[Federal Register Volume 83, Number 67 (Friday, April 6, 2018)]
[Notices]
[Pages 14861-14865]
[FR Doc No: 2018-07031]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0362]

Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Current Good Manufacturing Practice
Regulations for Finished Pharmaceuticals

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by May 7,
2018.

ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
Fax:<PHONE_NUMBER>, or emailed to [email protected]. All
comments should be identified with the OMB control number 0910-0139.
Also include the FDA docket number found in brackets in the heading of
this document.

FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations,
Food and Drug Administration, Three White Flint North, 10A-12M, 11601
Landsdown St., North Bethesda, MD 20852,<PHONE_NUMBER>,
[email protected].

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.

Current Good Manufacturing Practice Regulations for Finished
Pharmaceuticals (21 CFR parts 210 and 211)

OMB Control Number 0910-0139--Extension

    This information collection supports FDA regulations. Specifically,
under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act
(21 U.S.C. 351(a)(2)(B)), a drug is adulterated if the methods used in
or the facilities or controls used for its manufacture, processing,
packing, or holding do not conform to or are not operated or
administered in conformity with Current Good Manufacturing Practice
(CGMP). The CGMP regulations help ensure drug products meet the
statutory requirements for safety and have their purported or
represented identity, strength, quality, and purity characteristics.
The information collection requirements in the CGMP regulations provide
FDA with the necessary information to perform its duty to protect
public health and safety. CGMP requirements establish accountability
for manufacturing and processing drug products, provide for meaningful
FDA inspections, and enable manufacturers to improve the quality of
drug products over time. The CGMP recordkeeping requirements also serve
preventive and remedial purposes and provide crucial information if it
is necessary to recall a drug product.
    The general requirements for recordkeeping under part 211 (21 CFR
part 211) are set forth in Sec.  211.180. Any production, control, or
distribution record associated with a batch and required to be
maintained in compliance with part 211 must be retained for at least 1
year after the expiration date of the batch and, for certain over-the-
counter (OTC) drugs, 3 years after distribution of the batch (Sec.
211.180(a)). Records for all components, drug product containers,
closures, and labeling are required to be maintained for at least 1
year after the expiration date and 3 years for certain OTC products
(Sec.  211.180(b)).
    All part 211 records must be readily available for authorized
inspections during the retention period (Sec.  211.180(c)), and such
records may be retained either as original records or as true copies
(Sec.  211.180(d)). Additionally, Sec.  11.2(a) (21 CFR 11.2(a))
provides that ``for records required to be maintained but not submitted
to the Agency, persons may use electronic records in lieu of paper
records or electronic signatures in lieu of traditional signatures, in
whole or in part, provided that the requirements of this part are
met.'' To the extent this electronic option is used, the burden of
maintaining paper records should be substantially reduced, as should
any review of such records.
    To facilitate improvements and corrective actions, records must be
maintained so data can be used to evaluate the quality standards of
each drug product on at least an annual basis and determine whether to
change any drug product specifications or manufacturing or control
procedures (Sec.  211.180(e)). Written procedures for these evaluations
are to be established and include provisions for a review of a
representative number of batches and, where applicable, records
associated with the batch; provisions for a review of complaints,
recalls, returned or salvaged drug products; and investigations
conducted under Sec.  211.192 for each drug product.
    The specific information collection provisions are as follows:
     Section 211.34--Consultants advising on the manufacture,
processing, packing, or holding of drug products must have sufficient
education, training, and experience to advise on the subject for which
they are retained. Records must be maintained stating the name,
address, and qualifications of any consultants and the type of service
they provide.
     Section 211.67(c)--Records must be kept of maintenance,
cleaning, sanitizing, and inspection as specified in Sec. Sec.  211.180
and 211.182.
     Section 211.68--Appropriate controls must be exercised
over computer or related systems to assure that changes in master
production and control records or other records are instituted only by
authorized personnel.
     Section 211.68(a)--Records must be maintained of
calibration checks, inspections, and computer or related system
programs for automatic, mechanical, and electronic equipment.
     Section 211.68(b)--All appropriate controls must be
exercised over all computers or related systems and control data
systems to assure that changes in master production and control records
or other records are instituted only by authorized persons.
     Section 211.72--Filters for liquid filtration used in the
manufacture, processing, or packing of injectable drug products
intended for human use must not release fibers into such products.
     Section 211.80(d)--Each container or grouping of
containers for components or drug product containers or closures must
be identified with a distinctive code for each lot in each shipment
received. This code must be used in recording the disposition of each
lot. Each lot must be appropriately identified as to its status.
     Section 211.100(b)--Written production and process control
procedures must be followed in the execution of the various production
and process control functions and must be documented at the time of
performance. Any deviation from the written procedures must be recorded
and justified.
     Section 211.105(b)--Major equipment must be identified by
a distinctive identification number or code that must be recorded in
the batch production record to show the specific equipment used in the
manufacture of each batch of a drug product. In cases where only one of
a particular type of equipment exists in a manufacturing facility, the
name of the equipment may be used in lieu of a distinctive
identification number or code.
     Section 211.122(c)--Records must be maintained for each
shipment received of each different labeling and packaging material
indicating receipt, examination, or testing.
     Section 211.130(e)--Inspection of packaging and labeling
facilities must be

made immediately before use to assure that all drug products have been
removed from previous operations. Inspection must also be made to
assure that packaging and labeling materials not suitable for
subsequent operations have been removed. Results of inspection must be
documented in the batch production records.
     Section 211.132(c)--Certain retail packages of OTC drug
products must bear a statement that is prominently placed so consumers
are alerted to the specific tamper-evident feature of the package. The
labeling statement is required to be so placed that it will be
unaffected if the tamper-resistant feature of the package is breached
or missing. If the tamper-evident feature chosen is one that uses an
identifying characteristic, that characteristic is required to be
referred to in the labeling statement.
     Section 211.132(d)--A request for an exemption from
packaging and labeling requirements by a manufacturer or packer is
required to be submitted in the form of a citizen petition under 21 CFR
10.30.
     Section 211.137--Requirements regarding product expiration
dating and compliance with 21 CFR 201.17.
     Section 211.160(a)--The establishment of any
specifications, standards, sampling plans, test procedures, or other
laboratory control mechanisms, including any change in such
specifications, standards, sampling plans, test procedures, or other
laboratory control mechanisms, must be drafted by the appropriate
organizational unit and reviewed and approved by the quality control
unit. These requirements must be followed and documented at the time of
performance. Any deviation from the written specifications, standards,
sampling plans, test procedures, or other laboratory control mechanisms
must be recorded and justified.
     Section 211.165(e)--The accuracy, sensitivity,
specificity, and reproducibility of test methods employed by a firm
must be established and documented. Such validation and documentation
may be accomplished in accordance with Sec.  211.194(a)(2).
     Section 211.166--Stability testing program for drug
products.
     Section 211.173--Animals used in testing components, in-
process materials, or drug products for compliance with established
specifications must be maintained and controlled in a manner that
assures their suitability for their intended use. They must be
identified, and adequate records must be maintained showing the history
of their use.
     Section 211.180(e)--Written records required by part 211
must be maintained so that data can be used for evaluating, at least
annually, the quality standards of each drug product to determine the
need for changes in drug product specifications or manufacturing or
control procedures. Written procedures must be established and followed
for such evaluations and must include provisions for a representative
number of batches, whether approved or unapproved or rejected, and a
review of complaints, recalls, returned or salvaged drug products, and
investigations conducted under Sec.  211.192 for each drug product.
     Section 211.180(f)--Procedures must be established to
assure that the responsible officials of the firm, if they are not
personally involved in or immediately aware of such actions, are
notified in writing of any investigations, conducted under Sec.
211.198, Sec.  211.204, or Sec.  211.208, any recalls, reports of
inspectional observations issued, or any regulatory actions relating to
good manufacturing practices brought by FDA.
     Section 211.182--Specifies requirements for equipment
cleaning records and the use log.
     Section 211.184--Specifies requirements for component,
drug product container, closure, and labeling records.
     Section 211.186--Specifies master production and control
records requirements.
     Section 211.188--Specifies batch production and control
records requirement.
     Section 211.192--Specifies the information that must be
maintained on the investigation of discrepancies found in the review of
all drug product production and control records by the quality control
staff.
     Section 211.194--Explains and describes laboratory records
that must be retained.
     Section 211.196--Specifies the information that must be
included in records on the distribution of the drug.
     Section 211.198--Specifies and describes the handling of
all complaint files received by the applicant.
     Section 211.204--Specifies that records be maintained of
returned and salvaged drug products and describes the procedures
involved.
    Written procedures, referred to here as standard operating
procedures (SOPs), are required for many part 211 records. Current SOP
requirements were initially provided in a final rule published in the
Federal Register of September 29, 1978 (43 FR 45014), and are now an
integral and familiar part of the drug manufacturing process. The major
information collection impact of SOPs results from their creation.
Thereafter, SOPs need to be periodically updated. A combined estimate
for routine maintenance of SOPs is provided in table 1. The 25 SOP
provisions under part 211 in the combined maintenance estimate include:
     Section 211.22(d)--Responsibilities and procedures of the
quality control unit;
     Section 211.56(b)--Sanitation procedures;
     Section 211.56(c)--Use of suitable rodenticides,
insecticides, fungicides, fumigating agents, and cleaning and
sanitizing agents;
     Section 211.67(b)--Cleaning and maintenance of equipment;
     Section 211.68(a)--Proper performance of automatic,
mechanical, and electronic equipment;
     Section 211.80(a)--Receipt, identification, storage,
handling, sampling, testing, and approval or rejection of components
and drug product containers or closures;
     Section 211.94(d)--Standards or specifications, methods of
testing, and methods of cleaning, sterilizing, and processing to remove
pyrogenic properties for drug product containers and closures;
     Section 211.100(a)--Production and process control;
     Section 211.110(a)--Sampling and testing of in-process
materials and drug products;
     Section 211.113(a)--Prevention of objectionable
microorganisms in drug products not required to be sterile;
     Section 211.113(b)--Prevention of microbiological
contamination of drug products purporting to be sterile, including
validation of any sterilization process;
     Section 211.115(a)--System for reprocessing batches that
do not conform to standards or specifications to insure that
reprocessed batches conform with all established standards,
specifications, and characteristics;
     Section 211.122(a)--Receipt, identification, storage,
handling, sampling, examination and/or testing of labeling and
packaging materials;
     Section 211.125(f)--Control procedures for the issuance of
labeling;
     Section 211.130--Packaging and label operations,
prevention of mixup and cross contamination, identification and
handling of filled drug product containers that are set aside and held
in unlabeled condition, and identification of the drug product with a
lot or control number that permits determination of

the history of the manufacture and control of the batch;
     Section 211.142--Warehousing;
     Section 211.150--Distribution of drug products;
     Section 211.160--Laboratory controls;
     Section 211.165(c)--Testing and release for distribution;
     Section 211.166(a)--Stability testing;
     Section 211.167--Special testing requirements;
     Section 211.180(f)--Notification of responsible officials
of investigations, recalls, reports of inspectional observations, and
any regulatory actions relating to good manufacturing practice;
     Section 211.198(a)--Written and oral complaint procedures,
including quality control unit review of any complaint involving
specifications failures, and serious and unexpected adverse drug
experiences;
     Section 211.204--Holding, testing, and reprocessing of
returned drug products; and
     Section 211.208--Drug product salvaging.
    In addition, the following regulations in parts 610 and 680 (21 CFR
parts 610 and 680) reference certain CGMP regulations in part 211:
Sec. Sec.  610.12(g), 610.13(a)(2), 610.18(d), 680.2(f), and 680.3(f).
In table 1, the burden associated with the information collection
requirements in these regulations is included in the burden estimates
under Sec. Sec.  211.165, 211.167, 211.188, and 211.194, as
appropriate.
    Although most CGMP provisions covered in this document were created
many years ago, some existing firms expanding into new manufacturing
areas and startup firms will need to create SOPs. As provided in table
1, FDA assumes approximately 50 firms will have to create up to 25 SOPs
for a total of 1,250 records, estimating 20 hours per recordkeeper to
create 25 new SOPs for a total of 25,000 hours.
    In the Federal Register of December 14, 2017 (82 FR 58811) we
published a 60-day notice requesting public comment on the proposed
collection of information. No comments were received in response to the
notice and we therefore retain those burden estimates, which are as
follows:

                                                   Table 1--Estimated Annual Recordkeeping Burden \1\
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                                                               Number of
         21 CFR section/activity              Number of       records per     Total annual   Average burden per recordkeeping (in hours)    Total hours
                                            recordkeepers     recordkeeper       records                         \1\
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SOP Maintenance..........................            3,270  ...............           3,270  25.........................................          81,750
New Startup SOPs.........................               50               25           1,250  20.........................................          25,000
211.34--Consultants......................            3,270             0.25             818  5..........................................           4,090
211.67(c)--Equipment cleaning and                    3,270               50         163,500  0.25 (15 minutes)..........................          40,875
 maintenance.
211.68--Changes in master production and             3,270                2           6,540  1..........................................           6,540
 control records or other records.
211.68(a)--Automatic, mechanical, and                3,270               10          32,700  0.5 (30 minutes)...........................          16,350
 electronic equipment.
211.68(b)--Computer or related systems...            3,270                5          16,350  0.25 (15 minutes)..........................           4,088
211.72--Filters..........................              416             0.25             104  1..........................................             104
211.80(d)--Components and drug product               3,270             0.25             818  0.1 (6 minutes)............................              82
 containers or closures.
211.100(b)--Production and process                   3,270                3           9,810  2..........................................          19,620
 controls.
211.105(b)--Equipment identification.....            3,270             0.25             818  0.25 (15 minutes)..........................             205
211.122(c)--Labeling and packaging                   3,270               50         163,500  0.25 (15 minutes)..........................          40,875
 material.
211.130(e)--Labeling and packaging                   3,270               50         163,500  0.25 (15 minutes)..........................          40,875
 facilities.
211.132(c)--Tamper-evident packaging.....            1,613               20          32,260  0.5 (30 minutes)...........................          16,130
211.132(d)--Tamper-evident packaging.....            1,613              0.2             323  0.5 (30 minutes)...........................             162
211.137--Expiration dating...............            3,270                5          16,350  0.5 (30 minutes)...........................           8,175
211.160(a)--Laboratory controls..........            3,270                2           6,540  1..........................................           6,540
211.165(e)--Test methodology.............            3,270                1           3,270  1..........................................           3,270
211.166--Stability testing...............            3,270                2           6,540  0.5 (30 minutes)...........................           3,270
211.173--Laboratory animals..............               33                1              33  0.25 (15 minutes)..........................               8
211.180(e)--Production, control, and                 3,270              0.2             654  0.25 (15 minutes)..........................             164
 distribution records.
211.180(f)--Procedures for notification              3,270              0.2             654  1..........................................             654
 of regulatory actions.
211.182--Equipment cleaning and use log..            3,270                2           6,540  0.25 (15 minutes)..........................           1,635
211.184--Component, drug product                     3,270                3           9,810  0.5 (30 minutes)...........................           4,905
 container, closure, and labeling records.
211.186--Master production and control               3,270               10          32,700  2..........................................          65,400
 records.
211.188--Batch production and control                3,270               25          81,750  2..........................................         163,500
 records.
211.192--Discrepancies in drug product               3,270                2           6,540  1..........................................           6,540
 production and control records.
211.194--Laboratory records..............            3,270               25          81,750  0.5 (30 minutes)...........................          40,875
211.196--Distribution records............            3,270               25          81,750  0.25 (15 minutes)..........................          20,438
211.198--Compliant files.................            3,270                5          16,350  1..........................................          16,350
211.204--Returned drug products..........            3,270               10          32,700  0.5 (30 minutes)...........................          16,350
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    Total................................  ...............  ...............  ..............  ...........................................         651,139
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\1\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of minutes per response]/60''.

    The recordkeeping requirement estimates provided in table 2 are
specific to medical gases. In particular, on June 29, 2017, FDA
published a Notice of Availability (NOA) in the Federal Register
regarding revised draft guidance for industry entitled ``Current Good
Manufacturing Practice for Medical Gases'' (82 FR 29565). This
guidance, when finalized, is intended to help medical gas manufacturers
comply with applicable CGMP regulations found in parts 210 and 211. In
the NOA for the revised draft guidance, FDA noted the guidance includes
information collection provisions subject to review by the OMB under
the PRA and, in accordance with the PRA, before publication of the
final guidance, FDA intends to solicit public comment and obtain OMB
approval for any recommended new information collections or material
modifications to previously approved collections of information found
in FDA regulations. This notice is intended to solicit such public
comment.
    The regulations addressed in table 2 are the same as those listed
in table 1, but the estimated information collection

burden differs and is specific to medical gas manufacturing.
    FDA estimates the burden of this collection of information as
follows:

                                                     Table 2--Estimated Annual Recordkeeping Burden
                                                                   [Medical Gases] \1\
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                                                               Number of
         21 CFR section/activity              Number of       records per     Total annual   Average burden per recordkeeping (in hours)    Total hours
                                            recordkeepers     recordkeeper       records                         \1\
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SOP Maintenance..........................            2,284             0.65           1,485  25.........................................          37,125
New startup SOPs.........................              100               25           2,500  20.........................................          50,000
211.34--Consultants......................            2,284             0.25             571  0.5 (30 minutes)...........................             286
211.67(c)--Equipment cleaning and                    2,284             32.5          74,230  0.25 (15 minutes)..........................          18,558
 maintenance.
211.68--Changes in master production and             2,284                2           4,568  1..........................................           4,568
 control records or other records.
211.68(a)--Automatic, mechanical, and                2,284               10          22,840  0.5 (30 minutes)...........................          11,420
 electronic equipment.
211.68(b)--Computer or related systems...            2,284                5          11,420  0.25 (15 minutes)..........................           2,855
211.72--Filters..........................            2,284              .25             571  1..........................................             571
211.80(d)--Components and drug product               2,284             0.25             571  0.1 (6 minutes)............................              57
 containers or closures.
211.100(b)--Production and process                   2,284                3           6,382  2..........................................          13,704
 controls.
211.105(b)--Equipment identification.....            2,284             0.25             571  0.25 (15 minutes)..........................             143
211.122(c)--Labeling and packaging                   2,284               50         114,200  0.25 (15 minutes)..........................          28,550
 material.
211.130(e)--Labeling and packaging                   2,284               50         114,200  0.25 (15 minutes)..........................          28,550
 facilities.
211.132(c)--Tamper-evident packaging.....            2,284               20          45,680  0.5 (30 minutes)...........................          22,840
211.132(d)--Tamper-evident packaging.....            2,284               .2             457  0.5 (30 minutes)...........................             229
211.137--Expiration dating...............            2,284             3.25           7,423  0.33 (20 minutes)..........................           2,450
211.160(a)--Laboratory controls..........            2,284                2           4,568  1..........................................           4,568
211.165(e)--Test methodology.............            2,284                1           2,284  1..........................................           2,284
211.166--Stability testing...............            2,284              1.3           2,969  0.33 (20 minutes)..........................             980
211.173--Laboratory animals..............            2,284                1           2,284  0.25 (15 minutes)..........................             571
211.180(e)--Production, control, and                 2,284              0.2             457  0.25 (15 minutes)..........................             114
 distribution records.
211.180(f)--Procedures for notification              2,284              0.2             457  1..........................................             457
 of regulatory actions.
211.182--Equipment cleaning and use log..            2,284              1.3           2,969  0.16 (10 minutes)..........................             475
211.184--Component, drug product                     2,284             1.95           4,454  0.33 (20 minutes)..........................           1,470
 container, closure, and labeling records.
211.186--Master production and control               2,284               10          22,840  2..........................................          45,680
 records.
211.188--Batch production and control                2,284            16.25          37,115  1.3........................................          48,250
 records.
211.192--Discrepancies in drug product               2,284                2           4,568  1..........................................           4,568
 production and control records.
211.194--Laboratory records..............            2,284               25          57,100  0.5 (30 minutes)...........................          28,550
211.196--Distribution records............            2,284               25          57,100  0.25 (15 minutes)..........................          14,275
211.198--Complaint files.................            2,284                5          11,420  1..........................................          11,420
211.204--Returned drug products..........            2,284               10          22,840  0.5 (30 minutes)...........................          11,420
    Total................................  ...............  ...............  ..............  ...........................................         396,988
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\1\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of minutes per response]/60''.

    The information collection reflects an increase in the number of
respondents that results in a corresponding increase to the number of
annual burden hours. This is consistent with our experience with the
information collection.

    Dated: April 2, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-07031 Filed 4-5-18; 8:45 am]
 BILLING CODE 4164-01-P


[Federal Register Volume 80, Number 52 (Wednesday, March 18, 2015)]
[Notices]
[Pages 14146-14147]
[FR Doc No: 2015-06119]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-0684]

Identification of Alternative In Vitro Bioequivalence Pathways
Which Can Reliably Ensure In Vivo Bioequivalence of Product Performance
and Quality of Non-Systemically Absorbed Drug Products for Animals;
Public Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification of public meeting; request for comments.

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

    The Food and Drug Administration (FDA) is announcing a public
meeting entitled ``Identification of Alternative In Vitro
Bioequivalence Pathways Which Can Reliably Ensure In Vivo
Bioequivalence of Product Performance and Quality of Non-Systemically
Absorbed Drug Products for Animals''. The purpose of the public meeting
is to discuss the use of in vitro methods as a mechanism for assessing
the in vivo product bioequivalence (BE) of non-systemically absorbed
drug products intended for use in veterinary species. FDA is seeking
additional public comment to the docket, and is requesting that any
written comments be submitted by May 18, 2015.
    Date and Time: The public meeting will be held on April 16, 2015,
from 9 a.m. to 4 p.m.
    Location: The public meeting will be held at the Center for
Veterinary Medicine (CVM), Food and Drug Administration, 7519 Standish
Pl., 3rd Floor, Conference Room A, Rockville, MD 20855. Parking is
free.
    Contact Person: Aleta Sindelar, CVM, Food and Drug Administration,
7519 Standish Pl., Rm. 144, Rockville, MD 20855,<PHONE_NUMBER>, FAX:
240-276-9241, email:
<EMAIL_ADDRESS>    Registration: Registration is free and available on a first-come,
first-served basis. Persons interested in requesting an opportunity to
speak during the open public comment period must register by April 8,
2015, and must include a brief summary of comments with their
registration. Those individuals will be contacted prior to the meeting
regarding their participation. Persons interested in attending this
meeting who are not requesting an opportunity to speak at the meeting
must register by April 14, 2015. For general questions about the
meeting, for assistance registering for the meeting, to request an
opportunity to make an oral presentation, or to request special
accommodations due to a disability, contact Aleta Sindelar (see Contact
Person). Please include your name, organization, and contact
information. Early registration for the meeting is encouraged due to
limited time and space.

SUPPLEMENTARY INFORMATION:

I. Background

    Given the imprecision and logistic challenges associated with
clinical endpoint BE studies, FDA is exploring alternative pathways
that can be applied to help ensure the equivalence of product
performance and quality for those products that are non-systemically
absorbed (locally acting).
    The assessment of in vivo BE of non-systemically absorbed drug
products has been a longstanding challenge facing drug manufacturers
and regulators of human and animal health products. Although blood
level BE trials remain the standard for comparing drug products that
are systemically absorbed and that act at a target site reached via the
blood (systemic circulation), such studies cannot confirm product in
vivo BE when a drug is either not systemically absorbed or when it is
associated with therapeutic effects occurring proximal to the site of
absorption. To date, unless the active pharmaceutical ingredient met
the criteria for highly soluble, as defined in CVM Guidance #171
entitled ``Waivers of In Vivo Demonstration of Bioequivalence of Animal
Drugs in Soluble Powder Oral Dosage Form Products and Type A Medicated
Articles,'' clinical endpoint BE trials have provided the only option
for generating inter-product comparisons. FDA is exploring whether an
alternative in vitro BE approach may be considered when blood level BE
studies are either not feasible or not appropriate, and when products
do not meet the criteria for applying a Guidance #171-based biowaiver.
    The assumption underlying the application of the in vitro BE
approach is that equivalence in product physicochemical attributes and
in vitro product performance translates to equivalence in product in
vivo behavior. For sponsors with a right of reference to underlying
safety and effectiveness data, the criteria for similarity of
physicochemical attributes would be defined on the basis of the
underlying dataset to confirm the comparability of the original
formulation and pre- and post-approval changes in formulation or method
of product manufacture. In the case of generic products, a more rigid
approach to sameness would be used in terms of product composition and
physicochemical characteristics. In both situations, physicochemical
comparisons would be based upon a battery of in vitro test procedures,
including a comparison of in vitro dissolution behavior under a range
of physiologically-relevant conditions.
    Examples of the kinds of products where in vitro bioequivalence
concepts can potentially be applied include some orally administered
products (e.g., Type A medicated articles), solutions, emulsions,
ointments, creams, suspensions, transdermal products, and intra-mammary
formulations. Due to unique issues raised by products

employing modified release technologies, only immediate release
formulations would be candidates for the in vitro BE assessment. For
orally administered products, in vitro BE would be limited to
disintegrated dosage forms. In cases when the administered drug acts
both locally and systemically, blood level data may be used to confirm
drug product BE of the systemic effects (and to confirm comparability
of in vivo product disintegration in cases where multiple drugs are
combined in a single solid oral dosage forms), while the additional in
vitro dissolution data could be used to support the comparability of
the local actions.
    The in vitro BE approach should not be construed as a biowaiver,
but rather as an alternative set of tests that would be handled in a
manner consistent with that of an in vivo BE study. Specifically, (1)
because an in vitro BE approach is not a biowaiver, sponsors would
still need to meet the same environmental safety and human food safety
requirements associated with products undergoing in vivo BE studies;
(2) one in vitro study may not suffice when there are multiple product
strengths (e.g., varying concentrations of an intra-mammary infusion);
and (3) the in vitro method could be applied both to fully soluble and
poorly soluble compounds. In vitro BE determinations would be based
upon a battery of in vitro dissolution studies and physicochemical
tests. Links to additional background material are provided on the
Agency's Web site at: http://www.fda.gov/AnimalVeterinary/NewsEvents/WorkshopsConferencesMeetings/ucm435459.htm.
    To assist FDA in developing guidance for demonstrating in vitro BE,
with this notice the Agency is convening an open forum, providing a
summary of what the Agency envisions as considerations pivotal to the
BE assessment and inviting public comment on the various components of
an in vitro BE determination.

II. Participation in a Public Meeting

    While oral presentations from specific individuals and
organizations may be limited due to time constraints during the public
meeting, stakeholders may submit electronic or written comments
discussing any issues of concern to the administrative record (the
docket) for the rulemaking. All relevant data and documentation should
be submitted with the comments. Submit electronic comments 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. 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.

III. Comments, Transcripts, and Recorded Video

    Information and data submitted voluntarily to FDA during the public
meeting will become part of the administrative record for the
rulemaking and will be accessible to the public at http://www.regulations.gov. The transcript of the proceedings from the public
meeting will become part of the administrative record for the
rulemaking. Please be advised that as soon as a transcript is
available, it will be accessible at http://www.regulations.gov under
the docket number found in brackets in the heading of this document,
and at FDA's Web site at http://www.fda.gov/AnimalVeterinary/NewsEvents/WorkshopsConferencesMeetings/ucm435459.htm. It may also be
viewed at the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. A
transcript will also be available in either hardcopy or on CD-ROM,
after submission of a Freedom of Information request. Written requests
are to be sent to the Division of Freedom of Information (ELEM-1029),
Food and Drug Administration, 12420 Parklawn Dr., Element Bldg.,
Rockville, MD 20857.
    Additionally, the public can access the meeting remotely by using
the following Adobe Connect link: https://collaboration. fda. gov/
cvm_bioequivalence_meeting/. The link will become active shortly before
the meeting begins at 9 a.m. on April 16, 2015. Anyone interested in
viewing the meeting remotely using this link will need to register as a
guest using the registration information in this document. The Agency
will be recording the meeting for subsequent viewing by the public.
Once the recording has been made 508 compliant, it will be accessible
at FDA's CVM Web site at http://www.fda.gov/AnimalVeterinary/NewsEvents/WorkshopsConferencesMeetings/ucm435459.htm.

    Dated: March 12, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-06119 Filed 3-17-15; 8:45 am]
 BILLING CODE 4164-01-P


[Federal Register Volume 80, Number 90 (Monday, May 11, 2015)]
[Notices]
[Pages 26924-26925]
[FR Doc No: 2015-11324]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

Combined Notice of Filings

    Take notice that the Commission has received the following Natural
Gas Pipeline Rate and Refund Report filings:

Filings Instituting Proceedings

    Docket Numbers: RP15-912-000.
    Applicants: Gulf South Pipeline Company, LP.
    Description: Sec.  4(d) rate filing per 154.204: Amendment to Neg
Rate Agmt (Sequent 34693-28) to be effective 4/28/2015.
    Filed Date: 4/28/15.
    Accession Number: 20150428-5232.
    Comments Due: 5 p.m. ET 5/11/15.

    Docket Numbers: RP15-913-000.
    Applicants: East Cheyenne Gas Storage, LLC.
    Description: Compliance filing per 154.203: ECGS 2015 Operational
Purchase and Sales Report filing.
    Filed Date: 4/28/15.
    Accession Number: 20150428-5294.

    Comments Due: 5 p.m. ET 5/11/15.

    Docket Numbers: RP15-914-000.
    Applicants: Trailblazer Pipeline Company LLC.
    Description: Sec.  4(d) rate filing per 154.204: Neg Rate 2015-04-
28 Koch, Green Plains to be effective 5/1/2015.
    Filed Date: 4/28/15.
    Accession Number: 20150428-5360.
    Comments Due: 5 p.m. ET 5/11/15.

    The filings are accessible in the Commission's eLibrary system by
clicking on the links or querying the docket number.
    Any person desiring to intervene or protest in any of the above
proceedings must file in accordance with Rules 211 and 214 of the
Commission's Regulations (18 CFR 385.211 and Sec.  385.214) on or
before 5:00 p.m. Eastern time on the specified comment date. Protests
may be considered, but intervention is necessary to become a party to
the proceeding.
    eFiling is encouraged. More detailed information relating to filing
requirements, interventions, protests, service, and qualifying
facilities filings can be found at: http://www.ferc.gov/docs-filing/efiling/filing-req.pdf. For other information, call<PHONE_NUMBER>
(toll free). For TTY, call<PHONE_NUMBER>.

    Dated: April 29, 2015.
Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. 2015-11324 Filed 5-8-15; 8:45 am]
 BILLING CODE 6717-01-P


[Federal Register Volume 83, Number 36 (Thursday, February 22, 2018)]
[Rules and Regulations]
[Pages 7614-7616]
[FR Doc No: 2018-03526]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 52

[EPA-R09-OAR-2017-0468; FRL-9974-68--Region 9]

Approval of Arizona Air Plan Revisions, Arizona Department of
Environmental Quality

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: The Environmental Protection Agency (EPA) is taking final
action to approve a revision to the Arizona Department of Environmental
Quality (ADEQ) portion of the Arizona State Implementation Plan (SIP).
This revision concerns emissions of lead-bearing fugitive dust from
roads, storage piles and other activities associated with the primary
copper smelter located in Hayden, Arizona. We are approving a state
rule and associated appendix to regulate these emissions under the
Clean Air Act (CAA or the Act).

DATES: This rule is effective on March 26, 2018.

ADDRESSES: The EPA has established a docket for this action under
Docket ID No. EPA-R09-OAR-2017-0468. All documents in the docket are
listed on the http://www.regulations.gov website. Although listed in
the index, some information is not publicly available, e.g.,
Confidential Business Information (CBI) or other information whose
disclosure is restricted by statute. Certain other material, such as
copyrighted material, is not placed on the internet and will be
publicly available only in hard copy form. Publicly available docket
materials are available through http://www.regulations.gov, or please
contact the person identified in the FOR FURTHER INFORMATION CONTACT
section for additional availability information.

FOR FURTHER INFORMATION CONTACT: Christine Vineyard, EPA Region IX,
(415) 947-4125, [email protected].

SUPPLEMENTARY INFORMATION: Throughout this document, ``we,'' ``us'' and
``our'' refer to the EPA.

Table of Contents

I. Proposed Action
II. Public Comments and EPA Responses
III. EPA Action
IV. Incorporation by Reference
V. Statutory and Executive Order Reviews

I. Proposed Action

    On November 27, 2017 (82 FR 55966), the EPA proposed to approve the
following rule and appendix into the Arizona SIP.

----------------------------------------------------------------------------------------------------------------
        Local agency                           Rule No.                         Rule title           Submitted
----------------------------------------------------------------------------------------------------------------
ADEQ........................  R18-2-B1301.01...........................  Limits on Lead-Bearing         04/06/17
                                                                          Fugitive Dust from the
                                                                          Hayden Smelter.
ADEQ........................  Appendix 15..............................  Test Methods for               04/06/17
                                                                          Determining Opacity
                                                                          and Stabilization of
                                                                          Unpaved Roads.
----------------------------------------------------------------------------------------------------------------

    We proposed to approve the rule and associated appendix because we
determined that they comply with the relevant CAA requirements. Our
proposed action contains more information on the rule and associated
appendix and our evaluation.

II. Public Comments and EPA Responses

    The EPA's proposed action provided a 30-day public comment period.
During this period, we received three comments. Two commenters raised
issues that are outside of the scope of this rulemaking, including
forest management, wildfire suppression, and greenhouse-gas and other
emissions from wildfires. A third commenter requested that the EPA
``regulate the amount of poisonous dust that is kicked up into the
air.'' As explained in our proposed action, Rule R18-2-B1301.01
establishes requirements to control lead-bearing fugitive dust
emissions surrounding the Hayden copper smelter. Our approval of this
rule into the Arizona SIP will make these requirements federally
enforceable. Commenters did not raise any specific issues germane to
the approvability of the rule and appendix.

III. EPA Action

    No comments were submitted that change our assessment of the rule
and associated appendix as described in our proposed action. Therefore,
as authorized in section 110(k)(3) of the Act, the EPA is fully
approving this rule and associated appendix into the Arizona SIP.

IV. Incorporation by Reference

    In this rule, the EPA is finalizing regulatory text that includes
incorporation by reference. In accordance with requirements of 1 CFR
51.5, the EPA is finalizing the

incorporation by reference of the ADEQ rule and associated appendix
described in the amendments to 40 CFR part 52 set forth below. The EPA
has made, and will continue to make, these documents available through
www.regulations.gov and at the EPA Region IX Office (please contact the
person identified in the FOR FURTHER INFORMATION CONTACT section of
this preamble for more information).
    Therefore, these materials have been approved by the EPA for
inclusion in the SIP, have been incorporated by reference by the EPA
into that plan, are fully federally enforceable under sections 110 and
113 of the CAA as of the effective date of the final rulemaking of the
EPA's approval, and will be incorporated by reference by the Director
of the Federal Register in the next update to the SIP compilation.\1\
---------------------------------------------------------------------------

    \1\ 62 FR 27968 (May 22, 1997).
---------------------------------------------------------------------------

V. Statutory and Executive Order Reviews

    Under the CAA, the Administrator is required to approve a SIP
submission that complies with the provisions of the Act and applicable
Federal regulations. 42 U.S.C. 7410(k); 40 CFR 52.02(a). Thus, in
reviewing SIP submissions, the EPA's role is to approve state choices,
provided that they meet the criteria of the Act. Accordingly, this
action merely approves state law as meeting Federal requirements and
does not impose additional requirements beyond those imposed by state
law. For that reason, this action:
     Is not a significant regulatory action subject to review
by the Office of Management and Budget under Executive Orders 12866 (58
FR 51735, October 4, 1993) and 13563 (76 FR 3821, January 21, 2011);
     Is not an Executive Order 13771 (82 FR 9339, February 2,
2017) regulatory action because SIP approvals are exempted under
Executive Order 12866;
     Does not impose an information collection burden under the
provisions of the Paperwork Reduction Act (44 U.S.C. 3501 et seq.);
     Is certified as not having a significant economic impact
on a substantial number of small entities under the Regulatory
Flexibility Act (5 U.S.C. 601 et seq.);
     Does not contain any unfunded mandate or significantly or
uniquely affect small governments, as described in the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4);
     Does not have Federalism implications as specified in
Executive Order 13132 (64 FR 43255, August 10, 1999);
     Is not an economically significant regulatory action based
on health or safety risks subject to Executive Order 13045 (62 FR
19885, April 23, 1997);
     Is not a significant regulatory action subject to
Executive Order 13211 (66 FR 28355, May 22, 2001);
     Is not subject to requirements of Section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (15 U.S.C. 272
note) because application of those requirements would be inconsistent
with the CAA; and
     Does not provide the EPA with the discretionary authority
to address, as appropriate, disproportionate human health or
environmental effects, using practicable and legally permissible
methods, under Executive Order 12898 (59 FR 7629, February 16, 1994).
    In addition, the SIP is not approved to apply on any Indian
reservation land or in any other area where the EPA or an Indian tribe
has demonstrated that a tribe has jurisdiction. In those areas of
Indian country, the rule does not have tribal implications and will not
impose substantial direct costs on tribal governments or pre-empt
tribal law as specified by Executive Order 13175 (65 FR 67249, November
9, 2000).
    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. The EPA will submit a report containing this action 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. A major rule cannot
take effect until 60 days after it is published in the Federal
Register. This action is not a ``major rule'' as defined by 5 U.S.C.
804(2).
    Under section 307(b)(1) of the CAA, petitions for judicial review
of this action must be filed in the United States Court of Appeals for
the appropriate circuit by April 23, 2018. Filing a petition for
reconsideration by the Administrator of this final rule does not affect
the finality of this action for the purposes of judicial review nor
does it extend the time within which a petition for judicial review may
be filed, and shall not postpone the effectiveness of such rule or
action. This action may not be challenged later in proceedings to
enforce its requirements. (See section 307(b)(2).)

List of Subjects in 40 CFR Part 52

    Environmental protection, Air pollution control, Incorporation by
reference, Intergovernmental relations, Lead, Particulate matter,
Reporting and recordkeeping requirements.

    Dated: February 12, 2018.
Alexis Strauss,
Acting Regional Administrator, Region IX.
    Part 52, Chapter I, Title 40 of the Code of Federal Regulations is
amended as follows:

PART 52--APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS

0
1. The authority citation for part 52 continues to read as follows:

    Authority:  42 U.S.C. 7401 et seq.

Subpart D--Arizona

0
2. Section 52.120 is amended by adding in paragraph (c), under the
table heading ``Table 2--EPA-Approved Arizona Regulations'' a
subheading for ``Article 13 (State Implementation Plan Rules for
Specific Locations)'' and entries for ``R18-2-B1301.01'' and ``Appendix
15'' after the entry for ``Table 6'' to read as follows:

Sec.  52.120  Identification of plan.

* * * * *
    (c) * * *

                                    Table 2--EPA-Approved Arizona Regulations
----------------------------------------------------------------------------------------------------------------
                                                                                Additional
     State citation          Title/subject       State effective date     EPA approval date       explanation
----------------------------------------------------------------------------------------------------------------
                                           Arizona Administrative Code
----------------------------------------------------------------------------------------------------------------

                                                  * * * * * * *
----------------------------------------------------------------------------------------------------------------
                       Article 13 (State Implementation Plan Rules For Specific Locations)
----------------------------------------------------------------------------------------------------------------
R18-2-B1301.01..........  Limits on Lead-      December 1, 2018........  [INSERT Federal      Submitted on April
                           Bearing Fugitive                               Register             6, 2017.
                           Dust from the                                  CITATION],
                           Hayden Smelter.                                February 22, 2018.
Appendix 15.............  Test Methods for     May 7, 2017.............  [INSERT Federal      Submitted on April
                           Determining                                    Register             6, 2017.
                           Opacity and                                    CITATION],
                           Stabilization of                               February 22, 2018.
                           Unpaved Roads.

                                                  * * * * * * *
----------------------------------------------------------------------------------------------------------------

* * * * *
[FR Doc. 2018-03526 Filed 2-21-18; 8:45 am]
 BILLING CODE 6560-50-P


[Federal Register Volume 78, Number 212 (Friday, November 1, 2013)]
[Notices]
[Page 65690]
[FR Doc No: 2013-26017]

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DEPARTMENT OF HOMELAND SECURITY

Federal Emergency Management Agency

[Docket ID FEMA-2012-0025]

Trees and Plantings Associated With Eligible Facilities, RP9524.5

AGENCY: Federal Emergency Management Agency, DHS.

ACTION: Notice.

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SUMMARY: This document provides notice of the availability of the final
policy Trees and Plantings Associated with Eligible Facilities. The
Federal Emergency Management Agency (FEMA) published a notice of
availability and request for comment for the proposed policy on August
6, 2012, at 77 FR 46767.

DATES: This policy is effective September 4, 2013.

ADDRESSES: This final policy is available online at http://www.regulations.gov and on FEMA's Web site at http://www.fema.gov. The
proposed and final policy, all related Federal Register Notices, and
all public comments received during the comment period are available at
http://www.regulations.gov under docket ID FEMA-2012-0025. You may also
view a hard copy of the final policy at the Office of Chief Counsel,
Federal Emergency Management Agency, 8NE, 500 C Street SW., Washington,
DC 20472.

FOR FURTHER INFORMATION CONTACT: William Roche, Federal Emergency
Management Agency, 500 C Street SW., Washington, DC 20472, 202-646-
3834.

SUPPLEMENTARY INFORMATION: The purpose of this policy is to provide
guidance on eligible and ineligible work related to trees, shrubs, and
other plantings, including limited eligibility for replacement of grass
and sod associated with facilities eligible for repair and restoration.
This policy applies to any measure taken with respect to trees, shrubs,
and other plantings, including but not limited to replacement, non-
emergency removal for the purposes of replacement, and remedial actions
taken to abate disaster damage. It does not affect eligible debris
removal and emergency protective measures that may be taken under
Sections 403 and 407 of the Stafford Act, as amended.
    FEMA received one comment on the proposed policy; it did not make
any changes to the final policy.
    This final policy does not have the force or effect of law.

    Authority: 42 U.S.C. 5121-5207.

David J. Kaufman,
Director, Office of Policy and Program Analysis, Federal Emergency
Management Agency.
[FR Doc. 2013-26017 Filed 10-31-13; 8:45 am]
BILLING CODE 9111-23-P