81_FR_45008 81 FR 44876 - Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Current Good Manufacturing Practice for Positron Emission Tomography Drugs

81 FR 44876 - Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Current Good Manufacturing Practice for Positron Emission Tomography Drugs

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 81, Issue 132 (July 11, 2016)

Page Range44876-44878
FR Document2016-16360

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.

Federal Register, Volume 81 Issue 132 (Monday, July 11, 2016) 
[Federal Register Volume 81, Number 132 (Monday, July 11, 2016)]
[Notices]
[Pages 44876-44878]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2016-16360]



[[Page 44876]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Current Good 
Manufacturing Practice for Positron Emission Tomography Drugs

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

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 August 
10, 2016.

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: 202-395-7285, or emailed to [email protected]. All 
comments should be identified with the OMB control number 0910-0667 and 
title ``Current Good Manufacturing Practice for Positron Emission 
Tomography Drugs.'' Also include the FDA docket number found in 
brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, Three White Flint North 10A63, 11601 
Landsdown St., North Bethesda, MD 20852, [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 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 Current Good Manufacturing Practice (CGMP) regulations at 21 CFR 
part 212 are intended to ensure that positron emission tomography (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 informal 
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.
    In the Federal Register of December 29, 2015 (80 FR 81332), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information and the estimated annual burden for 
recordkeeping and third party disclosure. In response to the notice, 
FDA received several comments. The comments raised a number of issues 
that are discussed as follows.
    (Comment 1) The comment disagreed with FDA's estimate that 129 PET 
drug production facilities are required to comply with part 212. Based 
on its records, the comment said that approximately 150 facilities are 
subject to the PET CGMP requirements.
    (Response) We have revised the burden estimates to account for 150 
PET drug production facilities.
    (Comment 2) The comment disagreed with FDA's statement in section I 
of the December 29, 2015, Federal Register notice, ``Investigational 
and Research PET Drugs.'' The comment said that PET facilities devote 
resources to comply with USP 32 Chapter 823, and that FDA should 
estimate the recordkeeping burden under USP 32 Chapter 823.
    (Response) FDA agrees with the comment that facilities incur a 
burden to comply with USP 32 Chapter 823. However, compliance with USP 
provisions is beyond the scope of this information collection, which 
only pertains to the requirements under part 212.
    (Comment 3) The comment said FDA ``averages'' the burden across 
different categories of respondents and responses, and that this 
approach results in lower burden estimates. For example, the comment 
said that most recordkeeping will continue to be with a paper-based 
system and not an electronic system, and that the costs are different 
for each system. In addition, there are differences between the costs 
incurred by commercial and academic facilities.
    (Response) All commercial PET drug facilities are currently 
utilizing electronic records for recordkeeping as well as paper-based 
records. Commercial PET drug manufacturers comprise approximately 90 
percent of the manufacturing sites. Many academic PET facilities still 
use paper-based records. However, academic PET sites produce fewer 
batches for clinical use compared to commercial sites, and have fewer 
records. Sufficient resources and personnel are needed to perform the 
PET drug production activities, and academic PET drug sites limited in 
personnel and resources do bear more of the regulatory burden. After a 
firm's recordkeeping process is established, the burdens are generally 
the same for entering records into an electronic system or a paper-
based system. We question whether it is worthwhile to prepare separate 
estimates for commercial versus academic sites because academic sites 
are a small percentage of the total. Also, providing an average 
estimate is consistent with PRA requirements and, based on our 
calculations, the number of academic sites that apply for drug 
applications represents a small percentage.
    (Comment 4) The comment questioned FDA's methodology for 
determining the burden estimates, especially in table 2 where the 
actual burden may be underestimated ``by a factor of 10 to 100.''
    (Response) In estimating the time to comply with these information 
collection requirements, we relied on

[[Page 44877]]

informal communications we have had with PET producers, visits by our 
staff to PET facilities, our familiarity with both PET and general 
pharmaceutical manufacturing practices, and the different facilities 
listed in new drug applications (NDAs) and abbreviated new drug 
applications (ANDAs) submitted to FDA for PET drugs. FDA is willing to 
consider any specific estimates to replace the data we used in the 
tables, just as we did for the 150 facilities submitted by the comment. 
However, other than the 150 facilities, the comment has submitted no 
other specific estimates upon which we could base alternative 
estimates.
    (Comment 5) The comment said more time is needed to prepare its 
analysis of FDA's information collection burden for part 212. The 
comment also offered to work with FDA in the future to develop 
estimates that more fairly reflect the burden to comply with these 
regulations.
    (Response) As required under the Paperwork Reduction Act (PRA), FDA 
provided 60 days for respondents to submit comment in response to the 
December 29, 2015, notice. Upon submission to OMB, respondents are 
afforded 30 additional days to submit comments. Finally, because FDA 
must seek OMB approval for any information collection at least every 
three years, respondents are invited to submit comments accordingly. 
FDA considers all comments it receives and continually seeks ways to 
improve its burden estimates as well as the efficiency of its 
information collection activities, including suggestions from PET drug 
producers and facilities in estimating the burden of the information 
collection in part 212. Any specific estimates submitted by PET drug 
producers and facilities subsequent to the comment period provided for 
under the PRA will be reviewed and considered by FDA for future 
renewals of this information collection.
    We estimate the burden of this collection of information as 
follows:

                                                   Table 1--Estimated Annual Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                    Number of
            Activity; 21 CFR section                Number of      records per    Total annual       Average burden per recordkeeper        Total hours
                                                  recordkeepers   recordkeeper       records                                                    \2\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Batch Production and Control Records--                      150            1.71           256.5  20.....................................           5,130
 212.20(c); 212.20(e); 212.50(a); 212.50(b).
Batch Production and Control Records--212.20(d)             150             501          75,150  0.50 (30 mins.)........................          37,575
 and (e); 212.50(c); 212.80(c).
Equipment and Facilities Records--212.20(c);                150              15           2,250  1......................................           2,250
 212.30(b); 212.50(d); 212.60(f).
Equipment and Facilities Records--212.30(b);                150           3,758         563,700  0.08 (5 mins.).........................          45,096
 212.50(d); 212.60(f).
Records of Components, Containers, and                      150               2             300  1......................................             300
 Closures--212.20(c); 212.40(a); 212.40(b).
Records of Components, Containers, and                      150              36           5,400  0.17 (10 mins.)........................             918
 Closures--212.40(e).
Laboratory Testing Records--212.20(c);                      150              25           3,750  1......................................           3,750
 212.60(a); 212.60(b); 212.61(a); 212.70(a);
 212.70(b); 212.70(d).
Laboratory Testing Records--212.60(g);                      150             501          75,150  0.17 (10 mins.)........................          12,776
 212.61(b); 212.70(d)(2); 212.70(d)(3).
Conditional Final Releases--212.70(f)..........             150               1             150  1......................................             150
Out-of-Specification Investigations--212.20(c);             150              36           5,400  1......................................           5,400
 212.71(a); 212.71(b).
Reprocessing Procedures--212.20(c); 212.71(d)..             150               1             150  1......................................             150
Distribution Records--212.20(c); 212.90(a);                 150             501          75,150  0.25 (15 mins.)........................          18,788
 212.90(b).
Complaints--212.20(c); 212.100(a)..............             150               1             150  1......................................             150
Complaints--212.100(b); 212.100(c).............             150               1             150  0.50 (30 mins.)........................              75
                                                --------------------------------------------------------------------------------------------------------
    Total......................................  ..............  ..............  ..............  .......................................         132,508
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Number rounded to the nearest whole number.


                                               Table 2--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                         Number of
                           21 CFR section                               Number of     disclosures per    Total annual    Average burden  Total hours \2\
                                                                       respondents       respondent      disclosures     per disclosure
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sterility Test Failure Notices--212.70(e)..........................             150              .25             37.5                1               38
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this information collection.
\2\ Number rounded to the nearest whole number.

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.

[[Page 44878]]

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 256.5 PET 
drugs produced, with a total recordkeeping burden of approximately 
5,130 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 37,575 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 2,250 
hours. We estimate that recording maintenance and cleaning information 
would take approximately 5 minutes a day for each piece of equipment, 
for a total recordkeeping burden of approximately 45,096 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 300 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 918 
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 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) and (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 3,750 
hours, and the associated annual burden for recording laboratory test 
results is approximately 12,776 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 notices per year to receiving facilities. The 
notice would be provided using email or fax 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 5,400 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 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 
addressed.

    Dated: July 5, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-16360 Filed 7-8-16; 8:45 am]
 BILLING CODE 4164-01-P

44876 Federal Register / Vol. 81, No. 132 / Monday, July 11, 2016 / Notices DEPARTMENT OF HEALTH AND the Federal Food, Drug, and Cosmetic with USP 32 Chapter 823, and that FDA HUMAN SERVICES Act (the FD&C Act) regarding safety, should estimate the recordkeeping identity, strength, quality, and purity. burden under USP 32 Chapter 823. Food and Drug Administration The CGMP requirements for PET drugs (Response) FDA agrees with the are issued under the provisions of the [Docket No. FDA–2013–N–0242] comment that facilities incur a burden Food and Drug Administration Modernization Act of 1997 (the to comply with USP 32 Chapter 823. Agency Information Collection However, compliance with USP Activities; Submission for Office of Modernization Act). These CGMP requirements are designed to take into provisions is beyond the scope of this Management and Budget Review; information collection, which only Comment Request; Current Good account the unique characteristics of PET drugs, including their short half- pertains to the requirements under part Manufacturing Practice for Positron lives, and the fact that most PET drugs 212. Emission Tomography Drugs are produced at locations that are very (Comment 3) The comment said FDA AGENCY: Food and Drug Administration, close to the patients to whom the drugs ‘‘averages’’ the burden across different HHS. are administered. categories of respondents and responses, ACTION: Notice. The CGMP regulations are intended to and that this approach results in lower ensure that approved PET drugs meet burden estimates. For example, the SUMMARY: The Food and Drug the requirements of the FD&C Act as to comment said that most recordkeeping Administration (FDA) is announcing safety, identity, strength, quality, and will continue to be with a paper-based that a proposed collection of purity. The regulations address the information has been submitted to the following matters: Personnel and system and not an electronic system, Office of Management and Budget resources; quality assurance; facilities and that the costs are different for each (OMB) for review and clearance under and equipment; control of components, system. In addition, there are the Paperwork Reduction Act of 1995. in-process materials, and finished differences between the costs incurred products; production and process by commercial and academic facilities. DATES: Fax written comments on the collection of information by August 10, controls; laboratory controls; acceptance (Response) All commercial PET drug 2016. criteria; labeling and packaging controls; facilities are currently utilizing distribution controls; complaint electronic records for recordkeeping as ADDRESSES: To ensure that comments on handling; and recordkeeping. well as paper-based records. the information collection are received, The CGMP regulations establish Commercial PET drug manufacturers OMB recommends that written several recordkeeping requirements and comments be faxed to the Office of comprise approximately 90 percent of a third-party disclosure requirement for Information and Regulatory Affairs, the manufacturing sites. Many academic the production of PET drugs. In making OMB, Attn: FDA Desk Officer, FAX: PET facilities still use paper-based our estimates of the time spent in 202–395–7285, or emailed to oira_ complying with these information records. However, academic PET sites submission@omb.eop.gov. All collection requirements, we relied on produce fewer batches for clinical use comments should be identified with the informal communications we have had compared to commercial sites, and have OMB control number 0910–0667 and with PET producers, visits by our staff fewer records. Sufficient resources and title ‘‘Current Good Manufacturing to PET facilities, and our familiarity personnel are needed to perform the Practice for Positron Emission with both PET and general PET drug production activities, and Tomography Drugs.’’ Also include the pharmaceutical manufacturing academic PET drug sites limited in FDA docket number found in brackets practices. personnel and resources do bear more of in the heading of this document. In the Federal Register of December the regulatory burden. After a firm’s FOR FURTHER INFORMATION CONTACT: FDA 29, 2015 (80 FR 81332), FDA published recordkeeping process is established, PRA Staff, Office of Operations, Food a 60-day notice requesting public the burdens are generally the same for and Drug Administration, Three White comment on the proposed collection of entering records into an electronic Flint North 10A63, 11601 Landsdown information and the estimated annual system or a paper-based system. We St., North Bethesda, MD 20852, burden for recordkeeping and third question whether it is worthwhile to PRAStaff@fda.hhs.gov. party disclosure. In response to the prepare separate estimates for SUPPLEMENTARY INFORMATION: In notice, FDA received several comments. commercial versus academic sites compliance with 44 U.S.C. 3507, FDA The comments raised a number of issues because academic sites are a small has submitted the following proposed that are discussed as follows. percentage of the total. Also, providing collection of information to OMB for (Comment 1) The comment disagreed an average estimate is consistent with review and clearance. with FDA’s estimate that 129 PET drug PRA requirements and, based on our production facilities are required to Current Good Manufacturing Practice calculations, the number of academic comply with part 212. Based on its for Positron Emission Tomography records, the comment said that sites that apply for drug applications Drugs OMB Control Number 0910– approximately 150 facilities are subject represents a small percentage. 0667—Extension to the PET CGMP requirements. (Comment 4) The comment Positron emission tomography is a (Response) We have revised the questioned FDA’s methodology for medical imaging modality involving the burden estimates to account for 150 PET determining the burden estimates, sradovich on DSK3GDR082PROD with NOTICES use of a unique type of drug production facilities. especially in table 2 where the actual radiopharmaceutical drug product. (Comment 2) The comment disagreed burden may be underestimated ‘‘by a FDA’s Current Good Manufacturing with FDA’s statement in section I of the factor of 10 to 100.’’ Practice (CGMP) regulations at 21 CFR December 29, 2015, Federal Register part 212 are intended to ensure that notice, ‘‘Investigational and Research (Response) In estimating the time to positron emission tomography (PET) PET Drugs.’’ The comment said that PET comply with these information drug products meet the requirements of facilities devote resources to comply collection requirements, we relied on VerDate Sep<11>2014 17:39 Jul 08, 2016 Jkt 238001 PO 00000 Frm 00039 Fmt 4703 Sfmt 4703 E:\FR\FM\11JYN1.SGM 11JYN1

Federal Register / Vol. 81, No. 132 / Monday, July 11, 2016 / Notices 44877 informal communications we have had (Comment 5) The comment said more respondents are invited to submit with PET producers, visits by our staff time is needed to prepare its analysis of comments accordingly. FDA considers to PET facilities, our familiarity with FDA’s information collection burden for all comments it receives and continually both PET and general pharmaceutical part 212. The comment also offered to seeks ways to improve its burden manufacturing practices, and the work with FDA in the future to develop estimates as well as the efficiency of its different facilities listed in new drug estimates that more fairly reflect the information collection activities, applications (NDAs) and abbreviated burden to comply with these including suggestions from PET drug new drug applications (ANDAs) regulations. producers and facilities in estimating submitted to FDA for PET drugs. FDA (Response) As required under the the burden of the information collection is willing to consider any specific Paperwork Reduction Act (PRA), FDA in part 212. Any specific estimates estimates to replace the data we used in provided 60 days for respondents to submitted by PET drug producers and the tables, just as we did for the 150 submit comment in response to the facilities subsequent to the comment December 29, 2015, notice. Upon period provided for under the PRA will facilities submitted by the comment. submission to OMB, respondents are be reviewed and considered by FDA for However, other than the 150 facilities, afforded 30 additional days to submit future renewals of this information the comment has submitted no other comments. Finally, because FDA must collection. specific estimates upon which we could seek OMB approval for any information We estimate the burden of this base alternative estimates. collection at least every three years, collection of information as follows: TABLE 1—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1 Number of Total Average Number of Total Activity; 21 CFR section records per annual burden per recordkeepers hours 2 recordkeeper records recordkeeper Batch Production and Control Records—212.20(c); 150 1.71 256.5 20 ..................... 5,130 212.20(e); 212.50(a); 212.50(b). Batch Production and Control Records—212.20(d) and 150 501 75,150 0.50 (30 mins.) 37,575 (e); 212.50(c); 212.80(c). Equipment and Facilities Records—212.20(c); 212.30(b); 150 15 2,250 1 ....................... 2,250 212.50(d); 212.60(f). Equipment and Facilities Records—212.30(b); 212.50(d); 150 3,758 563,700 0.08 (5 mins.) ... 45,096 212.60(f). Records of Components, Containers, and Closures— 150 2 300 1 ....................... 300 212.20(c); 212.40(a); 212.40(b). Records of Components, Containers, and Closures— 150 36 5,400 0.17 (10 mins.) 918 212.40(e). Laboratory Testing Records—212.20(c); 212.60(a); 150 25 3,750 1 ....................... 3,750 212.60(b); 212.61(a); 212.70(a); 212.70(b); 212.70(d). Laboratory Testing Records—212.60(g); 212.61(b); 150 501 75,150 0.17 (10 mins.) 12,776 212.70(d)(2); 212.70(d)(3). Conditional Final Releases—212.70(f) ............................. 150 1 150 1 ....................... 150 Out-of-Specification Investigations—212.20(c); 150 36 5,400 1 ....................... 5,400 212.71(a); 212.71(b). Reprocessing Procedures—212.20(c); 212.71(d) ............ 150 1 150 1 ....................... 150 Distribution Records—212.20(c); 212.90(a); 212.90(b) .... 150 501 75,150 0.25 (15 mins.) 18,788 Complaints—212.20(c); 212.100(a) .................................. 150 1 150 1 ....................... 150 Complaints—212.100(b); 212.100(c) ................................ 150 1 150 0.50 (30 mins.) 75 Total ........................................................................... ........................ ........................ ........................ ........................... 132,508 1 There are no capital costs or operating and maintenance costs associated with this collection of information. 2 Number rounded to the nearest whole number. TABLE 2—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1 Number of Total Average Number of disclosures Total 21 CFR section annual burden per respondents per hours 2 disclosures disclosure respondent Sterility Test Failure Notices—212.70(e) ............................. 150 .25 37.5 1 38 1 There are no capital costs or operating and maintenance costs associated with this information collection. 2 Number rounded to the nearest whole number. sradovich on DSK3GDR082PROD with NOTICES I. Investigational and Research PET Committee (RDRC), the requirement are currently substantially complying Drugs under the FD&C Act to follow current with the recordkeeping requirements of Section 212.5(b)(2) provides that for good manufacturing practice is met by USP 32 Chapter 823 (see section 121(b) investigational PET drugs produced complying with the regulations in part of the Modernization Act), and under an investigational new drug (IND) 212 or with USP 32 Chapter 823. We accordingly, we do not estimate any and research PET drugs produced with believe that PET production facilities recordkeeping burden for this provision. approval of a Radioactive Drug Research producing drugs under INDs and RDRCs VerDate Sep<11>2014 16:55 Jul 08, 2016 Jkt 238001 PO 00000 Frm 00040 Fmt 4703 Sfmt 4703 E:\FR\FM\11JYN1.SGM 11JYN1

44878 Federal Register / Vol. 81, No. 132 / Monday, July 11, 2016 / Notices II. Batch Production and Control occurrence, and we do not estimate any procedures for each PET production Records recordkeeping burden for documenting facility. We also estimate, for purposes Sections 212.20(c) through (e), process verification. of the PRA, that 36 out-of-specification 212.50(a) through (c), and 212.80(c) set VI. Laboratory Testing Records investigations would be conducted at forth requirements for batch and each facility each year and that it would Sections 212.20(c), 212.60(a), (b), and take approximately 1 hour to document production records as well as written (g), 212.61(a) and (b), and 212.70(a), (b), the investigation, which results in an control records. We estimate that it and (d) set out requirements for would take approximately 20 hours annual burden of 5,400 hours. documenting laboratory testing and annually for each PET production facility to prepare and maintain written specifications referred to in laboratory X. Reprocessing Procedures production and control procedures and testing, including final release testing and stability testing. Each PET drug Sections 212.20(c) and 212.71(d) to create and maintain master batch require PET drug producers to establish records for each PET drug produced. We production facility will need to establish procedures and create forms and document procedures for also estimate that there will be a total of for the different tests for each product reprocessing PET drugs. We estimate approximately 256.5 PET drugs produced, with a total recordkeeping they produce. We estimate that it will that it will take approximately 1 hour a burden of approximately 5,130 hours. take each facility an average of 1 hour year to document these procedures for We estimate that it would take a PET to establish procedures and create forms each PET production facility. We do not production facility an average of 30 for one test. The estimated annual estimate a separate burden for recording minutes to complete a batch record for burden for establishing procedures and the actual reprocessing, both because we each of approximately 501 batches. Our creating forms for these records is believe it would be an uncommon event estimated burden for completing batch approximately 3,750 hours, and the and because the recordkeeping burden records is approximately 37,575 hours. associated annual burden for recording has been included in our estimate for laboratory test results is approximately batch production and control records. III. Equipment and Facilities Records 12,776 hours. Sections 212.20(c), 212.30(b), XI. Distribution Records VII. Sterility Test Failure Notices 212.50(d), and 212.60(f) contain Section 212.70(e) requires PET drug Sections 212.20(c) and 212.90(a) requirements for records dealing with producers to notify all receiving require that written procedures equipment and physical facilities. We estimate that it would take facilities if a batch fails sterility tests. regarding distribution of PET drug approximately 1 hour to establish and We believe that sterility test failures products be established and maintained. maintain these records for each piece of might occur in only 0.05 percent of the We estimate that it will take equipment in each PET production batches of PET drugs produced each approximately 1 hour annually to facility. We estimate that the total year. Therefore, we have estimated in establish and maintain records of these burden for establishing procedures for table 2 that each PET drug producer will procedures for each PET production these records would be approximately need to provide approximately 0.25 facility. Section 212.90(b) requires that 2,250 hours. We estimate that recording sterility test failure notices per year to distribution records be maintained. We maintenance and cleaning information receiving facilities. The notice would be estimate that it will take approximately would take approximately 5 minutes a provided using email or fax 15 minutes to create an actual day for each piece of equipment, for a transmission and should take no more distribution record for each batch of total recordkeeping burden of than 1 hour. PET drug products, with a total burden approximately 45,096 hours. VIII. Conditional Final Releases of approximately hours for all PET IV. Records of Components, Containers, Section 212.70(f) requires PET drug producers. and Closures producers to document any conditional XII. Complaints Sections 212.20(c) and 212.40(a), (b), final releases of a product. We believe and (e) contain requirements on records that conditional final releases will be Sections 212.20(c) and 212.100 regarding receiving and testing of fairly uncommon, but for purposes of require that PET drug producers components, containers, and closures. the PRA, we estimated that each PET establish written procedures for dealing We estimate that the annual burden for production facility would have one with complaints, as well as document establishing these records would be conditional final release a year and how each complaint is handled. We approximately 300 hours. We estimate would spend approximately 1 hour estimate that establishing and that each facility would receive documenting the release and notifying maintaining written procedures for approximately 36 shipments annually receiving facilities. The estimate of one complaints will take approximately 1 and would spend approximately 10 conditional final release per year per hour annually for each PET production minutes per shipment entering records. facility is an appropriate average facility and that each facility will The annual burden for maintaining number because many facilities may receive approximately one complaint a these records would be approximately have no conditional final releases while year and will spend approximately 30 918 hours. others might have only a few. minutes recording how the complaint V. Process Verification IX. Out-of-Specification Investigations was addressed. Section 212.50(f)(2) requires that any Sections 212.20(c) and 212.71(a) and Dated: July 5, 2016. sradovich on DSK3GDR082PROD with NOTICES process verification activities and (b) require PET drug producers to Leslie Kux, results be recorded. Because process establish procedures for investigating Associate Commissioner for Policy. verification is only required when products that do not conform to [FR Doc. 2016–16360 Filed 7–8–16; 8:45 am] results of the production of an entire specifications and conduct these BILLING CODE 4164–01–P batch are not fully verified through investigations as needed. We estimate finished-product testing, we believe that that it will take approximately 1 hour process verification will be a very rare annually to record and update these VerDate Sep<11>2014 16:55 Jul 08, 2016 Jkt 238001 PO 00000 Frm 00041 Fmt 4703 Sfmt 9990 E:\FR\FM\11JYN1.SGM 11JYN1


Document Created: 2016-07-09 00:21:47
Document Modified: 2016-07-09 00:21:47
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionNotices
ActionNotice.
DatesFax written comments on the collection of information by August 10, 2016.
ContactFDA PRA Staff, Office of Operations, Food and Drug Administration, Three White Flint North 10A63, 11601 Landsdown St., North Bethesda, MD 20852, [email protected]
FR Citation81 FR 44876 
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