0667 PET Drugs SSA 2019 Ext

UNITED STATES FOOD & DRUG ADMINISTRATION
Current Good Manufacturing Practice for
Positron Emission Tomography (PET) Drugs
OMB Control No. 0910-0667
SUPPORTING STATEMENT – Part A: Justification
1. Circumstances Making the Collection of Information Necessary
This information collection supports Food and Drug Administration (FDA, the agency, us or
we) regulations pertaining to the Current Good Manufacturing Practice (CGMP) for Positron
Emission Tomography (PET) drugs. PET is a medical imaging modality involving the use of
a unique type of radiopharmaceutical drug product. Our CGMP regulations codified in 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 to be 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.
We therefore request extension of OMB approval for the information collection provisions
found in part 212 of our regulations (21 CFR 212) and discussed in this supporting statement.
2. Purpose and Use of the Information Collection
Respondents to the information collection are manufacturers of PET drugs. We use the
information to ensure compliance with CGMP regulatory requirements applicable to PET
drugs, including: personnel and resources; quality assurance (QA); equipment and facilities;
control of components; in-process materials and finished products; production and process
controls; laboratory controls; and acceptance criteria.

3. Use of Improved Information Technology and Burden Reduction
While the regulations cover record availability, quality, and retention, they do not prescribe a
specific means of recordkeeping other than that records be reasonably accessible to FDA
upon inspection. Because electronic submissions are the standard means of submitting
information to the agency, however, we estimate most 85% respondents will use electronic
means to fulfill the recordkeeping requirements. The agency accepts any recordkeeping
method that complies with the applicable requirements.
Additionally, we have issued the following guidance documents to assist respondents to the
information collection. All guidance documents are issued in accordance with our GGP
regulations under 21 CFR part 10.115 and provide opportunity for comment at any time. All
guidance documents are available from our website at www.fda.gov:
Clinical/Medical
Procedural
Procedural;
Modernization Act
Procedural;
Modernization Act
Pharmaceutical
Quality/Manufacturing
Standards (CGMP)
and Small Entity
Compliance Guide
Procedural

Investigational New Drug Applications for Positron Emission
Tomography (PET) Drugs (PDF - 369KB)
FDA Oversight of PET Drug Products -- Questions and
Answers (PDF - 499KB)
PET Drug Applications - Content and Format for NDAs and ANDAs:
Attachment I: Sample formats for chemistry, manufacturing, and
controls (CMC) sections 2011 (PDF - 614KB)
PET Drug Applications - Content and Format for NDAs and
ANDAs_2011 (PDF - 429KB)
PET Drugs--Current Good Manufacturing Practice (CGMP); Small
Entity Compliance Guide (PDF - 229KB)
Positron Emission Tomography (PET) Drug SPL

4. Efforts to Identify Duplication and Use of Similar Information
We are unaware of duplicative information collection. Information collection is required in
accordance with statutory provisions that are exclusively the responsibility of FDA
pertaining to the manufacture and distribution of PET drugs, and pursuant to 21 CFR 212.
5. Impact on Small Businesses or Other Small Entities
Although the information collection applies to small and large businesses alike, we provide
resources, including small business and industry assistance, to respondents on our website at
https://www.fda.gov/industry/small-business-assistance and through staff within our Center
for Drug Evaluation and Research (CDER). No undue burden is posed on small entities as a
result of the information collection.

2

6. Consequences of Collecting the Information Less Frequently
The information collection schedule is consistent with statutory and regulatory requirements
associated with the CGMP regulations applicable to PET drugs.
7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5
There are no special circumstances for this collection of information.
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the Agency
In accordance with 5 CFR 1320.8(d), we published a 60-day notice inviting public comment
in the Federal Register of March 14, 2019 (84 FR 9347). We received three letters in
response. The comments submitted questioned the necessity of the proposed collection;
suggested we allow both paper recordkeeping and simplified electronic report submission;
questioned whether an Annual Product Review (APR) is required by the regulations; and
identified an inadvertent printed error in one of our burden estimates. A detailed response to
the comments was published in our 30-day notice of, where a summary is provided here:
FDA is Congressionally mandated to promulgate regulations that apply solely to PET drugs.
Accordingly, requirements applicable to PET drugs are codified part 212 of our regulations
(21 CFR 212). We therefore maintain that the information collection is necessary to ensure
the promotion and protection of the public health. Also, as stated previously, the regulations
prescribe no specific means for recordkeeping, however, records must be made reasonably
accessible, as prescribed under 212.110(a). Regarding the question pertaining to Annual
Product Review we defer to the regulations noting the applicable GMP review provisions.
Finally, we are appreciative of the editorial comment regarding the discrepancy in a
disclosure element as it appeared in the text and corresponding table. As correctly noted in
the table and here in this supporting statement, we attribute 2.5 hours, representative of the
industry average, for this information collection element which appears in Table x, row y
below at Question 12a.
9. Explanation of Any Payment or Gift to Respondents
No remuneration is provided to respondents to the information collection.
10. Assurance of Confidentiality Provided to Respondents
Certain data and information collected during an inspection of a drug manufacturing
establishment for the purpose of enforcing compliance with the CGMP regulations are
considered confidential and not releasable to the public. Confidentiality is maintained for
trade secret or confidential, commercial, or financial information under 21 CFR 20.61 and
investigatory records under 21 CFR 20.64. In addition, certain sections of 21 CFR 314.430
provide confidentiality of information contained in NDAs and ANDAs.

3

Upon review of the information collection with agency Privacy Act staff, we have concluded
that information collection does not involve solicitation or collection of personally
identifiable information (PII) by or on behalf of FDA/CDER. Specifically, we do not collect
personally identifiable information (PII) and will not maintain records subject to the Privacy
Act or otherwise operate a Privacy Act System of Records in relation to this specific
collection.
11. Justification for Sensitive Questions
There are no questions of a sensitive nature.
12. Estimates of Annualized Burden Hours and Costs
12a. Annualized Hour Burden Estimate
We estimate the burden of the information as follows:
Table 1.--Estimated One-Time Recordkeeping Burden for Corporate Firms1
Activity/Type of Respondent/21
No. of
No. of
OneAverage
CFR Section
Recordkeepers
Records per
Time
Burden per
Recordkeeper Records Recordkeeper
Batch Production and Control
3
9
27
8
Records
(§§ 212.20(c) and (e) and
212.50(a) and (b))

Total
Hours2
216

Equipment and Facilities
3
13
39
5
195
Records (SOP)
(§§ 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)
(§§ 212.20(c) and 212.40(a) and
(b))
Records of Components,
3
25
75
2
150
Containers, and Closures
(specifications data sheets)
(§§ 212.20(c) and 212.40(a) and
(b))
Out-of-Specification
3
1
3
8
24
Investigations (SOP)
(§§ 212.20(c) and 212.71(a))
Distribution Records (SOP)
3
1
3
8
24
(§§ 212.20(c) and 212.90(a))
Complaints, Recalls
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.

4

Table 2.--Estimated One-Time Recordkeeping Burden for Academia, Small Firms, and High-Risk Component
Manufacturers 1
Activity/Type of
No. of
No. of
One-Time
Average
Total
Respondent/21 CFR Section
Recordkeepers
Records per
Records
Burden per
Hours2
Recordkeeper
Recordkeeper
Batch Production and Control
61
8
488
8
3,904
Records
(§§ 212.20(c) and (e) and
212.50(a) and (b))
Equipment and Facilities
61
13
793
8
6,344
Records (SOP)
(§§ 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)
(§§ 212.20(c) and 212.40(a)
and (b))
Records of Components,
61
2
122
8
976
Containers, and Closures (SOP)
(§§ 212.20(c) and 212.40(a)
and (b))
Out-of-Specification
61
1
61
8
488
Investigations (SOP)
(§§ 212.20(c) and 212.71(a))
Distribution Records (SOP)
61
1
61
8
488
(§§ 212.20(c) and 212.90(a))
Complaints, Recalls
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 Firms1
Activity/21 CFR Section
No. of
No. of
Total
Average
Recordkeepers
Records per
Annual
Burden per
Recordkeeper
Records
Recordkeeper
Batch Production (Creating
115
144
16,560
0.50
Manufacturing Records
(30 minutes)
(creating batch-related
records per year)
(§§ 212.20(c) and (e) and
212.50(a) and (b))
Creating Any New Batch
3
9
27
8
Records/Quality Records
for New or Existing Drugs
(§§ 212.20(c) and (e) and
212.50(a) and (b))
Equipment and Facilities
115
164
18,860
0.50
Records (calibration and
(30 minutes)
cleaning records systems)
(§§ 212.30(b), 212.50(d),
and 212.60(f))

5

Total
Hours2
8,280

216

9,430

Records of Components,
Containers, and Closures
(§§ 212.20(c) and
212.40(a) and (b))
Laboratory Testing
Records (record laboratory
test results)
§§ 212.60(g), 212.61(b),
and 212.70(d)(2) and (3)
Out-of-Specification
Investigations (record
events and investigations)
(§ 212.71(b))
Complaints
(§§ 212.100(b) and (c))
QA and Release of Batches

115

24

2,760

0.50
(30 minutes)

1,380

115

144

16,560

0.50
(30 minutes)

8,280

115

2

230

2

460

115

2

230

2

460

115

144

16,560

0.25
(15 minutes)
0.25
(15 minutes)

4,140

Distribution Records
115
144
16,560
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.
Table 4.--Estimated Annual Recordkeeping Burden for Academia and Small Firms1
Activity/21 CFR Section
No. of
No. of
Total
Average
Recordkeepers
Records per
Annual
Burden per
Recordkeeper
Records
Recordkeeper
Batch Production (creating
52
24
1,248
0.50
manufacturing records) (filling
(30 minutes)
batch related records per year)
(§§ 212.20(c) and (e) and
212.50(a) and (b))
Creating Any New Batch
52
3
156
8
Records/Procedures for New
Drugs
(§§ 212.20(c) and (e) and
212.50(a) and (b))
Equipment and Facilities Records
52
34
1,768
0.50
(calibration and cleaning records)
(30 minutes)
(§§ 212.30(b), 212.50(d), and
212.60(f))
Records of Components,
52
12
624
0.50
Containers, and Closures
(30 minutes)
(incoming acceptance tests)
(§§ 212.20(c) and 212.40(a) and
(b))
Laboratory Testing Records (QC
test results) §§ 212.60(g),
212.61(b) and 212.70(d)(2) and (3)
Out-of-Specification Investigations
(record events and investigations)
(§ 212.71(b))

Total
Hours2
624

1,248

884

312

52

24

1,248

0.50
(30 minutes)

624

52

2

104

2

208

6

Complaints (Record events and
investigations)
(§§ 212.100(b) and (c))
QA and Release of Batches

52

2

104

2

208

52

24

1,248

0.25
(15 minutes)
0.25
(15 minutes)

312

Distribution Records
52
24
1,248
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.
Table 5.--Estimated Annual Recordkeeping Burden for High Risk Component Manufacturers1
Activity/21 CFR Section
No. of
No. of
Total
Average
Total
Recordkeepers
Records per
Annual
Burden per
Hours2
Recordkeeper
Records
Recordkeeper
Batch Production (creating
9
12
108
0.50
54
manufacturing records and
(30 minutes)
batch related records per year)
(§§ 212.20(c) and (e) and
212.50(a) and (b))
Equipment and Facilities
9
16
144
0.50
72
Records (calibration and
(30 minutes)
cleaning records systems)
(§§ 212.30(b), 212.50(d), and
212.60(f))
Records of Components,
9
6
54
0.50
27
Containers, and Closures
(30 minutes)
(incoming acceptance test)
(§§ 212.20(c) and 212.40(a)
and (b))
Laboratory Testing Records
9
12
108
0.50
54
(record QC test results)
(30 minutes)
§§ 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)
(§ 212.71(b))
QA and Release of Batches
9
12
108
0.25
27
(15 minutes)
Distribution Records
9
12
108
0.25
27
(§ 212.90(b))
(15 minutes)
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.

7

Table 6.--Estimated Annual Third-Party Disclosure Burden1
Activity/21 CFR Section
No. of Sterility
No. of
Total Annual
Average
Total
Failure
Disclosures
Disclosures
Burden per
Hours
Incidents
per
Disclosure
Respondent
Sterility Test Failure Notices
12
32
36
2.5
90
(§ 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.

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.
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
8

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.
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

9

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

10

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.

11

For §§ 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
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 nonradioactive 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.
12

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 above.
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.

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12b. Annualized Cost Burden Estimate
Number of
Establishments

Labor
(Months)

RECORDS DAILY IMPLEMENTATION, AUDITS, UPDATES
Academia and Small PET
61
2.25
Producers
Commercial PET Producers
115
1.0
TRAINING:
Academia and Small PET
61
.11
Producers
Commercial PET Producers
115
.11
TOTAL

Wage
(Annual
Salary)

Cost

$164,300

$554,512.23

$164,300

$1,519,774.26

$164,300

$27,109.49

$164,300

$167,175.17
$194,284.66

13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/Capital
Costs
There are no capital, start-up, or operating or maintenance costs associated with this
information collection.
14. Annualized Cost to the Federal Government
Costs for the information collection include periodic inspections of PET drug production
facilities. Assuming 5 full-time employees are needed to conduct these inspections annually,
we calculate $725,000 in total costs to the Federal Government.
15. Explanation for Program Changes or Adjustments
The information collection reflects adjustments. After a review of the information collection,
we have increased the number of respondents based on the number of current production
sites, and we have increased the time burden ascribed to some of the recordkeeping activities
based on informal communications with industry. However, because fewer PET drug
batches have been produced at the respective sites, the burden estimate reflects a decrease of
707,007 fewer records and 73,441 fewer hours, which we believe reflects the average burden
for all respondents. We have also uploaded previously disclosed cost information for
viewing at www.reginfo.gov.
16. Plans for Tabulation and Publication and Project Time Schedule
No tabulated results, or production or project schedules are associated with the information collection.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
The OMB expiration date will be displayed as required by 5 CFR 1320.5.

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18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

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