### 1 

## DRAFT GUIDANCE TO REGISTRANTS : PROCESS FOR MAKING CLAIMS AGAINST EMERGING VIRAL PATHOGENS NOT ON EPA

- REGISTERED DISINFECTANT LABELS

March 2 9 , 201 6

In this document :

I. Background and Purpose II. Viral Subgroup Classification III. Product Eligibility Criteria IV. Instruction s for Using the Process V

. Outbreak Criteria Associated with Emerging Pathogens Process V I References Attachment 1

- Additional Terms of Registration Attachment 2

- Process Example



### I. Background and Purpose Emerging pathogens are an increasing public health concern in the United States as well as globally

. M any of the emerging pathogens of greatest concern are pathogenic viruses
, and t he ability of some of these viruses to persist on environmental surfaces can play a role in human disease transmission

. Because the occurrence of emerging viral pathogens is less common and predictable than established pathogens, few if any EPA

- registered disinfectant product labels specify use against th is category of infectious agent. Also, the pathogens are often unavailable commercially, and standard methods for laboratory testing may not have been developed . Thus
, it can be difficult to assess the efficacy of EPA

- registered disinfectant s against such pathogens in a timely manner and to add these viruses to existing product regi stration s , which requires the submission of efficacy data for Agency review

. As a result, the Agency is provid ing a voluntary , two

- stage process to enable use of certain EPA

- registered disinfectant products against emerging viral pathogens not identified on the product label.
1) In the first stage
, which may be performed prior to any outbreak, registrant s with an eligible disinfectant product may submit a request via label amendment to add a designated statement (see Attachment 1) to the master label and additional terms to the product registration. If the product meets the eligibility criteria suggested in this Guidance
, the Agency generally will approve the amendment

. Approval of the amendment would include additional t erms and conditions of r egistration regarding how the designated statement may be published and communicated

. 2) The second stage of this process occurs during a human or animal disease outbreak caused by an emerging virus

. In this stage
, registrants of products with the previously mentioned label amendment and terms of registration would be allowed to use the designated statement in off

- label communications intended to inform the user community/public that the disinfectant product (s) may be used again st the specific emerging viral pathogen

. These off

- label statements can inform the public about the utility of these products against the emerging pathogen in the most expeditious manner and can be more easily removed once the outbreak has ended than statements on a label

.

### 2 Note that t his document provides general guidance to EPA, pesticide registrants, applicants for pesticide registrations, and the public. This guidance is not binding o n EPA or any outside parties, and EPA may depart from the guidance where circumstances warrant and without prior notice.



### II . Viral Subgroup Classification

EPA and C enters for Disease Control and Prevention (C DC ) recognize that certain microorganisms can be ranked with respect to their tolerance to chemical disinfect ants. The Spaulding Classification model, used by CDC, tiers microorganisms in accorda nce with the level of resistance to being killed (inactivation) by typical disinfectant products. 1 With this approach viruses are divided into three viral sub groups ( small non

- e nveloped, large non

enveloped, and e nveloped) based on their relative resistance to inactivation (see below)

. According to this hierarchy, if an antimicrobial product can kill a small, non

- enveloped virus it should be able to kill a ny large, non

- enveloped virus or any enveloped virus. Similarly, a product that can kill a large, non

- enveloped virus should be able to kill an y enveloped virus.

Small, Non

- Enveloped Viruses (<50 nm) : The se small, non

- enveloped viruses can be highly resistant to inactivation by disinfect ion . Despite the lack of a lipid envelope, these organ isms have a very resistant protein capsid

. The following are
v iral families in the small non

- enveloped subgroup : (1) Picornavi ri d a e , (2) Parvoviridae
, (3) Caliciviridae , (4 ) Astroviridae , and (5) Polyomaviridae

. Large, Non

- Enveloped Viruses : Compared to small, non

- enveloped viruses, these viruses are less resistant to inactivation by disinfection. Although they have a resistant protein capsid, their larger size (50

- 100nm) makes them more vulnerable than their smaller viral counterparts. The following are v iral families in the large
non

- enveloped subgroup : (1) Adenoviridae
, (2) Reoviridae , and (3) Papillomaviridae

.
Enveloped Viruses : E nveloped viruses are the least resistant to inactivation by disinfect ion . The structure of these viruses includes a lipid envelope, which is easily compromised by most disinfectants. Once the lipid envelope is damaged
, the integrity of the virus is compromised, thereby neutralizing its infectivity

. The following are viral families in the enveloped subgroup : (1) Arenaviridae
, (2) Bornaviridae
, (3) Bunyaviridae
, (4) Coronaviridae
, (5) Filoviridae , (6) Flaviviridae, (7) Hepadnaviridae, (8) Herpesviridae, (9) Orthomyxoviridae, (10) Paramyxoviridae, (11) Poxviridae, (12) Retroviridae, (13) Rhabdoviridae, and (14) Togaviriedae

.

Under the criteria outlined in Section III of this Guidance , this hierarchy is used to determine a product’s anticipated efficacy against an emerging viral pathogen.



## _____________________________________________

### 3 III . Product Eligibility Criteria

R egistrants s hould use the following criteria to determine if a n EPA

- reg istered disinfectant product is eligible to use the p rocess described in this Guidance

. An e ligible product should meet both of the following criteria :

1. The product is an EPA

- registered
, hospital/healthcare or broad

- spectrum disinfectant with directions for use on hard, porous or non

- porous surfaces 2

.
2. The currently accepted product label (from a n EPA registered product as described above in III.1) should have disinfectant efficacy claims against a t least one of the following viral pathogen groupings :
a) A product should be approved by EPA to inactivate at least one large or one small
non

- enveloped virus to be eligible for use against an enveloped emerging vi ral pathogen. b) A product should be approved by EPA to inactivate at least one small, non

enveloped virus to be eligible f or use against a large, non

- enveloped emerging viral pathogen

. c) A p roduct should be approved by EPA to inactivate at least two small, non

enveloped viruses to be eligible for use against a small, non

- enveloped emerging viral pathogen

. This approach, where disinfectant products registered for use against viral pathogens in one category of the Spaulding Classification model can be presumed effective against viral pathogens in less

- resistant categories
, is intended to serve as a conservative approach to identifying disinfectant products likely to be effective against emerging pathogens. However,
s ince there is no viral subgroup known to be more resistant than small, non

- enveloped viral pathogen , a disinfectant product must be proven to be efficacious against at least two different small, non

- enveloped viral pathogen s in order to be eligible for emerging pathogen cl aims pursuant to this guidance in regard to an outbreak of an emerging smal l, non

enveloped viral pathogen.



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I V

. Instructions for Using the Process

The following are instructions for r egistrants (with a product eligible under Section III above) who wish to use the process in this document for making claims against emerging viral pathogens

. Registrants are encouraged to s ubmit a n FQPA (fast

- track, non

- PRIA ) label amendment request (may also be submitted as part of a PRIA action) explaining why the product meets the criteria for use against one or more categories of emerging [ enveloped / large non

- enveloped / small non

- enveloped ] viral pathogens as suggested in this guidance

.

Th is la bel amendment request should include a request to amend the existing T erms of R egistration for the product to add a product

- specific version of the language in Attachment 1 , and include each of the conditions governing the use of such statements that appear in Attachment 1

. If the registration amendment is approved, the registrant will be authorized to make the product

- specific version of the statement(s) described in Attachment 1 in the

### 4 event of an applicable disease outbreak

. The conditions stated in Attachment 1 , which would be incorporated into the terms of registration
, identify the allowable statements, the outlets through which the use statements may be communicated
, and the time periods during which the use statements may be made. Use of the de signated statement s in circumstances other than those specified in the terms of registration would be a violation of FIFRA section 12(a)(1)(B)

, unless otherwise authorized by EPA.



## _ ____________________________ _________________
V

. Outbreak Criteria Associated with Emerging Pathogens Process

As stated above, the p rocess described in this Guidance is for use with emerging pathogens associated with certain human or animal disease outbreaks. Thus, registrants whose registrations have been amended as d escrib ed in Section IV above may publish the approved statements only upon a disease outbreak that meet s all the following criteria:

1. The causative organism should be a virus that causes an infectious disease that has appeared in a human or animal population for the first time, or that may have existed previously but is rapidly increasing in incidence or geographic range ("emerging viral pathogen")

. 3 It includes both new and re

- emerging viral pathogens listed by either the Centers for Disease Contro l and Prevention (CDC) or the World Organization for Animal Health (OIE) in one of the publications below

.

a. For human disease, the outbreak is listed in one of the following CDC publications: i. CDC Current Outbreak List for “U

. S

. Based Outbreaks” ( www.cdc.gov/outbreaks ), ii. CDC Current Outbreak List for “Outbreaks Affecting International Travelers” with an “Alert” or “Advisory” classification ( www.cdc.gov/outbreaks ) ( also released through the CDC’s Health Alert Network (HAN) notification process ) iii. Healthcare

- Associated Infections (HAIs) Outbreaks and Patient Notifications page ( www.cdc.gov/hai/outbreaks )

b. For ani mal disease, the outbreak is identified as an infectious disease outbreak in animals within the United States of America on the OIE Weekly Disease Information page (www.oie.int/wahis_2/public/wahid.php/Diseaseinformation/WI).

2. The CDC or OIE has identified the taxonomy , including the viral family and/or species, of the pathogen and provides notice to the public of the identity of the emerging virus that is responsible for an infectious disease outbreak. Based on the taxonomy of the outbreak pathogen identified by CDC or OEI
, the pathogen's viral subgroup (small non

- enveloped
, large non

- enveloped
, enveloped) should be determined

. See OIE technical disease cards ( www.oie.int/animal

- health

- in

- the

world/technical

- disease

- cards/ ).

3. The virus can be transmitted via environmental surfaces (non

- vector transmission)

, and environmental surface disinfection has been recommended by the CDC or OIE to control the spread of the pathogen.

### 5 An example of how both the application and outbreak process might work is presented in Attachment 2.



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VI . References

1 Spaulding E.H. 1968. Chemical disinfection of medical and surgical materials. Disinfection, Sterilization, & Preservation, 3rd Edition, Block S (Ed), ( Lea & Febiger, Philadelphia, PA).

2 Product Performance Test Guidelines: OCSPP 810.2200 Disinfectants for Use on Hard Surfaces

– Efficacy Data Recommendations [EPA 712

- C

- 07

- 074]

3 World Health Organization (WHO). 2015. Emerging Diseases. Available from: http://www. who.int/topics/emerging_diseases/en/



## ___________________________________________

### 6 Attachment 1
Example Terms of Registration Associated with th e Guidance for

Making Claims ag ainst Emerging Viral Pathogens N ot on EPA

Registered Disinfectant Labels

The following are examples of additional Terms of Registration that EPA anticipates resulting from a request to amend a registration for the reasons addressed in EPA 's 2016 Guidance to Registrants: Process for Making Claims against Emerging Viral Pathogen s N ot on EPA

Registered Disinfectant Labels :

1. The statements shall be made only through the following communications outlets: technical literature, "1

- 800" consumer information services, social media sites and company websites (non

- label related) . These statements shall not appear on marketed (final print) product labels.

2

. Statements shall adhere to one or both of the following formats:
[P roduct n ame] has demonstrated effectiveness against viruses similar to [n ame of emerging virus , which must be a small non

- enveloped, large non

enveloped, or enveloped virus ] on [eligible surface type(s)] . Therefore, [product name] can be used against [name of emerging virus , which must be a small non

- enveloped, large non

- enveloped, and/or enveloped virus] w hen used in accordance with the directions for use against [ name of supporting virus(es)] on [hard, porous/non

- porous surfaces ]

. Refer to the [CDC or OIE] website at [ pathogen

- specific website address] for additional information.
[Name of illness/outbreak] is caused by [name of emerging virus , which must be a small non

- enveloped, large non

- enveloped, and/or enveloped virus ]. [Product name] kills similar viruses and therefore can be used against [name of emerging virus , which must be a small non

- enveloped, large non

enveloped, and/or enveloped virus] when used in accordance with the directions for use against [ name of supporting virus(es)] on [hard, porous/non

- porous surfaces]

. Refer to the [CDC or OIE] website at [website address] for additional information.

3. The registrant may begin communications of the se statement(s)

, upon notification on the CDC or OIE website identified under Section V of the Guidance of a n outbreak of an emerging [small non

- enveloped, large non

- enveloped, and/or enveloped] viral pathogen

. The registrant shall cease and remove all such communi cations no later than 24 months after th e original notification of the outbreak o n the CDC or OIE website unless the Agency provides guidance to t he contrary due to continued public health concerns.

4. The registrant agrees that paragraphs 1 through 3 above shall become immediately void and ineffective if registration for use against [name of supporting virus(es)] is suspended or cancelled or no longer meets the criteria for a disinfectant claim (see EPA Product Performance Test Guideline 810.2200)

. In addition, evidence of ineffectiveness against any pathogen in a less

- resistant Spaulding category would also be grounds for voiding paragrap hs 1 through 3.

### 7 Attachment 2

Example of the Process

The following is a hypothetical scenario for how registrants and EPA could use the process identified in this Guidance
, u sing an Enterovirus D68 outbreak as an example

.
Before an outbreak occurs :

- P rior to the occurrence of an outbreak
, registrants interested in using this process apply for registration amendments as suggested in this Guidance to allow claims of anticipated efficacy against small non

- enveloped viruses

. Once EPA has approved the amendments , t he subject products ’ registrations will indicate that certain claims specified in the registration may be made regarding use against emerging small non

- enveloped viral pathogens , subject to the products’ Terms of Registra tion as described in Attachment 1

. For example, a registrant whose product is registered for use against two small non

- enveloped viral pathogens might request the following product

- specific statement : 

### Product Z has demonstrated effectiveness against viru ses similar to **[name of emerging virus, which must be either a small non** 

**- enveloped, large non** 

**- enveloped, or**  **enveloped virus]** on hard non

- porous surfaces. Therefore this product can be used against **[name of emerging virus, which must be either a small non**  **- enveloped, large non** 

**** **enveloped, or enveloped virus]** when used in accordance with the directions for use against Virus X and Virus Y on hard, non

- porous surfaces. Refer to the **[ CDC**  **or OEI]** website at **[website address]** for additional information.

- EPA would review the claims and
, if approved, add this statement to the product’s master label as a non

- label claim permitted only when certain emerging viral pathogen conditions are met.

After an outbreak occurs :

- In the event of an Enterovirus D68 publi c health outbreak, the Centers for Disease Control and Prevention would communicate the outbreak threat via its website ( www.cdc.gov/outbreaks ) , identif y the viral pathogen taxonomy
, and indicate that surface disinfection is recommended.

1. With the viral pathogen information provided by CDC, registrants would determine tha t the pathogen, Enterovirus D68 (a member of the Picornaviridae family)

, is a small non

enveloped virus.

2. At this point
, registrants with products whose registrations have been amended to allow certain claims of anticipated efficacy against two or more small non

- enveloped viral pathogen s would be allowed to make those claims specified in the terms of registration as illustrated in Attachment 1 regarding use of the products against Enterovirus D68 without further submissions to, or review by, EPA . For example, a registrant whose registratio n was previously amended to include the product

- specific language in the example above w ould
now be allowed to include the following statement in its technical literature
, non

- label related websites, consumer information services, and social media sites :

### 8 Product Z has demonstrated effectiveness against viruses similar to Enterovirus D68 on hard non

- porous surfaces . Therefore
, this product can be used against Enterovirus D68 when used in accordance with the directions for use against Virus X and Virus Y on hard,

non - porous surfaces. Refer to the CDC website at www.cdc.gov/... for additional information.