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Proving Antimicrobial Efficacy - A Continuing Controversy

Beveridge & Diamond, P.C. - Client Alert, July 9, 2009

Executive Summary

Antimicrobial pesticide products include sterilants, disinfectants, and sanitizers.  Because of their importance to public health, they must be shown to be effective in order to be registered under the Federal Insecticide, Fungicide, and Rodenticide Act (“FIFRA”).  However, EPA’s programs for ensuring antimicrobial efficacy have been strongly criticized on several fronts.  This memorandum discusses this longstanding issue and reports on recent developments. 

EPA’s antimicrobial pesticide registration review process has been faulted for failure to assure the quality of efficacy data.  In particular, one of EPA’s required test protocols for disinfectants and fungicides, the Association of Official Analytical Chemists (“AOAC”) Use-Dilution Test Method, has been criticized for decades as an unreliable and unfair test of product performance.  Indeed, despite the agency’s efforts to respond to these criticisms by attempting to improve the test and by increasing post-registration testing and enforcement actions, EPA’s Office of Inspector General (“OIG”) has repeatedly faulted the agency’s Antimicrobial Division for, among other issues, a continuing high failure rate of registered antimicrobial pesticides using the prescribed testing methods.  Conflicts and confusion regarding efficacy testing methods and guidelines have become a significant source of controversy regarding EPA’s proposed revisions to the antimicrobial pesticide registration regulations, which do not revise the existing product performance data requirements. 

Developments expected this year include finalization of the proposed registration regulations and the anticipated publication of new guidance on testing procedures.  They should be monitored closely in light of political pressures on EPA under the Obama Administration to increase enforcement, to take a more precautionary approach for public health protection, and to improve the healthcare system.  If the issues with the efficacy testing methods are not resolved, increased testing and enforcement could cause effective antimicrobial products to be removed from the market as a result of test failures due to flaws in the test procedure, rather than in the products themselves. 

I.    Introduction

Antimicrobial products are included under the broad definition of pesticides in FIFRA and are therefore regulated by the U.S. Environmental Protection Agency (“EPA”).  Under FIFRA, pesticides, including antimicrobial products, must be registered before they are sold in the United States, and each registrant must establish that its product is sufficiently safe and conforms to its label.  Label claims of sterilizing or disinfecting properties are policed more stringently than other pesticide performance claims, because of the large and rapid consequences of disinfectant failure, particularly in health care settings.  The Centers for Disease Control and Prevention (“CDC”) estimates a 4.5% chance of health care-associated infection for each hospital admission, amounting to well over a million infections and tens of thousands of deaths annually in the United States and costing billions of dollars.[1] 

However, EPA’s program for ensuring antimicrobial pesticide efficacy has faced strong criticism for quite some time.  Much of the criticism has focused on EPA’s required test methods, which can be unreliable.  EPA’s data review process has also come under repeated investigation, including one by EPA’s OIG earlier this year.  EPA has struggled to complete regulations and guidance documents and has received lengthy critical comments on its most recent updates to the data requirements for antimicrobial pesticides.  The current political climate is likely to shift additional attention to effective agency rulemaking and enforcement as well as to improving healthcare performance. 

II.    Antimicrobial Pesticide Products: Overview

The term “pesticide” under FIFRA includes “any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest.”[2]  The term “pest,” in turn, includes microbes such as viruses and bacteria.[3]  An “antimicrobial pesticide” is defined as one that “is intended to (i) disinfect, sanitize, reduce, or mitigate growth or development of microbiological organisms; or (ii) protect inanimate objects, industrial processes or systems, surfaces, water, or other chemical substances from contamination, fouling, or deterioration caused by bacteria, viruses, fungi, protozoa, algae, or slime;” and that is not subject to a food additive regulation or a pesticide tolerance under the Federal Food, Drug, and Cosmetic Act (“FFDCA”).[4]  This definition encompasses chemical sterilants (except liquid chemical sterilants used on some medical devices, which are excluded from the definition of “pesticide”), disinfectants, industrial microbiocides, and other products, but specifically excludes agricultural fungicides, aquatic herbicides, or certain wood or paint preservatives.[5]

Some antimicrobial pesticides are public health pesticides, defined in FIFRA as those “registered for use and used predominantly in public health programs for vector control or for other recognized health protection uses, including the prevention or mitigation of viruses, bacteria, or other microorganisms (other than [those] on or in living man or other living animal) that pose a threat to public health.”[6]  There are three types of public health pesticides:

  • Sterilizers, which eliminate all microbes including spores;
  • Disinfectants, either hospital type or general use, which destroy or permanently inactivate microbes but not necessarily bacterial spores or viruses; and
  • Sanitizers, which reduce microbes to levels considered safe. 

Non-public health antimicrobials, in contrast, primarily protect inanimate objects themselves, rather than the people who come in contact with them.  They are used in controlling the growth of algae and bacteria which can cause spoilage, deterioration, and other kinds of damage in products such as paints, fuels, and textiles and in locations such as cooling towers or rinsing operations. 

III.    Registration and Regulation of Conventional and Antimicrobial Pesticide Products

          A.    Overview

FIFRA prohibits the distribution of a pesticide in the United States unless it is registered and labeled for approved uses.  Persons wishing to register a new pesticide product, new active ingredient, or new use of an existing pesticide must submit an application containing data demonstrating to EPA under FIFRA Section 3(c) that the use will not cause “unreasonable adverse effects” on health or the environment, and that “[the pesticide’s] composition is such as to warrant the proposed claims.”[7]  EPA must publish a Federal Register notice and allow 30 days for public comment after receipt of an application for a new active ingredient or use.[8]  FIFRA provides EPA broad authority to require a range of scientific data to enable it to make its determination approving or denying registration.  (For pesticides to be used on food crops, EPA must also make a residue tolerance decision under the FFDCA prior to registration.) 

Pesticide registration data requirements under FIFRA Section 3(c) were first issued in 1984 in 40 C.F.R. Part 158.  The basic requirements are set forth in tables which specify whether dozens of categories of data, sometimes with reference to test guidelines, are required, conditionally required, or generally not required for particular pesticide types and use patterns.  Registration applicants must submit data on composition and chemistry and then must consult the tables to determine their data requirements regarding acute toxicity, ecological effects, human exposure, spray drift, environmental fate, residue chemistry, metabolism, chronic toxicity, and other endpoints.  Due to the generality and flexibility of the requirements, EPA also “encourages each applicant to consult with EPA to discuss the data requirements particular to its product prior to and during the registration process.”[9]  In particular, EPA has emphasized that more or different data may be needed and the general requirements are just a starting point.[10] 

          B.    Diverging Data Requirements for Conventional and Antimicrobial Pesticides

Until recently, the Part 158 data requirements applied both to conventional (i.e., primarily agricultural) and antimicrobial pesticides, despite advancements in science and regulation and a growing recognition that data requirements needed to be tailored to the different kinds of pesticides.  This situation was supposed to change after the Food Quality Protection Act of 1996 (“FQPA”) added subsection (h) to FIFRA Section 3, which mandated reforms to the registration process specifically for antimicrobial pesticides.[11]  However, while EPA proposed registration data requirements for antimicrobial pesticides in 1999,[12] it never issued these requirements as a final rule. 

When EPA reorganized 40 C.F.R. Part 158 and revised and tailored some of the data requirements for conventional pesticides in 2007, it preserved the existing requirements in a redesignated Part 161 for continued application to antimicrobial pesticides only until a rule tailored to antimicrobial pesticides could be promulgated.[13]  Subpart W of Part 158 was reserved for antimicrobial pesticide registration rules. 

Subpart W rules specific to antimicrobial pesticides were finally proposed several months ago, and have received extensive comments.[14]  The proposal would encompass not only antimicrobials under FIFRA but also pesticides for antimicrobial uses in or on food or feed, antifoulant paints and coatings, and wood preservatives, and would also cover experimental use permitting and tolerances.  EPA proposed a dozen antimicrobial pesticide use patterns and specific, sometimes tiered, data requirements for each (including nine new tests), indicated by data tables.  EPA also proposed to define a number of terms, including “disinfectant,” “sanitizer,” and “public health claim.”[15] 

          C.    Efficacy Data Requirements for Antimicrobial Pesticides

FIFRA specifically provides that “[i]n considering an application for the registration of a pesticide, the Administrator may waive data requirements pertaining to efficacy . . . .”[16]   EPA has waived the submission of efficacy data for many conventional pesticides, although it requires each applicant to generate the data and have them available if EPA asks to review them: 

The Agency has waived all requirements to submit efficacy data unless the pesticide product bears a claim to control pest microorganisms that pose a threat to human health and whose presence cannot readily be observed by the user . . . . However, each registrant must ensure through testing that his products are efficacious when used in accordance with label directions and commonly accepted pest control practices.  The Agency reserves the right to require, on a case-by-case basis, submission of efficacy data for any pesticide product registered or proposed for registration.[17] 

In other words, efficacy data must be generated, but need not be submitted to or reviewed by EPA at the time of registration application. 

In contrast, “[b]ecause users cannot see whether disinfectants kill bacteria, fungi, and viruses, the use of ineffective disinfectants poses a threat to public health . . . .”[18]  Therefore, registrants of end-use product public health antibacterial pesticides must submit efficacy data substantiating each claim and use.  The product performance data table in the current Part 161 requires submission of data for products used on surfaces, textiles, and water systems, as well as other products.  In the newly proposed Part 158 Subpart W, the requirements are “nearly identical” and “[t]he table is transferred essentially unchanged.”[19]  The efficacy tests are to be conducted by the registrant and reviewed by the Office of Pesticide Programs – Antimicrobials Division (“AD”). 

In addition to these pre-registration tests, the AD’s microbiology laboratory, in conjunction with several state laboratories, has conducted its own efficacy testing on many registered antimicrobial pesticides through its Antimicrobial Testing Program.[20]  The Antimicrobial Testing Program was initiated in 1991 in response to a 1990 General Accounting Office (“GAO,” now the Government Accountability Office) report,[21] and was supposed to be completed by the turn of the millennium.[22]  However, the program is still ongoing, though EPA anticipates completing testing of registered disinfectants this calendar year.[23]  Products that fail EPA’s testing can be subject to mandatory label revisions or reformulations, negative press releases by EPA, stop sale orders, and other enforcement actions. 

IV.    Issues in Efficacy Testing of Antimicrobial Pesticides

          A.    Test Procedures

There has been ongoing and intense scientific debate regarding how to effectively and fairly test product performance.  In particular, the AOAC Use-Dilution Test Methods, recommended and accepted by EPA for registration applications for disinfectants and fungicides and also used by EPA in its own Antimicrobial Testing Program, have been criticized for decades, with unfortunate consequences for the credibility of the disinfectant program.[24]  The test is notoriously variable and difficult to replicate, and is often considered to be too far removed from real-life conditions.  At least one industry group, the Efficacy Working Group, has challenged the AOAC Use-Dilution Test methods for the bacterium Pseudomonas aeruginosa under the Information Quality Act, arguing that it fell short of the “basic standard of quality” required.[25] 

However, efforts to replace the test protocol have as yet been unsuccessful.  EPA intends to hold a workshop in 2009 “to investigate procedural enhancements to the AOAC Use-Dilution Method.”[26] 

          B.    Test Failures: EPA Inspector General Investigations

The high stakes and low reliability of antimicrobial pesticide efficacy testing have contributed to a number of complaints over the years, leading the AD to be a target of several EPA OIG and GAO investigations.  In 1990, the GAO issued a lengthy report entitled Disinfectants: EPA Lacks Assurance That They Work, in which it found that “EPA does not know whether disinfectants kill the germs claimed on product labels for four reasons”:

First, although the validity of methods and performance standards used to assess the efficacy of disinfectants has been the source of scientific controversy for over a decade, EPA . . . lacks criteria to assess the validity of registrant-proposed test methods and modifications.  Second, EPA has made little progress in resolving these controversies because of budget constraints and inadequate research management.  Third, EPA lacks sufficient internal controls to ensure the quality and integrity of the data that registrants submit on disinfectant efficacy.  Fourth, EPA lacks an enforcement strategy to ensure that, once registered, disinfectants sold and distributed in the marketplace work as claimed. [27]

In a 2006 update to the GAO, EPA stated that it was investigating new and existing efficacy test methods and had developed guidance documents.  Moreover, it stated that following post-registration testing under the Antimicrobial Testing Program it had brought enforcement actions or encouraged voluntary action to remove a third of tuberculocides and hospital sterilants from the marketplace after failures.[28]  Enforcement actions have included the citation of the largest U.S. manufacturer of hospital-use disinfectants for allegedly making false claims,[29] as well as a number of other actions.[30]  EPA’s microbiology laboratories, in association with outside laboratories, continue to test hundreds of antimicrobial pesticides.[31]

However, in 2007, in response to a 2004 hotline complaint, the OIG reported that the post-registration test results available to it still showed a 40% test failure rate for tuberculocidal sterilants and a 30% failure rate for hospital-use disinfectants, and that EPA lacked a mechanism to track and analyze such failures.  It recommended that AD “[p]erform a detailed root cause analysis of antimicrobial pesticides . . . and identify appropriate actions to minimize the registration of failing products.”[32] 

More recently, OIG undertook another probe in January 2009 based on a pesticide hotline tip, investigating AD for allegedly withholding information on high failure rates among tuberculocides and hospital disinfectants.  OIG found that the allegations against AD were “unsubstantiated,” but observed that AD could improve its antimicrobial testing program by implementing and making public its planned efficacy tracking database and by increasing program capacity.[33]

AD recently stated that “Results of the testing program currently show that approximately two-thirds of the hospital disinfectants and half of the tuberculocides are fully efficacious when challenged at the highest bacterial challenge level. Those that have not met this high standard are brought into compliance through regulatory or enforcement measures, or a combination of both. The registrant may be required to reformulate, reduce the product claims, change the use directions or even cancel the product.”[34] 

          C.    Controversies Regarding the Proposed Part 158 Subpart W Efficacy Data Requirements

The proposed Part 158, Subpart W data requirements for antimicrobial pesticides received many comments, many of them critical.  Industry commenters generally found that the proposal failed to sufficiently clarify the data requirements and also imposed too many data requirements without recognizing the uniqueness of antimicrobial pesticides.  Some comments submitted to the docket for the proposed Subpart W rule objected to EPA’s proposed definitions of public health claims, disinfectants, and sanitizers, arguing that they effected an inappropriate and burdensome policy change. 

A number of comments also objected to the fact that the proposal (like the current rules in Part 161) refers to product performance data guidelines that are unavailable.  In particular, the rules list product performance guidelines from the 91 series, which have never been published and which EPA is replacing with new (but also unavailable) draft Series 810 guidelines for antibacterial pesticides.  EPA has stated that it will publish some of the Series 810 guidelines (for sterilant, disinfectant, and sanitizer products) for public comment in fiscal year 2009.[35]  EPA also stated that while the guidelines referenced are recommended, registration applicants “[are] not required to use these Guidelines, but may instead seek to fulfill the data requirement by other appropriate means.”[36]

V.    Conclusion and Projections

Several trends and developments are likely to shape the future of EPA’s antimicrobial pesticide efficacy program.  The Obama Administration has a large environmental agenda; while it is mainly focused on climate change, policymakers may also feel pressure (or freedom) to visibly increase the stringency of regulations and enforcement actions over the prior administration in other areas as well.  Public policy debates regarding health care reform, medical effectiveness, and cost control are likely to lend yet more urgency to long-standing calls for increased verification of product performance and reductions in hospital infections.  Increasing public and policymaker attention to the rise in antibiotic-resistant bacterial strains appears likely to increase attention to antimicrobial pesticide efficacy further still. 

At the EPA institutional level, the Use-Dilution Method workshop, Series 810 guidelines release, and final Part 158, Subpart W registration rules are all expected to occur this year.  These developments should be followed closely by interested parties as they will have a large impact on the registration and continued marketing of antimicrobial pesticides.  In addition, the proposed federal budget for fiscal year 2010 has allocated substantially increased funding to EPA, including for its regulation, research, and enforcement programs. 

Clarified guidance and a boost in research to improve on the AOAC Use-Dilution Method would be welcome.  However, in the absence of an improved efficacy testing program, increased post-registration testing of antimicrobial products could cause some genuinely effective antimicrobial pesticides to be pulled from the market due to problems with the testing program, rather than with the product. 

For more information, please contact Mark Duvall at mduvall@bdlaw.com.  This alert was prepared with the assistance of Alexandra M. Wyatt.

For a printable PDF of this article, please click here.


[1] R. Douglas Scott II, CDC National Center for Preparedness, Detection, and Control of Infectious Diseases, The Direct Medical Costs of Healthcare-Associated Infections in U.S. Hospitals and the Benefits of Prevention (Mar. 2009), available at http://www.cdc.gov/
ncidod/dhqp/pdf/Scott_CostPaper.pdf
.

[2] FIFRA § 2(u), 7 U.S.C. § 136(u). 

[3] FIFRA § 2(t), 7 U.S.C. § 136(t).

[4] FIFRA §2(mm)(1), 7 U.S.C. § 136(mm)(1) (citing 21 U.S.C. §§ 346a, 348).

[5] FIFRA §2(mm)(2)-(3), 7 U.S.C. § 136(mm)(2)-(3).

[6] FIFRA § 2(nn), 7 U.S.C. § 136(nn). 

[7] FIFRA § 3(c), 7 U.S.C. § 136a(c). 

[8] FIFRA § 3(c)(4), 7 U.S.C. § 136a(c)(4). 

[9] 40 C.F.R. § 158.30; see also 40 C.F.R. §§ 161.35(a), 161.40 (prior wording of same recommendation). 

[10] 40 C.F.R. § 158.30. 

[11] Pub. L. No. 104-170, 110 Stat. 1489 (1996).  The FQPA also removed EPA authority under FIFRA for liquid chemical sterilants, which are now regulated by the Food and Drug Administration (“FDA”). 

[12] 64 Fed. Reg. 50,672 (Sept. 17, 1999).

[13] 72 Fed. Reg. 60,251 (Oct. 24, 2007); 74 Fed. Reg. 29,957 (June 24, 2009) (technical amendment retitling Part 161). 

[14] 73 Fed. Reg. 59,382 (Oct. 8, 2008). 

[15] See Beveridge & Diamond, P.C. Client Alert, “EPA Proposes New Data Requirements for Antimicrobial Pesticide Products” (Nov. 10, 2008), http://www.bdlaw.com/news-409.html

[16] FIFRA § 3(c)(5), 7 U.S.C. § 136a(c)(5). 

[17] 40 C.F.R. §§ 161.640(b)(1), 158.400(e)(1).  (Registrants of conventional pesticides are required to submit reports on performance failure under certain circumstances.  See 40 C.F.R. § 159.188.)

[18] General Accounting Office, GAO/RCED-90-139, Disinfectants: EPA Lacks Assurance That They Work 2 (1990), available at http://archive.gao.gov/d23t8/142343.pdf (hereinafter “GAO”).

[19] 73 Fed. Reg. at 59,391. 

[20] EPA, Antimicrobial Testing Program (2009), http://www.epa.gov/
oppad001/antimicrobial-testing-program.html
.

[21] GAO, supra note 18.

[22] Lawrence E. Cullen, EPA’s Ongoing Antimicrobial Efficacy Testing Program, 5 ABA Pesticides, Chem. Reg., and Right-to-Know Comm. Newsletter 9 (Oct. 2003), available at http://www.abanet.org/environ/
committees/pesticides/newsletter/oct03/pdf/pesticides1003.pdf
.

[23] See EPA Antimicrobials Division, Work Plan for Fiscal Year 2009, at 14 (Feb. 17, 2009), available at http://www.epa.gov/oppad001/
pdf_files/adworkplan2009.pdf
; EPA OIG, Results of Hotline Complaint Review of EPA’s Antimicrobial Testing Program, Hotline Report No. 09-P-0152, at 4 (May 17, 2009), available at http://www.epa.gov/oig/
reports/2009/20090527-09-P-0152.pdf
.

[24] See GAO, supra note 18.

[25] Letter from Seth Goldberg, Efficacy Working Group, to EPA Information Quality Guidelines Staff, re: Information Quality Act Request for Correction, July 6, 2007, available at http://www.epa.gov/quality1/ informationguidelines/documents/07002.pdf; Letter from James Gulliford, EPA Assistant Administrator for the Office of Prevention, Pesticides, and Toxic Substances, to Seth Goldberg, Efficacy Working Group, re: RFC #07002, Oct. 5, 2007, available at http://www.epa.gov/QUALITY/
informationguidelines/ documents/07002-response.pdf
(deferring consideration of request).

[26] EPA AD, Work Plan for Fiscal Year 2009, supra note 23, at 10.

[27] GAO, supra note 18, at 2-3.

[28]  Memorandum from Michele Wingfield, OPP-AD, to Tapati Bhattacharyya, Office of Congressional and Public Liaison, re: GAO Report Recommendations 22-26 (July 7, 2006), available at http://www.epa.gov/
oig/reports/2007/20070329-2007-P-00018.pdf
.  The Antimicrobial Testing Program also tested liquid chemical sterilants prior to the FQPA’s enaction in 1996; “more than half” of liquid chemical sterilants were removed from the marketplace during that time. 

[29] 2008 Region 2 Compliance and Enforcement Annual Results, http://www.epa.gov/Region2/capp/08results.htm#case1.

[30] See, e.g., Press release, EPA orders Stop Sale Of Germ Pro Products, Inc. Product with MRSA Claims , May 6, 2009, available at  http://yosemite.epa.gov/
OPA/ADMPRESS.NSF/d0cf6618525a9efb85257359003fb69d/
abfdbfaf4857b24f852575ae006b654e!OpenDocument
; Press release, U.S. EPA settles for $20,800 with Petaluma company for pesticide violations, Apr. 6, 2007, available at http://yosemite.epa.gov/opa/admpress.nsf/0/ 86A61F05913303B9852572B50077800B; Press release, So. Calif. chemical company will pay $42K for pesticide violations, May 31, 2006, available at http://yosemite.epa.gov/opa/admpress.nsf/ a8f952395381d3968525701c005e65b5/eacb88e02c7bff2c
8525717f006dba8e!OpenDocument
.  

[31] EPA, Microbiology Laboratory (2007), http://www.epa.gov/
oppbead1/labs/microbiology_lab.htm
.

[32] EPA OIG, EPA Did Not Properly Process a Hospital Disinfectant and Sanitizer Registration, Public Liaison Report No. 2007-P-00018, at 12, (Mar. 29, 2007), available at http://www.epa.gov/oig/reports/2007/20070329-2007-P-00018.pdf.

[33] EPA OIG,  supra note 23.

[34] EPA, AD, Antimicrobial Testing Program (current as of June 12, 2009), available at http://www.epa.gov/oppad001/antimicrobial-testing-program.html.

[35] EPA AD, Work Plan for Fiscal Year 2009, supra note 23, at 10-11. 

[36] 73 Fed. Reg. 59,382, 59,387 (Oct. 8, 2008).

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