General Hospital and Personal Use Devices: Proposed Classification of Liquid Chemical Sterilants and General Purpose Disinfectants

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 880

[Docket No. 98N-0786]

General Hospital and Personal Use Devices: Proposed

Classification of Liquid Chemical Sterilants and General Purpose

Disinfectants

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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

classify both liquid chemical sterilants intended for use as the

terminal step in processing critical and semicritical medical devices

prior to patient use, and general purpose disinfectants intended to

process noncritical medical devices and equipment surfaces. Under the

proposal, liquid chemical sterilants would be classified into class II

(special controls) and general purpose disinfectants would be

classified into class I (general controls). FDA also proposes to exempt

general purpose disinfectants from the premarket notification

requirements. The agency is publishing in this document the

recommendations of the 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 February 4, 1999.

ADDRESSES: Submit written comments to the Dockets Management Branch

(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,

Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Chiu S. Lin, Center for Devices and

Radiological Health (HFZ-480), Food and Drug Administration, 9200

Corporate Blvd., Rockville, MD 20850, 301-443-8913.

SUPPLEMENTARY INFORMATION:

I. Background

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

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

1976 amendments) (Pub. L. 94-295), the Safe Medical Devices Act of 1990

(the SMDA) (Pub. L. 101-629), and the Food and Drug Administration

Modernization Act of 1997 (the FDAMA) (Pub. L. 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 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 preamendments devices, are

classified after FDA has: (1)

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Received a recommendation from a device classification panel (an FDA

advisory committee); (2) published the panel's recommendation for

comment, along with a proposed regulation classifying the device; and

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

classified most preamendments devices under these procedures.

Devices that were not in commercial distribution prior to May 28,

1976, generally referred to as postamendments 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: (1) The device is

reclassified into class I or II; (2) FDA issues an order classifying

the device into class I or II in accordance with new section 513(f)(2)

of the act, as amended by the FDAMA; or (3) FDA issues an order finding

the device to be substantially equivalent, in accordance with 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 part 807 (21 CFR part 807) of the regulations.

A preamendments device that has been classified into class III may

be marketed, by means of premarket notification procedures, without

submission of a premarket approval application (PMA) until FDA issues a

final regulation under section 515(b) of the act (21 U.S.C. 360e(b))

requiring premarket approval. Consistent with the act and the

regulations, FDA consulted the Panel, regarding the classification of

the device.

The FDAMA added a new section 510(l) to the act (21 U.S.C. 360(l)).

New section 510(l) of the act provides that a class I device is exempt

from the premarket notification requirements under section 510(k) of

the act, unless the device is intended for a use which is of

substantial importance in preventing impairment of human health or it

presents a potential unreasonable risk of illness or injury. Hereafter,

these are referred to as ``reserved criteria.'' FDA has considered the

general purpose disinfectants in accordance with the reserved criteria

and determine that the devices do not require premarket notification.

Such an exemption permits manufacturers to introduce into commercial

distribution generic types of devices without first submitting a

premarket notification to FDA.

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

classified (45 FR 69678 to 69737, October 21, 1980), FDA inadvertently

omitted liquid chemical germicides, such as liquid chemical sterilants

and general purpose disinfectants from the classification process. In

subsequent years, FDA actively regulated only liquid chemical

germicides that were used as accessories to specific class II devices,

such as hemodialyzers. FDA began actively regulating all liquid

chemical germicides in the early 1990's following efficacy testing by

FDA for the Environmental Protection Agency (EPA) and publication of

the 1993 General Accounting Office (GAO) report on Hospital Sterilants

(Ref. 1). Liquid chemical germicides were regulated as accessories to

other devices with the level of regulation applicable coinciding with

the classification of the other devices. FDA also determined that two

categories of liquid chemical germicides existed, liquid chemical

sterilants and general purpose disinfectants.

The first category consists of liquid chemical sterilants which are

intended for use as the terminal step in processing critical and

semicritical medical devices prior to patient use. Semicritical medical

devices contact mucous membranes or nonintact skin during use, while

critical devices contact normally sterile tissue or body spaces.

The second category of liquid chemical germicides consists of

general purpose disinfectants which are intended to process noncritical

medical devices and medical equipment surfaces, and can be used to

preclean or decontaminate critical or semicritical medical devices

prior to terminal sterilization or high level disinfection. Noncritical

medical devices only make topical contact with intact skin of the body.

In addition to being regulated by FDA, certain liquid chemical

germicides are regulated by EPA as pesticides under the Federal

Insecticide, Fungicide, and Rodenticide Act (FIFRA). On June 4, 1993, a

memorandum of understanding (MOU) was signed between FDA and EPA (Refs.

3 and 4). The purpose of the MOU was to resolve the confusion and

burden of dual regulation and, at the same time, ensure that the safety

and efficacy requirements of both statutes are met.

In 1996, liquid chemical sterilants used for processing critical

and semicritical medical devices were exempted from the definition of a

pesticide under FIFRA with passage of the Food Quality Protection Act

of 1996 (FQPA) and are no longer regulated by EPA. FDA now has sole

regulatory jurisdiction over liquid chemical sterilants and high level

disinfectants used to process reusable critical and semicritical

medical devices. Regulatory authority over general purpose

disinfectants was not affected by FQPA. Therefore, the MOU remains in

effect for general purpose disinfectants, and the dual regulatory

requirements for these germicides continue until the rulemaking process

for classification of the germicides is completed.

II. Recommendations of the Panel

During a public meeting which was held on July 18, 1995, the Panel

made the following recommendations regarding the classification of

liquid chemical sterilants and general purpose disinfectants.

A. Identification

The Panel recommended that the devices be identified as follows:

A liquid chemical sterilant is a germicide intended for use as the

terminal step in processing critical and semicritical medical devices

prior to patient use. Semicritical devices make contact with mucous

membranes or nonintact skin during use. Critical devices contact

normally sterile tissue or body spaces during use (Refs. 5 and 6).

A general purpose disinfectant is a germicide intended to process

noncritical medical devices and medical equipment surfaces. A general

purpose disinfectant can be used to preclean or decontaminate critical

or semicritical medical devices prior to terminal sterilization or high

level disinfection. Noncritical medical devices only make topical

contact with intact skin of the body (Refs. 5 and 6).

B. Recommended Classification of the Panel

The Panel unanimously recommended that liquid chemical sterilants

be classified into class II. The Panel believed that class II with the

special controls (the 510(k) guidance document (Ref. 2), voluntary

standards, and user information and training) would provide reasonable

assurance of the safety and effectiveness of the devices.

The Panel recommended that general purpose disinfectants be

classified into class I and that the devices should be exempt from the

premarket notification procedures.

C. Summary of Reasons for Recommendation

After reviewing the information provided by FDA, and after

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consideration of the open discussions during the Panel meeting and the

Panel members' personal knowledge of and clinical experience with the

device systems, the Panel gave the following reasons in support of its

recommendations to classify the generic type of liquid chemical

sterilants for use as the terminal step in processing critical and

semicritical medical devices prior to patient use into class II, and

general purpose disinfectants for use in processing noncritical medical

devices and medical equipment surfaces into class I:

1. The Panel believes that liquid chemical sterilants should be

classified into class II because special controls, in addition to

general controls, would be necessary to provide reasonable assurance of

the safety and effectiveness of the devices, and there is sufficient

information to establish special controls to provide such assurance.

2. The Panel believes that general purpose disinfectants should be

classified into class I because general controls would provide

reasonable assurance of the safety and effectiveness of the devices. In

addition to the Panel's recommendation, FDA has considered general

purpose disinfectants in accordance with the reserved criteria of new

section 510(l) of the act and determined that the general purpose

disinfectants do not require premarket notification.

D. Summary of Data Upon Which the Recommendation is Based

The Panel noted that liquid chemical sterilants include peracetic

acid, hydrogen peroxide, chlorine dioxide, and glutaraldehyde. These

substances are used to sterilize or high level disinfect heat sensitive

medical devices such as flexible endoscopes. Toxicity studies have

shown hydrogen peroxide and peracetic acid to be nontoxic,

nonsensitizing and, at most, minimally irritating. In addition, these

chemicals, as well as chlorine dioxide, are used at low concentrations

and readily degrade to nontoxic compounds, such as water and molecular

oxygen (Refs. 7, 8, and 9).

Toxicity studies have shown glutaraldehyde to be a skin, eye, and

respiratory system irritant and a skin sensitizer. Since glutaraldehyde

does not readily degrade, long-term effects of its residue as a skin or

eye irritant are of concern (Refs. 10 and 11). Although some injuries

and deaths have been reported following the use of these chemicals as

sterilants and disinfectants, they have been primarily associated with

failure of the user to follow the manufacturer's directions for use

(Ref. 12).

The Panel noted that general purpose disinfectants include

alcohols, chlorines, iodophors, phenolics, and quaternary ammonium

compounds. The hazards and adverse effects of these substances are well

known (Ref. 8). Toxicity is minimal because these substances are used

at low concentrations on equipment surfaces and noncritical devices

that only contact intact skin during use.

The use of liquid chemical sterilants and general purpose

disinfectants on medical devices is based on the infection control

classification system devised by E. H. Spaulding (Refs. 13 and 14), and

adopted by infection control practitioners, FDA, and the Centers for

Disease Control and Prevention. Spaulding's system is predicated on the

relative risks associated with the use of medical devices. According to

Spaulding's system, devices that contact normally sterile tissues or

body spaces during use are termed critical devices. Critical devices

should be sterilized prior to use.

Devices that contact mucous membranes, which can provide a barrier

to many, but not all microorganisms, are termed semicritical devices.

Semicritical devices should be sterilized prior to use when practical,

or should undergo high level disinfection (a high level disinfectant is

a sterilant used for a shorter contact time and that kills all

microbial pathogens except large numbers of bacterial endospores).

General purpose disinfectants can be used to clean or decontaminate

critical and semicritical devices prior to a terminal sterilization or

high level disinfection process.

E. Risks to Health

The following three risks are associated with the use of germicides

such as liquid chemical sterilants and general purpose disinfectants:

(1) Nosocomial infection, (2) toxicity associated with chemical

exposure, and (3) damage to medical devices.

The formulation of a germicide plays an important role in the

effectiveness of the germicide on the device. If the formulation is

inadequate for its intended use or if the germicide is improperly used,

the sterilization or disinfection process will be ineffective. As a

result, the processed device may serve as a potential vector for the

transmission of infectious microorganisms to the next patient.

In the Federal Register of December 6, 1996 (61 FR 64755), FDA

announced the availability of a draft guidance document entitled

``Draft Guidance on the Content and Format of Premarket Notification

(510(k)) Submissions for Liquid Chemical Germicides'' (Ref. 2). In the

Federal Register of May 22, 1997 (62 FR 28055), FDA extended the period

to comment on the draft guidance until August 20, 1997.

The guidance document suggests that manufacturers of these devices

are to submit, for review and evaluation, microbiological studies

supporting all germicidal claims, and adequate instructions for use.

EPA registration for general purpose disinfectants requires similar

information.

With regard to chemical exposure, health-care workers who process

medical devices with either liquid chemical sterilants or general

purpose disinfectants are potentially exposed to toxic substances

during use of the germicides. In addition, the patient may be exposed

to germicide residues if the device is inadequately rinsed.

Labeling recommendations in the guidance document include warnings

and precautions regarding the proper use and handling of liquid

chemical sterilants and other toxic substances. Additionally, the

guidance document recommends a toxicological assessment of germicide

residues remaining following rinsing. EPA registration of general

purpose disinfectants requires similar information.

Lastly, both liquid chemical sterilants and general purpose

disinfectants may damage medical devices causing them to function

improperly or create areas that cannot be effectively cleaned,

disinfected or sterilized. The guidance document recommends that data

demonstrating device materials compatibility with the liquid chemical

germicides be included in the 510(k).

F. Special Controls

Based on the available information, FDA believes that, in addition

to general controls, the special controls discussed as follows are

adequate to address the risks to health which were identified

previously.

1. The 510(k) guidance document;

2. Voluntary standards; and

3. User information and training.

The guidance document provides 510(k) applicants with specific

directions regarding data and information that should be submitted to

FDA in a 510(k) submission for liquid chemical germicides. The document

incorporates voluntary standards and guidelines from professional

organizations as part of its recommendation for performance testing.

Compliance with the recommendations made in the document for liquid

chemical sterilants is important in preventing nosocomial infections.

[[Page 59920]]

Voluntary standards provide assurance of consistency and uniformity

in germicide effectiveness.

User information and training programs are critical to ensure that

users have full knowledge and assume responsibility for the safe and

effective use of the liquid chemical sterilants.

Adherence to these special controls can provide the user community

a greater assurance of effectiveness and appropriate use in order to

minimize nosocomial infection through improperly sterilized or

disinfected reusable medical devices.

III. Proposed Classification

FDA believes that liquid chemical sterilants should be classified

into class II because special controls, 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.

FDA believes that general purpose disinfectants should be

classified into class I because general controls under the act and the

EPA registration requirements would provide reasonable assurance of

safety and effectiveness of these products. FDA also believes that

these devices do not meet the reserved criteria of new section 510(l)

of the act and should be exempt from premarket notification

requirements.

IV. 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. U.S. General Accounting Office, Report to the Ranking

Minority Member Committee on Government Operations, House of

Representatives, Hospital Sterilants: Insufficient FDA Regulation

May Pose a Public Health Risk, GAO/HRD-93-79, June 1993.

2. FDA, Center for Devices and Radiological Health, Office of

Device Evaluation, ``Draft Guidance on the Content and Format of

Premarket Notification (510(k)) Submissions for Liquid Chemical

Germicides,'' January 1992; revised April 26, 1995.

3. Memorandum of Understanding Between the Food and Drug

Administration, Public Health Service, Department of Health and

Human Services and the Environmental Protection Agency, Notice

Regarding Matters of Mutual Responsibility--Regulation of Liquid

Chemical Germicides Intended for Use on Medical Devices, June 4,

1993.

4. Amendment to the June 4, 1993, Memorandum of Understanding

Between the Food and Drug Administration, Public Health Service,

Department of Health and Human Services and the Environmental

Protection Agency, June 30, 1994.

5. General Hospital and Personal Use Devices Panel, Thirtieth

Meeting, Transcript, July 18, 1995.

6. General Hospital and Personal Use Devices Panel, Thirtieth

Meeting, Summary of Minutes, July 18, 1995.

7. Malchesky, P. S., ``Peracetic Acid and Its Application to

Medical Instrument Sterilization,'' Artificial Organs, vol. 17, no.

3, pp. 147-152, 1993.

8. Block, S. S., ``Peroxygen Compounds,'' Disinfection,

Sterilization, and Preservation, pp. 167-181, Philadelphia, 1991.

9. Dychdala, G. R., ``Chlorine and Chlorine Compounds,''

Disinfection, Sterilization, and Preservation, pp. 131-151,

Philadelphia, 1991.

10. Scott, E. M., and S. P. Gorman, ``Glutaraldehyde,'' in

Disinfection, Sterilization, and Preservation, pp. 596-614,

Philadelphia, 1991.

11. Australian Government Publishing Service, ``Priority

Existing Chemical No.3, Glutaraldehyde,'' pp. 53-62, Canberra, July

1994.

12. Spach, D. H., F. E. Silverstein, and W. E. Stamm,

``Transmission of Infection by Gastrointestinal Endoscopy and

Bronchoscopy,'' Annals of Internal Medicine, vol. 118, no. 2, pp.

117-128, 1993.

13. Spaulding, E. H., ``Role of Chemical Disinfection in the

Prevention of Nosocomial Infections,'' Proceedings of International

Conference on Nosocomial Infections, pp. 247-254, Chicago, 1970.

14. Spaulding, E. H., ``Chemical Disinfection and Antisepsis in

the Hospital,'' Journal of Hospital Research, vol. 9, pp. 5-31,

1972.

V. 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.

VI. 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 (Pub. L. 104-121), and the Unfunded Mandates Reform Act of 1995

(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 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. Because the proposed rule classifying these devices

eliminates duplicative registration, and may enable additional small

competitors to enter the marketplace by eliminating the cost of

complying with two sets of requirements, it will impose no significant

economic impact on any small entities. The agency 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.

VII. Paperwork Reduction Act of 1995

FDA tentatively concludes that this proposed rule contains no

collection of information. Therefore, clearance by the Office of

Management and Budget under the Paperwork Reduction Act of 1995 is not

required.

VIII. Submission of Comments and Proposed Dates

Interested persons may, on or before February 4, 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.

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

proposal become effective 30 days after its date of publication in the

Federal Register.

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, it is

proposed that 21 CFR part 880 be amended to read as follows:

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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. Sections 880.6885 and 880.6890 are added to subpart G to read as

follows:

Sec. 880.6885 Liquid chemical sterilants.

(a) Identification. A liquid chemical sterilant is a germicide that

is intended for use as the terminal step in processing critical and

semicritical medical devices prior to patient use. Critical devices

make contact with normally sterile tissue or body spaces during use.

Semicritical devices make contact with mucous membranes or nonintact

skin during use.

(b) Classification. Class II (special controls). (Guidance on the

Content and Format of Premarket Notification (510(k)) Submissions for

Liquid Chemical Germicides, voluntary standards, and user information

and training.)

Sec. 880.6890 General purpose disinfectants.

(a) Identification. A general purpose disinfectant is a germicide

intended to process noncritical medical devices and equipment surfaces.

A general purpose disinfectant can be used to preclean or decontaminate

critical or semicritical medical devices prior to terminal

sterilization or high level disinfection. Noncritical medical devices

make only topical contact with intact skin of the body.

(b) Classification. Class I (general controls). The device is

exempt from the premarket notification procedures in subpart E of part

807 of this chapter subject to the limitations in Sec. 880.9.

Dated: October 2, 1998.

D.B. Burlington,

Director, Center for Devices and Radiological Health.

[FR Doc. 98-29566 Filed 11-5-98; 8:45 am]

BILLING CODE 4160-01-F