[Federal Register Volume 64, Number 190 (Friday, October 1, 1999)]
[Proposed Rules]
[Pages 53294-53298]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-25554]


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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