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EPA Response to Written Comments Received from HHS 

On the Proposed Rule: Declaration of Prion as a Pest under FIFRA and 

Amendment of EPA’s Regulatory Definition of Pests to Include Prion 

RIN 2070-AJ26; Docket ID No. EPA–HQ–OPP–2010–0427 

Prions_NPRM_HHS-FDAcomments_EPAresponses_2010-10-18.docx 

In accordance with section 21(a) of the Federal Insecticide, Fungicide, and Rodenticide 

Act (FIFRA), EPA submitted a draft of the proposed rule to the Secretary of Health and Human 

Services (HHS). Written comments received from HHS/Food and Drug Administration (FDA) 

on August 12, 2010, and EPA responses to those comments provided on August 30, 2010, are 

presented in this document. HHS participated in the interagency review process under Executive 

Order 12866, and changes made to the proposed rule in response to all comments received 

during that interagency review are documented in the docket as required by Executive Order 

12866. 

1. FDA Comment: Pages 1, 4, 5, etc.: Scope of Prions to Be Defined as Pests: The proposed 

rule would add “prion” to the list of things that are defined as pests under 40 CFR 152.5(d). The 

draft proposed rule states that this change would mean that “a product intended to reduce the 

infectivity of any prion on inanimate surfaces” would be considered a pesticide regulated under 

the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The EPA states that this 

change would codify the agency’s current policy regarding prions and products intended to 

inactivate prions. 

 Because the draft proposed rule describes prion-inactivating pesticides as products intended to 

reduce the infectivity of prions on inanimate surfaces, the degree to which FDA-regulated 

products might be affected by the proposal is unclear. Our understanding is that the EPA’s 

reference to prions on “inanimate surfaces” is simply a shorthand way of referring to those 

prions that are not found “on or in living man or other living animals and those on or in 

processed food or processed animal feed, beverages, drugs (as defined in FFDCA sec. 201(g)(1)) 

and cosmetics (as defined in FFDCA sec. 201(i)),” consistent with 40 CFR 152.5(d). To 

eliminate any potential confusion concerning prions that would be regarded as pests under 

FIFRA and prions that would be subject to FDA regulation, the proposed rule should make clear 

that prions that meet the definition of pest under § 152.5(d) would not include prions on or in 

living man or other living animals and prions on or in processed food or processed animal feed, 

beverages, drugs, and cosmetics. The proposed rule also should make clear that, even if a 

product may be considered a “pesticide” if it is “intended to reduce the infectivity of any prion 

on inanimate surfaces,” the product may not necessarily be considered a “pesticide chemical” or 

“pesticide chemical residue” for purposes of sections 201(q) and 408 of the FFDCA (see the 

statutory exclusions to “pesticide chemical” and “pesticide chemical residue” in section 201(q) 

of the FFDCA). 

We also recommend that the proposed rule identify the exception, in the definition of “pesticide” 

in 7 U.S.C. 136(u), for liquid chemical sterilant products for use on a critical or semi-critical 

medical device as defined in 21 CFR 321. Correspondingly, we recommend inclusion of a 

statement that the rule would not change the 1994 memorandum of understanding (MOU) 

between the EPA and FDA concerning regulatory oversight of liquid chemical sterilants 

and general purpose germicides, along with a statement that germicides used to reduce prion 

infectivity are outside the scope of that MOU. We further recommend that the proposed rule 

state that the EPA is not exercising primary regulatory authority over germicide products (that 
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might also be considered by the EPA to be pesticides) that are used to reduce prion infectivity on 

medical devices. 

EPA Response: EPA generally agrees and will add the following paragraph to the preamble of 

the proposed rule to make clear the limits of EPA’s regulatory authority over products intended 

to reduce the infectivity of prions on inanimate surfaces: 

“EPA would like to make clear that not all prions and prion-related products are affected 

by the proposed rule. Firstly, EPA’s regulations at 40 CFR 152.5(d) exclude pests “...in 

or on living man or other living animals and those on or in processed food or processed 

animal feed, beverages, drugs...and cosmetics.” Therefore, the proposed rule would not 

apply to those uses of prion-related products. Secondly, the definition of “pesticide” in 

FIFRA Section 2(u) excludes new animal drugs and liquid chemical sterilants intended 

for use on a critical or semi-critical device. Accordingly, products which fall into the 

latter categories would not be covered by the proposed rule.” 

2. FDA Comment: Pages 1, 4, etc.: “Prion Product”: The draft proposed rule would designate 

a product that is intended to reduce the infectivity of any prion on inanimate surfaces as a “prion 

product.” We recommend that such a product be called a “prion-inactivating product” or an 

“anti-prion product.” 

EPA Response: The term “prion product” has been created for convenience and has no legal 

significance since it is not used in the regulation itself. FDA’s recommendation for “prioninactivating product” conflicts with the FDA’s and EPA’s current position that “inactivation” of 

prions (i.e., complete and irreversible destruction) has not yet been demonstrated, so that term is 

not acceptable. FDA’s recommendation of “anti-prion product” is reasonable, but EPA prefers 

the term “prion-related product” since EPA has previously used similar designations such as 

“anthrax-related products” and “mold-related products.” Accordingly, EPA will use “prionrelated product” in the Preamble to the proposed rule. 

3. FDA Comment: Page 3: Potentially Affected Entities: We recommend adding the 

following to the list of entities that might be affected by the proposed rule: morticians, 

manufacturers of medical tissue devices of human and animal origin, manufacturers of other 

human cellular and tissue products, organ procurement and transplantation programs, and blood 

and plasma establishments. 

EPA Response: Although all of these entities are currently unaffected by the proposed rule, it is 

possible that some of them could be interested in commenting on it. Therefore, EPA will add 

these entities to the list of potentially affected parties in proposed rule. 

4. FDA Comment: Pages 5 and 7: All-Protein Theory of Prions: The draft proposed rule 

appears to endorse without qualification the all-protein theory of the nature of prions, i.e., that a 

prion is composed entirely of a misfolded, host-encoded, ubiquitous protein devoid of nucleic 

acid. Page 5 of the proposal states that prions “may occur in the central nervous system tissues 

of animals as an abnormal (‘misfolded’), infectious form of prion protein.” Page 7 states: “One 

entity that shares the characteristics of pathogenicity, infectivity, transmissibility, the ability to 

increase in number and the ability to evolve (but which, like viruses, is not alive) is the prion, 

which is an infectious conformation of misfolded prion protein that causes TSE diseases in 

humans and animals.” Some scientists, including some members of the EPA’s FIFRA Scientific 

Advisory Panel, do not agree with this view of prions. In addition, the draft proposed rule 

appears to suggest that prions are found only in the central nervous system tissues, while prions 
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actually are widely distributed in tissues outside the nervous system in both humans and animals 

with TSEs. Therefore, we suggest that the draft proposed rule be revised to state: “A prion is an 

infectious agent occurring in the tissues of animals that is widely, though not universally, 

believed to be composed of an abnormal (misfolded) protein without nucleic acid.” As a 

reference for this statement, the proposed rule could cite the minutes from the March 31-April 1, 

2009, FIFRA Scientific Advisory Panel meeting (Ref. 3 in the draft proposed rule). 

EPA Response: EPA agrees that not all scientists agree with that misfolded prion proteins are 

the causative agent of TSEs. Therefore, EPA will adopt FDA’s proposed change to make that 

point clear in the preamble. 

5. FDA Comment: Page 5: Different Types of Prions: The draft proposed rule states: 

“Different types of prions are designated by the type of diseases they produce, such as PrPSc

(prions associated with scrapie) and PrPBSE (prions associated with bovine spongiform 

encephalopathy—mad cow disease).” We do not believe that this terminology is widely used in 

the TSE field. Therefore, we recommend that this sentence be deleted (along with the references 

to PrPSc in the subsequentsentence on page 5 of the draft). 

EPA Response: EPA has observed in the scientific literature concerning TSE research that the 

designations to which FDA refers are commonly used, but not by everyone in this field. In 

addition, EPA believes that these designations are useful in distinguishing the different isoforms 

of prions. Accordingly, EPA intends to revise the sentence that FDA has quoted by inserting the 

word “commonly” in front of “designated” to indicate that these designations are common but 

not necessarily used by all scientists in the TSE field. 

6. FDA Comment: Page 5: Discussion of Human and Animal TSEs: We believe that the 

discussion of animal and human TSEs is selective and somewhat incomplete. Forms of CJD 

other than cattle/beef-related vCJD, such as “sporadic CJD (sCJD),” “familial CJD (fCJD),” and 

“iatrogenic CJD (iCJD)” are not mentioned; the latter is particularly significant from an 

FDA perspective because of its association with corneal transplants and dura mater grafts, 

contaminated surgical instruments, and cadaver-pituitary sources. Additionally, other commonly 

known animal TSEs such as transmissible mink encephalopathy (TME) and feline spongiform 

encephalopathy (FSE) are not discussed; nor, other than kuru, are human TSEs such as Fatal 

(Familial) Insomnia (FFI)) and Gerstmann-Straussler Syndrome (GSS) (see J. Bjornsson, et al., 

eds., Slow Infections of the Central Nervous System: The Legacy of Dr. Bjorn Sigurdsson, 

Annals of the New York Academy of Sciences, New York, Vol. 724; C. Soto (op. cit.)). 

EPA Response: The EPA’s “white paper,” which was provided to the FIFRA Scientific 

Advisory Panel (SAP) for review in 2009, describes most of the additional types of TSEs 

mentioned here by FDA. This paper will be posted in the docket to the proposed rule and be 

available for comment. Because the purpose of the preamble to the proposed rule is to 

summarize key information which is available in detail in EPA’s support documents, EPA not 

does believe it is necessary to include all known TSEs in the Preamble. 

7. FDA Comment: Page 5: Legal/Regulatory Background: To help place the proposed rule in 

the proper context, we suggest that the proposed rule briefly mention some of the actions that 

other Federal agencies, including USDA and FDA, have taken to prevent prions from harming 

the public. These steps have been well documented in the literature, are integral parts of the 

domestic inspectional programs and import policies of both agencies, and are publicly available 

on the agencies’ Web sites. For example, FDA has issued an interim final rule (69 FR 42256, 

July 14, 2004) prohibiting the use of certain cattle materials in human food and cosmetics to 
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address the potential risk of BSE (21 CFR 189.5 and 700.27); USDA regulations concerning 

BSE include those set forth at 9 CFR 94.18 and 9 CFR 95.4. 

EPA Response: EPA agrees and will add a brief description of some of FDA’s and USDA’s 

efforts to protect the public from prions. 

8. FDA Comment: Page 6: “Reproduction” of Prions: The draft proposed rule states that 

“microbiologists do not generally classify viruses as microorganisms because they are not alive 

(i.e., they cannot reproduce, grow or perform self-maintenance). Therefore, the term ‘other 

micro-organism’ as used in FIFRA appears broad enough to include some entities that are not 

alive.” Both viruses and prions are self-replicating, and we believe that most microbiologists 

would consider self-replication of a pathogen to be reproduction. Therefore, we recommend 

deleting this paragraph. 

EPA Response: EPA disagrees that replication and reproduction are synonymous. Historically 

to biologists, “reproduction” refers to sexual or asexual reproduction, which involves the 

independent copying of genetic material in order for a living organism to produce “offspring.” 

Viruses have genetic material but are incapable of independent replication. The nature of prion 

replication is not entirely clear, but it is dependent upon a host. To make clear the historical 

meaning of “reproduce” EPA will insert the phrase “sexually or asexually” after that term in the 

preamble of the proposed rule. 

EPA’s and FDA’s differences on this issue notwithstanding, adopting FDA’s definition of 

reproduction would not change EPA’s observations on in the Preamble. There EPA states that 

microbiologists generally do not classify viruses as microorganisms because they are not alive 

(i.e., they cannot reproduce, grow or perform self-maintenance). The Preamble goes on to point 

out that the term “other micro-organism” as used in FIFRA appears broad enough to include 

some entities that are not alive. Even if one were to adopt FDA’s apparent definition of 

reproduction as including or being equivalent to replication, EPA’s statement would still stand 

based on the inability of viruses to grow or perform self-maintenance. 

9. FDA Comment: Page 7: Effect of Prions on Neuronal Cells: The draft proposed rule states: 

“These infectious particles [prions], once introduced into an animal or human, can induce 

neuronal cells to change into prions that in turn attack other neuronal cells, primarily in the 

central nervous system.” We do not believe that this description of the pathogenesis of TSEs is 

accurate. Because this sentence is not essential to the proposal, we recommend deleting it. 

EPA Response: EPA will correct the sentence to read, “These infectious particles [prions], once 

introduced into an animal or human host, can induce the formation of new prions in the animal or 

human host.” 

10. FDA Comment: P. 9: Draft Performance Test Guidelines: The draft proposed rule states 

that the EPA has developed draft guidelines for performance tests that will ensure that the EPA 

receives the data needed to make determinations on whether a prion-inactivating product meets 

the agency’s efficacy data requirements for registration. Does the EPA intend to publish notice 

of the availability of the draft guidelines concurrently with the issuance of the proposed rule? 

EPA Response: Yes, EPA intends to publish the draft guidance for public comment 

concurrently with the proposed rule. 

11. FDA Comment: Regarding defining different types of prions: More rigorous definitions of 

terms such as PrP (BSE) and PrP (Sc) should be given and used, if available. Alternative and 
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more science-based nomenclature is available in the literature. For example, a more recent 

definition for PrP (Sc) than that given in the NPR (i.e., "prions associated with scrapie", p. 5, 

paragraph 1) has been given elsewhere as: "...Disease-associated misfolded prion protein present 

in individuals affected by TSE. This form is infectious, rich in beta-sheet conformation, 

insoluble, and mostly protease-resistant..." (see "The Infectious Agent and the Prion Hypothesis" 

in C. Soto, Prions. The New Biology of Proteins, CRC Press/Taylor Francis Group-Informa, 

Boca Raton, FL (2006), Chapter 2, p.16). 

EPA Response: EPA appreciates the FDA’s suggestion that EPA adopt more scientific 

definitions of different types of prions. However, in this opening section of the preamble, EPA 

is intending to provide only a basic introduction to the general public concerning prions, prion 

proteins, types of prions, and the types of TSE diseases associated with prions. Toward that end, 

EPA has provided simplified descriptions of several key terms such as the ones mentioned by 

FDA. EPA believes that these descriptions are accurate and appropriate for the preamble, and 

that more detailed, scientific descriptions of the key terms are not needed in the preamble. The 

terminology of prions is discussed in greater detail in EPA’s scientific “white paper,” which will 

be made available in the docket for those who wish to delve further into available, relevant 

scientific information. 

Attachment: 

Incoming Written Comments from FDA, 08/12/2010 
08/12/2010 

FDA Comments on EPA’s Draft Proposed Rule to Declare Prions as Pests 

 

The Food and Drug Administration appreciates the opportunity to comment on the 

Environmental Protection Agency’s (EPA’s) draft proposed rule entitled “Declaration of Prion as 

a Pest under FIFRA and Amendment of EPA’s Regulatory Definition of Pests to Include Prion.” 

Our comments are set forth below. 

1. Pages 1, 4, 5, etc.: Scope of Prions to Be Defined as Pests 

The proposed rule would add “prion” to the list of things that are defined as pests under 40 CFR 

152.5(d). The draft proposed rule states that this change would mean that “a product intended to 

reduce the infectivity of any prion on inanimate surfaces” would be considered a pesticide 

regulated under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The EPA 

states that this change would codify the agency’s current policy regarding prions and products 

intended to inactivate prions. 

 

Because the draft proposed rule describes prion-inactivating pesticides as products intended to 

reduce the infectivity of prions on inanimate surfaces, the degree to which FDA-regulated 

products might be affected by the proposal is unclear. Our understanding is that the EPA’s 

reference to prions on “inanimate surfaces” is simply a shorthand way of referring to those 

prions that are not found “on or in living man or other living animals and those on or in 

processed food or processed animal feed, beverages, drugs (as defined in FFDCA sec. 201(g)(1)) 

and cosmetics (as defined in FFDCA sec. 201(i)),” consistent with 40 CFR 152.5(d). To 

eliminate any potential confusion concerning prions that would be regarded as pests under 

FIFRA and prions that would be subject to FDA regulation, the proposed rule should make clear 

that prions that meet the definition of pest under § 152.5(d) would not include prions on or in 

living man or other living animals and prions on or in processed food or processed animal feed, 

beverages, drugs, and cosmetics. The proposed rule also should make clear that, even if a 

product may be considered a “pesticide” if it is “intended to reduce the infectivity of any prion 

on inanimate surfaces,” the product may not necessarily be considered a “pesticide chemical” or 

“pesticide chemical residue” for purposes of sections 201(q) and 408 of the FFDCA (see the 

statutory exclusions to “pesticide chemical” and “pesticide chemical residue” in section 201(q) 

of the FFDCA). 

We also recommend that the proposed rule identify the exception, in the definition of “pesticide” 

in 7 U.S.C. 136(u), for liquid chemical sterilant products for use on a critical or semi-critical 

medical device as defined in 21 CFR 321. Correspondingly, we recommend inclusion of a 

statement that the rule would not change the 1994 memorandum of understanding (MOU) 

between the EPA and FDA concerning regulatory oversight of liquid chemical sterilants 

and general purpose germicides, along with a statement that germicides used to reduce prion 

infectivity are outside the scope of that MOU. We further recommend that the proposed rule 

state that the EPA is not exercising primary regulatory authority over germicide products (that 

might also be considered by the EPA to be pesticides) that are used to reduce prion infectivity on 

medical devices. 
2

2. Pages 1, 4, etc.: “Prion Product” 

The draft proposed rule would designate a product that is intended to reduce the infectivity of 

any prion on inanimate surfaces as a “prion product.” We recommend that such a product be 

called a “prion-inactivating product” or an “anti-prion product.” 

3. Page 3: Potentially Affected Entities 

We recommend adding the following to the list of entities that might be affected by the proposed 

rule: morticians, manufacturers of medical tissue devices of human and animal origin, 

manufacturers of other human cellular and tissue products, organ procurement and 

transplantation programs, and blood and plasma establishments. 

4. Pages 5 and 7: All-Protein Theory of Prions 

The draft proposed rule appears to endorse without qualification the all-protein theory of the 

nature of prions, i.e., that a prion is composed entirely of a misfolded, host-encoded, ubiquitous 

protein devoid of nucleic acid. Page 5 of the proposal states that prions “may occur in the central 

nervous system tissues of animals as an abnormal (‘misfolded’), infectious form of prion 

protein.” Page 7 states: “One entity that shares the characteristics of pathogenicity, infectivity, 

transmissibility, the ability to increase in number and the ability to evolve (but which, like 

viruses, is not alive) is the prion, which is an infectious conformation of misfolded prion protein 

that causes TSE diseases in humans and animals.” Some scientists, including some members of 

the EPA’s FIFRA Scientific Advisory Panel, do not agree with this view of prions. In addition, 

the draft proposed rule appears to suggest that prions are found only in the central nervous 

system tissues, while prions actually are widely distributed in tissues outside the nervous system 

in both humans and animals with TSEs. Therefore, we suggest that the draft proposed rule be 

revised to state: “A prion is an infectious agent occurring in the tissues of animals that is widely, 

though not universally, believed to be composed of an abnormal (misfolded) protein without 

nucleic acid.” As a reference for this statement, the proposed rule could cite the minutes from 

the March 31-April 1, 2009, FIFRA Scientific Advisory Panel meeting (Ref. 3 in the draft 

proposed rule). 

5. Page 5: Different Types of Prions 

The draft proposed rule states: “Different types of prions are designated by the type of diseases 

they produce, such as PrPSc (prions associated with scrapie) and PrPBSE (prions associated with 

bovine spongiform encephalopathy—mad cow disease).” We do not believe that this 

terminology is widely used in the TSE field. Therefore, we recommend that this sentence be 

deleted (along with the references to PrPSc in the subsequentsentence on page 5 of the draft). 

6. Page 5: Discussion of Human and Animal TSEs 

We believe that the discussion of animal and human TSEs is selective and somewhat incomplete. 

 Forms of CJD other than cattle/beef-related vCJD, such as “sporadic CJD (sCJD),” “familial 
3

CJD (fCJD),” and “iatrogenic CJD (iCJD)” are not mentioned; the latter is particularly 

significant from an FDA perspective because of its association with corneal transplants and dura 

mater grafts, contaminated surgical instruments, and cadaver-pituitary sources. Additionally, 

other commonly known animal TSEs such as transmissible mink encephalopathy (TME) and 

feline spongiform encephalopathy (FSE) are not discussed; nor, other than kuru, are human TSEs 

such as Fatal (Familial) Insomnia (FFI)) and Gerstmann-Straussler Syndrome (GSS) (see J. 

Bjornsson, et al., eds., Slow Infections of the Central Nervous System: The Legacy of Dr. Bjorn 

Sigurdsson, Annals of the New York Academy of Sciences, New York, Vol. 724; C. Soto (op. 

cit.)). 

7. Page 5: Legal/Regulatory Background 

To help place the proposed rule in the proper context, we suggest that the proposed rule briefly 

mention some of the actions that other Federal agencies, including USDA and FDA, have taken 

to prevent prions from harming the public. These steps have been well documented in the 

literature, are integral parts of the domestic inspectional programs and import policies of both 

agencies, and are publicly available on the agencies’ Web sites. For example, FDA has issued an 

interim final rule (69 FR 42256, July 14, 2004) prohibiting the use of certain cattle materials in 

human food and cosmetics to address the potential risk of BSE (21 CFR 189.5 and 700.27); 

USDA regulations concerning BSE include those set forth at 9 CFR 94.18 and 9 CFR 95.4. 

 

8. Page 6: “Reproduction” of Prions 

The draft proposed rule states that “microbiologists do not generally classify viruses as 

microorganisms because they are not alive (i.e., they cannot reproduce, grow or perform selfmaintenance). Therefore, the term ‘other micro-organism’ as used in FIFRA appears broad 

enough to include some entities that are not alive.” Both viruses and prions are self-replicating, 

and we believe that most microbiologists would consider self-replication of a pathogen to be 

reproduction. Therefore, we recommend deleting this paragraph. 

9. Page 7: Affect of Prions on Neuronal Cells 

 

The draft proposed rule states: “These infectious particles [prions], once introduced into an 

animal or human, can induce neuronal cells to change into prions that in turn attack other 

neuronal cells, primarily in the central nervous system.” We do not believe that this description 

of the pathogenesis of TSEs is accurate. Because this sentence is not essential to the proposal, 

we recommend deleting it. 

10. P. 9: Draft Performance Test Guidelines 

The draft proposed rule states that the EPA has developed draft guidelines for performance tests 

that will ensure that the EPA receives the data needed to make determinations on whether a 

prion-inactivating product meets the agency’s efficacy data requirements for registration. Does 

the EPA intend to publish notice of the availability of the draft guidelines concurrently with the 

issuance of the proposed rule?