Implanted Blood Access Devices for 
Hemodialysis 
 
Guidance for Industry and Food and 
Drug Administration Staff 
Document issued on January 21, 2016.  
 
The draft of this document was issued on June 28, 2013. 
 
For questions regarding this document, contact the Division of Reproductive, Gastro-renal, and 
Urological Devices, 301-796-7030 and Frank Hurst, MD, (301) 796-5960 or  
frank.hurst@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 
  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-2013-D-0749. 
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 1781 to identify the guidance you are requesting. 
  Contains Nonbinding Recommendations 
 
Table of Contents 
 
I.  Introduction ...................................................................................................................... 1 
II.  Background ...................................................................................................................... 1 
III.  Scope ................................................................................................................................ 2 
IV.  510(k) Submission Recommendations ............................................................................ 2 
A. DEVICE DESCRIPTION ................................................................................................................................... 2 
B.  DEVICE MATERIALS ..................................................................................................................................... 5 
C.  BIOCOMPATIBILITY....................................................................................................................................... 5 
D. PERFORMANCE TESTING - BENCH ................................................................................................................. 6 
E.  STERILITY AND SHELF-LIFE .......................................................................................................................... 8 
F.  LABELING ................................................................................................................................................... 10 
G. ANIMAL AND CLINICAL TESTING ................................................................................................................ 12 
(1)  Performance Testing  Animal ................................................................................................................ 12 
(2)  Performance Testing  Clinical ............................................................................................................... 12 
H. SPECIAL CONSIDERATIONS ......................................................................................................................... 13 
(1)  Subcutaneous Catheters ........................................................................................................................... 13 
(2)  Coatings .................................................................................................................................................... 14 
(3)  Arteriovenous (A-V) shunt cannulae (with vessel tips) ........................................................................... 15 
Appendix A ............................................................................................................................. 17 
 
  Contains Nonbinding Recommendations 
 
Implanted Blood Access Devices for 
Hemodialysis 
Guidance for Industry and Food and 
Drug Administration Staff 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic. It does not establish any rights for any person and is not binding on 
FDA or the public. You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff 
responsible for this guidance as listed on the title page.  
I.  Introduction 
This guidance document provides recommendations for complying with special controls issued 
as part of the reclassification of Implanted Blood Access Devices for Hemodialysis into class II 
(special controls).1 The devices are intended to provide access to a patients blood for 
hemodialysis.  
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidances describe the Agency's 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.  Background 
FDA has issued a final order reclassifying implanted blood access devices for hemodialysis, 
which were preamendments Class III devices, into Class II (special controls) and subject to 
premarket notification. FDA finalized the reclassification under the Federal Food, Drug and 
Cosmetic Act (FD&C Act) based on new information pertaining to the device. This guidance 
is intended to provide recommendations on how to comply with the special controls codified 
in 21 CFR 876.5540(b)(1) and indicate what information is recommended for submission to 
FDA in a 510(k) to demonstrate that the special controls have been met. Throughout the 
guidance, requirements per the special controls are noted in italic font for clarity.   
                                                 
1 79 FR 43241, July 25, 2014 
1  Contains Nonbinding Recommendations 
 
This document supplements other FDA documents regarding the specific content requirements of 
a premarket notification [510(k)] submission. You should also refer to 21 CFR 807.87 and FDAs 
guidance, Format for Traditional and Abbreviated 510(k)s 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm0
84365.htm). 
III.  Scope 
The scope of this document is limited to the implanted blood access devices for hemodialysis 
regulated under 21 CFR  876.5540(a)(1) and with product codes listed in the table below: 
Product Code  Name 
FIQ  A-V shunt cannula 
FKW  vessel tip 
LFJ  subclavian catheter 
MSD  implanted hemodialysis catheter 
NYU  implanted coated hemodialysis catheter 
PKI  fully subcutaneous implanted hemodialysis catheter 
Implanted blood access devices outside of this aspect of this subpart of the classification 
regulation are not within the scope of this guidance.  
IV.  510(k) Submission Recommendations 
The sections below provide recommendations on information to include in a 510(k) submission 
for implanted blood access devices for hemodialysis. These recommendations include 
recommendations for compliance with special controls. 
A.  Device Description 
The implanted blood access device for hemodialysis is described in 21 CFR  876.5540 as a 
device intended to provide access to a patients blood for hemodialysis or other chronic uses. 
When used in hemodialysis, it is part of an artificial kidney system for the treatment of patients 
with renal failure or toxemic conditions and provides access to a patients blood for 
hemodialysis. 
As defined in 21 CFR  876.5540(a)(1), the implanted blood access device is a prescription 
device and consists of various flexible or rigid tubes, such as catheters, or cannulae, which are 
surgically implanted in appropriate blood vessels, may come through the skin, and are intended 
to remain in the body for 30 days or more. This generic type of device includes various catheters, 
shunts, and connectors specifically designed to provide access to blood. Examples include single 
and double lumen catheters with cuff(s), fully subcutaneous port-catheter systems, and A-V 
shunt cannulae (with vessel tips). The implanted blood access device may also contain coatings 
or additives, which may provide additional functionality to the device. 
2  Contains Nonbinding Recommendations 
 
We recommend that you identify your device by the regulation and product code described in 
Section III. Scope. Per 21 CFR 807.87 you must also identify the common name of your 
device (e.g., double lumen hemodialysis catheter) as well as the trade or proprietary name. We 
recommend you also provide the following information:  
a.  classification name (e.g., blood access device); 
b.  a listing of all model numbers (if known);  
c.  a clear description of the proposed device's intended use 
d.  the CFR classification regulation number under which you believe the device and any 
components/accessories are regulated. 
The device description should include a labeled diagram and the specifications (e.g., lengths, 
inner and outer diameters, French size, cuff positions, connectors2, extension lengths, hole 
diameters and positions) for each model included in the submission. The physical description 
should include: 
a.  a description of the overall device system including accessories, pictures, samples (if 
practical), and engineering diagrams; 
 
b.  a functional description (including specifications, if applicable) of the individual 
components of the catheter system; and 
c.  a description of the accessories that may be used to place the catheter or shunt. Any 
accessory device that is labeled for use with the proposed catheter system should either 
be currently legally marketed for use with such a hemodialysis catheter system or 
submitted as part of the 510(k) submission for the proposed catheter system. Information 
on the accessory device to allow a determination of substantial equivalence should be 
provided. 
 
The 510(k) should include a comparison of the proposed device to a legally marketed device, 
commonly referred to as the predicate device.3 FDA recommends that all comparisons be 
                                                 
2 The currently FDA recognized versions of the following standards may apply to connectors for implanted blood 
access devices: ISO 80369: Small-bore connectors for liquids and gases in healthcare applications and ISO 594: 
Conical fittings with a 6 % (Luer) taper for syringes, needles and certain other medical equipment - Part 1: General 
requirements. 
FDAs currently recognized version of standards and the extent of recognition can be located via FDAs standards 
database (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfstandards/search.cfm) 
3 A legally marketed device, as described in 21 CFR 807.92(a)(3), is a device that (i) was legally marketed prior to 
May 28, 1976 (preamendments device), for which a PMA is not required; or (ii) has been reclassified from Class III 
to Class II or I; or (iii) has been found SE through the 510(k) process. The legally marketed device for purposes of 
determining substantial equivalence is commonly referred to as the "predicate device." 
3  Contains Nonbinding Recommendations 
 
provided in a manner that is clear and comprehensible, such as in tabular form that lists the 
similarities and differences between the proposed and predicate device in terms of intended use, 
technological features, performance specifications, and other important information necessary to 
determine substantial equivalence between the proposed and predicate device. 
The 510(k) should identify the predicate device to which the proposed device is compared. The 
510(k) should provide as much information as possible regarding the predicate device, such as, 
the proprietary and common name, manufacturer, model number, 510(k) reference number, 
preamendments status4 (i.e., marketed in the United States prior to May 28, 1976), etc.  
You should provide information to describe how your device is similar to and different from the 
predicate device (21 CFR 807.87(f)). Side by side comparisons, whenever possible, are 
desirable.  
The comparison between the proposed and predicate device should include, at a minimum, the 
following information: 
a.  Intended Use/Indications for use to include, as appropriate: 
1.  general purpose of device (e.g., blood access for hemodialysis treatment) 
2.  location of use (e.g., internal jugular, femoral, subclavian, transhepatic, translumbar); 
3.  lengths and diameters of the catheters; 
4.  duration of use (e.g., long-term [>30days]; and 
5.  conditions of use (e.g., acute renal failure, chronic renal failure). 
b.  Materials used, including the supplier, the material name, and the material designation 
numbers, for each device component, when applicable, including: 
1.  catheter lumens and extensions; 
2.  clamps; 
3.  cuffs; 
4.  luer adapters (bloodline connectors); 
5.  hub; 
6.  suture wing; 
7.  caps; 
8.  coatings; 
9.  adhesives; and 
10. colorants or inks. 
                                                                                                                                                             
Section 513(i) of the FD&C Act states that for a new device to be considered substantially equivalent to a predicate 
device, the new device must have the same intended use as the (primary) predicate device and the same 
technological characteristics or different technological characteristics that do not raise different questions of safety 
and effectiveness than the predicate device.  
4 See Preamendment Status 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ComplianceActivities/ucm072746.htm) 
4  Contains Nonbinding Recommendations 
 
c.  Performance specifications 
d.  Design parameters, including: 
1.  catheter type; 
2.  number of cuffs; 
3.  outer and inner diameters; 
4.  length; and 
6.  tunneler information. 
B.  Device Materials  
FDA has established a special control that requires that material names and specific designation 
numbers must be provided (21 CFR 876.5540(b)(1)(i)). 
Recommendation: As specified in Section A. Device Description above, in the 510(k), you 
should provide the identification of all materials used to fabricate all components of the 
hemodialysis catheter, including any colorants (inks, dyes, markings, etc.), plasticizers 
(including di-(2-Ethylhexyl) phthalate or DEHP), lubricants, mold release agents, additives, or 
coatings (as further discussed in section I. Special Considerations  Coatings). We recommend 
you group these materials according to whether they have direct or indirect contact with the 
circulating blood. As also discussed in Section A. Device Description, you should provide a 
detailed comparison of your materials to those of the predicate device.  
C.  Biocompatibility 
FDA has established a special control that requires that components of the device that come into 
human contact must be demonstrated to be biocompatible (21 CFR 876.5540(b)(1)(i)).  
 
Recommendation: For all patient contacting materials, you should provide appropriate 
biocompatibility testing on finished, sterilized device(s) as recommended in the ODE General 
Program Memorandum #G95-1 (1995), entitled "Use of International Standard ISO-10993, 
Biological Evaluation of Medical Devices Part 1: Evaluation and Testing 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm
080735.htm). Hemodialysis catheters are considered External communicating devices, 
Circulating blood, Permanent contact duration  (Category C).  
If you are unable to identify a legally marketed predicate device with similar location/duration of 
contact and intended use that uses the same materials as used in your device, we recommend you 
conduct and provide a biocompatibility risk assessment. The assessment should explain the 
relationship between the identified biocompatibility risks, the information available to mitigate 
the identified risks, and identify any knowledge gaps that remain. You should then identify any 
biocompatibility testing or other evaluations that were conducted to mitigate any remaining 
risks. Unless otherwise mitigated, the following biocompatibility evaluations should be 
conducted: 
5  Contains Nonbinding Recommendations 
 
  Cytotoxicity 
  Sensitization (Guinea pig maximization with polar and non-polar extracts) 
  Irritation or intracutaneous reactivity 
  Systemic toxicity (acute) 
  Sub-chronic toxicity 
  Implantation5 
  Hemocompatibility 
  Genotoxicity 
D.  Performance Testing - Bench 
FDA has established a special control that requires that performance data must demonstrate that 
the device performs as intended under anticipated conditions of use (21 CFR 876.5540(b)(1)(ii)).  
Recommendation: The 510(k) should include adequate information describing the performance 
characteristics of the device. At a minimum, this should include functional testing. 
 
The performance testing outlined below should be conducted on a minimum of three (3) devices 
of each model. If you choose to test one or more models to represent subsets of the product 
portfolio, you should provide a sample selection rationale detailing why this is appropriate. The 
special controls established the following requirements for testing and performance 
characteristics. 
 
a.  Pressure versus flow rates for both arterial and venous lumens, from the minimum flow 
rate to the maximum flow rate in 100 ml/min increments, must be established. The fluid 
and its viscosity used during testing must be stated (21 CFR 876.5540(b)(1)(ii)(A)).  
Recommendation: In order to provide pressure versus flow rate characterization data that 
is representative of clinical use of the device, a fluid with a viscosity analogous to that of 
blood (viscosity = 3.2  3.8 cP) should be used during the testing. This is consistent with 
current practice for most manufacturers. The test results should be compared to the 
predicate device (preferably in tabular format). The predicate device should be tested 
concurrently with the subject device using the same methodology and test fluid. 
b.  Recirculation rates for both forward and reverse flow configurations must be established, 
along with the protocol used to perform the assay, which must be provided (21 CFR 
876.5540(b)(1)(ii)(B)). 
 
Recommendation: The recirculation rates should be compared with the predicate device 
(preferably in tabular format). The predicate device should be tested concurrently with 
the proposed device using the same methodology. 
                                                 
5 Patients are exposed to hemodialysis catheter and shunt materials over a long period of time, and potentially with 
repeated use. A long-term (90 to 120 days) implantation study with histopathology may replace sub-chronic 
toxicity. 
6  Contains Nonbinding Recommendations 
 
c.  Priming volumes6 must be established (21 CFR 876.5540(b)(1)(ii)(C)). 
d.  Tensile testing of joints and materials must be conducted. The minimum acceptance 
criteria must be adequate for its intended use (21 CFR 876.5540(b)(1)(ii)(D)).  
Recommendation: The minimum acceptance criteria should be at least equal to the 
predicate device. We recommend the minimum force at break should be 10 pounds for 
polyurethane joints and polyurethane materials that comprise the main lumens of the 
catheter excluding the catheter tip (due to the more frequent handling of hemodialysis 
catheters compared to general catheters). Testing should be completed as specified in the 
FDA currently recognized version of consensus standard ISO 10555-1, Sterile, single-use 
intravascular catheters  Part 1: General requirements.7  
e.  Air leakage testing and liquid leakage testing must be conducted (21 CFR 
876.5540(b)(1)(ii)(E)). 
Recommendation: Testing should be completed as specified in the FDA recognized 
version of consensus standard ISO 10555-1 Annex D and Liquid leakage testing as 
specified in ISO 10555-1 Annex C. 
f.  Testing of the repeated clamping of the extensions of the catheter that simulates use over 
the life of the catheter must be conducted, and retested for leakage (21 CFR 
876.5540(b)(1)(ii)(F)).  
Recommendation: Assuming that five clampings are done at each treatment, with an 
average of three treatments per week, an average catheter life of 26 weeks, and a three 
times safety factor, repeatedly clamping at least 1,200 times, followed by tensile strength 
and leakage testing, as described in d and e above, should provide assurance of 
extension durability. 
g.  Mechanical hemolysis testing must be conducted for new or altered device designs which 
affect the blood flow pattern (21 CFR 876.5540(b)(1)(ii)(G)). 
Recommendation: In vitro mechanical hemolysis testing should be conducted for new 
hemodialysis catheter designs. Devices consisting of alterations to a previous design 
(e.g., catheters with an added coating) should also undergo in vitro hemolysis testing if 
the blood flow pattern or surface characteristics of the device are affected. Hemolysis 
testing should be performed on shelf-life aged devices (which would include sterilization 
and thermal cycling from exposure to simulated shipping and storage conditions). 
However, testing on sterilized, non-aged devices is acceptable if justification is provided 
that shows that the chemical and physical properties of the blood contacting surfaces do 
not change over the shelf-life of the device. The hemolysis data for the proposed device 
                                                 
6 The priming volume is the amount of fluid required to fill the inside of the catheter from the hubs to the tip. 
7 FDAs currently recognized version of standards and the extent of recognition can be located via FDAs standards 
database (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfstandards/search.cfm) 
7  Contains Nonbinding Recommendations 
 
should be compared to that of the predicate device and demonstrate that no more red 
blood cell lysis occurs with the proposed design in comparison to the predicate device. 
The testing should utilize the maximum labeled blood flow rate for the proposed device 
(see also Appendix A for considerations for testing). For a family of catheters, hemolysis 
testing should be performed on the model with the greatest expected hemolysis potential 
(e.g., smallest internal diameter and longest length). 
h.  Chemical tolerance of the device to repeated exposure to commonly used disinfection 
agents must be established (21 CFR 876.5540(b)(1)(ii)(H)). 
Recommendation: FDA considers the following to be commonly used disinfection 
agents8: chlorhexidine, sodium hypochlorite, povidone-iodine (ointment and solution), 
70% alcohol, mupirocin, polysporin or triple antibiotic ointment, hydrogen peroxide, and 
gentamycin. At a minimum, testing should include these, but additional agents should 
also be tested if the manufacturer recommends alternative specific agents. Test conditions 
should simulate the intended clinical use. 
 
Results of performance testing for the proposed device should be compared to those obtained for 
the predicate device. If test results for the proposed device are outside the range of the predicate 
device, the 510(k) should include an explanation of why this difference supports the substantial 
equivalence of the proposed device. The variances should be noted and any significant 
deviations from those of the predicate device should be justified in the 510(k) submission. 
E.  Sterility and Shelf-Life 
FDA has established special controls that require performance data must demonstrate sterility of 
the device and must support the shelf-life of the device for continued sterility, package integrity, 
and functionality over the requested shelf life, that must include tensile, repeated clamping and 
leakage testing (21 CFR 876.5540(b)(1)(iii) and (21 CFR 876.5540(b)(1)(iv)).  
Recommendation: FDAs guidance, Submission and Review of Sterility Information in 
Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile, 
(http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocu
ments/ucm109897.pdf) provides basic information on sterility issues. All sterile devices intended 
for internal use are generally expected to meet the sterility assurance level (SAL) of 10-6. Your 
submission should include the following information: 
a.  sterilization method; 
 
b.  radiation dose or the maximum residual levels of ethylene oxide and ethylene 
chlorohydrin that remain on the finished sterilized device, whichever is applicable. For 
ethylene oxide residuals, you may refer to the FDA currently recognized version of the 
                                                 
8 Patel PR, Coutts K, Sauer AG, Shugart A, Melville AM, Arduino MJ, Thompson ND, Kallen A. 2012 National 
Survey of Hemodialysis Infection Prevention and Vascular Access Practices. #SA-OR044 Presented at American 
Society of Nephrology (ASN) Kidney Week; 2013 Nov 9, Atlanta, GA. 
8  Contains Nonbinding Recommendations 
 
consensus standard ANSI/AAMI/ISO 10993-7: Biological Evaluation of Medical 
Devices  Part 7: Ethylene Oxide sterilization residuals);Error! Bookmark not defined. 
c.  validation method for the sterilization cycle and Sterilization Assurance Level (SAL); 
d.  since the product should be labeled "non-pyrogenic," a description of the method used to 
make the determination, e.g., limulus amebocyte lysate (LAL) and the sensitivity of the 
method in Endotoxin Units per milliliter (EU/mL); 
e.  a description of the packaging system, and  
f.  testing to demonstrate that the package and its contents remain sterile.  
FDA has established a special control that requires that labeling of implanted blood access 
devices for hemodialysis catheters must specify an expiration date and, as stated above, that 
performance data must support the shelf life of the device (21 CFR 876.5540(b)(1)(v)(D) and (21 
CFR 876.5540(b)(1)(iv)).  
 
Recommendation: The following test results or an appropriate rationale should be provided to 
substantiate the validity of the specified expiration date: 
a.  performance testing on aged samples to include, at a minimum, the performance testing 
as described in Section D. Performance Testing  Bench for tensile, repeated clamping, 
and leakage; and 
b.  package integrity testing (to demonstrate sterility and non-pyrogenicity over the labeled 
shelf life) as specified in the FDA currently recognized version of ASTM F1980-7: 
Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices.7 
For devices with established materials and designs, accelerated conditions for establishing an 
expiration date or an acceptable scientific rationale may be used to support a 510(k). In such 
cases, it is typically acceptable to provide accelerated aging results for an initial time point such 
as 6-months equivalent within a submission. Coatings or additives may make accelerated 
aging inappropriate. The labeled shelf life should reflect the initial test results provided in the 
510(k), but may be increased by the manufacturer as subsequent accelerated aging results 
conducted under a protocol that FDA has found acceptable, which represent longer time points, 
become available.9 In addition, a scientific rationale should be provided to support the chosen 
conditions for the accelerated testing. Real-time testing results should be included in the device 
history file for subsequent review by FDA.10  
                                                 
9 For more information on deciding when a change to the device or labeling requires submission of a new 510(k) 
submission, please see FDAs guidance, Deciding When to Submit a 510(k) for a Change to an Existing Device 
(K97-1) (http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm080235.htm) 
10 21 CFR 820.30 Device History File 
9  Contains Nonbinding Recommendations 
 
F.  Labeling  
The 510(k) submission must include labeling in sufficient detail to satisfy the requirements of 21 
CFR 807.87(e). The following recommendations are provided to assist you in preparing labeling 
that satisfies the requirements of 21 CFR Part 801 and the special controls for this device type.  
 
As a prescription device, under 21 CFR 801.109, the device is exempt from having adequate 
directions for lay use. Labeling must, however, include adequate information for practitioner use 
of the device, including indications, effects, routes, methods, and any relevant hazards, 
contraindications, side effects and precautions. (21 CFR 801.109(d)). 
 
Proposed labels, labeling, and advertisements sufficient to describe the device, its intended use, 
and the directions for its use (21 CFR 807.87(e)) must be provided. In addition, a specific 
intended use statement and any warnings, contraindications, or limitations should be clearly 
displayed. 
 
Under 21 CFR 801.109, the instructions for use must include indications for use, and warnings, 
precautions, and contraindications associated with the use of the device. The instructions for use 
should also include principle of operation, device description, features and/or accessories, 
directions for device use, implantation procedures, and troubleshooting. Detailed instructions on 
catheter care should be provided, for example cleaning, site care, and disinfection. 
The device label affixed to the device packaging must include the name and place of business of 
the manufacturer, packer, or distributor (21 CFR 801.1). The label should also include the device 
name, U.S. point of contact, storage conditions, priming volume, sterility status and method, lot 
number, and expiration date.  
In addition to the general labeling recommendations and provisions above, we recommend the 
following labeling considerations specific to hemodialysis catheters:  
a.  The intended use statement should include the specific indications and intended patient 
population.  
b.  Device labeling for the hemodialysis catheter should address the following potential 
complications of the device related to insertion location: 
1.  If a femoral catheter is indicated, the labeling should include: 
i.  language to specify the placement site such as Catheters greater than 40 cm are 
intended for femoral vein insertion;  
ii.  potential complications specific to femoral placement (femoral artery bleed, 
femoral nerve damage, retroperitoneal bleed, and venous stenosis); 
iii. suggestions to avoid infections such as tunneling the catheter to a pelvic area 
rather than an inguinal area; and  
iv. a caution that increased infections are a possibility. 
10  Contains Nonbinding Recommendations 
 
2.  If a trans-lumbar catheter is indicated, the labeling should include: 
i.  language to specify the placement site; and 
ii.  potential complications specific to trans-lumbar placement, including migration of 
the catheter tip into subcutaneous tissues, retroperitoneum or iliac veins (causing 
hematoma or frank bleeding). 
3.  If a subclavian catheter is indicated, the labeling should include: 
i.  language to specify the placement site;  
ii.  potential complications specific to subclavian placement, including pneumothorax 
and hemothorax; 
iii. a caution statement related to the risk of subclavian vein stenosis if the subclavian 
vein site is used; and 
iv. a caution statement which states that subclavian access should only be used when 
no other upper-extremity or chest-wall options are available. 
 
c.  If applicable, the labeling should summarize the results of clinical performance data 
needed to demonstrate substantial equivalence. 
FDA has established a special control that requires that the labeling for use of the implanted 
blood access devices for hemodialysis, include the following: 
a.  Labeling must provide arterial and venous pressure versus flow rates, either in tabular 
or graphical format. The fluid and its viscosity used during testing must be stated (21 
CFR 876.5540(b)(1)(v)(A)).  
 
b.  Labeling must specify the forward and reverse recirculation rates (21 CFR 
876.5540(b)(1)(v)(B)).  
Recommendation: It is recommended that catheters with greater than 50% recirculation 
in the reverse direction should include a caution in the labeling listing the percent reverse 
recirculation. 
c.  Labeling must provide the arterial and venous priming volumes (21 CFR 
876.5540(b)(1)(v)(C)). 
Recommendation: If possible, these should be printed directly on the catheter.  
d.  Labeling must specify an expiration date (21 CFR 876.5540(b)(1)(v)(D)). 
 
Recommendation: For additional details, please see Section E Sterility and Shelf Life. 
 
e.  Labeling must identify any disinfecting agents that cannot be used to clean any 
components of the device (21 CFR 876.5540(b)(1)(v)(E)). 
11  Contains Nonbinding Recommendations 
 
f.  Any contraindicated disinfecting agents due to material incompatibility must be 
identified by printing a warning on the catheter. Alternatively, contraindicated 
disinfecting agents must be identified by a label affixed to the patients medical record 
and with written instructions provided directly to the patient (21 CFR 
876.5540(b)(1)(v)(F)). 
 
g.  Labeling must include a patient implant card (21 CFR 876.5540(b)(1)(v)(G)). 
Recommendation: The implant card should be provided to the patient at the time of 
implantation and should include the name and model number (or serial number/unique 
device identifier as applicable) of the device, the name and contact information of the 
company, a reference to the complete instructions for use, and a blank space to be filled 
in with the name and contact information for the implanting physician. Additional 
information may be recommended for unique circumstances such as contraindicated 
disinfection agents, MRI compatibility, or other specific instructions. 
h.  The labeling must contain comprehensive instructions for the following (21 CFR 
876.5540(b)(1)(v)(H)(1-6)): 
1.  preparation and insertion of the device, including recommended site of insertion, 
method of insertion, and a reference on the proper location for tip placement; 
2.  proper care and maintenance of the device and device exit-site; 
3.  removal of the device;  
4.  anticoagulation; 
5.  management of obstruction and thrombus formation; 
6.  qualifications for clinical providers performing the insertion, maintenance, and 
removal of the devices. 
G.  Animal and Clinical Testing 
Implanted blood access devices for hemodialysis will generally not be subject to animal or 
clinical testing if they are similar to legally marketed implanted blood access devices in design 
and technology except as noted in Section H (Special Considerations). However, modifications 
in the indication for use or significantly different technological characteristics may warrant 
animal or clinical testing in addition to nonclinical performance testing to demonstrate 
substantial equivalence. 
(1)  Performance Testing  Animal  
Testing performed in animals may be used to support substantial equivalence. Some areas that 
animal testing has been useful are for demonstrating anti-thrombotic properties, or testing for 
adequate flow. Such testing must comply with 21 CFR Part 58, which prescribes Good 
Laboratory Practices for nonclinical studies. 
(2)  Performance Testing  Clinical  
Clinical evidence is generally not warranted for implanted blood access devices for hemodialysis 
except as noted in Section H (Special Considerations); however, such testing may be requested 
in situations such as the following:  
12  Contains Nonbinding Recommendations 
 
a.  indications for use dissimilar from legally marketed devices of the same type; 
b.  different technology, i.e., technology different from that used in legally marketed devices 
of the same type, yet does not raise different questions of safety or effectiveness; or 
c.  cases where engineering and/or animal testing raise issues that warrant further evaluation 
with clinical evidence. 
FDA will consider alternatives to clinical testing when the proposed alternatives are supported 
by an adequate scientific rationale.  
 
Any labeling claims about performance of the device in vivo should be supported with 
appropriate bench testing, in addition to either animal and/or clinical testing.  
FDA believes that implanted blood access devices for hemodialysis addressed in this guidance 
document are considered significant risk as defined in 21 CFR 812.3(m)(4). Hence, if a 
prospective clinical study is needed to demonstrate substantial equivalence, the study must be 
approved by FDA and conducted under the Investigational Device Exemptions (IDE) regulation, 
21 CFR Part 812, if conducted in the United States. In addition to the requirements of 21 CFR 
812, sponsors of such studies must comply with the regulations governing institutional review 
boards (21 CFR Part 56) and informed consent (21 CFR Part 50). Also, FDAs Guidance for 
Clinical Investigators, Industry, and FDA Staff Financial Disclosure by Clinical Investigators 
(http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM341008.pdf) provides 
recommendations to assist clinical investigators and sponsors in interpreting and complying with 
the regulations governing financial disclosure by clinical investigators, 21 CFR part 54. 
 
A clinical study for implanted blood access devices should include endpoints that address both 
the safety and effectiveness of the proposed device that supports its substantial equivalence to 
the predicate device(s). Effectiveness endpoints should focus on the ability of the device to 
properly function over a long period of time, such as 180 days. Safety should focus on an 
evaluation of the adverse events that may be expected with implanted blood access devices. FDA 
encourages that you utilize the opportunity to seek advice on prospective IDE clinical studies 
prior to the submission of an IDE application. FDAs guidance 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/guidancedocumen
ts/ucm311176.pdf) outlines the recommended procedures for seeking feedback from FDA on a 
clinical study design.  
H.  Special Considerations 
(1)  Subcutaneous Catheters 
Subcutaneous catheters refer to those catheters that are completely implanted below the skin 
surface and have no part of the device exposed to the outside of the body. Subcutaneous 
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catheters warrant more testing than described above in order to resolve issues of infection rates, 
adequacy of dialysis, maintenance of blood flow, and long-term patency.  
In addition to the aforementioned considerations, in accordance with the established special 
controls, implanted blood access devices that include subcutaneous ports must include the 
following: 
a.  Labeling must include the recommended type of needle for access as well as detailed 
instructions for care and maintenance of the port, subcutaneous pocket, and skin 
overlying the port (21 CFR 876.5540(b)(1)(vi)(A)). 
 
b.  Performance testing must include results on repeated use of the ports that simulates use 
over the intended life of the device (21 CFR 876.5540(b)(1)(vi)(B)).  
c.  Clinical performance testing must demonstrate safe and effective use and capture any 
adverse events observed during clinical use (21 CFR 876.5540(b)(1)(vi)(C)).  
Recommendation: The clinical performance data should demonstrate that the device is as 
safe and as effective as currently marketed hemodialysis vascular access devices such as 
implanted hemodialysis catheters.  
(2)  Coatings 
Implanted blood access devices for hemodialysis may include coatings, additives, or have 
material properties that impart antithrombotic, antimicrobial, or other novel properties to the 
device.  
In accordance with the established special controls, in addition to the aforementioned 
requirements for implanted blood access devices for hemodialysis, implanted blood access 
devices with coatings or additives must include the following: 
a.  A description and material characterization of the coating or additive material, the 
purpose of the coating or additive, duration of effectiveness, and how and where the 
coating is applied (21 CFR 876.5540(b)(1)(vii)(A)). 
b.  An identification in the labeling of any coatings or additives and a summary of the results 
of performance testing for any coating or material with special characteristics, such as 
decreased thrombus formation or antimicrobial properties (21 CFR 
876.5540(b)(1)(vii)(B)). 
c.  A Warning Statement in the labeling for potential allergic reactions including 
anaphylaxis if the coating or additive contains known allergens (21 CFR 
876.5540(b)(1)(vii)(C)). 
d.  Performance data must demonstrate efficacy of the coating or additive and the duration 
of effectiveness (21 CFR 876.5540(b)(1)(vii)(D)). 
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Recommendation: If there is a clinical benefit for such coatings, FDA recommends that 
the results of a clinical study be provided in the labeling in support of these benefits.  
Antimicrobial coatings generally require a clinical study to demonstrate a clinically and 
statistically significant decrease in the rate of infection or microbial colonization compared to an 
uncoated catheter. Coatings identical to previously cleared coatings for similar indications may 
not need new supportive clinical data. 510(k) submissions should include at a minimum, a 
comparison of the chemical entity, concentration, physical specifications (particle size, surface 
texture, etc.), elution profile, and manufacturing method. 
Antimicrobial coatings may lead to the development of microorganisms that are resistant to the 
antimicrobial in the coating as well as other antimicrobial products. The 510(k) submission 
should address the potential for the coating to lead to antimicrobial resistance, and if necessary, 
include testing to demonstrate that the coating does not lead to the induction of resistant 
microorganisms. 
 
Inclusion of a coating with a new drug entity or a coating that is released from the catheter may 
either change the intended use or raise different questions of safety and effectiveness. An 
antimicrobial coating could create a combination product. In situations where you are proposing 
inclusion of a drug that is not included on a predicate device, we would strongly encourage the 
submission of a pre-submission.  
(3)  Arteriovenous (A-V) shunt cannulae (with vessel tips) 
The arteriovenous (A-V) shunt cannula (with vessel tips) was the first vascular access used for 
hemodialysis, but has not been used in clinical practice in the US since the early 1980s with the 
advent of newer implanted blood accesses which have lower rates of complications; however, it 
remains a part of the Implanted Blood Access Devices for Hemodialysis regulatory 
classification. Compared with contemporary implanted blood access devices such as implanted 
hemodialysis catheters, A-V shunt cannulae have a higher risk of hemorrhage and have unique 
risks of arterial stenosis, arterial thrombosis and vascular access steal syndrome given that the 
device accesses the arterial circulation.  
 
In addition to the aforementioned requirements for implanted blood access devices for 
hemodialysis (except for performance testing and labeling related to recirculation rates and 
priming volumes, which are not applicable) (21 CFR 876.5540(b)(1)(viii)(A)), in accordance 
with the special controls for this device type, the following requirements must be met: 
a.  Labeling must include Warning Statements to address the potential for vascular access 
steal syndrome, arterial stenosis, arterial thrombosis, and hemorrhage including 
exsanguination given that the device accesses the arterial circulation (21 CFR 
876.5540(b)(1)(viii)(B)). 
 
b.  Clinical performance testing must demonstrate safe and effective use and capture any 
adverse events observed during clinical use (21 CFR 876.5540(b)(1)(viii)(C)).  
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Recommendation: The clinical performance data should demonstrate that the device is as 
safe and as effective as currently marketed hemodialysis vascular access devices such as 
implanted hemodialysis catheters or arteriovenous grafts (21 CFR 870.3450).  
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Appendix A 
Mechanical Hemolysis Testing of Hemodialysis Catheters 
To evaluate the potential for hemodialysis catheters to cause blood damage, in vitro testing 
simulating clinical use is usually conducted using animal blood. As animal blood is tested in an 
artificial in vitro environment and is more resilient to physical damage than the blood of 
hemodialysis patients, extrapolating the results of the bench testing to the clinical environment 
has limited value. However, by performing paired testing using blood from the same animal 
source, a relative comparison between a new and a predicate device can be made.  
 
The references included in this Appendix address many of the issues related to in vitro hemolysis 
testing, represent FDAs current state of knowledge for performing this type of testing, and can 
be used as guides for the testing of hemodialysis catheters.11,12,13,14,15 The testing is composed of 
three sections: setting up the test, performing the test, and reporting and interpreting the results.  
 
Setting up the test: 
1. Standardized guidelines for the collection and preparation of blood to be used in the in vitro 
assessment of blood damage caused by a medical device under dynamic test conditions have 
been previously described.11 Briefly, the blood should be obtained from a healthy animal and 
immediately mixed with an appropriate anticoagulant (e.g., 4000-6000 USP units of heparin per 
liter of collected blood). If not used immediately, the blood can be refrigerated at 2 to 8o C, but 
should be used within 48 hours of drawing. Prior to testing, the blood should be filtered and the 
hematocrit adjusted to a standard level (e.g., 35 +/- 2%).  
 
2. For performing paired testing, two separate and identical mock circulation blood loops should 
be assembled; one for the predicate device and one for the new device. The components of the 
flow loops should include a blood pump, hemodialysis tubing with a side-port for drawing blood 
                                                 
11 ASTM F1830-97: Standard practice for selection of blood for in vitro evaluation of blood pumps. 
American Society for Testing and Materials (ASTM) International, West Conshohocken, PA. 
12 ASTM F1841-97: Standard practice for assessment of hemolysis in continuous flow blood pumps. 
American Society for Testing and Materials (ASTM) International, West Conshohocken, PA. 
13 Guidance for cardiopulmonarybypass oxygenators 510(k) submissions; Final guidance for industry and 
FDA staff 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm073668.ht
m)  
 
14 Mueller, MR, Schima, H, et al. In vitro hematological testing of rotary blood pumps: Remarks on 
standardization and data interpretation. Artificial Organs, 17(2): 103-110, 1993. 
15 Malinauskas, R. Plasma hemoglobin measurement techniques for the in vitro evaluation of blood 
damage caused by medical devices. Artificial Organs, 21(12): 1255-67, 1997. 
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samples, Luer connectors to attach the catheters, a system for measuring the pressure in both the 
arterial and venous catheter components, a calibrated method to measure blood flow rate under 
appropriate clinical arterial and venous pressure conditions, and a reservoir made of a 
hemocompatible material (which can be heated to physiologically relevant temperatures to hold 
the blood). Due to the inherent variability in the blood from different animals, on each test date, 
the blood should be used from the same blood pool in both mock loops in a paired test 
configuration (operating under the same flow conditions and at the same time). 
3. Blood pumps used in hemodialysis are positive-displacement roller-occlusive pumps. 
Following the Users Manual, carefully check the occlusion setting of the blood pumps prior to 
the testing. The blood flow rate through the pump should be calibrated under appropriate clinical 
arterial and venous pressure conditions.  
4. The total volume of blood in the two test circuits should be identical and minimized to 
increase the sensitivity of the testing. However, the blood volume in the reservoirs must be 
sufficient such that all of the inlet and exit ports of the catheters are completely submerged and 
the blood is well-mixed, yet there is not significant mixing at the air-blood interface (e.g., 
cylindrical containers or blood bags should be considered for use as reservoirs).  
5. Using the paired testing scheme described above, the new devices are typically compared to 
the predicate device using a sample size of five devices for each cohort. The testing should be 
performed at the maximum labeled blood flow rate for the proposed device. For a family of 
catheters, hemolysis testing should be performed on the model with the greatest expected 
hemolysis potential (e.g. smallest internal diameter, longest length, greatest pressure loss, and 
highest blood flow rate). 
 
Performing the test: 
 
6. Prior to testing with blood, buffered saline should be circulated through the loop for five 
minutes to rinse the surfaces.  
 
7. The blood should be warmed and maintained at a physiological temperature (35 38oC) prior 
to and during the testing, while avoiding exposing the blood to temperatures (e.g., from a water 
bath) in excess of 39oC. The saline from the loop should be drained, the warmed blood should be 
introduced, and air bubbles should be cleared from the mock circuit. The blood should be 
allowed to circulate in the loop for approximately three minutes before taking a baseline sample 
(time = 0). The baseline sample should be evaluated for blood hematocrit, total blood 
hemoglobin concentration, and the plasma hemoglobin concentration.  A validated method 
should be used to assess the critical measurement parameter, the plasma hemoglobin 
concentration.15  
 
8. The in vitro testing with blood is usually conducted for as long as the device will be labeled 
for a clinical treatment. For a four hour test, blood samples can be taken at time 0, 30, 60, 120, 
180, and 240 minutes for plasma hemoglobin concentration analysis.  
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9. To insure a well-mixed blood sample, blood can be gently withdrawn from the tubing Luer 
side-port. As the use of small sampling needles may induce hemolysis, it is recommended that 
needle-less syringes be used. Clear the port first by drawing out some fresh blood (1 mL) into a 
needle-less syringe. Then, a new syringe should be used to draw out a fresh sample for analysis. 
It is recommended that two samples be drawn at each time period. Avoid pulling the plunger of 
the syringe too rapidly, or pushing the collected blood forcefully into the blood sample collection 
tube, to prevent pressure or velocity-induced hemolysis.  
10. The arterial and venous catheter pressures, the blood temperatures, and the blood flow rates 
in each loop should be measured and recorded periodically throughout the testing.  
Reporting the test results/ interpretation: 
11. A detailed protocol for performing the blood damage testing should be provided along with a 
diagram of the in vitro test circuit. The date, time, and blood pool that were used in each testing 
circuit should be documented in the final report. 
 
12.  Data from individual experiments should be provided in both tabular and graphical format. 
The plasma hemoglobin should be reported as a concentration (mg/dL) that increases over time 
using overlaying line plots for each of the different test circuits. As these plots are generally 
linear over time, a least squares fit to the data for each of the individual test circuits can be 
calculated. The slope of the least fit line is the rate of plasma hemoglobin generation. 
 
13.   Mean (+/- SD) results should also be tabulated and graphed for each of the different 
catheter groups.  
 
14.   Using paired statistical testing between the matched individual test circuits, the rate of 
plasma hemoglobin generation between the new and the predicate catheters can be compared.  
19