[Federal Register Volume 78, Number 54 (Wednesday, March 20, 2013)]
[Notices]
[Pages 17215-17217]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-06351]


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

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.

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

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 May 20, 2013.

ADDRESSES: Submit electronic comments on the collection of information 
to http://www.regulations.gov. Submit written comments on the 
collection of information to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane., Rm. 1061, 
Rockville, MD 20852. All comments should be identified with the docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Ila S. Mizrachi, Office of Information 
Management, Food and Drug Administration, 1350 Piccard Dr., P150-400B, 
Rockville, MD 20850, 301-796-7726, [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 (FDAMA). 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

[[Page 17216]]

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. Table 1 provides an estimate of the annual 
recordkeeping burdens. Table 2 provides an estimate of the annual 
third-party disclosure burdens associated with this collection.

A. 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 FDAMA), and accordingly, we do not estimate any 
recordkeeping burden for this provision.

B. 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 32,315 hours.

C. 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 1,935 
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 40,237 hours.

D. 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 771 
hours.

E. 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.

F. 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 3,225 hours, and the annual burden for 
recording laboratory test results is approximately 10,728 hours.

G. 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.

H. 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.

I. 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 4,644 hours.

J. 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.

[[Page 17217]]

K. 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 16,157 hours for 
all PET producers.

L. 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\
----------------------------------------------------------------------------------------------------------------
                                                  Number of
        21 CFR Section            Number of      records per    Total annual     Average burden     Total hours
                                recordkeepers   recordkeeper       records      per recordkeeper
----------------------------------------------------------------------------------------------------------------
212.20(c) and (e); 212.50(a)              129            1.71             221  20...............           4,420
 and (b).
212.20(d) and (e); 212.50(c);             129             501          64,629  .5...............          32,315
 212.80(c).                                                                    (30 min.)........
212.20(c); 212.30(b);                     129              15           1,935  1................           1,935
 212.50(d), 212.60(f).
212.30(b); 212.50(d);                     129           3,758         484,782  .08..............          40,237
 212.60(f).                                                                    (5 min.).........
212.20(c); 212.40(a) and (b).             129               2             258  1................             258
212.40(e)....................             129              36           4,644  .166.............             771
                                                                               (10 min.)........
212.20(c); 212.60(a) and (b);             129              25           3,225  1................           3,225
 212.61(a); 212.70(a), (b),
 and (d).
212.60(g); 212.61(b);                     129             501          64,629  .16..............          10,728
 212.70(d)(2) and (d)(3).                                                      (10 min.)........
212.70(f)....................             129               1             129  1................             129
212.20(c); 212.71(a).........             129              36           4,644  1................           4,644
212.71(b)....................             129               1             129  1................             129
212.20(c); 212.71(d).........             129               1             129  1................             129
212.20(c); 212.90(a).........             129               1             129  1................             129
212.90(b)....................             129             501          64,629  .25..............          16,157
                                                                               (15 min.)........
212.20(c); 212.100(a)........             129               1             129  1................             129
212.100(b) and (c)...........             129               1             129  .5...............              65
                                                                               (30 min.)........
                              ----------------------------------------------------------------------------------
    Total....................  ..............  ..............  ..............  .................         115,400
----------------------------------------------------------------------------------------------------------------
\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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                           Annual
                           21 CFR Section                               Number of       frequency of    Total  annual      Hours per       Total hours
                                                                       respondents       disclosure      disclosures       disclosure
--------------------------------------------------------------------------------------------------------------------------------------------------------
212.70(e)..........................................................             129              .25               32                1               32
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: March 14, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-06351 Filed 3-19-13; 8:45 am]
BILLING CODE 4160-01-P