[Federal Register Volume 79, Number 151 (Wednesday, August 6, 2014)]
[Rules and Regulations]
[Pages 45688-45693]
[FR Doc No: 2014-18458]

=======================================================================
-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2014-0225; FRL-9914-37]

Fluopicolide; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: This regulation amends tolerances for residues of fluopicolide
in or on potato, processed potato waste; and vegetable, tuberous and
corm, subgroup 1C. Valent U.S.A. Corporation requested these tolerances
under the Federal Food, Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective August 6, 2014. Objections and
requests for hearings must be received on or before October 6, 2014,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: The docket for this action, identified by docket
identification (ID) number EPA-HQ-OPP-2014-0225, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory
Public Docket (OPP Docket) in the Environmental Protection Agency

Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334,
1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through
Friday, excluding legal holidays. The telephone number for the Public
Reading Room is<PHONE_NUMBER>, and the telephone number for the OPP
Docket is<PHONE_NUMBER>. Please review the visitor instructions and
additional information about the docket available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Lois Rossi, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; main telephone
number:<PHONE_NUMBER>; email address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
The following list of North American Industrial Classification System
(NAICS) codes is not intended to be exhaustive, but rather provides a
guide to help readers determine whether this document applies to them.
Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

B. How can I get electronic access to other related information?

    You may access a frequently updated electronic version of EPA's
tolerance regulations at 40 CFR part 180 through the Government
Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an
objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2014-0225 in the subject line on the first
page of your submission. All objections and requests for a hearing must
be in writing, and must be received by the Hearing Clerk on or before
October 6, 2014. Addresses for mail and hand delivery of objections and
hearing requests are provided in 40 CFR 178.25(b).
    In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing (excluding any Confidential Business Information (CBI)) for
inclusion in the public docket. Information not marked confidential
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without
prior notice. Submit the non-CBI copy of your objection or hearing
request, identified by docket ID number EPA-HQ-OPP-2014-0225, by one of
the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider to be CBI or other
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC
20460-0001.
     Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at http://www.epa.gov/dockets/contacts.html. Additional
instructions on commenting or visiting the docket, along with more
information about dockets generally, is available at http://www.epa.gov/dockets.

II. Summary of Petitioned-For Tolerance

    In the Federal Register of May 23, 2014 (79 FR 29729) (FRL-9910-
29), EPA issued a document pursuant to FFDCA section 408(d)(3), 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
3F8191) by Valent U.S.A. Corporation, 1600 Riviera Avenue, Suite 200,
Walnut Creek, CA 94596. The petition requested that 40 CFR 180.627 be
amended by establishing tolerances for residues of the fungicide
fluopicolide, 2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-
pyridinyl]methyl]benzamide, in or on potato, processed waste at 0.3
parts per million (ppm); and vegetable, tuberous and corm, subgroup 1C
at 0.3 ppm. That document referenced a summary of the petition prepared
by Valent U.S.A. Corporation, the registrant, which is available in the
docket, http://www.regulations.gov. Comments were received on the
notice of filing. EPA's response to these comments is discussed in Unit
IV.C.
    Based upon review of the data supporting the petition, EPA has
revised the proposed tolerance in or on potato, processed waste from
0.3 ppm to 1.0 ppm, and has revised the commodity terminology. The
reasons for these changes are explained in Unit IV.D.

III. Aggregate Risk Assessment and Determination of Safety

    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) of FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical residue. . .
.''
    Consistent with FFDCA section 408(b)(2)(D), and the factors
specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available
scientific data and other relevant information in support of this
action. EPA has sufficient data to assess the hazards of and to make a
determination on aggregate exposure for fluopicolide including exposure
resulting from the tolerances established by this action. EPA's
assessment of exposures and risks associated with fluopicolide follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children.
    Fluopicolide shares a metabolite, 2,6-dichlorobenzamide (BAM), with
another active ingredient, dichlobenil. Residues of BAM are considered
to be of regulatory concern, and separate toxicity data and endpoints
for risk assessment have been identified for

BAM. However, since increased tolerances on the commodities affected by
this action do not add significantly to the BAM dietary exposure, the
conclusions from the most recently conducted BAM human health risk
assessment remain unchanged.
    The subchronic and chronic toxicity studies for fluopicolide showed
that the primary effects following exposure are in the liver. Kidney
and thyroid toxicity were observed in rats only. Fluopicolide is not
neurotoxic, carcinogenic, nor mutagenic. Developmental toxicity in the
rabbit occurred only at doses that caused severe maternal toxicity,
including death. In the rat, developmental effects were seen only at
high dose levels, in the presence of maternal toxicity. Similarly,
offspring effects (decreased body weight and body weight gain) in the
multi-generation reproductive toxicity study occurred only at levels
causing significant toxicity in parents. There is no evidence of
increased quantitative susceptibility of rat or rabbit fetuses to in
utero or postnatal exposure to fluopicolide. No toxic effects were
observed in studies in which fluopicolide was administered by the
dermal routes of exposure. The toxicological profile for fluopicolide
suggests that increased durations of exposure do not significantly
increase the severity of observed effects. Toxic effects observed in
the rabbit developmental and rat chronic/cancer studies were selected
as risk assessment endpoints for all durations of exposure.
Fluopicolide is classified as not likely to be carcinogenic to humans
and no quantification of cancer risks is required.
    The toxicity profile for BAM has not changed since the last
assessment EPA conducted for BAM; an analysis of the toxicology profile
of BAM can be found in ``2,6-Dichlorobenzamide (BAM). 2,6-
Dichlorobenzamide (BAM) as a Metabolite/Degradate of Fluopicolide and
Dichlobenil. Human Health Risk Assessment for Proposed Uses of Rhubarb,
Dichlobenil on Caneberries (Subgroup 13-07A), and Bushberries (Subgroup
13-07B).'' dated June 19, 2008, in docket ID number EPA-HQ-OPP-2007-
0604.
    Specific information on the studies received and the nature of the
adverse effects caused by fluopicolide as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in document: ``Fluopicolide and its Metabolite,
2,6-Dichlorobenzamide (BAEM). Human Health Risk Assessment to Support a
Petition for an Increased Tolerance on Tuberous and Corm Subgroup 1C
Vegetables,'' pp. 31-35 in docket ID number EPA-HQ-OPP-2014-0225.

B. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA
identifies toxicological points of departure (POD) and levels of
concern to use in evaluating the risk posed by human exposure to the
pesticide. For hazards that have a threshold below which there is no
appreciable risk, the toxicological POD is used as the basis for
derivation of reference values for risk assessment. PODs are developed
based on a careful analysis of the doses in each toxicological study to
determine the dose at which no adverse effects are observed (the NOAEL)
and the lowest dose at which adverse effects of concern are identified
(the LOAEL). Uncertainty/safety factors are used in conjunction with
the POD to calculate a safe exposure level--generally referred to as a
population-adjusted dose (PAD) or a reference dose (RfD)--and a safe
margin of exposure (MOE). For non-threshold risks, the Agency assumes
that any amount of exposure will lead to some degree of risk. Thus, the
Agency estimates risk in terms of the probability of an occurrence of
the adverse effect expected in a lifetime. For more information on the
general principles EPA uses in risk characterization and a complete
description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
    A summary of the toxicological endpoints for fluopicolide and BAM
used for human risk assessment is discussed in Unit III.B. of the final
rule published in the Federal Register of April 20, 2011 (76 FR 22045)
(FRL-8859-9).

C. Exposure Assessment

    The fluopicolide exposure assessment considers exposure from
fluopicolide only. EPA did not reassess exposures from BAM since the
proposed change in use pattern does not add significantly to the BAM
dietary exposure, and residues of BAM due to fluopicolide applications
are significantly lower than those from dichlobenil applications. EPA
is relying on conclusions from the 2008 BAM Human Health Risk
Assessment, which remain unchanged. A discussion of how BAM exposures
were assessed can be found in Unit III.C. of the final rule published
in the Federal Register of August 27, 2008 (73 FR 50563) (FRL-8377-7).
    1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to fluopicolide, EPA considered exposure under the petitioned-
for tolerances as well as all existing fluopicolide tolerances in 40
CFR 180.627. EPA assessed dietary exposures from fluopicolide in food
as follows:
    i. Acute exposure. Quantitative acute dietary exposure and risk
assessments are performed for a food-use pesticide, if a toxicological
study has indicated the possibility of an effect of concern occurring
as a result of a 1-day or single exposure. No such effects were
identified in the toxicological studies for fluopicolide; therefore, a
quantitative acute dietary exposure assessment is unnecessary.
    ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the Dietary Exposure Evaluation Model software with
Food Commodity Intake Database (DEEM-FCID) Version 3.16. This software
uses 2003-2008 food consumption data from the U.S. Department of
Agriculture's (USDA's) National Health and Nutrition Examination
Survey, What We Eat in America (NHANES/WWEIA). As to residue levels in
food, EPA assumed 100 percent crop treated (PCT) and tolerance-level
residues. iii. Cancer. Based on the data summarized in Unit III.A., EPA
has concluded that fluopicolide does not pose a cancer risk to humans.
Therefore, a quantitative dietary exposure assessment for the purpose
of assessing cancer risk is unnecessary.
    iv. Anticipated residue and PCT information. EPA did not use
anticipated residue and/or PCT information in the dietary assessment
for fluopicolide. Tolerance level residues and/or 100 PCT were assumed
for all food commodities.
    2. Dietary exposure from drinking water. The Agency used screening
level water exposure models in the dietary exposure analysis and risk
assessment for fluopicolide in drinking water. These simulation models
take into account data on the physical, chemical, and fate/transport
characteristics of fluopicolide. Further information regarding EPA
drinking water models used in pesticide exposure assessment can be
found at http://www.epa.gov/oppefed1/models/water/index.htm.
    Based on the surface water concentrations estimated using the
Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/
EXAMS); and Screening Concentrations in Ground Water (SCI-GROW) models,
the estimated environmental concentrations (EECs) of fluopicolide for
chronic exposure (non-cancer) assessments are estimated to be 24.14

ppb for surface water and 0.5 ppb for ground water. Acute and cancer
dietary risks were not quantified, as previously discussed.
    3. From non-dietary exposure. i. The term ``residential exposure''
is used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets).
    ii. Fluopicolide is currently registered for the use on residential
turf grass, recreational sites, and ornamental plants that could result
in short-term residential exposures. EPA assessed residential exposure
using the following assumptions:
    a. Residential handler short-term dermal and inhalation exposures
to fluopicolide when mixing, loading, and applying the formulations.
    b. Residential post-application exposures via the dermal route for
adults and children entering treated lawns or treated gardens and
during mowing and golfing activities. and
    c. Incidental non-dietary ingestion (i.e., hand-to-mouth, object-
to-mouth, and soil ingestion) by children during post-application
activities on treated turf.
    Further information regarding EPA standard assumptions and generic
inputs for residential exposures may be found at http://www.epa.gov/pesticides/trac/science/trac6a05.pdf.
    4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
    Unlike other pesticides for which EPA has followed a cumulative
risk approach based on a common mechanism of toxicity, EPA has not made
a common mechanism of toxicity finding as to fluopicolide and any other
substances. Although fluopicolide shares a common metabolite, BAM, with
dichlobenil, quantification of risks for residues of BAM resulting from
fluopicolide was not done as part of this assessment because they
contribute an insignificant amount to the total BAM exposure.
Furthermore, aggregate risks to BAM are not of concern. For the
purposes of this tolerance action, EPA has not assumed that
fluopicolide has a common mechanism of toxicity with other substances.
    For information regarding EPA's efforts to determine which
chemicals have a common mechanism of toxicity and to evaluate the
cumulative effects of such chemicals, see the policy statements
released by EPA's Office of Pesticide Programs concerning common
mechanism determinations and procedures for cumulating effects from
substances found to have a common mechanism on EPA's Web site at:
http://www.epa.gov/pesticides/cumulative/.

D. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the FQPA Safety
Factor (SF). In applying this provision, EPA either retains the default
value of 10X, or uses a different additional safety factor when
reliable data available to EPA support the choice of a different
factor.
    2. Prenatal and postnatal sensitivity. There is no evidence of
quantitative susceptibility following in utero and/or postnatal
fluopicolide exposure in the rabbit and rat developmental toxicity
studies or in the 2-generation rat reproduction study. Qualitative
susceptibility was observed in the rat developmental toxicity study. In
this study, fetal effects (reduced growth and skeletal defects) and
late-term abortions were observed at doses at which only decreased body
weight gain were observed in maternal animals. There is low concern for
this qualitative susceptibility because the fetal effects and late-term
abortions have been well characterized and only occurred at a dose
level near the limit dose. Protection for the maternal effects also
protects for any effects that may occur during development. There are
no residual uncertainties concerning prenatal and postnatal toxicity
for fluopicolide.
    3. Conclusion regarding fluopicolide. EPA has determined that
reliable data show the safety of infants and children would be
adequately protected if the FQPA SF were reduced to 1X. That decision
is based on the following findings:
    i. The toxicity database for fluopicolide is complete.
    ii. There is no indication that fluopicolide is a neurotoxic
chemical and there is no need for a developmental neurotoxicity study
or additional UFs to account for neurotoxicity.
    iii. There is no evidence that fluopicolide results in increased
susceptibility in in utero rabbits in the prenatal developmental
studies or in young rats in the 2-generation reproduction study.
Although there was some evidence of qualitative susceptibility in the
rat developmental toxicity study, as discussed in Unit III.D.2., the
degree of concern for the prenatal and/or postnatal toxicity is low;
thus, there is no need for the 10X FQPA safety factor to account for
potential prenatal or postnatal toxicity.
    iv. There are no residual uncertainties identified in the exposure
databases. The chronic dietary food exposure assessments were performed
based on 100 PCT and tolerance-level residues. EPA made conservative
(protective) assumptions in the ground and surface water modeling used
to assess exposure to fluopicolide in drinking water. Although EPA has
required additional data on transferable residues from treated turf for
fluopicolide, EPA is confident that it has not underestimated turf
exposure due to the conservativeness of the default turf transfer value
and conservative assumptions in the short-term turf assessment
procedures (e.g., assuming residues do not degrade over the thirty-day
assessment period and assuming high-end activities on turf for every
day of the assessment period). Therefore, EPA is confident that it has
not underestimated postapplication exposure of children as well as
incidental oral exposure of toddlers. These assessments will not
underestimate the exposure and risks posed by fluopicolide.
    4. Conclusion regarding BAM. For reasons explained in the Unit
III.D.3.ii. of the preamble to the final rule published in the Federal
Register of August 27, 2008, EPA reduced the FQPA safety factor for BAM
to 1X for inhalation and dermal exposure scenarios and retained the 10X
FQPA safety factor for all other BAM exposure scenarios. EPA is relying
on the findings in the preamble of the August 27, 2008 final rule and
the 2008 BAM Risk Assessment for the BAM FQPA safety factor
determinations for this action.

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic dietary pesticide
exposures are safe by comparing aggregate exposure estimates to the
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA
calculates the lifetime

probability of acquiring cancer given the estimated aggregate exposure.
Short-, intermediate-, and chronic-term risks are evaluated by
comparing the estimated aggregate food, water, and residential exposure
to the appropriate PODs to ensure that an adequate MOE exists.
    1. Acute risk. An acute aggregate risk assessment takes into
account acute exposure estimates from dietary consumption of food and
drinking water. No adverse effect resulting from a single oral exposure
was identified and no acute dietary endpoint was selected. Therefore,
fluopicolide is not expected to pose an acute risk.
    2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
fluopicolide from food and water will utilize 13% of the cPAD for
children 1-2 years old, the population group receiving the greatest
exposure. Based on the explanation in Unit III.C.3., regarding
residential use patterns, chronic residential exposure to residues of
fluopicolide is not expected.
    3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level). Fluopicolide
is currently registered for uses that could result in short-term
residential exposure, and the Agency has determined that it is
appropriate to aggregate average exposure through food and water with
short-term residential exposures to fluopicolide.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water,
and residential exposures result in aggregate MOEs of 110 for adults
and 180 for children aged 6 to less than 11 years old. Because EPA's
level of concern for fluopicolide is a MOE of 100 or below, these MOEs
are not of concern.
    4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account intermediate-term residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level). An intermediate-term adverse effect was identified; however,
fluopicolide is not registered for any use patterns that would result
in intermediate-term residential exposure. Intermediate-term risk is
assessed based on intermediate-term residential exposure plus average
dietary exposure. Because there is no intermediate-term residential
exposure and chronic dietary exposure has already been assessed under
the appropriately protective cPAD (which is at least as protective as
the POD used to assess intermediate-term risk), no further assessment
of intermediate-term risk is necessary, and EPA relies on the chronic
dietary risk assessment for evaluating intermediate-term risk for
fluopicolide.
    5. Aggregate cancer risk for U.S. population. Based on the lack of
evidence of carcinogenicity in two adequate rodent carcinogenicity
studies, fluopicolide is not expected to pose a cancer risk to humans.
    6. BAM. As noted in Unit III.C., EPA does not expect the increased
tolerances in this action to increase BAM exposure above what was
assessed in the June 19, 2008 BAM risk assessment. None of the results
of this BAM risk assessment indicated a risk from aggregate BAM
exposures, including for acute and chronic risks. Similarly, since
short- and intermediate-term aggregate MOEs for BAM are greater than
the LOC, they represent risk estimates that are below the Agency's
level of concern. Finally, EPA has determined that BAM does not pose an
aggregate cancer risk for the U.S. population. EPA has relied upon the
conclusions from the June 19, 2008 BAM Risk Assessment in order to make
these determinations.
    7. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, or to infants and children from aggregate
exposure to fluopicolide residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology, liquid chromatography/tandem mass
spectrometry (LC/MS/MS), is available to enforce the tolerance
expression.
    The method may be requested from: Chief, Analytical Chemistry
Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD
20755-5350; telephone number:<PHONE_NUMBER>; email address:
<EMAIL_ADDRESS>
B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S.
tolerances with international standards whenever possible, consistent
with U.S. food safety standards and agricultural practices. EPA
considers the international maximum residue limits (MRLs) established
by the Codex Alimentarius Commission (Codex), as required by FFDCA
section 408(b)(4). The Codex Alimentarius is a joint United Nations
Food and Agriculture Organization/World Health Organization food
standards program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level.
    The Codex has not established an MRL for fluopicolide on the
subject commodities.

C. Response to Comments

    EPA received one comment to the Notice of Filing that made a
request to reconsider ``loosening tolerances'' for several pesticide
petitions, including for fluopicolide. The commenter additionally noted
that, ``It is an issue of environmental justice that our youngest
citizens--our children--are disproportionately exposed to health
risks.'' The commenter points to an American Academy of Pediatrics
Policy statement regarding pesticide exposure in children, a Centers
for Disease Control and Prevention report on human exposure to
environmental chemicals, and a President's Cancer Panel regarding
reducing environmental cancer risks in supporting the request to
reconsider the tolerance amendments proposed for fluopicolide.
    The Agency understands the commenter's concerns and recognizes that
some individuals believe that certain pesticide chemicals should not be
permitted in our food, or that pesticide tolerances should be
``significantly tightened'' as the commenter notes. However, the
existing legal framework provided by section 408 of the FFDCA states
that tolerances may be set when EPA determines that aggregate exposure
to that pesticide is safe, i.e., that there is a reasonable certainty
that no harm will result from aggregate exposure to the pesticide
chemical residue. When making this determination, EPA considers the
toxicity, including any potential carcinogenicity, of the pesticide and
all anticipated dietary exposures and all other exposures for which
there is reliable information. EPA also gives special consideration to
the potential susceptibility and exposures of infants and children to
the pesticide chemical residue when making this determination. For
fluopicolide, the Agency has considered all the available data,
including all available data concerning the potential for
carcinogenicity of fluopicolide and its metabolites, and concluded
after conducting a risk assessment, that there is a reasonable
certainty that no harm

will result from aggregate human exposure to fluopicolide and that,
accordingly, the amended fluopicolide tolerances on potato, processed
potato waste and vegetable, tuberous and corm, subgroup 1C, are safe.

D. Revisions to Petitioned-For Tolerances

    Based on the data supporting the petition, EPA has determined that
the proposed tolerance in or on potato, processed waste at 0.3 ppm
should be established at 1.0 ppm. That determination was based on the
following: Processing data previously provided for the use of
fluopicolide on potato indicate that residues of fluopicolide
concentrate in wet peels. Residues of fluopicolide found in or on
potatoes are estimated to be in the range of 0.2 ppm to 0.25 ppm
following directed soil application. Using the highest estimated value
of residues found in or on potato and the theoretical concentration
factor of 4.0X for potato processed waste (in accordance with EPA's
Residue Chemistry Test Guidelines), EPA has determined that a tolerance
of 1.0 ppm is appropriate for residues on potato, processed waste.
Additionally, EPA has revised the commodity terminology to potato,
processed potato waste in order to reflect the preferred designation.

 V. Conclusion

    Therefore, tolerances are established for residues of fluopicolide,
2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-
pyridinyl]methyl]benzamide, in or on potato, processed potato waste at
1.0 ppm; and vegetable, tuberous and corm, subgroup 1C at 0.3 ppm.

VI. Statutory and Executive Order Reviews

    This final rule establishes tolerances under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled ``Regulatory Planning and
Review'' (58 FR 51735, October 4, 1993). Because this final rule has
been exempted from review under Executive Order 12866, this final rule
is not subject to Executive Order 13211, entitled ``Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use'' (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled
``Protection of Children from Environmental Health Risks and Safety
Risks'' (62 FR 19885, April 23, 1997). This final rule does not contain
any information collections subject to OMB approval under the Paperwork
Reduction Act (PRA) (44 U.S.C. 3501 et seq.), nor does it require any
special considerations under Executive Order 12898, entitled ``Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations'' (59 FR 7629, February 16, 1994).
    Since tolerances and exemptions that are established on the basis
of a petition under FFDCA section 408(d), such as the tolerances in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.), do not apply.
    This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4). As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled ``Federalism'' (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
``Consultation and Coordination with Indian Tribal Governments'' (65 FR
67249, November 9, 2000) do not apply to this final rule. In addition,
this final rule does not impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (2 U.S.C. 1501 et seq.).
    This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (NTTAA) (15 U.S.C. 272 note).

VII. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.),
EPA will submit a report containing this rule and other required
information to the U.S. Senate, the U.S. House of Representatives, and
the Comptroller General of the United States prior to publication of
the rule in the Federal Register. This action is not a ``major rule''
as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.

    Dated: July 29, 2014.
Lois Rossi,
 Director, Registration Division, Office of Pesticide Programs.
    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

     Authority: 21 U.S.C. 321(q), 346a and 371.

0
2. In Sec.  180.627, revise the following entries in the table in
paragraph (a) to read as follows:

Sec.  180.627  Fluopicolide; tolerances for residues.

    (a) * * *

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------

                                * * * * *
Potato, processed potato waste.............................          1.0

                                * * * * *
Vegetable, tuberous and corm, subgroup 1C..................          0.3
------------------------------------------------------------------------

* * * * *
[FR Doc. 2014-18458 Filed 8-5-14; 8:45 am]
BILLING CODE 6560-50-P


[Federal Register Volume 79, Number 127 (Wednesday, July 2, 2014)]
[Notices]
[Pages 37743-37747]
[FR Doc No: 2014-15370]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-D-0779]

Draft Guidance for Industry on Current Good Manufacturing
Practice--Interim Guidance for Human Drug Compounding Outsourcing
Facilities Under the Federal Food, Drug and Cosmetic Act; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance for industry entitled ``Current Good
Manufacturing Practice--Interim Guidance for Human Drug Compounding
Outsourcing Facilities under Section 503B of the FD&C Act.'' This draft
guidance describes FDA's current expectations regarding compliance with
current good manufacturing practice (CGMP) requirements for facilities
that compound human drugs and register with FDA as outsourcing
facilities under the Federal Food, Drug, and Cosmetic Act (the FD&C
Act), in accordance with provisions added by the Drug Quality and
Security Act (DQSA). FDA is also soliciting public input on specific
potential alternative approaches regarding certain CGMP requirements.
These potential approaches are explained in detail in the draft
guidance.

DATES: Although you can comment on any guidance at any time (see 21 CFR
10.115(g)(5)), to ensure that the Agency considers your comment on this
draft guidance before it begins work on the final version of the
guidance, submit either electronic or written comments on the draft
guidance by September 2, 2014.

ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 2201, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the draft guidance document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Brian Hasselbalch, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 4364, Silver Spring, MD 20993-0002, 301-
796-3279.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry
entitled ``Current Good Manufacturing Practice-Interim Guidance for
Human Drug Compounding Outsourcing Facilities under Section 503B of the
FD&C Act.'' On November 27, 2013, President Obama signed the DQSA
(Public Law 113-54), which added section 503B to the FD&C Act (21
U.S.C. 353b). Under section 503B(b) of the FD&C Act, a compounder can
register as an outsourcing facility with FDA. Drug products compounded
in a registered outsourcing facility can qualify for exemptions from
the FDA approval requirements in section 505 of the FD&C Act (21 U.S.C.
355) and the requirement to label products with adequate directions for
use under section 502(f)(1) of the FD&C Act (21 U.S.C. 352(f)(1)) if
the requirements in section 503B are met. Outsourcing facilities will
be inspected by FDA and must comply with other provisions of the FD&C
Act, including CGMP requirements under section 501(a)(2)(B) (21 U.S.C.
351(a)(2)(B)).
    Under section 501(a)(2)(B) of the FD&C Act, a drug is deemed to be
adulterated if it is not produced in accordance with CGMP. FDA's
regulations regarding CGMP requirements for the preparation of drug
products have been established in 21 CFR parts 210 and 211. FDA intends
to issue more specific CGMP regulations for outsourcing facilities.
Until final regulations are issued, this draft guidance describes FDA's
expectations regarding outsourcing facilities and the CGMP requirements
in parts 210 and 211 during this interim period. This draft guidance
reflects FDA's intent to recognize the differences between compounding
outsourcing facilities and conventional drug manufacturers, and to
tailor CGMP requirements to the nature of the specific compounding
operations conducted by outsourcing facilities while maintaining the
minimum standards necessary to protect patients from the risks of
contaminated or otherwise substandard compounded drug products. This
draft guidance is only applicable to drugs compounded in accordance
with section 503B of the FD&C Act.
    FDA intends to focus its inspectional and enforcement efforts on
those aspects of compounding operations that pose the highest risk to
patient safety. In particular, the primary focus of this draft guidance
is on those aspects of part 211 that relate to sterility assurance of
sterile drug products and the safety of compounded drug products more
generally, with respect to strength (e.g., subpotency, superpotency),
and labeling or drug product mix-ups.

II. Specific Request for Comments and Information

    In addition to comments on the draft guidance generally, FDA is
requesting comments and related supporting information on the following
specific issues: (1) alternative approaches that would enable an
outsourcing facility to have confidence in the quality of incoming
components from sources used by multiple outsourcing facilities without
each individual outsourcing facility having to conduct periodic
laboratory testing to confirm the information in the third-party
supplier's certificate of analysis and (2) alternative approaches that
would minimize the need for outsourcing facilities to establish an in-
house laboratory while providing confidence about the accuracy of
testing performed by a third party used by more than one outsourcing
facility. FDA has described these potential alternative approaches in
the draft guidance and is seeking public comment on these and any other
alternative approaches.
    This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will

represent the Agency's current thinking on ``Current Good Manufacturing
Practice-Interim Guidance for Human Drug Compounding Outsourcing
Facilities under Section 503B of the FD&C Act.'' It does not create or
confer any rights for or on any person and does not operate to bind FDA
or the public. An alternative approach may be used if such approach
satisfies the requirements of the applicable statutes and regulations.

III. Comments

    Interested persons may submit electronic comments regarding this
document to http://www.regulations.gov, or written comments to the
Division of Dockets Management (see ADDRESSES). It is only necessary to
send one set of comments. Identify comments with the docket number
found in brackets in the heading of this document. Received comments
may be seen in the Division of Dockets Management between 9 a.m. and 4
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

IV. Paperwork Reduction Act of 1995

    This draft guidance contains information collection provisions that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). The title, description, and respondent description of the
information collection are given under this section with an estimate of
the annual recordkeeping, third-party disclosure, and reporting
burdens. Included in the estimate is the time for reviewing
instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing the
collection of information.
    We invite comments on these topics: (1) Whether the proposed
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
    Title: Guidance for Industry, Current Good Manufacturing Practice--
Interim Guidance for Human Drug Compounding Outsourcing Facilities
under Section 503B of the FD&C Act.
    Description: The draft guidance describes FDA's expectations
regarding compliance with CGMP requirements for facilities that
register with FDA as outsourcing facilities under section 503B of the
FD&C Act. The primary focus of the draft guidance is on sterility
assurance of sterile products and the safety of compounded drug
products with respect to strength (e.g., subpotency, superpotency), and
labeling or drug product mix-ups. OMB has already approved the
information collection (recordkeeping) contained in FDA's CGMP
regulations in part 211 (OMB control number 0910-0139). FDA believes
that much of the recordkeeping burden that would result from the draft
guidance is already incurred by outsourcing facilities in the normal
course of their business activities. Thus, the burden estimates for
these ``usual and customary'' business practices are not included in
the calculation of burden that follows (see 5 CFR 1320.3(b)(2).
    The draft guidance contains the following collections of
information under the PRA:

1. Facility Design

    The draft guidance describes those elements of facility design of
outsourcing facilities that are considered critical to assuring the
quality of compounded sterile drug products at those facilities. For
example, the draft guidance states that sterile drugs should be
produced only in ISO 5 or better air quality, and that the ISO 5 zone
or critical area must be qualified (i.e., shown to meet the
specifications). In section III.A, the draft guidance lists certain
studies and tests which should be successfully performed for
outsourcing facilities, and states that the results of these studies
and tests should be documented.
    We estimate that annually a total of approximately 50 outsourcing
facilities \1\ (``No. of Recordkeepers'' in table 1, row 1) will
individually document approximately 20 studies and tests (``Total
Annual Records'' in table 1, row 1) that are critical to assuring the
quality of compounded sterile drug products. We also estimate that
preparing and maintaining each record as described in the draft
guidance will take on average approximately 1.5 hours for each record
(``Average Burden per Recordkeeping'' in table 1, row 1).
---------------------------------------------------------------------------

    \1\ This is an estimate of the number of facilities that will
register as outsourcing facilities in fiscal year 2014 (which runs
from October 1, 2013 to September 30, 2014). As of April 30, 2014,
40 facilities had registered as outsourcing facilities, and on
average, 2 facilities have registered each month for the past 3
months, but these estimates are highly uncertain. Annual
establishment fees will be assessed for each outsourcing facility
registered on or after October 1, 2014. It is unknown how many
facilities will remain as registered outsourcing facilities once
these fees take effect.
---------------------------------------------------------------------------

2. Control Systems and Procedures for Maintaining Suitable Facilities

    The draft guidance describes certain controls, procedures, and
documentation that should be established and followed for maintaining
suitable facilities and to prevent contamination and mix-ups during the
course of aseptic operations at outsourcing facilities. Procedures must
be established that assign responsibility for and describe cleaning
schedules, methods, equipment, and materials. In addition, the guidance
describes that procedures should ensure recording of instances when
there is a loss of positive pressure in the clean room during
production.
    We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 2) will
individually establish and maintain approximately 3 records (procedures
and documentation) for maintaining suitable outsourcing facilities
(``Total Annual Records'' in table 1, row 2). We also estimate that
preparing and maintaining each record as described in section III.B of
the draft guidance will take on average approximately 5 hours for each
record (``Average Burden per Recordkeeping'' in table 1, row 2).

3. Environmental and Personnel Monitoring

    Under the draft guidance, procedures for environmental and
personnel monitoring in the aseptic processing area for viable,
nonviable, and total particulate matter should be established and
followed in outsourcing facilities. The procedures should include
establishing the validity of the microbiological media, including the
preparation, sterilization, and growth potential of the media used in
performing tests.
    We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 3) will
individually establish approximately 1,200 environmental and personnel
monitoring procedures and records to document test results (``Total
Annual Records'' in table 1, row 3) for the aseptic processing areas.
We also estimate that preparing and maintaining the environmental and
personnel monitoring procedures as described in section III.C of the
draft guidance will take on average approximately 0.25

hours for each record (``Average Burden per Recordkeeping'' in table 1,
row 3).

4. Equipment, Containers, and Closures

    Procedures and documentation should be established and maintained
for testing compounding equipment and containers and closures to ensure
the quality of compounded drug products at outsourcing facilities.
    We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 4) will
individually establish and maintain approximately 1,000 procedures and
documentation for testing equipment, containers, and closures (``Total
Annual Records'' in table 1, row 4) in the aseptic processing areas. We
also estimate that preparing and maintaining these procedures and
documentation as described in section III.D of the draft guidance will
take on average approximately 0.25 hours for each record (``Average
Burden per Recordkeeping'' in table 1, row 4).

5. Components

    Procedures should be established and records maintained concerning
the source and quality of components such as raw materials or
ingredients used in producing compounded sterile drug products at
outsourcing facilities.
    We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 5) will
individually establish and maintain approximately 240 records of
testing to ensure the quality of components used in producing
compounded drugs, as recommended in section III.E of the draft guidance
(``Total Annual Records'' in table 1, row 5). We also estimate that
preparing and maintaining these records will take on average
approximately 4 hours for each record (``Average Burden per
Recordkeeping'' in table 1, row 5).

6. Production and Process Controls

    Production and process documentation and procedures, such as batch
records, must be established to assure the quality of compounded
sterile drug products at outsourcing facilities. Training on aseptic
technique, cleanroom behavior, gowning, and procedures covering aseptic
manufacturing area operations must be established. Sterilization
validation of operations (e.g., holding vessels, filling equipment,
lyophilizer) and periodic verification activities and results must be
documented.
    We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 6) will
individually establish and maintain approximately 5,000 records
pertaining to production and process controls, such as validation
procedures and training, to assure the quality of compounded sterile
drug products (``Total Annual Records'' in table 1, row 6). We also
estimate that preparing and maintaining these records, as described in
section III.F of the draft guidance, will take on average approximately
0.25 hours for each record (``Average Burden per Recordkeeping'' in
table 1, row 6).

7. Release Testing

    Compounded drug products produced at outsourcing facilities must be
tested to determine whether they meet final product specifications
prior to release for distribution, and procedures for final release
testing must be established and followed.
    We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 7) will
individually establish and maintain approximately 240 records
pertaining to final release testing of compounded drug products,
including release testing procedures and documentation (``Total Annual
Records'' in table 1, row 7). We also estimate that preparing and
maintaining these records, as described in section III.G of the draft
guidance, will take on average approximately 4 hours for each record
(``Average Burden per Recordkeeping'' in table 1, row 7).
    If sterility testing is not completed prior to release under
certain conditions described in section III.G of the draft guidance,
procedures must be established that specify that if the product fails
to meet a criterion for sterility, all healthcare and other facilities
that received the product must be immediately notified of the test
results and provided with any appropriate information and
recommendations to aid in the treatment of patients; the notification
must be documented; and FDA must be notified in writing.
    We estimate that annually a total of approximately 10 outsourcing
facilities (``No. of Respondents'' in table 2, row 1) will individually
send approximately 1 notification of test results to all healthcare and
other facilities that received the compounded drug product and provide
them with any appropriate information and recommendations to aid in the
treatment of patients (``Total Annual Disclosures'' in table 2, row 1).
We also estimate that preparing and sending each notification will take
approximately 5 hours (``Average Burden per Disclosure'' in table 2,
row 1).
    We also estimate that annually, a total of approximately 10
outsourcing facilities (``No. of Respondents'' in table 3) will
individually submit to FDA 1 notification of the test results for any
compounded drug product that fails to meet a sterility criterion
(``Total Annual Responses'' in table 3). Preparing and submitting this
information will take approximately 5 hours per notification (``Average
Burden per Response'' in table 3).

8. Laboratory Controls

    Each laboratory used to conduct testing of components, in-process
materials, and finished drug products for outsourcing facilities must
follow written procedures for the conduct of each test and document the
results, establish sampling and testing procedures to ensure that
components, in-process materials, and drug products conform to the
product specifications, and keep complete records of all tests
performed to ensure compliance with established specifications and
standards, including examinations and assays.
    We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 8) will
individually establish and maintain approximately 1,000 laboratory
records as described in section III.H of the draft guidance (``Total
Annual Records'' in table 1, row 8). We also estimate that preparing
and maintaining these records will take on average approximately 0.5
hours for each record (``Average Burden per Recordkeeping'' in table 1,
row 8).

9. Stability/Expiration Dating

    Stability testing is used to ensure that a drug product will retain
its quality (in particular, strength) and remain sterile through the
labeled expiration date. The draft guidance recommends that procedures
established by outsourcing facilities for assessing the stability of
drug products should include: (1) using stability-indicating test
methods that are reliable, meaningful and specific; (2) evaluating
samples of the drug product in the same container closure system in
which the drug product will be marketed; (3) evaluating samples for
stability that are representative of the lot or batch from which they
were obtained and are stored under suitable conditions; and (4) testing
to evaluate antimicrobial effectiveness (resistance to antimicrobial
contamination) for drug products labeled or intended to be multiple
dose.
    We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row

9) will individually establish and maintain approximately 90 procedures
for stability studies to determine an expiration date (``Total Annual
Records'' in table 1, row 9) for compounded drug products. We also
estimate that preparing and maintaining these procedures as described
in section III.I of the draft guidance will take approximately 5 hours
for each record (``Average Burden per Recordkeeping'' in table 1, row
9).

10. Packaging and Labels

    Packaging of sterile drugs must ensure the sterility and integrity
of the product until it is administered to a patient, and product
labels must contain required information and labeling operations must
include controls to prevent mix-ups. Procedures should be established
by outsourcing facilities for packaging and labeling operations for
compounded sterile drug products, including the following: (1) The
container, closure, and packaging systems should provide adequate
protection against foreseeable external factors in storage, shipment,
and use that can cause contamination or deterioration; (2) packaging
records should include specimens of all labels used; procedures should
be established for issuance of labels, examination of issued labels,
reconciliation of used labels to prevent mix-ups; (3) there should be
physical/spatial separation between different labeling and packaging
operations to prevent mix-ups; and (4) controls should be established
that assure proper identification of any filled containers of sterile
products that are stored unlabeled for any period of time.
    We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 10) will
individually establish and maintain approximately 20 procedures and
records for packaging operations and labels (``Total Annual Records''
in table 1, row 10) for compounded drug products. We also estimate that
preparing and maintaining these procedures and records as described in
section III.J of the draft guidance will take approximately 5.5 hours
for each record (``Average Burden per Recordkeeping'' in table 1, row
10).

11. Quality Assurance Activities

    A quality control unit must be established by outsourcing
facilities to oversee various aspects of compounded sterile drug
production and to monitor quality assurance. The responsibilities of
the quality control unit must be established in procedures and should
include investigations and development and oversight of appropriate
corrective actions and preventive actions regarding: Rejected lots of
finished product, unexpected results or trends, validation and
stability failures, and process deviations or equipment malfunctions
that involve critical equipment. The quality control unit also is
responsible for ensuring that sampling and testing are conducted to
ensure that appropriate specifications are met, and for product
complaint handling.
    We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 11) will
individually establish approximately 8 procedures on the
responsibilities of the quality control unit (``Total Annual Records''
in table 1, row 10) as described in section III.K of the draft
guidance. We also estimate that preparing and maintaining these
procedures will take approximately 3 hours for each record (``Average
Burden per Recordkeeping'' in table 1, row 11).
    The total estimated recordkeeping, third party disclosure, and
reporting burdens for the draft guidance are as follows:

                               Table 1--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                   Number of                     Average burden
     Type of recordkeeping         Number of      records per    Total annual          per          Total hours
                                 recordkeepers   recordkeeper       records       recordkeeping
----------------------------------------------------------------------------------------------------------------
Facility Design...............              50              20           1,000  1.5.............           1,500
Control Systems and Procedures              50               3             150  5...............             750
 For Maintaining Suitable
 Facilities.
Environmental and Personnel                 50           1,200          60,000  0.25 (15                  15,000
 Monitoring.                                                                     minutes).
Equipment, Containers, and                  50           1,000          50,000  0.25 (15                  12,500
 Closures.                                                                       minutes).
Components....................              50             240          12,000  4...............          48,000
Production and Process                      50           5,000         250,000  0.25 (15                  62,500
 Controls.                                                                       minutes).
Release Testing...............              50             240          12,000  4...............          48,000
Laboratory Controls...........              50           1,000          50,000  0.5 (30 minutes)          25,000
Stability/Expiration Dating...              50              90           4,500  5...............          22,500
Packaging and Labels..........              50              20           1,000  5.5.............           5,500
Quality Assurance Activities..              50               8             400  3...............           1,200
                               ---------------------------------------------------------------------------------
    Total.....................              50           8,821         441,050  ................         242,450
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

                           Table 2--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
 Type of disclosure & proposed     Number of     Frequency per   Total annual    Average burden
        21 CFR section            respondents     disclosure      disclosures    per disclosure     Total hours
----------------------------------------------------------------------------------------------------------------
Notification that a compounded              10               1              10  5...............              50
 drug product fails to meet a
 sterility criterion.
An expiration date is added to              50             540          27,000  0.25 (15                   6,750
 the compounded drug product's                                                   minutes).
 label.
                               ---------------------------------------------------------------------------------
    Total.....................           6,800
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

                                 Table 3--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
 Type of reporting & proposed 21     Number of     responses per   Total annual     burden per      Total hours
           CFR section              respondents     respondent       responses       response
----------------------------------------------------------------------------------------------------------------
Notification to FDA that a                    10               1              10               5              50
 compounded drug product fails
 to meet a sterility criterion..
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

V. Electronic Access

    Persons with access to the Internet may obtain the document at
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

    Dated: June 25, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-15370 Filed 7-1-14; 8:45 am]
BILLING CODE 4164-01-P


June 21, 2009

VIA EMAIL

Amanda Geldard

Office of Resource Conservation and Recovery

Materials Recovery and Waste Management Division, MC 5304P

Environmental Protection Agency

1200 Pennsylvania Ave., NW

Washington, D.C. 20240

<EMAIL_ADDRESS>
Re:  Request for extension of the comment period for the Definition of
Solid Waste Rule

Dear Ms. Geldard:

I respectfully request that the Environmental Protection Agency (EPA)
provide the public with an additional thirty (30) days in which to file
comments pertaining to the Definition of Solid Waste Rule.  The purpose
of this extension would be to afford the public a reasonable opportunity
to respond to the detailed comments in the docket and to the testimony
presented at the June 30, 2009 public meeting.  The close of the public
comment period on July 14, 2009 does not afford an adequate opportunity
for full and meaningful public input.

The EPA announced on May 27, 2009 that it would conduct a public meeting
regarding the Definition of Solid Waste Rule promulgated under Subtitle
C of the Resource Conservation and Recovery Act (RCRA).  74 Fed. Reg.
25200.  According to the federal register notice, EPA decided that “it
would be advisable to hear from a broader range of stakeholders before
making a decision” on whether to repeal or revise the rule.  Id. at
25202.  The Agency “determined that a public meeting, with
opportunities to provide comments both verbally and in writing, is an
efficient and transparent method for obtaining public input.”  Id.  We
agree that public meetings and the opportunity to submit written
comments can be effective in providing robust and meaningful input to
Agency decision makers.

However, the Agency in this case has offered the public only one public
meeting in Arlington, Virginia.  Because of resource constraints on
state employees, nonprofit organizations and affected citizens, this
affords only a very few the opportunity to present oral comments.
Further, the agency only afforded the public approximately 45 days to
submit written comments.  This is an insufficient period of time given
the complexity of the issues raised by the final rule, which, together
with the preamble, comprise over 120 pages.  See Revisions to the
Definition of Solid Waste, 73 Fed. Reg. 64668 (October 30, 2008).

Furthermore, in the May 27, 2009 federal register notice, the EPA
alerted the public to new documents in the docket pertaining to the
Definition of Solid Waste Rule.  74 Fed. Reg. at 25202.  In view of
these new documents, the complexity of the issues presented, and the
significance of the rule to the protection of health and the environment
nationwide, the Agency should extend the opportunity to submit written
comments for an additional 30 days.

An extension of the public comment period will allow the EPA to receive
comments from groups and individuals from across the country, who, as a
result of limited resources, cannot attend the public meeting in
Virginia and who need additional time to assemble comments on this
complex rule.  It is our hope that in weighing the merits of a comment
period extension, the EPA will acknowledge the great value of receiving
a broader diversity and depth of comments and will recognize that such
an extension will not cause undue delay to the Agency’s
decision-making process.

Thank you in advance for your consideration of this request.

Sincerely,

/s/ Lisa Evans

Lisa Evans

Attorney

Earthjustice 		Page   PAGE  2  of   NUMPAGES  2

21 Ocean Ave., Marblehead, MA 01945

T.<PHONE_NUMBER>  F.<PHONE_NUMBER>  E.   HYPERLINK
<EMAIL_ADDRESS><EMAIL_ADDRESS>
 W: www.earthjustice.org