Medical Devices; Exemptions From Premarket Notification; Class II Devices

Federal RegisterNov 3, 1998

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 862, 864, 866, 876, 880, 882, 886, 890, and 892

[Docket No. 98-0015]

Medical Devices; Exemptions From Premarket Notification; Class II

Devices

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is codifying the

exemption from premarket notification of all 62 class II (special

controls) devices listed as exempt in a January 21, 1998, Federal

determined that for these exempted devices, manufacturers' submissions

of premarket notifications are unnecessary to provide a reasonable

assurance of safety and effectiveness. These devices will remain

subject to current good manufacturing practice (CGMP) regulations and

other general controls. This rulemaking implements new authorities

delegated to FDA under the Food and Drug Administration Modernization

Act (FDAMA).

EFFECTIVE DATE: November 3, 1998.

FOR FURTHER INFORMATION CONTACT: Heather S. Rosecrans, Center for

Devices and Radiological Health (HFZ-404), Food and Drug

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

1190.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of January 21, 1998 (63 FR 3142)

(hereinafter referred to as the January 21, 1998, notice), FDA issued a

notice stating that 62 class II (special controls) devices were exempt

from the requirement of premarket notification, with limitations. This

notice was issued in accordance with FDAMA (Pub. L. 105-115), which the

President signed into law on November 21, 1997. Section 206 of FDAMA,

in part, added a new section 510(m) to the Federal Food, Drug, and

Cosmetic Act (the act) (21 U.S.C. 360(m)). Section 510(m)(1) of the act

required FDA, within 60 days after enactment of FDAMA, to publish in

the Federal Register a list of each type of class II device that does

not require a report under section 510(k) of the act (generally

referred to as a premarket notification or ``510(k)'') to provide

reasonable assurance of safety and effectiveness. Section 510(m) of the

act further provided that a 510(k) will no longer be required for these

devices upon the date of publication of the list in the Federal

comment on the notice.

Section 510(m)(2) of the act also provides that, 1 day after date

of publication of the list under section 510(m)(1) FDA may exempt a

device on its own initiative or upon petition of an interested person,

if FDA determines that a 510(k) is not necessary to provide reasonable

assurance of the safety and effectiveness of the device.

An exemption from the requirement of premarket notification does

not mean that the device is exempt from any other statutory or

regulatory requirements, unless such exemption is explicitly provided

by order or regulation. Indeed, FDA's determination that premarket

notification was unnecessary to provide a reasonable assurance of

safety and effectiveness for devices listed in this document was based,

in part, on the assurance of safety and effectiveness that other

regulatory controls, such as current good manufacturing practice

requirements, provide. Persons with pending 510(k) submissions for

devices that are now exempt from premarket notification, subject to the

limitations on exemptions, should withdraw their submissions.

FDA is codifying the exemption from premarket notification of all

62 class II devices listed as exempt in the January 21, 1998, notice,

subject to the limitations on exemptions. These devices will remain

subject to CGMP requirements and other general controls under the

statute as well as any special controls.

The Administrative Procedure Act (the APA) (Pub. L. 79-404) and FDA

regulations provide that the agency may issue a regulation without

notice and comment procedures when the agency for good cause finds (and

incorporates the finding and a brief statement of reasons thereof in

the rules issued) that notice and public procedure thereon are

impracticable, unnecessary, or contrary to the public interest (5

U.S.C. 553(b)(8), Sec. 10.40(e)(1) (21 CFR 10.40).) The Commissioner of

Food and Drugs (the Commissioner) finds for good cause that there is

reason to dispense with notice and comment rulemaking to amend the

codified language in the Code of Federal Regulations (CFR) to reflect

that certain class II devices are exempt.

Notice and comment rulemaking to codify the exemptions for these

class II devices would be both impracticable and unnecessary. As

previously stated, under the authority provided by section 206 of

FDAMA, these exemptions have already taken effect by operation of the

statute on January 21, 1998. Accordingly, it is both impracticable and

unnecessary to provide notice and comment on a regulation that merely

codifies that which has already occurred. Furthermore, interested

persons were provided an opportunity to comment when the January 21,

1998, notice published.

II. Effective Date

Section 553(d) of the APA requires that the effective date of a

substantive rule shall occur not less than 30 days after the

publication or service unless, under section 553(d)(1), the rule grants

or recognizes an exemption or relieves a restriction, or unless, under

section 553(d)(3), the agency finds good cause to make the effective

date less than 30 days and publishes the basis with the rule.

The Commissioner finds that because the exemptions are already in

effect, providing a delayed effective date for the regulation

conforming the CFR to reflect the exemptions is impracticable and

unnecessary. Accordingly, there is good cause, under section 553(d)(3)

of the APA and Sec. 10.40(c)(4)(ii), to provide an immediate effective

date. Additionally, an immediate effective date is authorized under

section 553(d)(1) and Sec. 10.40(c)(4)(i) because the codification of

the exemptions recognizes an exemption.

III. Comments

FDA received 8 sets of comments from respondents, both supporting

and opposing the exemption of the 62 class II devices.

1. Two comments suggested that FDA remove the following in vitro

diagnostic, class II devices from the list of exempted devices: 21 CFR

866.3060 Blastomyces dermatitidis, 866.3085 Brucella spp. serological

reagents, 866.3135 Coccidioides immitis serological reagents, 866.3320

Histoplasma capsulatum serological reagents, 866.3165 Crytococcus

[[Page 59223]]

neoformans serological reagents, 866.3220 Entamoeba histoloytica

serological reagents, 866.3280 Franciscella tularensis serological

reagents, 866.3350 Leptospira spp. serological reagents, and 866.3460

Rabiesvirus immunofluorescent reagents. The comments stated that these

devices fail to meet the criteria for exemption as described in the

regulatory notice as ``Limitations on Exemptions.'' Also, a third

comment suggested that two ``in vitro devices * * * intended for the

screening of familial and acquired genetic disorders''(21 CFR 866.5210

Ceruloplasmin immunological test system and 866.5470 Hemoglobin

immunological test system) fail to meet criteria for exemption under

FDAMA.

Devices that are listed as exempt from 510(k) requirements are

subject to the limitations to those exemptions described in the January

21, 1998, notice. The limitations to the exemptions state that for

certain uses, in vitro diagnostic devices that are otherwise exempt are

still subject to 510(k) requirements. Accordingly, a generic device

type may be exempt from 510(k) requirements for some uses, and not

exempt from those requirements if it is intended for other uses

described in the limitations language. For example, the January 21,

1998, notice states that a generic type of device that is otherwise

exempt is not exempt if it is used in screening or diagnosis of

familial and acquired genetic disorders, or for measuring analytes that

serve as a surrogate marker for screening, diagnosis, or monitoring

life-threatening diseases.

FDA does not agree that all the marketed uses for the devices

addressed by the comments (with the exceptions of rabiesvirus

immunofluorescent reagents, the ceruloplasmin immunological test

system, and the hemoglobin immunological test system) fall within the

limitations to the exemptions language in the January 21, 1998, notice.

These devices can be exempt, for example, when they are marketed for

the determination of immune status, or for epidemiological uses. If

these same devices, however, are used in the diagnosis of a life-

threatening disease, they would not be exempt.

FDA agrees, however, that all marketed uses for rabiesvirus

immunofluorescent reagents are for the detection of rabies, a life-

threatening disease, and that all marketed uses for the ceruloplasmin

immunological test system and the hemoglobin immunological test system

are for the screening or diagnosis of familial and acquired genetic

disorders. Accordingly, all intended uses for these devices would fall

within the limitations to exemptions for devices that are for use in

screening or diagnosis of familial and acquired genetic disorders, or

for measuring analytes that serve as surrogate markers for screening,

diagnosis, or monitoring life-threatening diseases.

FDA believes that it erroneously listed the generic device types

rabiesvirus immunofluorescent reagents, ceruloplasmin immunological

test systems, and hemoglobin immunological test systems as exempt from

510(k) requirements in the January 21, 1998, notice. Therefore, FDA

intends to issue a proposal to clarify that none of these devices are

exempt from 510(k) requirements. Until such rulemaking is final,

however, these devices will be listed, in accordance with the January

21, 1998, notice, as exempt subject to the limitations to the

exemptions. Sponsors should be aware, however, that FDA believes that

all marketed uses for these devices fall within the limitations to the

exemptions, and that sponsors, therefore, should continue to submit

510(k) submissions.

2. One comment requested more information on devices covered by 21

CFR 864.9160 Blood group substances of nonhuman origin for in vitro

diagnostic use.

FDA believes that devices in this classification traditionally have

been used for neutralization studies to assist in identification of

antibodies in patients with multiple antibodies. There does not appear

to be a high demand for these devices. FDA believes that there are

quality control practices and procedures in place that make continued

active premarket regulation unnecessary to ensure safety and

effectiveness.

3. The Health Care Financing Administration (HCFA) raised concerns

about the effect that exemptions may have on HCFA's implementation of

the Clinical Laboratory Improvements Amendments. HCFA subsequently

commented that they believed that their concerns could be addressed

without affecting the exemption process.

FDA intends to continue to meet with the HCFA staff to address

these concerns, which relate to inspection procedures in laboratories.

4. One comment questioned the limitations on exemptions stated in

the January 21, 1998, notice, particularly the limitations applicable

to in vitro diagnostic devices that are noninvasive tests. The comment

criticized the use of the words ``noninvasive testing'' as being overly

broad.

FDA disagrees with this comment. FDA believes that the limitations

are necessary to ensure that devices are not marketed that are

significantly different from the devices exempted from premarket

notification, particularly in the area of in vitro diagnostic devices

where devices are often subject to changes in intended use and

conditions of use. Noninvasive testing devices should not be exempt

because they almost always involve novel matrices and novel

technologies.

5. One comment suggested that the limitations on exemptions are

unnecessary, confusing, and difficult to apply, especially to in vitro

diagnostic devices. This comment additionally notes ``we question the

basis for FDA's broad restrictions in such a specific category of

devices.''

FDA does not agree that the language is unnecessary, confusing, or

difficult to apply. The limitations language in the January 21, 1998,

notice, that applies to class II devices listed therein, modifies the

limitations on exemptions currently found in ``.9'' of each device

classification regulation part (e.g., 21 CFR 862.9, 864.9, etc.) only

in three ways. First, FDA has referenced class II devices to reflect

that class II devices may be exempted in accordance with new section

510(m) of the act. Second, the limitations language modifies current

limitations language by stating that devices are to be compared to

``any legally marketed device in that generic type of device'' rather

than a device on the market ``before May 28, 1976'' or a

``preamendments device to which it has been determined substantially

equivalent.'' Third, the limitations language adds specific language

relating to in vitro diagnostic devices. The agency cannot predict all

possible different intended uses or changes in fundamental scientific

technologies that may significantly affect safety and effectiveness;

limitations on exemptions are, therefore, in the best interest of the

public health because they ensure that devices incorporating such

changes will be reviewed for safety and effectiveness by the agency

before they go to market. Furthermore, FDA believes that in vitro

diagnostic devices are unique because their safety and effectiveness

relates primarily to the information generated by these devices rather

than the direct interaction between device and patient. FDA has more

fully discussed the need for these limitations in the January 21, 1998,

notice. In order to efficiently allocate review resources, the agency

has developed a risk-based approach toward use of the limitations on

exemptions to ensure that high-risk devices remain subject to premarket

review. The limitations on exemptions continue to take into account two

[[Page 59224]]

critical risk elements: Intended use and novelty of technology.

6. One comment stated that body fat testers meet the criteria for

exemption from 510(k) and should therefore be exempt. Another comment

stated that film dosimetry systems are quality control devices and

should not be regulated as a class II device.

Neither of these devices were listed as exempt in the January 21,

1998, notice. Body fat analyzers have been found to be substantially

equivalent to legally marketed devices classified under 21 CFR 870.2770

Impedance plethysmograph. Film dosimetry systems are regulated under 21

CFR 892.5050 Medical charged-particle radiation therapy system. This

document is codifying the exemptions only for devices listed in the

January 21, 1998, notice.

Under new section 510(m)(2) of the act, any person now may petition

the agency for additional exemptions from the requirements of 510(k)

for a class II device type. FDA has provided guidance for submitting a

petition for exemption of a class II device and has requested that

these comments submit such petitions for these device types.

7. One comment believed the limitations on exemptions required

clarification as follows:

With regard to the first limitation (``has an intended use that

is different from the intended use of a legally marketed device in

that generic type''), we believe that current law is clear that if a

device has an intended use different than that expressed in the

definition contained in the Code of Federal Regulations (CFR), such

device would not be the same as the exempted device. The exemption

would simply not apply to that device. However, ``intended use'' can

encompass many different concepts that go beyond the general

intended use statements that comprised the CFR definitions. There

has been some controversy, for instance, over the extent to which

indications for use can change intended use. Our position is that

any indication for use that has been included in a previous 510(k)

order of classification identifies the scope of the intended use for

each exempt type of device. Minor variances of indications for use

within the intended use of an exempt type of device should have no

effect on the status of a 510(k) exemption.

FDA has interpreted paragraph``.9(a)'' of each device

classification regulation part (e.g., 21 CFR 862.9, 864.9, etc.) in the

limitations on exemptions under the current regulation to mean that any

legally marketed device (as defined in 21 CFR 807.92(a)(3)) within a

device classification regulation, may serve as a predicate for another

manufacturer's device, and the other manufacturer's device may be

exempt. FDA believes that any additional indication for use for an

exempt classification device type (i.e., an indication not previously

cleared) is considered a different intended use and does not meet the

limitations on exemptions, and therefore, requires a new premarket

notification. FDA agrees that minor variances in indications would not

affect the exemption status of the classification. FDA notes that in

our guidance entitled ``Deciding When to Submit a 510(k) for a Change

to an Existing Device,'' FDA states, in regard to minor variances in

indications of closely related populations, ``If the expansion is to a

population with similar demographics, diagnosis, prognosis, comorbidity

and potential for complications as the original, then a new 510(k) is

not ordinarily expected.''

IV. 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 or an environmental impact statement is required.

V. Analysis of Impacts

FDA has examined the impacts of the final rule under Executive

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

under the Unfunded Mandates Reform Act (Pub. L. 104-4). Executive Order

12866 directs agencies to assess all costs and benefits of available

regulatory alternatives and, when regulation is 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 final rule is consistent with the regulatory philosophy on

principles identified in the Executive Order. In addition, the final

rule is not a significant regulatory action as defined by the Executive

Order and so is not subject to review under the Executive Order.

If there is a significant economic impact on a substantial number

of small entities, the Regulatory Flexibility Act requires agencies to

analyze regulatory options that would minimize any significant impact

of a rule on small entities. Because this final rule would reduce a

regulatory burden by exempting manufacturers of devices subject to the

requirements of premarket notification, the agency certifies that the

final rule will not have a significant economic impact on a substantial

number of small entities. Therefore, under the Regulatory Flexibility

Act, no further analysis is required.

VI. Paperwork Reduction Act of 1995

This final rule contains no collections of information. Therefore,

clearance from the Office of Management and Budget under the Paperwork

Reduction Act of 1995 is not required.

List of Subjects

21 CFR Parts 862, 876, 880, 882, and 890

Medical devices.

21 CFR Part 864

Blood, Medical devices, Packaging and containers.

21 CFR Part 866

Biologics, Laboratories, Medical devices.

21 CFR Part 886

Medical devices, Ophthalmic goods and services.

21 CFR Part 892

Medical devices, Radiation protection, X-rays.

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

authority delegated to the Commissioner of Food and Drug, 21 CFR parts

862, 864, 866, 876, 880, 882, 886, 890, and 892 are amended as follows:

PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES

1. The authority citation 21 CFR part 862 continues to read as

follows:

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

2. Section 862.9 is amended by revising the section heading, by

designating the introductory text as paragraph (a), by redesignating

paragraphs (a) and (b) as paragraphs (a)(1) and (a)(2), respectively,

and by adding new paragraph (b) to read as follows:

Sec. 862.9 Limitations of exemptions from section 510(k) of the

Federal Food, Drug, and Cosmetic Act (the act).

* * * * *

(b) The exemption from the requirement of premarket notification

for a generic type of class II device applies only to those class II

devices that have existing or reasonably foreseeable characteristics of

commercially distributed devices within that generic type, or, in the

case of in vitro diagnostic devices, for which a misdiagnosis, as a

result of using the device, would not be associated with

[[Page 59225]]

high morbidity or mortality. A class II device for which FDA has

granted an exemption from the requirement of premarket notification

must still submit a premarket notification when:

(1) The device is intended for a use different from the intended

use of a legally marketed device in that generic type of device; e.g.,

the device is intended for a different medical purpose, or the device

is intended for lay use where the former intended use was by health

care professionals only; or

(2) The modified device operates using a different fundamental

scientific technology than a legally marketed device in that generic

type of device; e.g., a surgical instrument cuts tissue with a laser

beam rather than with a sharpened metal blade, or an in vitro

diagnostic device detects or identifies infectious agents by using

deoxyribonucleic acid (DNA) probe or nucleic acid hybridization

technology rather than culture or immunoassay technology; or

(3) The device is an in vitro device that is intended:

(i) For use in the diagnosis, monitoring, or screening of

neoplastic diseases with the exception of immunohistochemical devices;

(ii) For use in screening or diagnosis of familial and acquired

genetic disorders, including inborn errors of metabolism;

(iii) For measuring an analyte that serves as a surrogate marker

for screening, diagnosis, or monitoring life-threatening diseases such

as acquired immune deficiency syndrome (AIDS), chronic or active

hepatitis, tuberculosis, or myocardial infarction or to monitor

therapy;

(iv) For use in assessing the risk of cardiovascular diseases;

(v) For use in diabetes management;

(vi) For use in identifying or inferring the identity of a

microorganism directly from clinical material;

(vii) For detection of antibodies to microorganisms other than

immunoglobulin G (IgG) and IgG assays when the results are not

qualitative, or are used to determine immunity, or the assay is

intended for use in matrices other than serum or plasma;

(viii) For noninvasive testing; and

(ix) For near patient testing (point of care).

3. Section 862.1440 is amended by revising paragraph (b) to read as

follows:

Sec. 862.1440 Lactate dehydrogenase test system.

* * * * *

(b) Classification. Class II (special controls). The device is

exempt from the premarket notification procedures in subpart E of part

807 of this chapter subject to Sec. 862.9.

4. Section 862.1635 is amended by revising paragraph (b) to read as

follows:

Sec. 862.1635 Total protein test system.

* * * * *

(b) Classification. Class II (special controls). The device is

exempt from the premarket notification procedures in subpart E of part

807 of this chapter subject to Sec. 862.9.

PART 864--HEMATOLOGY AND PATHOLOGY DEVICES

5. The authority citation for 21 CFR part 864 continues to read as

follows:

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

6. Section 864.9 is amended by designating the introductory text as

paragraph (a), by redesignating paragraphs (a) and (b) as paragraphs

(a)(1) and (a)(2), respectively, and by adding new paragraph (b) to

read as follows:

Sec. 864.9 Limitations of exemptions from section 510(k) of the

Federal Food, Drug, and Cosmetic Act (the act).

* * * * *

(b) The exemption from the requirement of premarket notification

for a generic type of class II device applies only to those class II

devices that have existing or reasonably foreseeable characteristics of

commercially distributed devices within that generic type, or, in the

case of in vitro diagnostic devices, for which a misdiagnosis, as a

result of using the device, would not be associated with high morbidity

or mortality. A class II device for which FDA has granted an exemption

from the requirement of premarket notification must still submit a

premarket notification when:

(1) The device is intended for a use different from the intended

use of a legally marketed device in that generic type of device; e.g.,

the device is intended for a different medical purpose, or the device

is intended for lay use where the former intended use was by health

care professionals only; or

(2) The modified device operates using a different fundamental

scientific technology than a legally marketed device in that generic

type of device; e.g., a surgical instrument cuts tissue with a laser

beam rather than with a sharpened metal blade, or an in vitro

diagnostic device detects or identifies infectious agents by using

deoxyribonucleic acid (DNA) probe or nucleic acid hybridization

technology rather than culture or immunoassay technology; or

(3) The device is an in vitro device that is intended:

(i) For use in the diagnosis, monitoring, or screening of

neoplastic diseases with the exception of immunohistochemical devices;

(ii) For use in screening or diagnosis of familial and acquired

genetic disorders, including inborn errors of metabolism;

(iii) For measuring an analyte that serves as a surrogate marker

for screening, diagnosis, or monitoring life-threatening diseases such

as acquired immune deficiency syndrome (AIDS), chronic or active

hepatitis, tuberculosis, or myocardial infarction or to monitor

therapy;

(iv) For assessing the risk of cardiovascular diseases;

(v) For use in diabetes management;

(vi) For identifying or inferring the identity of a microorganism

directly from clinical material;

(vii) For detection of antibodies to microorganisms other than

immunoglobulin G (IgG) and IgG assays when the results are not

qualitative, or are used to determine immunity, or the assay is

intended for use in matrices other than serum or plasma;

(viii) For noninvasive testing; and

(ix) For near patient testing (point of care).

7. Section 864.6100 is amended by revising paragraph (b) to read as

follows:

Sec. 864.6100 Bleeding time device.

* * * * *

(b) Classification. Class II (special controls). The device is

exempt from the premarket notification procedures in subpart E of part

807 of this chapter subject to Sec. 864.9.

8. Section 864.6400 is amended by revising paragraph (b) to read as

follows:

Sec. 864.6400 Hematocrit measuring device.

* * * * *

(b) Classification. Class II (special controls). The device is

exempt from the premarket notification procedures in subpart E of part

807 of this chapter subject to Sec. 864.9.

9. Section 864.9160 is amended by revising paragraph (b) to read as

follows:

Sec. 864.9160 Blood group substance of nonhuman origin for in vitro

diagnostic use.

* * * * *

(b) Classification. Class II (special controls). The device is

exempt from the premarket notification procedures in subpart E of part

807 of this chapter subject to Sec. 864.9.

10. Section 864.9550 is amended by revising paragraph (b) to read

as follows:

Sec. 864.9550 Lectins and protectins.

* * * * *

[[Page 59226]]

(b) Classification. Class II (special controls). The device is

exempt from the premarket notification procedures in subpart E of part

807 of this chapter subject to Sec. 864.9.

11. Section 864.9575 is amended by revising paragraph (b) to read

as follows:

Sec. 864.9575 Environmental chamber for storage of platelet

concentrate.

* * * * *

(b) Classification. Class II (special controls). The device is

exempt from the premarket notification procedures in subpart E of part

807 of this chapter subject to Sec. 864.9.

12. Section 864.9600 is amended by revising paragraph (b) to read

as follows:

Sec. 864.9600 Potentiating media for in vitro diagnostic use.

* * * * *

(b) Classification. Class II (special controls). The device is

exempt from the premarket notification procedures in subpart E of part

807 of this chapter subject to Sec. 864.9.

13. Section 864.9700 is amended by revising paragraph (b) to read

as follows:

Sec. 864.9700 Blood storage refrigerator and blood storage freezer.

* * * * *

(b) Classification. Class II (special controls). The device is

exempt from the premarket notification procedures in subpart E of part

807 of this chapter subject to Sec. 864.9.

PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES

14. The authority citation for 21 CFR part 866 continues to read as

follows:

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

15. Section 866.9 is amended by designating the introductory text

as paragraph (a), by redesignating paragraphs (a) and (b) as paragraphs

(a)(1) and (a)(2), respectively, and by adding new paragraph (b) to

read as follows:

Sec. 866.9 Limitations of exemptions from section 510(k) of the