General Hospital and Personal Use Devices; Classification of the Subcutaneous, Implanted, Intravascular Infusion Port and Catheter and the Percutaneous, Implanted, Long-term Intravascular Catheter

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 880

[Docket No. 99N-2099]

General Hospital and Personal Use Devices; Classification of the

Subcutaneous, Implanted, Intravascular Infusion Port and Catheter and

the Percutaneous, Implanted, Long-term Intravascular Catheter

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to

classify the subcutaneous, implanted, intravascular (IV) infusion port

and catheter, and the percutaneous, implanted, long-term catheter

intended for repeated vascular access into class II (special controls).

The agency is also publishing the recommendations of FDA's General

Hospital and Personal Use Devices Panel (the panel) regarding the

classification of these devices. After considering public comments on

the proposed classification, FDA will publish a final regulation

classifying these devices. This action is being taken to establish

sufficient regulatory controls that will provide reasonable assurance

of the safety and effectiveness of these devices.

DATES: Written comments by December 30, 1999. See section IX of this

document for the proposed effective date of a final rule based on this

document.

ADDRESSES: Written comments to the Dockets Management Branch (HFA-305),

Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville,

MD 20857.

FOR FURTHER INFORMATION CONTACT: Patricia M. Cricenti, Center for

Devices and Radiological Health (HFZ-480), Food and Drug

Administration, 9200 Corporate Blvd., Rockville, MD 20850, 301-594-

1287.

SUPPLEMENTARY INFORMATION:

I. Regulatory Authorities

The Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301

et. seq.), as amended by the Medical Device Amendments of 1976 (the

1976 amendments) (Public Law 94-295), the Safe Medical Devices Act of

1990 (the SMDA) (Public Law 101-629), and the Food and Drug

Administration Modernization Act of 1997 (FDAMA) (Public Law 105-115)

established a comprehensive system for the regulation of medical

devices intended for human use. Section 513 of the act (21 U.S.C. 360c)

established three categories (classes) of devices, depending on the

regulatory controls needed to provide reasonable assurance of their

safety and effectiveness. The three categories of devices are class I

(general controls), class II (special controls), and class III

(premarket approval). Under the 1976 amendments, class II devices were

defined as those devices for which there is insufficient information to

show that general controls themselves will ensure safety and

effectiveness, but for which there is sufficient information to

establish performance standards to provide such assurance.

The SMDA broadened the definition of class II devices to mean those

devices for which there is insufficient information to show that

general controls themselves will assure safety and effectiveness, but

for which there is sufficient information to establish special controls

to provide such assurance. Special controls may include performance

standards, postmarket surveillance, patient registries, development and

dissemination of guidelines, recommendations, and any other appropriate

actions the agency deems necessary (section 513(a)(1)(B) of the act).

Under section 513 of the act, devices that were in commercial

distribution before May 28, 1976 (the date of enactment of the 1976

amendments), generally referred to as preamendment devices, are

classified after FDA has met the following three requirements: (1)

[[Page 53295]]

FDA has received a recommendation from a device classification panel

(an FDA advisory committee); (2) FDA has published the panel's

recommendation for comment, along with a proposed regulation

classifying the device; and (3) FDA has published a final regulation

classifying the device. FDA has classified most preamendment devices

under these procedures. Devices that were not in commercial

distribution prior to May 28, 1976, generally referred to as

postamendment devices, are classified automatically by statute (section

513(f) of the act) into class III without any FDA rulemaking process.

Those devices remain in class III and require premarket approval,

unless and until FDA issues an order finding the device to be

substantially equivalent, under section 513(i) of the act, to a

predicate device that does not require premarket approval. The agency

determines whether new devices are substantially equivalent to

previously offered devices by means of premarket notification

procedures in section 510(k) of the act (21 U.S.C. 360(k)) and 21 CFR

part 807 of the regulations. A preamendment device that has been

classified into class III may be marketed, by means of premarket

notification procedures, without submission of a premarket approval

application until FDA issues a final regulation under section 515(b) of

the act (21 U.S.C. 360e(b)) requiring premarket approval.

In 1980, when other general hospital and personal use devices were

classified (45 FR 69678, October 21, 1980), FDA was not aware that two

vascular access devices intended for repeated vascular access, the

subcutaneous, implanted, IV infusion port and catheter and the

percutaneous, implanted, long-term IV catheter were preamendments

devices, and inadvertently omitted classifying them.

II. Device Identifications

FDA is proposing the following device identifications based on the

panel's recommendations (Ref. 1) and the agency's review:

(1) A subcutaneous, implanted, intravascular infusion port and

catheter is a device that consists of a subcutaneous, implanted

reservoir that connects to a long-term intravascular catheter. The

device allows for repeated access to the vascular system for the

infusion of fluids and medications and the sampling of blood. The

device consists of a portal body which houses a resealable septum with

an outlet made of metal, plastic, or a combination of these materials

and a long-term intravascular catheter that is either preattached to

the port or attached to the port at the time of device placement. The

device is available in various profiles and sizes and can be of a

single or multiple lumen design.

(2) A percutaneous, implanted, long-term intravascular catheter is

a device that consists of a slender tube and any necessary connecting

fittings, such as luer hubs, and accessories that facilitate the

placement of the device, such as a stylet or guide wire. The device

allows for repeated access to the vascular system for long-term use of

30 days or more for administration of fluids, medications, and

nutrients; the sampling of blood; and the monitoring of blood pressure

and temperature. The device may be made of metal, rubber, plastic,

composite materials, or any combination of these materials and may be

of single or multiple lumen design.

III. Recommendations of the Panel

During a public meeting held on March 11, 1996, the panel

unanimously recommended that the subcutaneous, implanted, IV infusion

port and catheter and the percutaneous, implanted, long-term IV

catheter be classified into class II (special controls) (Ref. 1). The

panel also recommended that two existing FDA guidance documents,

``Guidance on 510(k) Submissions for Implanted Infusion Ports'' (Ref.

2) and ``Guidance Premarket Notification [510(k)] Submission for Short-

Term and Long-Term Intravascular Catheters'' (Ref. 3), and prescription

use of the devices by practitioners licensed by law to use the devices

(Sec. 801.109 (21 CFR 801.109)) be the special controls for the

devices.

IV. Summary of the Reasons for the Recommendations

The panel concluded that the safety and effectiveness of the

subcutaneous, implanted, IV infusion port and catheter and the

percutaneous, implanted, long-term IV catheter could be reasonably

assured by special controls in addition to general controls. The panel

also believed that sufficient information exists to establish special

controls to provide such assurance, specifically the existing premarket

notification guidances and prescription use labeling of the devices.

V. Risks to Health

After considering the panel's deliberations, as well as the

published literature and medical device reports, FDA has evaluated the

risks to health associated with the use of the subcutaneous, implanted,

IV infusion port and catheter and the percutaneous, implanted, long-

term IV catheter. FDA now believes the following are risks to health

associated with the use of the devices:

A. Infection

Infection is the most significant complication associated with the

use of venous access devices. Infection occurs in 5 to 30 percent of

the patients implanted with the device, depending on the patient's

diagnosis, the type of device used, and the criteria used to establish

the presence of an infection (Refs. 4 through 7 and 13 through 24).

B. Occlusion

Occlusion may result from clot formation inside the lumen of the

catheter, precipitate formation inside the port or catheter from

incompatible drugs, or from catheter tip placement against a vein wall

or valve. An occluded catheter lumen may lead to infection,

thromboembolism, and propagation of the clot, which may cause venous

thrombosis. Proper flushing techniques can prevent some causes of

occlusion, and thrombolytic therapy can successfully clear most

catheter occlusions (Refs. 11 through 13 and 17 through 24).

C. Thrombophlebitis

Thrombophlebitis occurs in 12.5 to 23 percent of patients implanted

with the devices (Refs. 5 through 11 and 20 through 23). The incidence

varies with the patient population.

D. Pneumothorax

Pneumothorax is the presence of air within the thoracic cavity. The

incidence, secondary to procedural or device-related complications, is

believed to be up to 5 percent, depending on the manner in which the

venous system is accessed (Refs. 8 through 12 and 19 through 24).

E. Other Risks to Health

Less frequent complications associated with the use of vascular

access devices include the following: Catheter malposition; migration

and inadequate anchoring; hemorrhage; vessel trauma, including

puncture, laceration and erosion of vessel and the skin; catheter

pinch-off (compression of the catheter between the clavicle and the

first rib); and drug extravasation (leakage) (Refs. 4 through 24).

VI. Summary of Data Upon Which the Recommendation is Based

In addition to the potential risks of the subcutaneous and

percutaneous implanted vascular access systems described in section V

of this document, there is reasonable knowledge of the benefits of the

devices. Specifically,

[[Page 53296]]

these long-term implanted devices provide convenient, reliable access

to the vascular system while requiring less maintenance than

alternative vascular access devices, and they improve the quality of

life of patients (Refs. 8 through 11, 18 through 20, and 24).

Based on the available information, FDA believes that existing

premarket notification guidance documents are adequate special controls

capable of providing reasonable assurance of the safety and

effectiveness of the subcutaneous, implanted, IV infusion port and

catheter and the percutaneous, implanted, long-term IV catheter with

regard to the identified risks to health of these devices. The panel

also recommended including the prescription statement (Sec. 801.109) as

a special control. Because the prescription statement is already

required by Sec. 801.109, FDA believes it is unnecessary to list

prescription labeling as a separate special control for these devices.

VII. Special Controls

In addition to general controls, FDA agrees with the panel that the

identified premarket notification guidance documents ``Guidance on

510(k) Submissions for Implanted Infusion Ports'' (Ref. 2) and

``Guidance on 510(k) Submission for Short-Term and Long-Term

Intravascular Catheters'' (Ref. 3) are appropriate special controls to

address the risks to health described in section V of this document.

The premarket notification guidance documents address the following:

(1) Practitioner labeling, (2) patient labeling, (3) biocompatibility

testing, (4) mechanical testing, (5) clinical data requirement, and (6)

sterilization procedures.

In order to receive these guidance documents via your fax machine,

call the CDRH Facts-On-Demand (FOD) system at 800-899-0381 or 301-827-

0111 from a touch-tone telephone. At the first voice prompt press 1 to

access DSMA Facts, at second voice prompt press 2, and then enter the

document number followed by the pound sign (#). For ``Guidance on

510(k) Submissions for Implanted Infusion Ports,'' the document number

is 392. For ``Guidance on Premarket Notification [510(k)] Submission

for Short-Term and Long-Term Intravascular Catheters,'' the document

number is 824. Then follow the remaining voice prompts to complete your

request.

Persons interested in obtaining a copy of the draft guidances may

also do so using the World Wide Web (WWW). The CDRH home page may be

accessed at ``http://www.fda.gov/cdrh''.

A. Practitioner Labeling

The practitioner labeling section of the premarket notification

guidance documents can help control the risks of infection; occlusion;

thrombophlebitis; pneumothorax; catheter malposition, migration and

improper/or inadequate anchoring; catheter pinch-off; drug

extravasation; and septum leakage by having the manufacturer provide

information on the following: (1) Indications for use, including

patient and device selection; (2) contraindications for use in patients

with known or suspected infections, allergies, and intolerance to

implant materials; (3) warnings and precautions; (4) identification,

prevention, and treatment of complications; (5) directions for use,

including preparation of the patient, preparation of the device, site

selection, implant procedure, postoperative care, and different use

applications (bolus infusion, continuous infusion, blood sampling, and

monitoring of blood pressure and temperature).

B. Patient Labeling

The patient labeling section of the premarket notification guidance

documents can help control the risks of infection; occlusion;

thrombophlebitis; pneumothorax; catheter malposition, migration and

improper anchoring; catheter pinch-off; drug extravasation; septum

leakage; vessel trauma, including puncture, laceration and erosion of

vessel; and erosion of the skin by having the manufacturer provide

prospective patients information on the following: (1) Device

description and use; (2) implantation procedure; (3) care of the

implant site; and (4) minimization, recognition, and treatment of

complications.

C. Biocompatibility Testing

Adherence to the biocompatibility testing section of the premarket

notification guidance documents can control the risk of adverse tissue

reaction by having the manufacturer demonstrate that the patient

contacting materials of the subcutaneous, implanted, IV infusion port

and catheter, and the percutaneous, implanted, long-term IV catheter

are safe for long-term implantation.

D. Mechanical Testing

Adherence to the mechanical testing section of the premarket

guidance documents can help control the risk of erosion of the blood

vessel and the skin; catheter occlusion and migration; leaking catheter

to catheter and/or catheter to port connections; and septum and port

leakage.

E. Clinical Data Requirements

For subcutaeous, implanted, IV infusion port and catheters and

percutaneous, implanted, long-term IV catheters that appear to be

significantly different from devices already on the market, the

clinical data section of the premarket guidance documents can help

control the risks to health associated with the use of the devices by

assuring that these devices are safe and effective for their intended

uses.

F. Sterilization Procedures and Labeling

Adherence to sterilization procedures and labeling section of the

premarket notification guidances can help control the risk of infection

by guarding against the implantation of an unsterile device and

providing information on the proper maintenance of an implanted device.

VIII. Proposed Classification

FDA concurs with the panel's recommendations that the subcutaneous,

implanted, IV infusion port and catheter and the percutaneous,

implanted, long-term IV intended for repeated vascular access should be

classified into class II (special controls). FDA believes that the

special controls described in section VII of this document, in addition

to general controls, would provide reasonable assurance of the safety

and effectiveness of the devices, and there is sufficient information

to establish special controls to provide such assurance.

IX. Effective Date

FDA proposes that any final rule that may issue based on this

proposal become effective 30 days after its publication in the Federal

Register.

X. Environmental Impact

The agency has determined under 21 CFR 25.34(b) that this action is

of a type that does not individually or cumulatively have a significant

effect on the human environment. Therefore, neither an environmental

assessment nor an environmental impact statement is required.

XI. Analysis of Impacts

FDA has examined the impacts of the proposed rule under Executive

Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612) (as

amended by subtitle D of the Small Business Regulatory Fairness Act of

1996 (Public Law 104-121), and the Unfunded Mandates Reform Act of 1995

(Public Law 104-4)). Executive Order 12866 directs agencies to assess

all costs and benefits of available regulatory alternatives and, when

regulation is

[[Page 53297]]

necessary, to select regulatory approaches that maximize net benefits

(including potential economic, environmental, public health and safety,

and other advantages; distributive impacts; and equity). The agency

believes that this proposed rule is consistent with the regulatory

philosophy and principles identified in the Executive Order. In

addition, the proposed rule is not a significant regulatory action as

defined by the Executive Order and so is not subject to review under

the Executive Order.

The Regulatory Flexibility Act requires agencies to analyze

regulatory options that would minimize any significant impact of a rule

on small entities. As unclassified devices, these devices are already

subject to premarket notification and the general labeling provisions

of the act. FDA, therefore, believes that classification in class II

with premarket notification guidance and labeling guidance as special

controls will impose no significant economic impact on any small

entities. The Commissioner therefore certifies that this proposed rule,

if issued, will not have a significant economic impact on a substantial

number of small entities. In addition, this proposed rule will not

impose costs of $100 million or more on either the private sector or

State, local, and tribal governments in the aggregate, and therefore a

summary statement or analysis under section 202(a) of the Unfunded

Mandates Reform Act of 1995 is not required.

XII. Submission of Comments

Interested persons may, on or before December 30, 1999, submit to

the Dockets Management Branch (address above) written comments

regarding this proposal. Two copies of any comments are to be

submitted, except that individuals may submit one copy. Comments are to

be identified with the docket number found in brackets in the heading

of this document. Received comments may be seen in the office above

between 9 a.m. and 4 p.m., Monday through Friday.

XIII. References

The following references have been placed on display in the Dockets

Management Branch (address above) and may be seen by interested persons

between 9 a.m. and 4 p.m., Monday through Friday:

1. General Hospital and Personal Use Devices Panel, thirtieth

meeting, transcript, March 11, 1996.

2. ``Guidance on 510(k) Submissions for Implanted Infusion

Ports,'' FDA, October 1990.

3. ``Guidance Premarket Notification [510(k)] Submission for

Short-Term and Long-Term Intravascular Catheters,'' FDA, March 1995.

4. Abi-Nader, J., ``Peripherally Inserted Central Venous

Catheters in Critical Care Patients,'' Heart & Lung, 22:428-433,

1993.

5. Aitken, D., and J. Minton, ``The `Pinch-Off Sign': A Warning

of Impending Problems With Permanent Subclavian Catheters,''

American Journal of Surgery, 148:633-636, 1984.

6. Broviac, J.W., J. J. Cole, and B. A. Scribner, ``A Silicone

Rubber Atrial Catheter for Prolonged Parenteral Alimentation,''

Surgery, Gynecology and Obstetrics, 136:602-606, 1973.

7. Brown, J., ``Peripherally Inserted Central Catheters--Use in

Home Care,'' Journal of Intravenous Nursing, 12:144-150, 1989.

8. Camp-Sorrell, D., ``Implantable Ports,'' Journal of

Intravenous Nursing, 15:262-273, 1992.

9. Chathas, M. K., J. B. Paton, and D. E. Fisher, ``Percutaneous

Central Venous Catherization,'' American Journal of Diseases of

Children, 144: 1246-1250, 1990.

10. Girvan, D. P., L. L. deVeber, M. J. Inwood, and E. A. Clegg,

``Subcutaneous Infusion Ports in the Pediatric Patient with

Hemophilia,'' Journal of Pediatric Surgery, 29:1220-1223, 1994.

11. Harvey, M. P., R. J. Trent, D. E. Joshua, G. Ramsey-Stewart,

D.W. Storey, and M. Kronenberg, ``Complications Associated with

Indwelling Venous Hickman Catheters in Patients with Hematological

Disorders,'' Australian and New Zealand Journal of Medicine, 16:211-

215, 1986.

12. Hickman, R. O., C. D. Buckner, and R. A. Clift, ``A Modified

Right Atrial Catheter for Access to the Venous System in Marrow

Transplant Recipients,'' Surgery, Gynecology and Obstetrics,

148:871-875, 1979.

13. Hoppe, B., ``Central Venous Catheter-related Infections:

Pathogenesis, Predictors, and Prevention,'' Heart & Lung, 24:333-

339, 1995.

14. International Standards Organization (ISO) 1055-1, Sterile,

Single Use Intravascular Catheter, Part 2: Central Venous Catheters.

15. Kahn, M. L., R. Barboza, G. A. Kling, and J. E. Heisel,

``Initial Experience with Percutaneous Placement of the PAS Port

Implantable Venous Access Device,'' Journal of Vascular and

Interventional Radiology, 3:459-461, 1992.

16. Laffer, U., M. During, H. R. Bloch, and J. Landmann,

``Surgical Experiences with 191 Implanted Venous Port-a-Cath

Systems,'' Cancer Research, 121:189-197, 1991.

17. Lawson, M., ``Partial Occlusion of Indwelling Central Venous

Catheters,'' Journal of Intravenous Nursing, 14:157-159, 1991.

18. Lokich, J. J., A. Bothe, P. Benotti, and C. Moore,

``Complications and Management of Implanted Venous Access

Catheters,'' Journal of Clinical Oncology, 3:710-717, 1985.

19. McKee, J., ``Future Dimensions in Vascular Access,'' Journal

of Intravenous Nursing, 14:387-393, 1991.

20. Merrell, S. W., B. G. Peatross, M. D. Grossman, J. J.

Sullivan, and W. G. Harker, ``Peripherally Inserted Central Venous

Catheter: Low-risk Alternatives for Ongoing Venous Access,'' Western

Journal of Medicine, 160:25-30, 1994.

21. Morris, P., R. Buller, S. Kendall, and B. Anderson, ``A

Peripherally Implanted Permanent Central Venous Access Device,''

Obstetrics & Gynecology, 78:1138-1142, 1991.

22. Reed, W. P., K. A. Newman, and J. C. Wade, ``Choosing an

Appropriate Implantable Device for Long-Term Venous Access,''

European Journal of Cancer Clinical Oncology, 25:1383-1391, 1989.

23. Ryder, M. A., ``Peripherally Inserted Central Venous

Catheters,'' Nursing Clinics of North America, 28:937-971, 1993.

24. Scott, W. L., ``Complications Associated with Central Venous

Catheters,'' Chest, 94:1221-1224, 1988.

List of Subjects in 21 CFR Part 880

Medical devices.

Therefore, under the Federal Food, Drug, and Cosmetic Act and under

authority delegated to the Commissioner of Food and Drugs, FDA proposes

to amend part 880 to read as follows:

PART 880--GENERAL HOSPITAL AND PERSONAL USE DEVICES

1. The authority citation for 21 CFR part 880 continues to read as

follows:

Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

2. Section 880.5965 is added to subpart F to read as follows:

Sec. 880.5965 Subcutaneous, implanted, intravascular infusion port and

catheter.

(a) Identification. A subcutaneous, implanted, intravascular

infusion port and catheter is a device that consists of a subcutaneous,

implanted reservoir that connects to a long-term intravascular

catheter. The device allows for repeated access to the vascular system

for the infusion of fluids and medications and the sampling of blood.

The device consists of a portal body with a resealable septum and

outlet made of metal, plastic, or combination of these materials and a

long-term intravascular catheter is either preattached to the port or

attached to the port at the time of device placement. The device is

available in various profiles and sizes and can be of a single or

multiple lumen design.

(b) Classification. Class II (special controls) Guidance Document:

``Guidance on 510(k) Submissions for Implanted Infusion Ports.''

3. Section 880.5970 is added to subpart F to read as follows:

Sec. 880.5970 Percutaneous, implanted, long-term intravascular

catheter.

(a) Identification. A percutaneous, implanted, long-term

intravascular catheter is a device that consists of a

[[Page 53298]]

slender tube and any necessary connecting fittings, such as luer hubs,

and accessories that facilitate the placement of the device. The device

allows for repeated access to the vascular system for long-term use of

30 days or more, and it is intended for administration of fluids,

medications, and nutrients; the sampling of blood; and monitoring blood

pressure and temperature. The device may be constructed of metal,

rubber, plastic, composite materials, or any combination of these

materials and may be of single or multiple lumen design.

(b) Classification. Class II (special controls) Guidance Document:

``Guidance on Premarket Notification [510(k)] Submission for Short-Term

and Long-Term Intravascular Catheters.''

Dated: September 24, 1999.

Linda S. Kahan,

Deputy Director for Regulations Policy, Center for Devices and

Radiological Health.

[FR Doc. 99-25554 Filed 9-30-99; 8:45 am]

BILLING CODE 4160-01-F