
[Federal Register Volume 76, Number 56 (Wednesday, March 23, 2011)]
[Rules and Regulations]
[Pages 16285-16290]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-6792]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 172

[Docket No. FDA-2002-F-0198] (formerly Docket No. 2002F-0316)


Food Additives Permitted for Direct Addition to Food for Human 
Consumption; Bacteriophage Preparation

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule; response to objections and denial of requests for a 
hearing and stay of effective date.

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SUMMARY: The Food and Drug Administration (FDA) is responding to 
objections and is denying requests that it has received for a hearing 
on the final rule that amended the food additive regulations to provide 
for the use of a bacteriophage preparation as an antimicrobial agent 
against Listeria monocytogenes on ready-to-eat (RTE) meat and poultry 
products. After reviewing the objections to the final rule and the 
requests for a hearing, the Agency has concluded that the objections do 
not raise issues of material fact that justify a hearing or otherwise 
provide a basis for revoking the amendment to the regulation. FDA also 
is denying the request for a stay of the effective date of the final 
rule.

DATES: Effective date of the final rule published in the Federal 
Register of August 18, 2006 (71 FR 47729) confirmed: August 18, 2006.

FOR FURTHER INFORMATION CONTACT: James C. Wallwork, Center for Food 
Safety and Applied Nutrition (HFS-265), Food and Drug Administration, 
5100 Paint Branch Pkwy., College Park, MD 20740-3835, 301-436-1303.

SUPPLEMENTARY INFORMATION:

I. Introduction

    FDA published a notice in the Federal Register of July 22, 2002 (67 
FR 47823), announcing the filing of food additive petition, FAP 2A4738, 
by Intralytix Inc., to amend the food additive regulations by providing 
for the safe use of a

[[Page 16286]]

mixture of bacteriophages as an antimicrobial agent against L. 
monocytogenes on foods, including fresh meat products, fresh poultry, 
and poultry products. On December 18, 2003, the petitioner amended the 
petition to limit the petitioned use only to RTE meat and poultry 
products. In response to this petition, FDA issued a final rule in the 
Federal Register of August 18, 2006 (71 FR 47729), approving the use of 
the bacteriophage preparation on RTE meat and poultry products. This 
rule will be referred to in this document as the ``bacteriophage final 
rule.'' The preamble to the final rule advised that objections to the 
final rule and requests for a hearing were due within 30 days of the 
publication date (i.e., by September 18, 2006).

II. Objections, Requests for a Hearing, and Request for a Stay of 
Effective Date

    Section 409(f) of the Federal Food, Drug, and Cosmetic Act (the 
FD&C Act) (21 U.S.C. 348(f)) provides that, within 30 days after 
publication of an order relating to a food additive regulation, any 
person adversely affected by such order may file objections, specifying 
with particularity the provisions of the order ``* * * deemed 
objectionable, stating reasonable grounds therefor, and requesting a 
public hearing upon such objections * * *.'' FDA may deny a hearing 
request if the objections to the regulation do not raise genuine and 
substantial issues of fact that can be resolved at a hearing (Community 
Nutrition Institute v. Young, 773 F.2d 1356, 1364 (DC Cir. 1985), cert. 
denied, 475 U.S. 1123 (1986)).
    Under the food additive regulations at 21 CFR 171.110, objections 
and requests for a hearing are governed by part 12 (21 CFR part 12) of 
FDA's regulations. Under Sec.  12.22(a), each objection must meet the 
following conditions: (1) Must be submitted on or before the 30th day 
after the date of publication of the final rule; (2) must be separately 
numbered; (3) must specify with particularity the provision of the 
regulation or proposed order objected to; (4) must specifically state 
each objection on which a hearing is requested; failure to request a 
hearing on an objection constitutes a waiver of the right to a hearing 
on that objection; and (5) must include a detailed description and 
analysis of the factual information to be presented in support of the 
objection if a hearing is requested; failure to include a description 
and analysis for an objection constitutes a waiver of the right to a 
hearing on that objection.
    Following publication of the bacteriophage final rule, FDA received 
more than 70 objections within the 30-day objection period. All but one 
of these submissions expressed general opposition to the use of the 
bacteriophage preparation on RTE meat and poultry products; however, no 
evidence was submitted in support of these objections. As stated 
previously, under section 409(f)(1) of the FD&C Act, objections must 
``[specify] with particularity the provisions of the order deemed 
objectionable, stating reasonable grounds therefor * * *.'' These 
submissions did not provide reasonable grounds and identified no 
substantive issue to which the Agency can respond. Therefore, these 
submissions are denied and will not be considered further. The 
submission raising specific objections was a letter from Food & Water 
Watch (FWW) with six objections. The FWW letter sought a revocation of 
the bacteriophage final rule and requested a hearing on the issues 
raised by each objection. The letter also requested that the regulation 
be stayed pending a public hearing of the scientific issues. These 
objections are addressed in section IV of this document.

III. Standards for Granting a Hearing

    Specific criteria for deciding whether to grant or deny a request 
for a hearing are set out in Sec.  12.24(b). Under that regulation, a 
hearing will be granted if the material submitted by the requester 
shows, among other things, the following: (1) There is a genuine and 
substantial factual issue for resolution at a hearing; a hearing will 
not be granted on issues of policy or law; (2) the factual issue can be 
resolved by available and specifically identified reliable evidence; a 
hearing will not be granted on the basis of mere allegations or denials 
or general descriptions of positions and contentions; (3) the data and 
information submitted, if established at a hearing, would be adequate 
to justify resolution of the factual issue in the way sought by the 
requester; a hearing will be denied if the data and information 
submitted are insufficient to justify the factual determination urged, 
even if accurate; (4) resolution of the factual issue in the way sought 
by the person is adequate to justify the action requested; a hearing 
will not be granted on factual issues that are not determinative with 
respect to the action requested (e.g., if the action would be the same 
even if the factual issue were resolved in the way sought); (5) the 
action requested is not inconsistent with any provision in the FD&C Act 
or any FDA regulation; and (6) the requirements in other applicable 
regulations, e.g., 21 CFR 10.20 and Sec. Sec.  12.21 and 12.22, and in 
the notice issuing the final regulation or the notice of opportunity 
for hearing are met.
    A party seeking a hearing is required to meet a ``threshold burden 
of tendering evidence suggesting the need for a hearing'' (Costle v. 
Pacific Legal Foundation, 445 U.S. 198, 214-215 (1980), reh. denied, 
446 U.S. 947 (1980), citing Weinberger v. Hynson, Westcott & Dunning, 
Inc., 412 U.S. 609, 620-621 (1973)). An allegation that a hearing is 
necessary to ``sharpen the issues'' or to ``fully develop the facts'' 
does not meet this test (Georgia Pacific Corp. v. U.S. Environmental 
Protection Agency, 671 F.2d 1235, 1241 (9th Cir. 1982)). If a hearing 
request fails to identify any factual evidence that would be the 
subject of a hearing, there is no point in holding one. In judicial 
proceedings, a court is authorized to issue summary judgment without an 
evidentiary hearing whenever it finds that there are no genuine issues 
of material fact in dispute and a party is entitled to judgment as a 
matter of law. (See Rule 56, Federal Rules of Civil Procedure.) The 
same principle applies in administrative proceedings. (See Sec.  
12.28.)
    A hearing request must not only contain evidence, but that evidence 
should raise a material issue of fact concerning which a meaningful 
hearing might be held (Pineapple Growers Association v. FDA, 673 F.2d 
1083, 1085 (9th Cir. 1982)). Where the issues raised in the objection 
are, even if true, legally insufficient to alter the decision, the 
Agency need not grant a hearing (see Dyestuffs & Chemicals, Inc. v. 
Flemming, 271 F.2d 281, 286 (8th Cir. 1959), cert. denied, 362 U.S. 911 
(1960)). A hearing is justified only if the objections are made in good 
faith and if they ``draw in question in a material way the 
underpinnings of the regulation at issue'' (Pactra Industries v. 
Consumer Product Safety Commission, 555 F.2d 677, 684 (9th Cir. 1977)). 
A hearing need not be held to resolve questions of law or policy (see 
Citizens for Allegan County, Inc. v. Federal Power Commission, 414 F.2d 
1125, 1128-29 and n.5 (D.C. Cir. 1969); Sun Oil Co. v. Federal Power 
Commission, 256 F.2d 233, 240-41 (5th Cir.), cert. denied, 358 U.S. 872 
(1958)).
    Even if the objections raise material issues of fact, FDA need not 
grant a hearing if those same issues were adequately raised and 
considered in an earlier proceeding. Once an issue has been so raised 
and considered, a party cannot raise that same issue in a later 
proceeding without new evidence. The various judicial doctrines dealing 
with finality can be validly applied to the administrative process. In 
explaining

[[Page 16287]]

why these principles ``self evidently'' ought to apply to an Agency 
proceeding, the U.S. Court of Appeals for the District of Columbia 
Circuit wrote: ``The underlying concept is as simple as this: Justice 
requires that a party have a fair chance to present his position. But 
overall interests of administration do not require or generally 
contemplate that he will be given more than one fair opportunity.'' 
Retail Clerks Union, Local 1401 v. National Labor Relations Board, 463 
F.2d 316, 322 (DC Cir. 1972). (See Costle v. Pacific Legal Foundation, 
supra at 215-220. See also Pacific Seafarers, Inc. v. Pacific Far East 
Line, Inc., 404 F.2d 804 (DC Cir. 1968), cert. denied, 393 U.S. 1093 
(1969).)
    In summary, a hearing request must present sufficient credible 
evidence to raise a material issue of fact and the evidence must be 
adequate to resolve the issue as requested and to justify the action 
requested.

IV. Analysis of Objections and Response to Hearing Requests

    The FWW submission raises six objections based on issues that they 
believe to be factual and requests a hearing based on these objections. 
FDA addresses each of the objections in the following paragraphs, as 
well as the evidence and information filed in support of each, 
comparing each objection and the information submitted in support of it 
to the standards for granting a hearing in Sec.  12.24.

A. FWW's Assertion That FDA Failed To Follow Its Own Guidelines

    FWW claims that FDA failed to follow its own guidelines for 
assessing the safety of food additives. Specifically, FWW states that 
FDA did not ``certify'' that it followed the procedures stated in 
current publications of the National Academy of Sciences/National 
Research Council (NAS/NRC) when reviewing the bacteriophage petition, 
or if different procedures were used, FDA did not ``certify'' that they 
are as reliable as the NAS/NRC procedures, as FWW states is required by 
Sec.  170.20 (21 CFR 170.20). FWW also contends that FDA did not comply 
with the testing set forth in its own guidance entitled ``Toxicological 
Principles for the Safety Assessment of Food Ingredients,'' otherwise 
known as FDA's Redbook, or establish a 100-fold safety factor for the 
additive as set forth in 21 CFR 170.22. If a different safety factor 
was used, FWW asserts that FDA did not provide evidence to justify a 
different safety factor. FWW also questions the relevance and 
applicability of the various studies relied on by the petitioner to 
show safety because of either: (1) Deficiencies with how the studies 
were conducted, (2) the studies investigated efficacy rather than 
safety, or (3) the substance tested is not the same bacteriophage that 
is the subject of the petition.
    Contrary to what FWW appears to assert, FDA notes that the Agency 
does not ``certify'' that the procedures used in evaluating a food 
additive petition either followed the current NAS/NRC procedures or 
were as reliable as those procedures. Section 170.20 sets forth the 
general scientific principles that FDA uses in evaluating a food 
additive petition and cites the principles and procedures stated in 
current publications of the NAS/NRC as a guide that the Agency uses in 
its safety evaluations of food additives. Nevertheless, FDA has 
consistently taken the position that many scientifically valid types of 
data may properly support a finding that the proposed use of a food 
additive will cause ``no harm'' to consumers. Moreover, Sec.  170.20(a) 
specifically states that ``A petition will not be denied, however, by 
reason of the petitioner's having followed procedures other than those 
outlined in the publications of the National Academy of Sciences-
National Research Council if, from available evidence, the Commissioner 
finds that the procedures used give results as reliable as, or more 
reliable than, those reasonably to be expected from the use of the 
outlined procedures.'' Similarly, NAS/NRC acknowledges in the 
conclusions of its document regarding procedures for evaluating the 
safety of food chemicals that the document's purpose is to ``guide and 
stimulate--not replace--informed professional and administrative 
judgment'' (Ref. 1).
    FDA did not request the petitioner to carry out studies recommended 
in NAS/NRC guidelines because the bacteriophages that are the active 
component of the food additive infect L. monocytogenes exclusively, and 
not mammalian cells. (See discussion at 71 FR 47729 at 47730). As such, 
traditional animal testing of the additive as recommended by NAS/NRC 
for food chemicals, is neither necessary nor helpful to demonstrate 
that the petitioned use of the additive is safe.
    Regarding the use of safety factors, the use of a safety factor is 
intended to account for the uncertainty of extrapolating animal 
toxicity data to humans. Because bacteriophages do not infect mammals, 
the use of a safety factor is unnecessary to provide adequate assurance 
of safety.
    Similarly, due to the nature of this food additive, there is no 
need to assign a concern level as set forth in the Redbook. FDA's 
Redbook provides guidance that represents the Agency's current thinking 
on the information needed for the safety assessment of food 
ingredients. As with any Agency guidance, the Redbook does not bind the 
petitioner or the Agency to follow specific procedures that are 
recommended. Alternative approaches are permissible if such approaches 
satisfy the requirement of the applicable statute and regulations. 
Importantly, the statute does not prescribe the safety tests to be 
performed but leaves that determination to the discretion and 
scientific expertise of FDA. Not all food additives require the same 
amount or type of testing. The testing and data necessary to establish 
the safety of an additive will vary depending on the type and 
characteristics of a particular additive and its intended use. Concern 
levels are used to determine the recommended toxicity tests for an 
additive. It was unnecessary to assign a concern level in the present 
case, because FDA's primary concern about the subject additive was the 
safety of potential residual components from the host organism, L. 
monocytogenes, and not the bacteriophages themselves.
    One such residue of concern was Listeriolysin O (LLO), an exotoxin 
produced by the host organism. To address this concern, the petitioner 
analyzed the bacteriophage preparation for LLO and was unable to detect 
it using a method sensitive to 5 hemolytic units per milliliter (HU/
ml). Even when the food additive was concentrated 10-fold, the 
petitioner still did not detect any hemolytic activity. Although LLO 
was not detected in the bacteriophage preparation, FDA established a 
specification of 5 HU/ml for the maximum amount of LLO permitted in the 
bacteriophage preparation as a condition of safe use, which is the 
limit of detection for the method provided by the petitioner. FDA 
concluded that the potential residues of LLO that may be found in the 
food additive are negligible (i.e., 5 HU/ml or less) and do not pose a 
safety concern for the use of the food additive as an antimicrobial 
agent on RTE meat and poultry products. Furthermore, as discussed in 
the bacteriophage final rule, the presence of any small amount of LLO 
in the bacteriophage preparation may be mitigated by the following 
factors: Inactivation of LLO by cholesterol that is present in RTE meat 
and poultry products; inactivation of LLO by the low stomach pH; and 
inactivation of orally consumed LLO by human defense mechanisms (e.g., 
normal intestinal microflora and cell-mediated immunity reactions) and 
degradation by

[[Page 16288]]

proteolytic enzymes in the diet or in the stomach. FDA concluded that 
reliable alternative methods from NRC/NAS procedures were used to 
establish the safety of the bacteriophage preparation for its use on 
RTE meat and poultry products, and that the data considered for this 
regulation, when evaluated in its entirety, are sufficient to support 
the safety of the bacteriophage preparation for that use.
    FWW's submission provides no evidence that FDA failed to follow its 
own guidelines for assessing the safety of food additives. The FWW 
submission does not raise a genuine and substantial issue of fact and 
does not provide any specifically identified reliable evidence that, if 
established at a hearing, would be adequate to demonstrate that FDA 
acted in violation of its governing statutes and regulations. Thus, a 
hearing is not justified based on this objection (Sec.  12.24(b)(1), 
(b)(2), and (b)(3)).

B. Inactivation of LLO By Stomach Acid and Cholesterol

    FWW contends that FDA relies on conjecture in concluding that foods 
treated with a bacteriophage preparation are safe for human 
consumption. Specifically, FWW asserts that FDA's conclusion that any 
residual LLO will be inactivated by factors such as cholesterol in the 
meat or poultry, acidity within the stomach, and proteolytic enzymes 
present in the food or in the stomach is based on unsupported 
assumptions and not experimental data. Regarding the inactivation of 
LLO by cholesterol, FWW's asserts that FDA's conclusion about 
mitigation of LLO by cholesterol was not based on any data on the 
levels of cholesterol in meat necessary to inactivate LLO, and that the 
mechanism for the inactivation of LLO by cholesterol is ``not yet fully 
understood by researchers.'' FWW also states that there is a need for a 
more thorough study to investigate the reaction of certain sensitive 
population groups to this bacteriophage preparation.
    As stated in the bacteriophage final rule, the toxicity of LLO has 
been shown to be significantly reduced--by as much as 200- to 2,000-
fold--following pre-incubation of LLO with added cholesterol in vitro, 
based on results of a study conducted by Jacobs et al (Ref. 2). The 
results showed that there is almost no hemolytic if LLO is pretreated 
with cholesterol at 1 milligram/100 grams (mg/100g). It is well 
established that there are relatively high concentrations of 
cholesterol in RTE meat and poultry products (approximately 38 to 156 
mg/100 g (Ref. 3)). Therefore, since the bacteriophage preparation is 
to be used on RTE meat and poultry products, and these products contain 
significant amounts of cholesterol, the findings from Jacobs et al. 
directly support FDA's conclusion about inactivation of LLO by 
cholesterol in RTE meat and poultry products. While the mechanism by 
which added cholesterol inhibits LLO may not be fully understood, that 
does not undermine the evidence that supports the Agency's conclusion.
    Regarding inactivation of LLO by acidity, the data considered by 
FDA in its review of the petition indicate that LLO has activity only 
within a pH range between 4.9 and 8 while losing activity at a pH 
outside this range, especially in very acidic (low pH) or very alkaline 
(high pH) environments. Since the pH inside the stomach is normally 
between 1.0 and 3.5 (Ref. 4), the acidic environment in the stomach 
would be a defense against any residual LLO from the use of the 
additive. No data were submitted by FWW to the contrary, nor was any 
information provided that would justify the need for studies to 
investigate the reaction of certain sensitive population groups to the 
bacteriophage preparation. Because FWW provided no evidence to support 
these contentions, FDA is denying the request for a hearing on these 
issues; a hearing will not be granted on the basis of mere allegations 
or denials or general positions and contentions (Sec.  12.24(b)(2)).

C. FWW's Contention That Petitioner's Efficacy Studies Are Inadequate

    FWW contends that the results of the efficacy studies for the 
bacteriophage preparation submitted by the petitioner are inadequate to 
show that the preparation will sufficiently control L. monocytogenes in 
RTE meat and poultry products. In addition, FWW points out that some 
other methods for killing bacteria achieve a greater log reduction of 
bacteria than the bacteriophage preparation.
    During its evaluation of FAP 2A4738, FDA consulted with the Food 
Safety and Inspection Service (FSIS) of the U.S. Department of 
Agriculture (USDA), consistent with 21 CFR 171.1(n) and with a 
memorandum of understanding (MOU) between the two Agencies for 
reviewing the safety of substances used in the production of meat and 
poultry products. Under the MOU, FDA is responsible for reviewing an 
ingredient's safety, and USDA/FSIS is responsible for evaluating its 
suitability. (MOU 225-00-2000; see also 65 FR 51758 at 51759, August 
25, 2000). Suitability relates to the effectiveness of the ingredient 
in performing the intended purpose of use and the assurance that the 
conditions of use will not result in an adulterated product or one that 
misleads consumers. As we stated in the bacteriophage final rule, ``FDA 
recognizes that there may be meat or poultry products considered RTE 
for which use of the additive may not be suitable within the meaning of 
those statutes. This regulation addresses only the safety standard 
under section 409 of the Federal Food, Drug, and Cosmetic Act and does 
not address requirements for suitability administered by the USDA.'' 
(71 FR 47729 at 47731). FSIS concurred with the issuance of FDA's final 
rule.
    FDA is denying the request for a hearing on this point because a 
hearing will not be granted unless there is a genuine and substantial 
factual issue to be resolved (Sec.  12.24(b)(1)), and resolution of the 
factual issue in the way sought is adequate to justify the action 
requested (Sec.  12.24(b)(4)).

D. FWW's Assertion That Key Research Used to Support the Rule Has Not 
Been Published in Peer-Reviewed Journals

    FWW asserts that key research submitted by the petitioner in 
support of their additive was not published in peer-reviewed journals, 
which they claim is required under Sec.  170.31(i) (21 CFR 170.3(i)). 
Specifically, FWW is referring to the definition of safe or safety 
which is defined in Sec.  170.3(i) as ``* * * a reasonable certainty in 
the minds of competent scientists that the substance is not harmful 
under the intended conditions of use. * * *''
    FWW has misinterpreted Sec.  170.3(i). This regulation does not 
require that in order to establish safety, the research submitted by a 
petitioner in support of a food additive must be published in a peer-
reviewed journal. This regulation states that ``Safety may be 
determined by scientific procedures or by general recognition of 
safety.'' Importantly, scientific procedures are defined under Sec.  
170.3(h) as `` * * * human, animal, analytical, and other scientific 
studies, whether published or unpublished, appropriate to establish the 
safety of a substance.'' Therefore, FDA does not require the key 
research submitted by a petitioner in support of a food additive be 
published in a peer-reviewed journal to establish safety. This 
objection does not raise a genuine and substantial issue of fact for 
resolution at a hearing. FDA is denying the request for a hearing on 
this point because a hearing will not be granted if there is no genuine 
and substantial factual issue to be resolved (Sec.  12.24(b)(1)).

[[Page 16289]]

E. FWW's Contention That FDA Did Not Adhere to Its Requirements on 
Making Information Publicly Available

    FWW contends that the Agency did not follow the requirements in 
Sec.  171.1(h) (21 CFR 171.1(h)) for making information publicly 
available. They cite Sec.  171.1(h)(1), which states: ``The following 
data and information in a food additive petition are available for 
public disclosure, unless extraordinary circumstances are shown, after 
the notice of filing of the petition is published in the Federal 
Register * * *.'' FWW states that FDA did not publicly disclose the 
releasable information from FAP 2A4738 after the notice of filing of 
the petition published in the Federal Register as required under Sec.  
171(h)(1). FWW also states ``as of the submission of these objections, 
FDA has still not made much of this information, including much of this 
petition, available.''
    FWW misinterprets Sec.  171.1(h)(1). That paragraph does not mean 
that the releasable data and information in a petition are publicly 
disclosed when the notice of filing publishes, but merely that the 
information in the petition is available for public disclosure. Before 
the information in a petition is actually disclosed, the Agency has to 
purge all data and information that are protected from disclosure. 
Because this is a labor intensive process, FDA does not preemptively 
disclose the information in a petition at this time, but rather 
releases it in response to requests made under the Freedom of 
Information Act (FOIA). To disclose the information in a petition 
before a request is received would not be an efficient use of Agency 
resources.
    In the case of FAP 2A4738, the notice of filing was published in 
the Federal Register of July 22, 2002, at which time the releasable 
information in the petition was available for public disclosure through 
the Agency's FOIA process. The final rule for this petition published 
in the Federal Register of August 18, 2006, and the period for 
submitting objections to this rule ended on September 18, 2006. Prior 
to the beginning of the objection period, FDA had not processed any 
FOIA requests for this information. The petition therefore had not been 
previously redacted.
    On September 7, 2006, arrangements were made for FWW to go to FDA's 
offices to review the petition, including specific sections in which 
the organization had expressed a particular interest. On September 8, 
2006, FWW came to FDA's offices and reviewed releasable parts of the 
petition. At the end of their visit, FWW left with approximately 250 
pages of documents. In addition, an FOIA request from Wenonah Hauter of 
FWW (dated August 31, 2006 and received and logged by FDA's Freedom of 
Information Staff on September 5, 2006) was processed, and the 
information sent to FWW on February 9, 2007.
    The objection provides no evidence to support the contention that 
FDA did not follow Sec.  171.1(h) regarding releasable information from 
FAP 2A4738. FDA is denying the request for a hearing on this point 
because a hearing will not be granted if there is no genuine and 
substantial factual issue to be resolved (Sec.  12.24(b)(1)).

F. FWW's Contention That FDA Did Not Provide Adequate and Timely Notice 
of the Standards Used To Evaluate the Petition

    FWW contends that FDA did not provide timely notice of the 
standards it used for evaluating the petition and how the data 
justifies the Agency's conclusion. Specifically, FWW contends that FDA 
made available the memoranda referenced in the bacteriophage final rule 
and select portions of the petition only after much pleading on the 
13th and 21st day, respectively, after the start of the statutorily 
required 30-day objection period.
    On August 17, 2006, the date the bacteriophage final rule was 
placed on public display and 1 day before the rule published in the 
Federal Register, the four references cited in the final rule were also 
placed on public display in the petition docket. However, after 
realizing that some of the references contained confidential 
information, FDA immediately removed them from the docket to redact any 
confidential information. The redacted references were placed back in 
the docket on August 31, 2006.
    The Agency was first contacted by FWW on August 18, 2006, about the 
unavailability of the four references listed in the bacteriophage final 
rule. FWW was informed that the review memos had been taken off the 
Agency's Web site to be purged of confidential information. While the 4 
references cited in the bacteriophage final rule were unavailable to 
FWW for 13 days after the publication of the final rule, FWW did obtain 
them with more than half the 30-day period for objection still left.
    With respect to the select portions of the petition that FWW 
objects to having received 21 days after the start of the 30-day 
objection period, we understand this objection to refer to the portions 
of the petition that FWW examined in FDA's offices on September 8, 
2006. These portions of the petition were not among the four references 
cited in the bacteriophage final rule and placed on public display as 
part of the petition docket. As is discussed previously, it would not 
be an efficient use of Agency resources to prepare the entire petition 
for release in advance of any requests to view the petition. However, 
FDA was nonetheless able to redact significant portions of the petition 
in an expedited manner and provide them for FWW's review on September 
8, 2006.
    FDA is denying the request for a hearing on this point because a 
hearing will not be granted unless there is a genuine and substantial 
factual issue to be resolved (Sec.  12.24(b)(1)), and resolution of the 
factual issue in the way sought is adequate to justify the action 
requested (Sec.  12.24(b)(4)). Furthermore, a hearing is justified only 
if the objections ``draw in question in a material way the 
underpinnings of the regulation at issue'' (Pactra Industries v. 
Consumer Product Safety Commission, 555 F.2d at 684), which is not the 
case with this objection.

V. Summary and Conclusions

    Section 409 of the FD&C Act requires that a food additive be shown 
to be safe prior to marketing. Under Sec.  170.3(i), a food additive is 
``safe'' if ``* * * there is a reasonable certainty in the minds of 
competent scientists that the substance is not harmful under the 
intended conditions of use.* * *'' In the final rule approving the use 
of a Listeria-specific bacteriophage preparation for treating RTE meat 
and poultry products, FDA concluded that the data presented by the 
petitioner to establish safety of the additive demonstrate that the use 
of the bacteriophage preparation is safe under the conditions of use 
stated in the regulation. The petitioner has the burden to demonstrate 
the safety of the additive in order to gain FDA approval. (See, e.g., 
Silverman v. Foreman, 631 F.2d 969, 972 (DC Cir. 1980).) Once FDA makes 
a finding of safety, the burden shifts to an objector, who must come 
forward with evidence that calls into question FDA's conclusion. (See 
section 409(f)(1) of the FD&C Act.)
    None of the objections received contained evidence to present a 
genuine and substantial issue of fact. Nor has the objector established 
that the Agency overlooked significant information in reaching its 
conclusion. Therefore, the Agency has determined that the objections 
that requested a hearing do not raise any substantial issue of fact 
that would justify an evidentiary hearing (Sec.  12.24(b)). 
Accordingly, FDA is not making any changes in response

[[Page 16290]]

to the objections and is denying the requests for a hearing. In 
addition, FWW's request for a stay of the effectiveness of the August 
18, 2006, regulation until a hearing is held is moot because FDA is 
denying the hearing request. FDA is confirming August 18, 2006, as the 
effective date of the regulation.

VI. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m. Monday through Friday.
    1. ``Evaluating the Safety of Food Chemicals,'' National Research 
Council, National Academy of Sciences, Washington DC, p. 55.
    2. Jacobs, T., A. Darji, N. Frahm, et al., ``Listeriolysin O: 
Cholesterol Inhibits Cytolysis But Not Binding to Cellular Membranes,'' 
Molecular Microbiology, 28:1081-1089, 1998.
    3. U.S. Department of Agriculture Nutritive Value of Foods, Home 
and Garden Bulletin Number 72, USDA, Agricultural Research Service.
    4. Guyton, A.C., J.E. Hall, Textbook of Medical Physiology (9th 
ed.) Philadelphia: W.B. Saunders Co., p. 817, 1996.

    Dated: March 17, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-6792 Filed 3-22-11; 8:45 am]
BILLING CODE 4160-01-P


