[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