[Federal Register Volume 84, Number 171 (Wednesday, September 4, 2019)]
[Notices]
[Pages 46537-46543]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-19030]


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

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 Practices 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 October 
4, 2019.

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. 
Also include the FDA docket number found in brackets in the heading of 
this document.

[[Page 46538]]


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: 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 (CGMP) for Positron Emission 
Tomography (PET) 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) 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.

[[Page 46539]]

    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. 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.

[[Page 46540]]

    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 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 
2.5 hours per incident in total.
    In the Federal Register of November 30, 2018 (83 FR 61653), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. Three comments were received and are 
summarized here.
    One comment questioned the necessity of this proposed collection. 
One comment suggested that FDA allow both paper recordkeeping and 
simplified electronic report submission. Two comments questioned some 
of FDA's burden collection estimates. Two comments questioned whether 
Annual Product Review (APR) is being required by the regulations. Two 
comments pertained to an inadvertent oversight in section VI. Third-
Party Disclosure.
    FDA believes that this proposed collection is necessary in keeping 
with the Agency's mission of ensuring the safety and efficacy of human 
drugs. Regarding the estimates included, FDA has taken a generalized 
approach for these estimates, assuming that corporate firms will take 
on certain burdens for all facilities under their purview, rather than 
calculating all burdens per facility, and understanding that due to 
variation among facilities the number of batches and products being 
produced will vary. We have also only included estimates for tasks that 
are included within part 212 and note that some of the comments 
referenced tasks, such as APR, that are outside that scope. Electronic 
recordkeeping is also outside the scope of this regulation. Regarding 
the typographical error in section VI. Third Party Disclosure, on page 
9350, we estimate that it will take PET drug producers 2 hours to 
submit to FDA notices of sterility test failures. We intended to 
estimate 2.5 hours as accurately shown in Table 6, page 9352. In 
section VI of this document, we have included this change. We 
appreciate these comments and will continue to consider the burden 
estimate. If commenters believe certain estimates are insufficient, we 
request comments on specific estimates for these requirements and why 
alternative estimates would be more accurate.
    The estimated burden of the information collection, therefore, is 
as follows:

                    Table 1--Estimated One-Time Recordkeeping Burden for Corporate Firms \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
 Activity/type of respondent/21      Number of      records per      One-time       burden 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)).

[[Page 46541]]

 
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.


       Table 2--Estimated One-Time Recordkeeping Burden for Academia, Small Firms, and High-Risk Component
                                                Manufacturers \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
 Activity/type of respondent/21      Number of      records per      One-time       burden 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                        Average
     Activity/21 CFR section         Number of      records per    Total annual     burden per      Total hours
                                   recordkeepers   recordkeeper       records      recordkeeper         \2\
----------------------------------------------------------------------------------------------------------------
Batch Production (Creating                   115             144          16,560          * 0.50           8,280
 Manufacturing 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/                3               9              27               8             216
 Quality Records for New or
 Existing Drugs (Sec.  Sec.
 212.20(c) and (e) and 212.50(a)
 and (b)).......................
Equipment and Facilities Records             115             164          18,860          * 0.50           9,430
 (calibration and cleaning
 records systems) (Sec.  Sec.
 212.30(b), 212.50(d), and
 212.60(f)).....................
Records of Components,                       115              24           2,760          * 0.50           1,380
 Containers, and Closures (Sec.
 Sec.   212.20(c) and 212.40(a)
 and (b)).......................
Laboratory Testing Records                   115             144          16,560          * 0.50           8,280
 (record laboratory test
 results) (Sec.  Sec.
 212.60(g), 212.61(b), and
 212.70(d)(2) and (3))..........
Out-of-Specification                         115               2             230               2             460
 Investigations (record events
 and investigations) (Sec.
 212.71(b)).....................
Complaints (Sec.  Sec.                       115               2             230               2             460
 212.100(b) and (c))............
QA and Release of Batches.......             115             144          16,560          + 0.25           4,140
Distribution Records (Sec.                   115             144          16,560          + 0.25           4,140
 212.90(b)).....................
                                 -------------------------------------------------------------------------------
    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.

[[Page 46542]]

 
* (30 minutes).
+ (15 minutes).


                 Table 4--Estimated Annual Recordkeeping Burden for Academia and Small Firms \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
     Activity/21 CFR section         Number of      records per    Total annual     burden per      Total hours
                                   recordkeepers   recordkeeper       records      recordkeeper         \2\
----------------------------------------------------------------------------------------------------------------
Batch Production (creating                    52              24           1,248          * 0.50             624
 manufacturing 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/               52               3             156               8           1,248
 Procedures for New Drugs (Sec.
 Sec.   212.20(c) and (e) and
 212.50(a) and (b)).............
Equipment and Facilities Records              52              34           1,768          * 0.50             884
 (calibration and cleaning
 records) (Sec.  Sec.
 212.30(b), 212.50(d), and
 212.60(f)).....................
Records of Components,                        52              12             624          * 0.50             312
 Containers, and Closures
 (incoming acceptance tests)
 (Sec.  Sec.   212.20(c) and
 212.40(a) and (b)).............
Laboratory Testing Records (QC                52              24           1,248          * 0.50             624
 test results) (Sec.  Sec.
 212.60(g), 212.61(b) and
 212.70(d)(2) and (3))..........
Out-of-Specification                          52               2             104               2             208
 Investigations (record events
 and investigations) (Sec.
 212.71(b)).....................
Complaints (Record events and                 52               2             104               2             208
 investigations) (Sec.  Sec.
 212.100(b) and (c))............
QA and Release of Batches.......              52              24           1,248          + 0.25             312
Distribution Records (Sec.                    52              24           1,248          + 0.25             312
 212.90(b)).....................
                                 -------------------------------------------------------------------------------
    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.
* (30 minutes).
+ (15 minutes).


            Table 5--Estimated Annual Recordkeeping Burden for High Risk Component Manufacturers \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
     Activity/21 CFR section         Number of      records per    Total annual     burden per      Total hours
                                   recordkeepers   recordkeeper       records      recordkeeper         \2\
----------------------------------------------------------------------------------------------------------------
Batch Production (creating                     9              12             108          * 0.50              54
 manufacturing records and batch
 related records per year) (Sec.
  Sec.   212.20(c) and (e) and
 212.50(a) and (b)).............
Equipment and Facilities Records               9              16             144          * 0.50              72
 (calibration and cleaning
 records systems) (Sec.  Sec.
 212.30(b), 212.50(d), and
 212.60(f)).....................
Records of Components,                         9               6              54          * 0.50              27
 Containers, and Closures
 (incoming acceptance test)
 (Sec.  Sec.   212.20(c) and
 212.40(a) and (b)).............
Laboratory Testing Records                     9              12             108          * 0.50              54
 (record QC test results) (Sec.
 Sec.   212.60(g), 212.61(b) and
 212.70(d)(2) and (3))..........
Out-of-Specification                           9               1               9               1               9
 Investigations (Record events
 and investigations) (Sec.
 212.71(b)).....................
QA and Release of Batches.......               9              12             108          + 0.25              27
Distribution Records (Sec.                     9              12             108          + 0.25              27
 212.90(b)).....................
                                 -------------------------------------------------------------------------------
    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.
* (30 minutes).
+ (15 minutes).


                           Table 6--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
                                     Number of       Number of
                                     sterility      disclosures    Total annual       Average
     Activity/21 CFR section          failure           per         disclosures     burden per      Total hours
                                     incidents      respondent                      disclosure
----------------------------------------------------------------------------------------------------------------
Sterility Test Failure Notices                12           \2\ 3              36             2.5              90
 (Sec.   212.70(e)).............
----------------------------------------------------------------------------------------------------------------
\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.


[[Page 46543]]

    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: August 26, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-19030 Filed 9-3-19; 8:45 am]
 BILLING CODE 4164-01-P