0139 SSA Finished Pharmaceuticals 2018 Ext

U.S. Food & Drug Administration
Current Good Manufacturing Practices (CGMP)
for Finished Pharmaceuticals, and CGMP for Medical Gases
OMB Control No. 0910-0139
SUPPORTING STATEMENT Part A: Justification
1. Circumstances Making the Collection of Information Necessary
This information collection supports Food and Drug Administration (FDA, us or we)
regulations regarding finished pharmaceuticals and biological products, including drug product
containers and closures for medical gas. Under Section 501(a)(2)(B) of the Federal Food,
Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 351(a)(2)(B)), a drug is adulterated if the
methods used in, or the facilities or controls used for, its manufacture, processing, packing, or
holding do not conform to or are not operated or administered in conformity with current good
manufacturing practice (CGMP) regulations. FDA is responsible for enforcing the FD&C Act
as well as related statutes, including the Public Health Service (PHS) Act. Congress enacted
these laws to ensure that covered products meet applicable requirements regarding the safety,
identity and strength, and the quality and purity characteristics they purport or are represented
to possess, and are labeled with adequate warnings and instructions for use.
The pharmaceutical or drug quality-related regulations appear in several parts of Title 21 (Food
and Drugs) CFR, including sections in parts 1-99, 200-299, 300-499, 600-799, and 800-1299.
The regulations enable a common understanding of the regulatory process by describing
requirements to be followed by drug manufacturers, applicants, and FDA. This particular
information collection supports regulations codified at 21 CFR Part 210: Current Good
Manufacturing Practice (CGMP) in manufacturing, processing, packing, or holding of drugs
that include general recordkeeping requirements applicable to drug products. The information
collection also supports regulations codified at 21 CFR Part 211: Current Good Manufacturing
Practice for Finished Pharmaceuticals which sets forth “minimum [CGMP] for preparation of
drug products (excluding positron emission tomography drugs) for administration to humans
or animals.” Under 21 CFR Part 211 (see 21 CFR Part 211.180) specific requirements for
medical gas containers and closures are also found in the regulations, which were finalized by
rulemaking on November 18, 2016 (82 FR 81685) (see 21 CFR Part 211 Subpart E). Finally,
the information collection also supports regulations codified under 21 CFR Subchapter F:
Biologics: Part 610 – General Biologicals Products Standards; and Part 680 – Additional
Standards for Miscellaneous Products. Specifically, parts 610 and 680 (21 CFR parts 610 and
680) reference certain CGMP regulations in part 211: §§ 610.12(g), 610.13(a)(2), 610.18(d),
680.2(f), and 680.3(f).
These regulations set forth information collection requirements that allow FDA to meet its
public health protection responsibilities. Products that fail to comply with CGMP requirements
may be rendered adulterated under section 501(a)(2)(B) of the FD&C Act. We therefore
request extension of OMB approval for the information collection found under 21 CFR Parts

211, 610, and 680 as identified and discussed in this supporting statement; and associated
guidance documents developed to assist respondents with the regulatory requirements.
2. Purpose and Use of the Information Collection
Consistent with the regulations, records maintained shall be made readily available for
authorized inspection. FDA is authorized to inspect these records under section 704 of the
FD&C Act (21 U.S.C. 374) (and its enforcement section under section 301(f) of the FD&C Act
21 U.S.C. 331(f)). We use the information to help determine compliance with regulatory
requirements established to ensure the safety and efficacy of the covered products. Our review
also serves to establish accountability in the manufacturing and processing of drug products,
facilitate productive inspections, and enable manufacturers to improve the quality of drug
products made available to consumers. The information collection also facilitates product
recall activities in the event a product recall becomes necessary.
3. Use of Improved Information Technology and Burden Reduction
While the regulations do not prescribe specific recordkeeping methods, we believe all
respondents will use electronic means to fulfill the information collection requirements. Also,
to assist respondents with the information collection requirements for medical gases, we
developed a draft guidance for industry entitled, “Current Good Manufacturing Practice for
Medical Gases.” The guidance document discusses our recommendations regarding
compliance with applicable requirements found in the regulations as they apply to these
products. We believe the recommendations, when followed, will help respondents focus their
information collection activities most efficiently with regard to demonstrating regulatory
compliance.
4. Efforts to Identify Duplication and Use of Similar Information
We are unaware of duplicative information collection. As previously mentioned, GMP or
quality system (QS) regulations appear in several parts of Title 21 (Food and Drugs) of the
CFR. This collection covers provisions associated with requirements for finished
pharmaceuticals under 21 CFR Part 211. Related collection OMB Control No. 0910-0585:
Medical Gas Containers and Closures; Current Good Manufacturing Practice Requirements
was established in support of recently finalized rulemaking (RIN 0910-AC53) and expires May
31, 2020. Before the next extension/renewal of either collection will consider how best to
consolidate the information collections.
5. Impact on Small Businesses or Other Small Entities
Any exemption or exceptions to the regulations would threaten the assurance of product safety
and thus pose unreasonable potential threats to the public health. At the same time, we do not
believe the information collection imposes undue burden on small entities. However, we
provide assistance to small businesses through agency staff and published resources, available
on our website at www.fda.gov.

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6. Consequences of Collecting the Information Less Frequently
The information collection schedule is consistent with statutory provisions and applicable
regulations.
7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5
There are no special circumstances for the 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), FDA published a 60-day notice for public comment in the
Federal Register of December 14, 2017 (82 FR 58811). FDA received no comments that
pertained to the information collection. At the same time, we engage with respondents to the
information collection both formally and informally through seminars, conferences, workshops,
academia and other forums to encourage open communication on evolving standards and other
topics related to safe drug product manufacturing and quality assurance.
9. Explanation of Any Payment or Gift to Respondents
No payment or gift was provided to respondents.
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 subparagraphs of 21 CFR
314.430 provide confidentiality of information contained in NDAs and ANDAs.
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 hourly burden of the information collection as follows:

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Table 1.- Estimated Annual Recordkeeping Burden1

21 CFR Section;
Activity
SOP Maintenance
New Startup SOPs
211.34; Consultants
211.67(c); Equipment cleaning
and maintenance
211.68; Changes in master
production and control records
or other records
211.68(a); Automatic,
mechanical, and electronic
equipment
211.68(b); Computer or related
systems
211.72; Filters
211.80(d); Components and
drug product containers or
closures
211.100(b); Production and
process controls
211.105(b); Equipment
identification
211.122(c); Labeling and
packaging material
211.130(e); Labeling and
packaging facilities
211.132(c); Tamper-evident
packaging
211.132(d); Tamper-evident
packaging
211.137; Expiration dating
211.160(a); Laboratory
controls
211.165(e); Test methodology
211.166; Stability testing
211.173; Laboratory animals
211.180(e); Production,
control, and distribution
records
211.180(f); Procedures for
notification of regulatory
actions
211.182; Equipment cleaning
and use log
211.184; Component, drug
product container, closure, and
labeling records

25
0.25

Total
Annual
Records
3,270
1,250
818

Avg. Burden
per
Recordkeeping
(in hours)1
25
20
5

Total
Hours
81,750
25,000
4090

3,270

50

163,500

0.25

40,875

3,270

2

6,540

1

6,540

3,270

10

32,700

0.5

16,350

3,270

5

16,350

0.25

4,088

416

0.25

104

1

104

3,270

0.25

818

0.1

82

3,270

3

9,810

2

19,620

3,270

0.25

818

0.25

205

3,270

50

163,500

0.25

40,875

3,270

50

163,500

0.25

40,875

1,613

20

32,260

0.5

16,130

1,613

0.2

323

0.5

162

3,270

5

16,350

0.5

8,175

3,270

2

6,540

1

6,540

3,270
3,270
33

1
2
1

3,270
6,540
33

1
0.5
0.25

3,270
3,270
8

3,270

0.2

654

0.25

164

3,270

0.2

654

1

654

3,270

2

6,540

0.25

1,635

3,270

3

9,810

0.5

4,905

No. of
Recordkeepers
3,270
50
3,270

No. of Records
per
Recordkeeper

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21 CFR Section;
Activity
211.186; Master production
and control records
211.188; Batch production and
control records
211.192; Discrepancies in drug
product production and control
records
211.194; Laboratory records
211.196; Distribution records
211.198; Compliant files
211.204; Returned drug
products
Total
1

Avg. Burden
per
Recordkeeping
(in hours)1

No. of
Recordkeepers

No. of Records
per
Recordkeeper

Total
Annual
Records

3,270

10

32,700

2

65,400

3,270

25

81,750

2

163,500

3,270

2

6,540

1

6,540

3,270
3,270
3,270

25
25
5

81,750
81,750
16,350

0.5
0.25
1

40,875
20,438
16,350

3,270

10

32,700

0.5

16,350

979,492

Total
Hours

654,820

There are no capital or operating and maintenance costs associated with the information collection.

Based on our experience with the collection and a review of our data, we estimate the CGMP
provisions apply to 3,270 firms and use this figure to calculate the respective recordkeeping
activities. In addition, we assume some existing firms will expand into new manufacturing
areas and that startup firms will need to create SOPs. As reflected above, we estimate 50 firms
will create up to 25 SOPs each for a total of 1,250 records, and that it will take 20 hours per
recordkeeper to create 25 new SOPs for a total of 25,000 hours. In addition, estimated burden
for information collection activity associated with regulations under 21 CFR §§ 610.12(g),
610.13(a)(2), 610.18(d), 680.2(f), and 680.3(f) is included in the burden estimates under
§§ 211.165, 211.167, 211.188, and 211.194, as appropriate.
Table 2 reflects burden associated with the same recordkeeping requirements as they apply to
medical gas containers and closures, as regulations covering these products have recently been
amended.
Table 2.--Estimated Annual Recordkeeping Burden (Medical Gases)1
Avg. Burden
No. of
Total
per
21 CFR Section;
No. of
Records per
Annual Recordkeeping
Activity
Recordkeepers Recordkeeper Records
(in hours)1
SOP Maintenance
2,284
0.65
1,485
25
New startup SOPs
100
25
2,500
20
211.34; Consultants
2,284
0.25
571
0.5
211.67(c); Equipment
2,284
32.5
74,230
0.25
cleaning and maintenance
211.68; Changes in master
production and control
2,284
2
4,568
1
records or other records
211.68(a); Automatic,
mechanical, and electronic
2,284
10
22,840
0.5
equipment
211.68(b); Computer or
2,284
5
11,420
0.25
related systems
211.72; Filters
2,284
0.25
571
1

5

Total
Hours
37,125
50,000
286
18,558
4,568

11,420
2,855
571

21 CFR Section;
Activity
211.80(d); Components and
drug product containers or
closures
211.100(b); Production and
process controls
211.105(b); Equipment
identification
211.122(c); Labeling and
packaging material
211.130(e); Labeling and
packaging facilities
211.132(c); Tamper-evident
packaging
211.132(d); Tamper-evident
packaging
211.137; Expiration dating
211.160(a); Laboratory
controls
211.165(e); Test methodology
211.166; Stability testing
211.173; Laboratory animals
211.180(e); Production,
control, and distribution
records
211.180(f); Procedures for
notification of regulatory
actions
211.182; Equipment cleaning
and use log
211.184; Component, drug
product container, closure,
and labeling records
211.186; Master production
and control records
211.188; Batch production
and control records
211.192; Discrepancies in
drug product production and
control records
211.194; Laboratory records
211.196; Distribution records
211.198; Complaint files
211.204; Returned drug
products
Total
1

No. of
Recordkeepers

No. of
Records per
Recordkeeper

Total
Annual
Records

Avg. Burden
per
Recordkeeping
(in hours)1

2,284

0.25

571

0.1

57

2,284

3

6,382

2

13,704

2,284

0.25

571

0.25

143

2,284

50

114,200

0.25

28,550

2,284

50

114,200

0.25

28,550

2,284

20

45,680

0.5

22,840

2,284

0.2

457

0.5

229

2,284

3.25

7,423

0.33

2,450

2,284

2

4,568

1

4,568

2,284
2,284
2,284

1
1.3
1

2,284
2,969
2,284

1
0.33
0.25

2,284
980
571

2,284

0.2

457

0.25

114

2,284

0.2

457

1

457

2,284

1.3

2,969

0.16

475

2,284

1.95

4,454

0.33

1,470

2,284

10

22,840

2

45,680

2,284

16.25

37,115

1.3

48,250

2,284

2

4,568

1

4,568

2,284
2,284
2,284

25
25
5

57,100
57,100
11,420

0.5
0.25
1

28,550
14,275
11,420

2,284

10

22,840

0.5

11,420

641,094

There are no capital or operating and maintenance costs associated with the information collection..

6

Total
Hours

396,988

12b. Annualized Cost Burden Estimate
Type of Respondent
Pharmaceutical industry average wage
grade for maintaining this information
collection

Total Burden
Hours
1,051,808

Hourly Wage
Rate
$85.00

Total Respondent
Costs
$89,403,680

13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/Capital Costs
There are no capital, start-up, operating or maintenance costs associated with this information
collection.
14. Annualized Cost to the Federal Government
FDA allocates approximately 283 full-time-employees (FTE’s) annually to ensure industry
compliance with the information collection. Using 2018 OPM and BOL data and assuming a
fully-loaded annual salary of $175,000, we calculate the annual cost to the Federal government
is 49,525,000.
15. Explanation for Program Changes or Adjustments
The information collection reflects changes and adjustments. The collection has been revised
to include new requirements applicable to medical gas containers and closures resulting from
rulemaking (0910-AC53). Also, we have reorganized and consolidated previously itemized
recordkeeping burdens found in the tables of our 60- and 30-day Federal Register notices as
they will appear at www.reginfo.gov. We believe this will better assist the reader in
understanding fluctuations to the information collection. In doing so, we discovered and made
corrections to nominal calculation errors that appeared in our notices and we regret this
oversight. Cumulatively, these changes and adjustments have resulted in an increase to the
collection of 319,491 annual responses and 169,605 burden hours.
16. Plans for Tabulation and Publication and Project Time Schedule
We have no such plans for the information collection.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
There is no display of the expiration date.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

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