PRN Notice 94-4: Interim Measures for the Registration of Antimicrobial Products/Liquid Chemical Germicides with Medical Device Use Claims Under the Memorandum of Understanding Between EPA and FDA

June 30, 1994

Notice To: Manufacturers, Producers, Formulators, and Registrants of Pesticide Products

Attention: Persons Responsible for Registration of Pesticides

Subject: Interim Measures for the Registration of Antimicrobial Products/Liquid Chemical Germicides with Medical Device Use Claims Under the Memorandum of Understanding Between EPA and FDA

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Purpose

This Notice is intended to provide the regulated community with detailed guidance on the interim EPA registration procedures for antimicrobial products affected by the June 4, 1993, Memorandum of Understanding (MOU) between the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA) as amended. Copies of the signed MOU and its amendment are included with this Notice.
Applicability

This Notice applies to all registrants of liquid chemical germicides which bear claims for use on medical devices. While EPA has regulatory authority over all antimicrobial products which bear claims to act against microorganisms on inanimate surfaces, FDA's regulatory purview extends to liquid chemical germicides which are used on medical devices and are therefore considered to be medical devices themselves. Because FDA's regulatory concern focuses on the application of chemical germicides to medical devices, the MOU is relevant only to those antimicrobial pesticides with medical device use claims.

The manner in which FDA determines the required level of processing needed for a medical device is based on Dr. E.H. Spaulding's infection control classification system, as adapted and recommended by the Centers for Disease Control and Prevention (CDC). In this system, medical devices are categorized according to the relative risk associated with their intended use patterns. The three primary categories are (1) critical surfaces which must be sterilized, (2) semi-critical surfaces which should be sterilized but must at least undergo high level disinfection, and (3) non-critical surfaces including medical equipment surfaces which should undergo intermediate or low level disinfection. These definitions are discussed in detail in the MOU.

The MOU divides antimicrobial pesticides into two categories based on label claims and medical device use patterns. The first category is liquid chemical germicides used as sterilants to reprocess reusable critical and semi-critical devices such as heat labile instruments, and endoscopes. The second category is general purpose disinfectants. The products in this second category are used on non-critical surfaces and dental and medical equipment surfaces such as wheel chairs, dental chairs, and medical beds in hospitals and related institutions. These products can be used for pre-cleaning or decontamination of critical or semi-critical surfaces as long as the label clearly states that this is done prior to the surface being sterilized or disinfected. Because of their intended use pattern, these two categories of antimicrobial pesticides are considered to be medical devices and are thus subject to the conditions of this Notice.
Background

Liquid chemical germicides which bear claims for use on medical devices are currently regulated both as pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and as medical devices under the Federal Food, Drug, and Cosmetic Act (FFDCA). In an effort to resolve the confusion and burden of dual regulation, a Memorandum of Understanding (MOU) was signed on June 4, 1993 between the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA). The MOU was amended on June 20, 1994. The objectives of the MOU are to (1) provide a framework under which both Agencies will undertake rulemaking to permanently vest exclusive jurisdiction for certain categories of chemical germicides in one Agency or the other, and (2) serve as interim guidance designed to minimize duplicate regulatory requirements in shared areas of jurisdiction between the two Agencies until the rulemaking is complete.

To briefly summarize the MOU, each Agency has been given primary jurisdiction over one of the two categories of liquid chemical germicides considered to be medical devices. FDA has primary responsibility over liquid chemical sterilants, which includes responsibility for subordinate claims on sterilant products such as tuberculocidal or virucidal claims which support a high level disinfectant use pattern. EPA has primary jurisdiction over the general purpose disinfectants. The MOU calls for both EPA and FDA to initiate rulemaking to give each Agency sole jurisdiction over their designated categories. However, since rulemaking may involve a long term process, the MOU sets forth interim procedures in order to reduce the condition of dual regulatory oversight.

The MOU itself cannot change the statutory responsibilities granted under FIFRA and FFDCA. Therefore, until rulemaking is finalized, both Agencies will continue to share jurisdiction over all liquid chemical germicides used on medical devices and will continue to maintain separate registration and premarket approval procedures. In addition, the June 1993 MOU and this PR Notice have no affect on EPA's authority to take actions based on test results from the ongoing EPA antimicrobial testing program. EPA will still act to remove inefficacious products from the market based on test results from that program. Products so removed from the market, however, must, in addition to meeting other applicable requirements, follow the procedures outlined in the MOU and this PR Notice before they may return to the market.

Although both Agencies must continue to fulfill their statutory responsibilities, the MOU attempts to alleviate the regulatory burden that may be associated with submitting duplicate data packages to both EPA and FDA. Essentially, the interim procedures state that only one Agency needs to review the product performance (efficacy) data which are required to support both an EPA registration and an FDA 510(k) premarket clearance. The MOU states that the FDA review and acceptance of efficacy data submitted in support of a 510(k) notice will meet EPA's product performance (efficacy) registration requirements for liquid chemical sterilant products. Likewise, the EPA review of product performance (efficacy) data submitted for a general purpose disinfectant will suffice for a 510(k) premarket approval notice. Each Agency will continue to administer any other applicable requirements.
Interim Procedures For Obtaining Or Amending An EPA Registration For Liquid Chemical Sterilant Products

As stated in the previous section, FDA will ultimately be responsible for the sole regulation of liquid chemical sterilant products used to reprocess critical and semi-critical devices. FDA will also be solely responsible for the subordinate claims on particular sterilant product labels which support a high level disinfectant use pattern including the hospital disinfectant, tuberculocidal, and virucidal claims. The FDA efficacy and product performance requirements for 510(k) clearance are comparable to EPA's FIFRA Section 3 efficacy registration requirements as listed in the Product Performance Guidelines Subdivision G. Therefore, under the interim provisions of the MOU, EPA will agree that the FDA review and acceptance of the efficacy and product performance data will fulfill EPA's product performance (efficacy) registration requirements under FIFRA.

The following step-by-step procedure describes the EPA interim registration process for liquid chemical sterilants and additional product claims which support a high level disinfectant use pattern for both new registrations and amendments to current registrations. The registrant will submit its registration package to EPA and FDA at the same time so that both Agencies can conduct concurrent reviews.
1. Registrant prepares the full EPA registration package including all toxicology, chemistry, ecological effects, and environmental fate data, proposed labeling, and associated administrative forms. Efficacy/product performance data should not be included in this package.
2. Registrant submits the EPA registration package to EPA for review. EPA will review this application concurrent with FDA's assessment of the 510(k) premarket clearance package.
3. Registrant prepares the full FDA 510(k) premarket clearance package. All efficacy/product performance data will be included in this package and reviewed by FDA. Once the efficacy/product performance data have been reviewed and accepted by FDA, they will satisfy the EPA efficacy/product performance registration data requirements. FDA may have additional requirements beyond EPA's current requirements. These data requirements and label/label insert requirements are published in FDA's Guidance on the Content and Format of Premarket Notification [510(k)] Submissions for Liquid Chemical Germicides, January 31, 1992.
4. Registrant submits the 510(k) premarket clearance package to FDA. Once FDA has completed its review, a copy of the FDA accepted labeling and 510(k) clearance will be transmitted by FDA to EPA.
5. Once EPA has received a copy of the 510(k) clearance from FDA and has completed the review of the FIFRA application package, the registration or amendment will be granted if EPA determines that registration or amendment is appropriate. EPA will include all comments from EPA and/or FDA regarding the proposed labeling in the acceptance letter and all required corrections or additions must be incorporated into the final label before the registered product may be legally released for shipment or sold or distributed. As currently required, five copies of the final printed labeling must be submitted to EPA.
Interim Procedures For Obtaining Or Amending An EPA Registration For General Purpose Disinfectants

Once rulemaking is complete, EPA will have sole jurisdiction for general purpose disinfectants. The process and requirements to register general purpose disinfectants with the EPA will be the same as they are now, including the requirements for efficacy, toxicology, and chemistry data. Current EPA label requirements remain in effect. However, in order to remain in compliance with FIFRA, the following restrictive label statement must be added to the label of any general purpose disinfectant that is registered for any medical device or medical equipment surface claims:

"This product is not to be used as a terminal sterilant/high level disinfectant on any surface or instrument that (1) is introduced directly into the human body, either into or in contact with the bloodstream or normally sterile areas of the body, or (2) contacts intact mucous membranes but which does not ordinarily penetrate the blood barrier or otherwise enter normally sterile areas of the body. This product may be used to preclean or decontaminate critical or semi-critical medical devices prior to sterilization or high level disinfection".
Label Revision Compliance Dates And Procedures

For products bearing sterilization claims, existing EPA labeling requirements remain in effect. FDA will promulgate a final rule establishing sole jurisdiction over such products. However, to comply with FDA's 510(k) requirements, registrants generally will be required to develop a package insert which clearly prescribes the steps to be followed in achieving high, intermediate, and low level disinfection, as well as provides other appropriate information. Registrants are reminded that this package insert becomes labeling under FIFRA and must comply with EPA labeling requirements at 40 CFR 156.10.

For general purpose disinfectants, EPA has determined that the incorporation of the label statement set forth in Section V above must take place as described below. Registrants of affected products must comply with these label specifications and deadlines in order to remain in compliance with FIFRA.
1. Within 6 months of the date of this Notice each registrant of a general purpose disinfectant product registered for use on any medical device or medical equipment surface (an "affected product") must submit a completed amendment (EPA form number 8570-1) with 5 copies of draft labeling which meets the requirements of #2(a) and (b) below. In order to expedite processing approval of the amendment application, registrants should clearly identify the submission in connection with this PR Notice by writing the words, "MOU COMPLIANCE PER PR NOTICE 94- " in Section II. of the application form. Applications are to be sent to the following address:
  
  For USPS Submissions:
  
  Document Processing Desk (AMEND)
  Office of Pesticide Programs (7504-C)
  U.S. Environmental Protection Agency
  401 M Street, S.W.
  Washington, D.C. 20460-0001
  
  For Courier Deliveries:
  
  Office of Pesticide Programs
  Document Processing Desk (AMEND)
  Room 266A, Crystal Mall 2
  1921 Jefferson Davis Highway
  Arlington, Virginia 22202
2. No later than October 1, 1995, the labeling of each affected product sold or distributed by registrants and distributors must:
  1. bear the exact statement set forth in Section V of this Notice and comply with the labeling requirements found in 40 CFR 156.10.
  2. have omitted or obliterated all specific claims of effectiveness, or directions for use on critical or semi-critical surfaces or instruments.
3. No later than October 1, 1997, each affected product sold or distributed by any person other than registrants or distributors must bear labeling which meets the requirements of #2(a) and (b) above.
4. At any time prior to the October 1, 1995 deadline, registrants may add the labeling statement in Section V of this Notice and may omit or obliterate the claims with respect to critical or semi-critical surfaces or instruments without waiting for approval of the amendment application submitted per #1 above.

Effective Date

The procedures described in this notice for affected products are effective immediately. All new registration and amendment applications for products bearing medical device use claims will be processed according to the steps outlined in this Notice. Any registrant not already in compliance with these label specifications must, in order to remain in compliance with FIFRA, submit appropriate registration and label amendments for affected products within the time periods specified in Section VI. Registrants must also make required label changes to affected products by the deadlines specified above in order to remain in compliance with FIFRA.
For Further Information

For further information contact Michele Wingfield, Microbiologist, Antimicrobial Program Branch, Registration Division at (703) 305-6653. /SIGNED/

Stephen L. Johnson, Director
Registration Division

PRN Notice 94-4: Interim Measures for the Registration of Antimicrobial Products/Liquid Chemical Germicides with Medical Device Use Claims Under the Memorandum of Understanding Between EPA and FDA

Purpose

Applicability

Background

Interim Procedures For Obtaining Or Amending An EPA Registration For Liquid Chemical Sterilant Products

Interim Procedures For Obtaining Or Amending An EPA Registration For General Purpose Disinfectants

Label Revision Compliance Dates And Procedures

Effective Date

For Further Information

Pesticide Registration