[Federal Register Volume 80, Number 249 (Tuesday, December 29, 2015)]
[Notices]
[Pages 81332-81335]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-32685]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0242]


Agency Information Collection Activities: Proposed Collection; 
Comment Request; Current Good Manufacturing Practice for Positron 
Emission Tomography Drugs

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing an 
opportunity for public comment on the proposed collection of certain 
information by the Agency. Under the Paperwork Reduction Act of 1995 
(the PRA), Federal Agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed extension of an existing collection of 
information, and to allow 60 days for public comment in response to the 
notice. This notice solicits comments on the information collection 
contained in FDA's regulations on current good manufacturing practice 
(CGMP) for positron emission tomography (PET) drugs.

DATES: Submit either electronic or written comments on the collection 
of information by February 29, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2013-N-0242 for ``Agency Information Collection Activities: 
Proposed Collection; Comment Request; Current Good Manufacturing 
Practice for Positron Emission Tomography Drugs.'' Received comments 
will be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION''. The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

[[Page 81333]]


FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver 
Spring, MD 20993-0002, [email protected].

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520) Federal 
Agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes Agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal Agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed extension of an existing collection of information, 
before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information set forth in this document.
    With respect to the following collection of information, FDA 
invites 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.

Current Good Manufacturing Practice for Positron Emission Tomography 
Drugs (OMB Control Number 0910-0667)--Extension

    Positron emission tomography is a medical imaging modality 
involving the use of a unique type of radiopharmaceutical drug product. 
FDA's CGMP regulations at 21 CFR part 212 are intended to ensure that 
PET drug products meet the requirements of the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act) regarding safety, identity, strength, 
quality, and purity. The CGMP requirements for PET drugs are issued 
under the provisions of the Food and Drug Administration Modernization 
Act of 1997 (the Modernization Act). These CGMP requirements are 
designed to take into account the unique characteristics of PET drugs, 
including their short half-lives and the fact that most PET drugs are 
produced at locations that are very close to the patients to whom the 
drugs are administered.
    The CGMP regulations are intended to ensure that approved PET drugs 
meet the requirements of the FD&C Act as to safety, identity, strength, 
quality, and purity. The regulations address the following matters: 
Personnel and resources; quality assurance; facilities and equipment; 
control of components, in-process materials, and finished products; 
production and process controls; laboratory controls; acceptance 
criteria; labeling and packaging controls; distribution controls; 
complaint handling; and recordkeeping.
    The CGMP regulations establish several recordkeeping requirements 
and a third-party disclosure requirement for the production of PET 
drugs. In making our estimates of the time spent in complying with 
these information collection requirements, we relied on communications 
we have had with PET producers, visits by our staff to PET facilities, 
and our familiarity with both PET and general pharmaceutical 
manufacturing practices. The estimated annual recordkeeping and third-
party disclosure burden is based on there being approximately 129 PET 
drug production facilities.
    As explained in this document, Table 1 provides an estimate of the 
annual recordkeeping burdens and Table 2 provides an estimate of the 
annual third-party disclosure burdens associated with this collection.

I. Investigational and Research PET Drugs

    Section 212.5(b)(2) provides that for investigational PET drugs 
produced under an investigational new drug (IND) and research PET drugs 
produced with approval of a Radioactive Drug Research Committee (RDRC), 
the requirement under the FD&C Act to follow current good manufacturing 
practice is met by complying with the regulations in part 212 or with 
USP 32 Chapter 823. We believe that PET production facilities producing 
drugs under INDs and RDRCs are currently substantially complying with 
the recordkeeping requirements of USP 32 Chapter 823 (see section 
121(b) of the Modernization Act), and accordingly, we do not estimate 
any recordkeeping burden for this provision.

II. Batch Production and Control Records

    Sections 212.20(c) through (e), 212.50(a) through (c), and 
212.80(c) set forth requirements for batch and production records as 
well as written control records. We estimate that it would take 
approximately 20 hours annually for each PET production facility to 
prepare and maintain written production and control procedures and to 
create and maintain master batch records for each PET drug produced. We 
also estimate that there will be a total of approximately 221 PET drugs 
produced, with a total recordkeeping burden of approximately 4,420 
hours. We estimate that it would take a PET production facility an 
average of 30 minutes to complete a batch record for each of 
approximately 501 batches. Our estimated burden for completing batch 
records is approximately 32,320 hours.

III. Equipment and Facilities Records

    Sections 212.20(c), 212.30(b), 212.50(d), and 212.60(f) contain 
requirements for records dealing with equipment and physical 
facilities. We estimate that it would take approximately 1 hour to 
establish and maintain these records for each piece of equipment in 
each PET production facility. We estimate that the total burden for 
establishing procedures for these records would be approximately 1,939 
hours. We estimate that recording maintenance and cleaning information 
would take approximately 5 minutes a day for each piece of equipment, 
with a total recordkeeping burden of approximately 40,238 hours.

IV. Records of Components, Containers, and Closures

    Sections 212.20(c) and 212.40(a), (b), and (e) contain requirements 
on records regarding receiving and testing of components, containers, 
and closures. We estimate that the annual burden for establishing these 
records would be approximately 259 hours. We estimate that each 
facility would receive approximately 36 shipments annually and would 
spend approximately 10 minutes per shipment entering records. The 
annual burden for maintaining these records would be approximately 773 
hours.

V. Process Verification

    Section 212.50(f)(2) requires that any process verification 
activities and results be recorded. Because process verification is 
only required when results of the production of an entire batch are not 
fully verified through finished-product testing, we believe that 
process verification will be a very rare

[[Page 81334]]

occurrence, and we do not estimate any recordkeeping burden for 
documenting process verification.

VI. Laboratory Testing Records

    Sections 212.20(c), 212.60(a), (b), and (g), 212.61(a) through (b), 
and 212.70(a), (b), and (d) set out requirements for documenting 
laboratory testing and specifications referred to in laboratory 
testing, including final release testing and stability testing. Each 
PET drug production facility will need to establish procedures and 
create forms for the different tests for each product they produce. We 
estimate that it will take each facility an average of 1 hour to 
establish procedures and create forms for one test. The estimated 
annual burden for establishing procedures and creating forms for these 
records is approximately 3,232 hours, and the annual burden for 
recording laboratory test results is approximately 10,730 hours.

VII. Sterility Test Failure Notices

    Section 212.70(e) requires PET drug producers to notify all 
receiving facilities if a batch fails sterility tests. We believe that 
sterility test failures might occur in only 0.05 percent of the batches 
of PET drugs produced each year. Therefore, we have estimated in Table 
2 that each PET drug producer will need to provide approximately 0.25 
sterility test failure notice per year to receiving facilities. The 
notice would be provided using email or facsimile transmission and 
should take no more than 1 hour.

VIII. Conditional Final Releases

    Section 212.70(f) requires PET drug producers to document any 
conditional final releases of a product. We believe that conditional 
final releases will be fairly uncommon, but for purposes of the PRA, we 
estimated that each PET production facility would have one conditional 
final release a year and would spend approximately 1 hour documenting 
the release and notifying receiving facilities. The estimate of one 
conditional final release per year per facility is an appropriate 
average number because many facilities may have no conditional final 
releases while others might have only a few.

IX. Out-of-Specification Investigations

    Sections 212.20(c) and 212.71(a) and (b) require PET drug producers 
to establish procedures for investigating products that do not conform 
to specifications and conduct these investigations as needed. We 
estimate that it will take approximately 1 hour annually to record and 
update these procedures for each PET production facility. We also 
estimate, for purposes of the PRA, that 36 out-of-specification 
investigations would be conducted at each facility each year and that 
it would take approximately 1 hour to document the investigation, which 
results in an annual burden of 4,654 hours.

X. Reprocessing Procedures

    Sections 212.20(c) and 212.71(d) require PET drug producers to 
establish and document procedures for reprocessing PET drugs. We 
estimate that it will take approximately 1 hour a year to document 
these procedures for each PET production facility. We do not estimate a 
separate burden for recording the actual reprocessing, both because we 
believe it would be an uncommon event and because the recordkeeping 
burden has been included in our estimate for batch production and 
control records.

XI. Distribution Records

    Sections 212.20(c) and 212.90(a) require that written procedures 
regarding distribution of PET drug products be established and 
maintained. We estimate that it will take approximately 1 hour annually 
to establish and maintain records of these procedures for each PET 
production facility. Section 212.90(b) requires that distribution 
records be maintained. We estimate that it will take approximately 15 
minutes to create an actual distribution record for each batch of PET 
drug products, with a total burden of approximately 16,160 hours for 
all PET producers.

XII. Complaints

    Sections 212.20(c) and 212.100 require that PET drug producers 
establish written procedures for dealing with complaints, as well as 
document how each complaint is handled. We estimate that establishing 
and maintaining written procedures for complaints will take 
approximately 1 hour annually for each PET production facility and that 
each facility will receive approximately one complaint a year and will 
spend approximately 30 minutes recording how the complaint was dealt 
with.

                                                    Table 1--Estimated Annual Recordkeeping Burden 1
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                                                   No. of         No. of records      Total annual          Average  burden per
               21 CFR Section                  recordkeepers     per recordkeeper       records                recordkeeping              Total hours
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Batch Production and Control Records                       129               1.71                221  20.............................              4,420
 212.20(c), 212.20(e); 212.50(a), 212.50(b).
Batch Production and Control Records                       129                501             64,640  0.5 (30 mins.)                              32,320
 212.20(d) and (e); 212.50(c); 212.80(c).
Equipment and Facilities Records 212.20(c);                129                 15              1,939  1..............................              1,939
 212.30(b); 212.50(d), 212.60(f).
Equipment and Facilities Records 212.30(b),                129              3,758            484,800  0.083 (5 mins.)                             40,238
 212.50(d); 212.60(f).
Records of Components, Containers, and                     129                  2                259  1..............................                259
 Closures 212.20(c); 212.40(a), 212.40(b).
Records of Components, Containers, and                     129                 36              4,654  0.166 (10 mins.)                               773
 Closures 212.40(e).
Laboratory Testing Records 212.20(c);                      129                 25              3,232  1..............................              3,232
 212.60(a), 212.60(b), 212.61(a);
 212.70(a), 212.70(b), 212.70(d).
Laboratory Testing Records 212.60(g);                      129                501             64,640  0.166 (10 min.)                             10,730
 212.61(b); 212.70(d)(2), 212.70(d)(3).
Conditional Final Releases 212.70(f).......                129                  1                129  1..............................                129
Out-of-Specification Investigations                        129                 36              4,654  1..............................              4,654
 212.20(c); 212.71(a).
Reprocessing Procedures 212.71(b)..........                129                  1                129  1..............................                129

[[Page 81335]]

 
Reprocessing Procedures 212.20(c);                         129                  1                129  1..............................                129
 212.71(d).
Reprocessing Procedures 212.20(c);                         129                  1                129  1..............................                129
 212.90(a).
Distribution Records 212.90(b).............                129                501             64,640  0.25 (15 mins.)                             16,160
Complaints 212.20(c); 212.100(a)...........                129                  1                129  1..............................                129
Complaints 212.100(b), 212.100(c)..........                129                  1                129  0.5 (30 mins.)                                  65
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    Total..................................  .................  .................  .................  ...............................            115,435
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\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
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                                                            No. of         Annual frequency      Total annual          Hours per
                   21 CFR section                         respondents        of disclosure        disclosures         disclosure          Total hours
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Sterility Test Failure Notices 212.70(e)............                129                0.25                  32                   1                  32
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\1\ There are no capital costs or operating and maintenance costs associated with this information collection.


    Dated: December 22, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-32685 Filed 12-28-15; 8:45 am]
 BILLING CODE 4164-01-P