 
 
In addition, for the connectors for which non-interconnectability is demonstrated, labeling and 
tagging or imprinting (e.g., feeding only, medication only) on the connector could be 
incorporated into the product design. 
 
G.  Usability and human factors testing 
Proprietary connectors with claims of non-interconnectability to all other medical application 
types should include usability and/or human factors testing to confirm there is no 
unacceptable risk, as described in the currently FDA recognized version of AAMI/ANSI 
HE75, Human Factors Engineering  Design of medical devices. For additional information 
on this topic see FDAs draft guidance Applying Human Factors and Usability Engineering 
to Optimize Medical Device Design 
(http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm25
9748.htm), which represents FDAs proposed approach on this topic. When final, this 
document will supersede FDAs guidance entitled Medical Device Use-Safety: Incorporating 
Human Factors Engineering into Risk Management 
(http://www.fda.gov/downloads/MedicalDevices/.../ucm094461.pdf) (Issued July 18, 2000). 
Usability testing in relation to enteral connectors is also described in AAMI/CN3:2014 (PS) 
Part 3 Annex E. 
VI.  Future Considerations 
AAMI/ANSI/ISO 80369-1 provides general requirements for demonstrating non- 
interconnectability of small-bore connectors, while AAMI/CN3:2014 (PS) Part 3 specifies the 
8  Contains Nonbinding Recommendations 
dimensions and requirements for the design and functional performance of small-bore 
connectors intended to be used on enteral medical devices and accessories. This guidance 
provides advice to manufacturers of enteral connectors on mitigation of the risk of enteral 
small-bore connector misconnection hazards. As future standards are developed and 
recognized for this clinical application, FDA will update this guidance as appropriate to 
communicate our recommendations to stakeholders. 
9  Contains Nonbinding Recommendations 
VII. References 
 
1.  Guenter P, Hicks RW, Simmons D. Enteral Feeding Misconnections: an update. NutrClin 
Pract. 2009; 24(3):325-334. 
 
 
2.   The Joint Commission Sentinel Event Alert. Tubing Misconnections: A persistent and 
Potentially Deadly Occurrence. April 3, 2006. 
(http://www.jointcommission.org/assets/1/18/SEA_36.PDF) 
  
3.   American National Standards Institute (ANSI)/ Association for the advancement of Medical 
instrumentation (AAMI): Enteral Feeding Set Adapters and Connectors. Arlington, VA: 
ANSI/AAMI, 1996. 
 
4.  Guenter P, Hicks RW, Simmons D, Crowley J, Joseph S, Croteau R, Gosnell C, Pratt NG, 
Vanderveen TW. Enteral feeding misconnections: a consortium position statement. Jt Comm J 
Qual Patient Saf 2008; 34(5):285-292, 245. 
 
5.  Wallace JR, Payne RW, Mack AJ. Inadvertent intravenous breast milk. Lancet 1:1264-1266, 
Jun 10, 1972 
 
6.  Huddleston K, Creekmore P, Wood B. Administration of infant formula through the intravenous 
route: Consequences and prevention. MCN Am J Matern Child Nurs 19:40-42, Jan-Feb. 1994. 
 
7.  Beyea SC, Simmons D, Hicks RW. Caution: tubing misconnections can be deadly.AORN J 
2007;85(3):633-5. 
 
8.  Institute for Safe Medication Practices. Medication safety alert newsletter. Purple is not an 
official standard for either enteral feeding equipment or PICC lines. Volume 13; issue 11; Jun 4, 
2009. 
 
9.  Bankhead R, Boullata J, Brantley S, Corkins M, Guenter P, Krenitsky J, Lyman B, Metheny 
NA, Mueller C, Robbins S, Wessel J and the A.S.P.E.N. Board of Directors. J Parenter Enteral 
Nutr 2009; 33; Jan 26, 2009.  
 
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