[Federal Register Volume 84, Number 50 (Thursday, March 14, 2019)]
[Notices]
[Pages 9347-9352]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-04716]



[[Page 9347]]

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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 Practices for Positron 
Emission Tomography Drugs

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
an opportunity for public comment on the proposed collection of certain 
information by the Agency. Under the Paperwork Reduction Act of 1995 
(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 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 13, 2019.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before May 13, 2019. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of May 13, 2019. Comments received 
by mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are postmarked or the delivery service 
acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://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 https://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): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, 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 
Practices for Positron Emission Tomography Drugs.'' Received comments, 
those filed in a timely manner (see ADDRESSES), will be placed in the 
docket and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at https://www.regulations.gov or at the Dockets 
Management Staff 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 https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. 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: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

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, 301-796-5733, 
[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

[[Page 9348]]

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 (CGMP) for Positron Emission 
Tomography Drugs

OMB Control Number 0910-0667--Extension

    PET is a medical imaging modality involving the use of a unique 
type of radiopharmaceutical drug product. Our CGMP regulations at part 
212 (21 CFR part 212) are intended to ensure that PET drug products 
meet the requirements of the Federal Food, Drug, and Cosmetic Act (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 (FDAMA) (Pub. L. 
105-115). These CGMP requirements are designed according to the unique 
characteristics of PET drugs, including their short half-lives, and the 
fact that most PET drugs are produced at locations close to the 
patients to whom the drugs are administered.
    The CGMP regulations require the establishment of written 
procedures as well as recordkeeping related to ongoing manufacturing of 
individual PET drugs, testing, and product release activities, 
including any third-party disclosure requirements for producing PET 
drugs. To estimate time spent to comply with the requirements, we 
relied on informal communications with PET producers, FDA staff visits 
to PET facilities, our familiarity with PET and general pharmaceutical 
manufacturing practices with application and supplement submissions, 
and various reports FDA received from 2016 through 2018.

I. Investigational and Research PET Drugs

    Section 212.5(b) (21 CFR 212.5(b)) provides that for 
investigational PET drugs produced under an investigational new drug 
application (IND) and research PET drugs produced with approval of a 
Radioactive Drug Research Committee (RDRC), the requirement (FD&C Act) 
to follow CGMP is met by complying with the regulations under part 212 
or complying with United States Pharmacopeia (USP) 32 Chapter 823. We 
believe that PET production facilities producing drugs under INDs and 
RDRCs are already substantially complying with the recordkeeping 
requirements of USP 32 Chapter 823 (see section 121(b) of FDAMA). Some 
IND and RDRC PET facilities also produce approved NDA (new drug 
application) and abbreviated new drug application (ANDA) PET drugs. 
While we do not have sufficient information to estimate burdens for all 
IND and RDRC PET facilities, our estimates have included those 
facilities that also produce NDA and ANDA PET drugs. Those facilities 
are included under academic and small firms.

II. Recordkeeping Burden

A. One-Time Burden for Corporate Firms

    We estimate corporate firms will have to employ one-time and 
ongoing annual recordkeeping. There are three major PET manufacturing 
corporations and most of the quality, manufacturing, and testing 
procedures are developed at the corporate level and then issued to the 
individual sites located in various States across the country. There 
are an estimated 115 such sites under three major corporations. Thus, 
the burden has been calculated for 3 recordkeepers instead of 115 
individual sites.
    It would take approximately 8 hours for each corporate firm to 
create one master batch record per drug, and an average of three PET 
drugs have been taken into consideration. We also estimate that 
approximately 3 firms will create and maintain approximately 27 records 
associated with production and quality testing for an average of 3 
drugs, with a total recordkeeping burden of approximately 216 hours.
    Sections 212.20(c), 212.30(b), 212.50(d), and 212.60(f) (21 CFR 
212.20(c), 212.30(b), 212.50(d), and 212.60(f)) contain standard 
operating procedures (SOPs) dealing with equipment operation, 
maintenance, and cleaning, including maintenance of physical 
facilities.
    It would take approximately 5 hours for each corporate firm to 
establish and maintain procedures for equipment and facility 
maintenance. We estimate that the 3 corporate firms will establish and 
maintain 39 procedures, with a total recordkeeping burden of 
approximately 195 hours.
    Sections 212.20(c) and 212.40(a) and (b) contain requirements on 
SOPs regarding receiving, testing, and accepting components. We 
estimate that the burden for corporate firms to create procedures for 
acceptance of raw materials and components would be approximately 8 
hours and that there will be approximately three corporate firms 
performing these activities, with a total recordkeeping burden of 
approximately 48 hours. The burden for corporate firms to create 
component specification data sheets would be approximately 2 hours with 
approximately 3 corporate firms performing these activities, with a 
total recordkeeping burden of approximately 150 hours for approximately 
25 component specification sheets for each firm.
    Sections 212.20(c) and 212.71(a) and (b) require that PET drug 
firms establish procedures for investigating ``deviations'' and ``out 
of specifications failures'' of products during manufacturing and 
testing that do not conform to specifications and to conduct these 
investigations and record them as needed. We estimate that it will take 
approximately 8 hours for three corporate firms to establish one 
procedure, with a total recordkeeping burden of approximately 24 hours.
    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 8 hours for 
each corporate firm to establish written procedures regarding 
distribution of PET drugs with a total of approximately three records, 
with a total recordkeeping burden of approximately 24 hours.
    Sections 212.20(c) and 212.100(a), (b), and (c) require that PET 
drug firms establish and maintain written procedures for handling 
complaints and procedures for field alert reports (FARs). We estimate 
that each corporate firm will create three written procedures to 
establish complaints and FARs process and it will take approximately 24 
hours for each corporate firm. A total of 72 hours will be required to 
create 27 procedures by 3 corporate firms.

B. One-Time Burden for Academia, Small Firms, and Precursors

    There is a total of 52 sites combined for academic and small 
commercial firms, including some IND and RDRC sites. There are nine 
starting material/precursors/sterile raw material manufacturing 
entities who are required to follow selected regulations from part 212, 
according to the PET drug definition under section 121(a) of FDAMA and 
codified in section 201(ii)(1)(A) of the FD&C Act (21 U.S.C. 
321(ii)(1)(A)). We will refer to them as high-risk component 
manufacturing firms in the tables and other sections of this document.
    It would take approximately 8 hours for each firm to perform the 
same activities as corporate firms regarding creating master batch 
records and manufacturing and quality procedures.

[[Page 9349]]

We estimate that there will be a total of approximately 488 records, 
with a total recordkeeping burden of approximately 3,904 hours.
    It would take approximately 8 hours for each firm to create 
equipment and facility related procedures as corporate firms. We also 
estimate that there will be a total of approximately 793 records, with 
a total recordkeeping burden of approximately 6,344 hours.
    We also estimate that the burden for each firm to create and 
maintain specification sheets would be approximately 2 hours and that 
there will be a total of approximately 61 firms performing these 
activities, with a total recordkeeping burden of approximately 3,050 
hours. Furthermore, the burden for these firms to create and maintain 
procedures for acceptance of raw materials and components would be 
approximately 8 hours and that there will be a total of approximately 
61 firms performing these activities, with a total recordkeeping burden 
of approximately 976 hours.
    It would take approximately 8 hours for each firm to perform the 
same activities as corporate firms. We estimate that there will be a 
total of approximately 61 records, with a total recordkeeping burden of 
approximately 488 hours.
    We estimate that 61 academia, small firms, and high-risk component 
manufacturers will create about one procedure related to deviations and 
out of specifications and that each firm will expend approximately 8 
hours, for a total of 488 hours. Similarly, 488 hours will be spent for 
procedures on distribution of PET drugs. There will be 3 procedures 
created by each firm related to customer complaints, recalls, and FARs, 
with a total of 156 records from 52 sites and a total of 1,248 hours.

C. Annual Burden for Corporate Firms

    In this section, we considered 115 individual corporate sites under 
the 3 major corporations in our estimates. These activities will be 
related to individual PET drugs manufactured at each of the sites 
located across the country. We estimate that it would take 30 minutes 
each to fill 144 batches (approximately 4 batches/month), for a total 
of 8,280 hours. In the second row of table 3, we have also estimated 
that on an annual basis, some new batch records or quality records may 
have to be created for newly introduced or existing drugs. It would 
take each firm approximately 24 hours for three new quality procedure/
master batch records, with a total recordkeeping burden of 
approximately 216 hours for nine records from three corporate 
organizations.
    We estimate that 115 individual corporate sites belonging to 3 
major corporate entities will create 164 records for equipment 
maintenance, cleaning, calibration, and facilities maintenance records, 
with a total recordkeeping burden of 9,430 hours.
    Sections 212.20(c) and 212.40(a) and (b) also set out requirements 
for raw material and component shipments received at the manufacturing 
facility on an ongoing basis. We estimate that the burden for each firm 
to create incoming raw material acceptance records for 2 shipments per 
month and 30 minutes per shipment will be 1,380 hours for 2,760 records 
from 115 sites.
    Sections 212.60(g), 212.61(b), and 212.70(d)(2) and (3) set out 
requirements for documenting laboratory testing results from each PET 
drug manufactured referred to in laboratory testing, including final 
release testing. Each firm must keep records of different tests for 
each of their products. We estimate that approximately 115 corporate 
sites will document 144 records of cumulative quality control (QC) test 
results (one record with 5 to 6 tests included), with a total 
recordkeeping burden of approximately 8,280 hours.
    We estimate that each firm will take approximately 1 hour to record 
out-of-specification (OOS) events and perform investigations for each 
incident. We also estimate an average of 2 ``Out of Specification'' 
investigations per firm, with a total of 230 records for ``OOS'' 
investigations from 115 sites, which results in a burden of 460 hours. 
This estimate includes any reprocessing or special release events, 
which are very rare.
    Section 212.100(b) and (c) requires that PET drug firms document 
how each complaint is handled. We estimate that this will take 
approximately 2 hours for each site to document and investigate one 
complaint. We estimated 2 complaints per year per site, with a total 
expended hour of 460 hours for 115 individual sites. We believe the 
estimate is appropriate since not all sites receive complaints.
    We also estimate annual recordkeeping for PET drug firms to perform 
quality assurance (QA) and release of manufactured PET drugs from the 
115 corporate sites to be 4,140 hours, for a total of 144 released 
batches estimating 15 minutes per batch.
    Section 212.90(b) requires that corporate firms maintain 
distribution records. We estimate that it will take each firm 
approximately 15 minutes to create a distribution record for each batch 
of PET drug products, with a total burden of approximately 4,140 hours 
for 144 released batches from 115 sites.

D. Annual Burden for Academia and Small Firms

    It is estimated that each firm will expend the same amount of time 
to perform the same activities as corporate firms. Approximately 52 
academia and small firms will fill 1,248 batch and production records, 
totaling 624 hours. For any new master batch record or quality 
procedures we have estimated 156 total records (3 per site), with a 
total of 1,248 hours.
    For calibration and cleaning records like filling information in 
log books for each piece of equipment and documenting calibration 
records in each PET production firm, we estimate approximately 30 
minutes on average for each piece of equipment for all firms. The 
calibration efforts are once per year per equipment, with estimated 10 
pieces of equipment per site. We estimate that 52 academic and small 
firms will record a total of 884 hours for 34 records per site and a 
total of 1,768 records.
    For Sec. Sec.  212.20(c) and 212.40(a) and (b), approximately 1,768 
raw material and component acceptance records will be filled on an 
ongoing annual basis. We estimate that the burden for each firm to 
create incoming raw material acceptance records for 12 shipments per 
year and 30 minutes per shipment will be 312 hours for 624 records from 
52 sites.
    We also estimate that approximately 52 academia and small firms 
will document 1,248 laboratory QC tests for 24 batches of drugs, with a 
total recordkeeping burden of approximately 624 hours.
    We estimate that each firm will take approximately 1 hour each to 
record OOS and customer complaint events and perform investigations. We 
also estimate that an average of two ``Out of Specification'' and 
customer complaints and investigations per firm, with a total of 208 
hours for each category. This estimate has included any reprocessing or 
special batch release events, which have been rarely observed.
    We also estimate annual recordkeeping for PET drug firms to perform 
QA and release of manufactured PET drugs from 52 sites to be 312 hours, 
for a total of 24 batches per site released if estimating 15 minutes 
per batch.
    Section 212.90(b) requires that corporate firms maintain 
distribution records. We estimate that it will take approximately 15 
minutes to create a distribution record for each batch of

[[Page 9350]]

PET drug products, with a total burden of approximately 312 hours for 
24 batches per site.

E. Annual Burden for High-Risk Component Manufacturers

    According to section 121(a) of FDAMA, the PET drug definition 
includes any non-radioactive or radioactive reagents, kits, nuclidic 
generators, target materials, synthesizers, and so forth. FDA performs 
risk assessments of each manufacturer and inspects such manufacturers. 
Sterile manufacturers and complex labels fall under this category, 
including sterile raw material or reagent manufactures. We have 
estimated nine such facilities based on inspections so far and have 
included them in this section. These manufacturers must comply with 
selected sections of part 212 since they are not final PET drug 
manufacturers. We will refer to them as high-risk component 
manufacturers in general in this document.
    We estimate that it would take 9 high-risk component manufacturers 
about 30 minutes to fill each manufacturing batch records (12 per year) 
and that there will be a total of approximately 108 records, with a 
total recordkeeping burden of approximately 54 hours.
    We also estimate that it will take nine component manufacturers 30 
minutes to fill and create equipment and facilities related records, 
with a total recordkeeping burden of 72 hours.
    We estimate that 9 high-risk component manufacturers will document 
54 components, containers, and closures for incoming acceptance tests, 
with a total recordkeeping burden of approximately 27 hours.
    We estimate that 9 high-risk component manufacturers will document 
12 QC records related to 12 batches, with a total recordkeeping burden 
of approximately 54 hours.
    We also estimate annual recordkeeping for PET drug firms to perform 
QA and release manufactured PET drugs from 9 sites to be 27 hours, for 
a total of 108 batches released, estimating 15 minutes per batch.
    We further estimate that it would take each precursor 15 minutes to 
create and maintain distribution records and that there will be 
approximately 108 records, with a total recordkeeping burden of 
approximately 27 hours.

III. Process Verification

    Section 212.50(f)(2) requires that any process verification 
activities and results be recorded. Process verification is usually 
performed as a one-time activity before a product is approved or if any 
major manufacturing process or equipment changes are made. This effort 
to conduct process verification has been estimated under annual new 
creation of master batch records and manufacturing and quality 
procedures in section II of this document.

IV. 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 uncommon, and we have them estimated under 
annual ``OOS'' investigations and final QA release efforts for each 
manufactured batch.

V. Reprocessing Procedures

    Sections 212.20(c) and 212.71(d) require PET drug producers to 
establish and document procedures for reprocessing PET drugs. We rarely 
see any reprocessing option being submitted for application of such 
drugs and, if reprocessing occurs, we have estimated such rare events 
under annual QA release efforts.

VI. Third-Party Disclosure Burden

    Section 212.70(e) requires that PET drug producers notify all 
receiving facilities if a batch fails sterility tests. FDA receives 
FARs reports based on confirmed sterility failures of released PET 
drugs. Based on our experience of such reporting, we estimated a total 
of 12 failures from all 167 sites (corporate, small firms, and 
academia). Therefore, we have estimated that 12 PET drug producers will 
file 2 reports to FDA and send a notification to the affected clinical/
receiving site per year. PET drug producers would transmit the notice 
by email or Fax and submit the FARs notice to FDA electronically, with 
2 hours per incident in total.
    We estimate the burden of the information collection as follows:

                    Table 1--Estimated One-Time Recordkeeping Burden for Corporate Firms \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                    Average burden
 Activity/type of respondent/21      Number of      records per      One-time           per         Total hours
           CFR section             recordkeepers   recordkeeper       records      recordkeeper         \2\
----------------------------------------------------------------------------------------------------------------
Batch Production and Control                   3               9              27               8             216
 Records (Sec.  Sec.   212.20(c)
 and (e) and 212.50(a) and (b)).
Equipment and Facilities Records               3              13              39               5             195
 (SOP) (Sec.  Sec.   212.20(c),
 212.30(b) 212.50(d), and
 212.60(f)).....................
Records of Components,                         3               2               6               8              48
 Containers, and Closures (SOP)
 (Sec.  Sec.   212.20(c) and
 212.40(a) and (b)).............
Records of Components,                         3              25              75               2             150
 Containers, and Closures
 (specifications data sheets)
 (Sec.  Sec.   212.20(c) and
 212.40(a) and (b)).............
Out-of-Specification                           3               1               3               8              24
 Investigations (SOP) (Sec.
 Sec.   212.20(c) and 212.71(a))
Distribution Records (SOP) (Sec.               3               1               3               8              24
  Sec.   212.20(c) and
 212.90(a)).....................
Complaints, Recalls (Sec.  Sec.                3               3               9               8              72
  212.20(c) and 212.100(a)).....
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............             729
----------------------------------------------------------------------------------------------------------------
\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.


[[Page 9351]]


       Table 2--Estimated One-Time Recordkeeping Burden for Academia, Small Firms, and High-Risk Component
                                                Manufacturers \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                    Average burden
 Activity/type of respondent/21      Number of      records per      One-time           per         Total hours
           CFR section             recordkeepers   recordkeeper       records      recordkeeper         \2\
----------------------------------------------------------------------------------------------------------------
Batch Production and Control                  61               8             488               8           3,904
 Records (Sec.  Sec.   212.20(c)
 and (e) and 212.50(a) and (b)).
Equipment and Facilities Records              61              13             793               8           6,344
 (SOP) (Sec.  Sec.   212.20(c),
 212.30(b) 212.50(d), and
 212.60(f)).....................
Records of Components,                        61              25           1,525               2           3,050
 Containers, and Closures
 (specification only) (Sec.
 Sec.   212.20(c) and 212.40(a)
 and (b)).......................
Records of Components,                        61               2             122               8             976
 Containers, and Closures (SOP)
 (Sec.  Sec.   212.20(c) and
 212.40(a) and (b)).............
Out-of-Specification                          61               1              61               8             488
 Investigations (SOP) (Sec.
 Sec.   212.20(c) and 212.71(a))
Distribution Records (SOP) (Sec.              61               1              61               8             488
  Sec.   212.20(c) and
 212.90(a)).....................
Complaints, Recalls (Sec.  Sec.               52               3             156               8           1,248
  212.20(c) and 212.100(a)).....
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............          16,498
----------------------------------------------------------------------------------------------------------------
\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 3--Estimated Annual Recordkeeping Burden for Corporate Firms \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 (Creating Manufacturing                  115             144          16,560  0.50 (30 minutes)........................           8,280
 Records) (creating batch-related records per
 year) (Sec.  Sec.   212.20(c) and (e) and
 212.50(a) and (b)).
Creating Any New Batch Records/Quality                      3               9              27  8........................................             216
 Records for New or Existing Drugs (Sec.
 Sec.   212.20(c) and (e) and 212.50(a) and
 (b)).
Equipment and Facilities Records (calibration             115             164          18,860  0.50 (30 minutes)........................           9,430
 and cleaning records systems) (Sec.  Sec.
 212.30(b), 212.50(d), and 212.60(f)).
Records of Components, Containers, and                    115              24           2,760  0.50 (30 minutes)........................           1,380
 Closures (Sec.  Sec.   212.20(c) and
 212.40(a) and (b)).
Laboratory Testing Records (record laboratory             115             144          16,560  0.50 (30 minutes)........................           8,280
 test results) (Sec.  Sec.   212.60(g),
 212.61(b), and 212.70(d)(2) and (3)).
Out-of-Specification Investigations (record               115               2             230  2........................................             460
 events and investigations) (Sec.
 212.71(b)).
Complaints (Sec.  Sec.   212.100(b) and (c)).             115               2             230  2........................................             460
QA and Release of Batches....................             115             144          16,560  0.25 (15 minutes)........................           4,140
Distribution Records (Sec.   212.90(b))......             115             144          16,560  0.25 (15 minutes)........................           4,140
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................          36,786
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 4--Estimated Annual Recordkeeping Burden for Academia and Small Firms \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 (creating manufacturing                   52              24           1,248  0.50 (30 minutes)........................             624
 records) (filling batch related records per
 year) (Sec.  Sec.   212.20(c) and (e) and
 212.50(a) and (b)).
Creating Any New Batch Records/Procedures for              52               3             156  8........................................           1,248
 New Drugs (Sec.  Sec.   212.20(c) and (e)
 and 212.50(a) and (b)).
Equipment and Facilities Records (calibration              52              34           1,768  0.50 (30 minutes)........................             884
 and cleaning records) (Sec.  Sec.
 212.30(b), 212.50(d), and 212.60(f)).
Records of Components, Containers, and                     52              12             624  0.50 (30 minutes)........................             312
 Closures (incoming acceptance tests) (Sec.
 Sec.   212.20(c) and 212.40(a) and (b)).
Laboratory Testing Records (QC test results)               52              24           1,248  0.50 (30 minutes)........................             624
 (Sec.  Sec.   212.60(g), 212.61(b) and
 212.70(d)(2) and (3)).

[[Page 9352]]

 
Out-of-Specification Investigations (record                52               2             104  2........................................             208
 events and investigations) (Sec.
 212.71(b)).
Complaints (Record events and investigations)              52               2             104  2........................................             208
 (Sec.  Sec.   212.100(b) and (c)).
QA and Release of Batches....................              52              24           1,248  0.25 (15 minutes)........................             312
Distribution Records (Sec.   212.90(b))......              52              24           1,248  0.25 (15 minutes)........................             312
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................           4,732
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 5--Estimated Annual Recordkeeping Burden for High Risk Component Manufacturers \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 (creating manufacturing                    9              12             108  0.50 (30 minutes)........................              54
 records and batch related records per year)
 (Sec.  Sec.   212.20(c) and (e) and
 212.50(a) and (b)).
Equipment and Facilities Records (calibration               9              16             144  0.50 (30 minutes)........................              72
 and cleaning records systems) (Sec.  Sec.
 212.30(b), 212.50(d), and 212.60(f)).
Records of Components, Containers, and                      9               6              54  0.50 (30 minutes)........................              27
 Closures (incoming acceptance test) (Sec.
 Sec.   212.20(c) and 212.40(a) and (b)).
Laboratory Testing Records (record QC test                  9              12             108  0.50 (30 minutes)........................              54
 results) Sec.  Sec.   212.60(g), 212.61(b)
 and 212.70(d)(2) and (3).
Out-of-Specification Investigations (Record                 9               1               9  1........................................               9
 events and investigations) (Sec.
 212.71(b)).
QA and Release of Batches....................               9              12             108  0.25 (15 minutes)........................              27
Distribution Records (Sec.   212.90(b))......               9              12             108  0.25 (15 minutes)........................              27
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................             270
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 6--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                    Number of
                                                                    sterility        Number of       Total annual    Average burden per
                    Activity/21 CFR section                          failure      disclosures per    disclosures         disclosure        Total hours
                                                                    incidents        respondent
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sterility Test Failure Notices (Sec.   212.70(e))..............              12            \2\ 3               36                  2.5               90
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ There are two reports sent to FDA per incident and notification to receiving site.

    These burden estimates reflect adjustments since last OMB approval. 
Previously we had based the estimated number of respondents on the 
number of individual production sites, however we believe using the 
number of registered organizations better reflects the burden 
attributable to information collection. This results in an overall 
decrease to the collection.

    Dated: March 8, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019-04716 Filed 3-13-19; 8:45 am]
BILLING CODE 4164-01-P