Draft Guidance for Industry and Food and Drug Administration Staff

DRAFT GUIDANCE

This guidance document is being distributed for comment purposes only.

Document issued on: June 20, 2012

You should submit comments and suggestions regarding this draft document within 90 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.regulations.gov. Identify all comments should with the docket number listed in the notice of availability that publishes in the Federal Register.

For questions regarding this document, contact Jeffrey Cooper, DVM at (301) 796-5590 or via email at [email protected].

 

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 and Renal Devices Branch

Preface

Additional Copies

Additional copies are available from the Internet. You may also send an e-mail request to [email protected] to receive an electronic copy of the guidance or send a fax request to 301-827-8149 to receive a hard copy. Please use the document number 1781 to identify the guidance you are requesting.

---

Table of Contents

1. Introduction
2. Background
3. Scope
4. Device Description
5. Risks to Health
6. Device Materials and Biocompatibility
7. Performance Testing – Bench
8. Sterility
9. Expiration Date Testing
10. Performance Testing – Animal
11. Performance Testing – Clinical
12. Co-Axial Flow Needles
13. Subcutaneous Catheters
14. Coatings
15. Labeling

• Appendix A
• Appendix B

Draft Guidance for Industry and Food and Drug Administration Staff – Class II Special Controls Guidance Document: Implanted Blood Access Devices for Hemodialysis

1. Introduction

This draft guidance document was developed as a special control guidance to support the reclassification of the Implanted Blood Access Devices for Hemodialysis into class II (special controls). The device, as proposed, is intended to provide access to a patient’s blood for hemodialysis. This draft guidance will be issued in conjunction with a Federal Register notice announcing the proposal to reclassify this device type. This guidance is issued for comment purposes only. If a final rule to reclassify this device type is not issued, this guidance document will not be issued as a special control.

When finalized, designation of a guidance document as a special control means that any firm currently marketing, or intending to market, Implanted Blood Access Devices for Hemodialysiswill need to address the issues covered in the special controls guidance. The firm will need to show that its device addresses the issues of safety and effectiveness identified in the guidance, either by meeting the recommendations of the guidance or by some other means that provides equivalent assurances of safety and effectiveness.

2. Background

FDA believes that special controls, when combined with the general controls, will be sufficient to provide reasonable assurance of the safety and effectiveness of Implanted Blood Access Devices for Hemodialysis. Thus, a manufacturer who intends to market a device of this generic type must (1) conform to the general controls of the Federal Food, Drug Cosmetic Act (the FDC Act), including the premarket notification requirements described in 21 CFR 807 Subpart E, (2) address the specific risks to health associated with Implanted Blood Access Devices for Hemodialysis identified in this guidance, and (3) obtain a substantial equivalence determination from FDA prior to marketing the device.

This special controls guidance document identifies the classification regulation and product code for Implanted Blood Access Devices for Hemodialysis (Please refer to Section 3. Scope). In addition, other sections of this special controls guidance document list the risks to health identified by FDA and describe measures that, if followed by manufacturers and combined with the general controls, will generally address the risks associated with Implanted Blood Access Devices for Hemodialysisand lead to timely 510(k) review. This document supplements other FDA documents regarding the specific content requirements of a premarket notification submission. You should also refer to 21 CFR 807.87, the guidance, Format for Traditional and Abbreviated 510(k)s¹ and the section of CDRH’s Device Advice, Premarket Notification Submission 510(k).²

As described in the guidance entitled, The New 510(k) Paradigm – Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications,³ a manufacturer may submit a Traditional 510(k) or has the option of submitting either an Abbreviated 510(k) or a Special 510(k). Manufacturers considering certain modifications to their own cleared devices may lessen the regulatory burden by submitting a Special 510(k).

4, for each device component, 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.

Performance specifications; and

Design parameters, including:

1. Catheter type
2. Number of cuffs
3. Outer diameter
4. Length
5. Biocompatibility
6. Tunneler information
7. Restrictions of implantation site (not common but some may be restricted)
8. Insertion technique(s)
9. Contraindications for use (e.g., thrombosed vessel)

Use of ISO-10993 Biological Evaluation of Medical Devices Part 1: Evaluation and Testing”⁵. Hemodialysis catheters are considered “External communicating devices,” “Circulating blood,” “Permanent contact – (Category C).”

If you are unable to identify a legally marketed predicate device that uses the exact materials as described above, we recommend you conduct the following tests:

• Cytotoxicity
• Sensitization (Guinea pig maximization with polar and non-polar extracts)
• Irritation or intracutaneous reactivity
• Systemic toxicity (acute)
• Sub-chronic toxicity
• Implantation⁶
• Hemocompatibility
• Genotoxicity

7;

tensile testing of joints and materials as specified in ISO 10555-1. 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 catheters (due to the more frequent handling of hemodialysis catheters compared to general catheters.)

air leakage as specified in ISO 10555-1 Annex D and Liquid leakage as specified in ISO 10555-1 Annex C;

repeated clamping of the extensions of the catheter. This simulates use over the life of the catheter. Assuming that three clampings are done at each treatment, with a maximum of 6 treatments per week, and a catheter life of 3 years, repeatedly clamping at least 3000 times should provide assurance of extension durability;

mechanical hemolysis (recommended for a new/altered hemodialysis catheter design affecting the blood flow pattern). The data should demonstrate that the catheter tip design does not cause excessive lysis of red blood cells. The testing should utilize the maximum recommended blood flow rates (see Appendix A for considerations for testing); and,

chemical tolerance of the catheter to repeated exposure to commonly used disinfection agents.

Results of performance testing should be compared to those obtained for the predicate device(s). If test results for the proposed device exceed the range for the predicate device, explain why this difference supports the substantial equivalence of the proposed device. The variances should be noted and any changes from those of the predicate device should be justified.

Updated 510(k) Sterility Review Guidance K90-1; Final Guidance for Industry and FDA(8/30/2002)”⁸. All sterile devices are generally required to meet the sterility assurance level (SAL) of 10 -6. Your submission should include the following information:

1. sterilization method;
2. radiation dose or the maximum residual levels of ethylene oxide and ethylene chlorohydrin that remain on the finished sterilized device, whichever is applicable. FDA recognizes the consensus standard ANSI/AAMI/ISO 10993-7:1995 and 2008 Biological Evaluation of Medical Devices – Part 7: Ethylene Oxide sterilization residuals,) for ethylene oxide residuals;
3. validation method for the sterilization cycle and Sterilization Assurance Level (SAL);
4. 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 ofthe method in Endotoxin Units per milliliter (EU/mL); and
5. a description of the packaging system.

9. In addition, a scientific rationale should be provided to support the chosen conditions for the accelerated testing.

10 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).

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 listed in Section 5 that may be expected with blood access devices. FDA encourages the opportunity to provide advice on prospective IDE clinical studies prior to the submission of an IDE application.

11 should also be followed.

Features that should be considered regarding the substantial equivalence of co-axial flow needles include:

1. Blood recirculation
2. Blood flow parameters
3. Hemolysis
4. Visual inspection for sharpness and lack of metal burrs

12

Coating information should include:

1. A description of the coating material;
2. The duration of effectiveness;
3. How the coating is applied ; and
4. Testing to show how well the coating performs.

Keep in mind that inclusion of a coating with a new drug entity will usually 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, we would strongly encourage the submission of a pre-IDE.

13

Directions for Use

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, frequency and duration of administration and any relevant hazards, contraindications, side effects and precautions. (21 CFR 801.109(d)).

Proposed labels, labeling, and advertisements sufficient to describe the hemodialysis catheter, its intended use, and the directions for use should be provided with a specific intended use statement and any warnings, contraindications, or limitations clearly displayed as described in 21 CFR 807.87(e).

The operator’s manual should include, at a minimum, the indications for use, principle of operation, device description, features, and/or accessories, instructions for use, troubleshooting, warnings, precautions, and contraindications associated with the use of the catheter. Detailed instructions on catheter care should be provided.

The device label affixed to the hemodialysis catheter packaging should include, at a minimum, the device name, U.S. point of contact, corporation name, address, and phone number, storage conditions, priming volume, sterility status and method, sterilization date, lot number, and expiration date.

In addition, device labeling for the hemodialysis catheter should address the following:

1. The intended use statement should include specific indications and intended patient population.
2. Contraindications, Warnings, and Precautions should be included in the labeling of the device.
   1. If a femoral catheter is indicated, the labeling should include:
      1. Language to specify the placement site such as “Catheters greater than 40 cm are intended for femoral vein insertion”; and
      2. Potential complications specific to femoral placement (femoral artery bleed, femoral nerve damage, retroperitoneal bleed, and venous stenosis).
      3. Suggestions to avoid infections such as tunneling the catheter to a pelvic area rather than an inguinal area; and
      4. A caution that increased infections are a possibility;
   2. If a trans-lumbar catheter is indicated, the labeling should include:
      1. Language to specify the placement site; and
      2. 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:
      1. Language to specify the placement site; and
      2. Potential complications specific to subclavian placement, including pneumothorax and hemothorax.
3. An arterial and venous pressure vs. flow rate table and graph, identification of the recommended flow rate and pressure range;
4. Arterial and venous priming volumes printed on the catheter;
5. Forward and reverse recirculation rates. Catheters with greater than 50% recirculation in the reverse direction should include a caution in the labeling listing the percent reverse recirculation;
6. Identification of any contraindicated disinfecting agents due to material incompatibility by printing a warning on the catheter or a label that can be affixed to the patient’s medical record.
7. The directions for use should contain at a minimum the following:
   1. Comprehensive instructions for the preparation and insertion of the hemodialysis catheter, including recommended site of insertion, method of insertion, a reference in the English language on the proper location for tip placement, method for removal of the catheter, anticoagulation, guidance for management of obstruction and thrombus formation, and site care.
   2. Any claims made in the labeling for clinical benefit of the hemodialysis catheters will need to be supported with the appropriate performance data.

Guidance for cardiopulmonary bypass oxygenators 510(k) submissions; Final guidance for industry and FDA staff (11.13.00). Food Drug Administration, Center for Devices and Radiological Health.

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.

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.

Format for Traditional and Abbreviated 510(k)s

²Device Advice – Premarket Notification Submission 510(k)

³The New 510(k) Paradigm – Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications

^{Draft Guidance for Industry and FDA Staff – Premarket Notification [510(k)] Submissions for Medical Devices that Include Antimicrobial Agents}

^{Updated 510(k) Sterility Review Guidance K90-1; Final Guidance for Industry and FDA}

^{Information Sheet Guidance for Institutional Review Boards (IRBs), Clinical Investigators, and Sponsors}

^{Guidance for Industry and FDA Staff: Medical Devices with Sharps Injury Prevention Features}

^{http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ GuidanceDocuments/ucm071380.htm.}

13 Final labeling must comply with the requirements of 21 CFR Part 801 and final labeling for prescription medical devices must comply with 21 CFR 801.109. Labeling recommendations in this guidance are consistent with the requirements of Part 801.