Document ID: FDA-1996-N-0028-0100
Agency: fda
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-08-01T04:00Z

XXIII  SEQ CHAPTER \h \r 1 . Paperwork Reduction Act of 1995

	This final rule contains information collection requirements that are
subject to review by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).  The title,
description, and respondent description of the information collection
requirements are given below, with estimates of the one-time burden of
establishing written procedures and the annual recordkeeping burden. 
Included in the burden estimates are the time for reviewing
instructions, searching existing data sources, gathering and maintaining
the data needed, and completing and reviewing each collection of
information.

Title: Current Good Manufacturing Practice in Manufacturing, Packaging,
Labeling, or Holding Operations for Dietary Supplements

Description: Section 402(g) of the act gives us explicit authority to
issue a rule establishing current good manufacturing practice
requirements for dietary supplements. Section 402(g)(1) of the act
states that a dietary supplement is adulterated if “it has been
prepared, packed, or held under conditions that do not meet current good
manufacturing practice regulations.”  Section 402(g)(2) of the act
authorizes us to, by regulation, “prescribe good manufacturing
practices for dietary supplements.”  Under section 701(a) of the act
(21 U.S.C. 371), FDA may issue regulations necessary for the efficient
enforcement of the act.  Other relevant legal authority is discussed in
section V of this document. 

We did not receive any direct comments on the Paperwork Reduction Act
analysis of the 2003 CGMP Proposal.  Many comments on the estimated
costs of the 2003 CGMP Proposal stated that we underestimated the annual
number of batches of dietary supplements produced.  Due to a
contractor’s error, we did underestimate the number of batches
produced.  This final paperwork reduction analysis corrects for this
error.  The final analysis also has been revised from the analysis of
the 2003 CGMP Proposal in order to incorporate the effects of revisions
to the proposed regulation, including reorganization. 

Records are an indispensable component of CGMP.  The records required by
this final rule provide the foundation for the planning, control, and
improvement processes that constitute a quality control system. 
Implementation of these processes in a manufacturing operation serves as
the backbone to CGMP.  The records will show what is to be manufactured;
what was, in fact, manufactured; and whether the controls that the
manufacturer put in place to control the identity, purity, strength, and
composition and limits on contaminants and to prevent adulteration were
effective.  Further, records will show whether and what deviations from
control processes occurred, facilitate evaluation and corrective action
concerning these deviations (including, where necessary, whether
associated batches of product should be recalled from the marketplace),
and enable a manufacturer to assure that the corrective action was
effective.  Further, records will show whether and what deviations from
control processes occurred, facilitate evaluation and corrective action
concerning these deviations (including, where necessary, whether
associated batches of product should be recalled from the marketplace),
and enable a manufacturer to assure that the corrective action was
effective. Written procedures and recordkeeping are necessary to provide
the type of documentation that will demonstrate that dietary supplements
are manufactured, packaged, labeled, and held in a manner that will
ensure the quality of the dietary supplements and that the dietary
supplement is packaged and labeled as specified in the master
manufacturing record.  Under section 701(a) of the act, we may issue
regulations necessary for the efficient enforcement of the act.  For
example, if you did not keep records documenting practices performed
during previous production runs, it would be difficult, if not
impossible, for us to determine whether, as stated under section
402(g)(1) of the act, the dietary supplement had been manufactured,
packaged, labeled, and held under conditions that meet these CGMP
requirements.  In addition, bBy requiring records, we will be able to
ensure that you follow CGMPS so that you ensure the quality of your
dietary supplements during manufacturing, packaging, labeling, or
holding operations.  The final rule establishes the minimum
manufacturing practices necessary to ensure that dietary supplements are
manufactured, packaged, labeled, or held in a manner that will ensure
the quality of the dietary supplements during manufacturing, packaging,
labeling or holding operations. 

The records requirements of this final rule include written procedures
and records pertaining to: (1) Personnel; (2) sanitation; (3)
calibration of instruments and controls; (4) calibration, inspection, or
checks of automated, mechanical, or electronic equipment; (5)
maintaining, cleaning, and sanitizing equipment and utensils and other
contact surfaces; (6) water used that may become a component of the
dietary supplement; (7) production and process controls; (8) quality
control; (9) components, packaging, labels and product received for
packaging and labeling; (10) master manufacturing and batch production;
(11) laboratory operations; (12) manufacturing operations; (13)
packaging and labeling operations; (14) holding and distributing
operations; (15) returned dietary supplements; and (16) product
complaints.

Description of Respondents: Manufacturers, dietary supplement
manufacturers, packagers and re-packagers, labelers and re-labelers,
holders, distributors, warehousers, exporters, importers, large
businesses, and small businesses.

The recordkeeping requirements of the final rule are set forth in each
subpart.  In table 18 we list the one-time burdens associated with
establishing written procedures.  In table 19 we list the annual burdens
associated with recordkeeping.  In each table, where the same records
are mentioned in more than one provision of a subpart, we list the
burden under the provisions corresponding to the heading, “Under this
subpart, what records must you make and keep?” For some provisions
listed in table 19, we did not estimate the annual frequency of
recordkeeping because recordkeeping occasions consist of frequent brief
entries of dates, temperatures, monitoring results, or documentation
that specific actions were taken.  Information might be recorded a few
times a day, week, or month.  When the records burden involves frequent
brief entries, we entered one as the default for the annual frequency of
recordkeeping.  For example, many of the records listed under final §
111.35 in table 19, such as final § 111.35(b)(2) (documentation, in
individual equipment logs, of the date of the use, maintenance,
cleaning, and sanitizing of equipment), involve many short sporadic
entries over the course of the year, varying across equipment and plants
in the industry.  We did not attempt to estimate the actual number of
recordkeeping occasions for these provisions, but instead entered an
estimate of the average number of hours per year.  We entered the
default value of 1 as the annual frequency of recordkeeping for these
and similar provisions.  For final § 111.35, the entry for annual
frequency is 1 as a default representing a large number of brief
recordkeeping occasions. 

In many rows of tables 18 and 19, we list a burden under a single
provision that covers the written procedures or records described in
several provisions.  The burden of the master manufacturing record
listed in table 18 under final § 111.210 includes the burden for final
§ 111.205 because the master manufacturing record must include those
written procedures.  Similarly, the burden of the batch production
records listed in table 19 under final § 111.260 includes the burden
for records listed under final § 111.255 because the batch production
records must include those records.  

The annual frequency for batch production records (and other records
kept on a batch basis in table 19) equals the annual number of batches. 
The estimated burden for records kept by batch includes both records
kept for every batch and records kept for some but not all batches.  We
use the annual number of batches as the frequency for records that will
not necessarily be kept for every batch, such as test results or
material review and disposition records, because such records are part
of records, if they are necessary, that will be kept for every batch. 

We estimate the burden of this collection of information as follows:

Table 18.--Estimated One-Time Burden to Establish Written Procedures1

21 CFR Section	Number of Recordkeepers	Annual Frequency per
Recordkeeping	Total Records	Hours per Record	Total Hours2

111.14	15,000	1	15,000	3.6	54,000

111.23	15,000	1	15,000	1	15,000

111.35	400	1	400	36	14,4000

111.95	250	1	250	686	176,5000

111.140	300	1	300	10.7	3,21000

111.180	200	1	200	10	2,000

111.210	250	1	250	12	3,000

111.325	150	1	150	454	67,6000

111.375	260	1	260	9	2,34000

111.430	250	1	250	12.6	3,15000

111.475	15,000	1	15,000	2.1	320,000

111.535	200	1	200	6	1,2000

111.570	30240	1	30240	121	3,3000

Total

	1547,7000

1There are no capital costs or operating costs associated with the
collection of information under this final rule.

Table 19.--Estimated Annual Recordkeeping Burden1 

21 CFR Section	Number of Recordkeepers	Annual Frequency per
Recordkeeping	Total Annual Records	Hours per Record	Total Hours

111.14	15,000	4	60,000	1	60,000

111.23	15,000	1	15,000	0.2	3,000

111.35	400	1 	400	12.5	45,8000

111.95 	250	1	250	45	11,25000

111.140	240	1408163	337280,92000	1	337280,92000

111.180	240	1408163	337280,92000	1	337280,92000

111.210	240	1	240	2.54	5761,000

111.260	17045	1408	23906,36000	1	23906,36000

111.325	120	1	120	15	21,8000

111.375	260	1	260	1.82	4681,000

111.430	50	1	150	12.6	6301,000

111.475	15,000	1	15,000	0.4	6,000

111.535	110	4	440	173.5	76,48000

111.570	2540	76040	17644,000	0.5	8872,000

Total 

	1,099933,204000

1There are no capital costs or operating costs associated with the
collection of information under this final rule.

The burden estimates above are based on our institutional experience
with other CGMP requirements and on data provided by Research Triangle
Institute (RTI) in the “Survey of Manufacturing Practices in the
Dietary Supplement Industry” (Refs. E1 and E2).  

The estimates in both tables of the number of firms affected by each
provision of the rule are based on the percentage of manufacturers,
packagers, labelers, holders, distributors, and warehousers that
reported in the survey that they have not established written SOPs or do
not maintain records that would be required under the final rule. 
Because we do not have survey results for general warehouses, we entered
the approximate number of facilities in that category for those
provisions covering general facilities.  For the dietary supplement
industry, the survey estimated that 1,460 firms would be covered by this
final rule, including manufacturers, packagers, labelers, holders,
distributors, and warehousers.  The time estimates include the burden
involved in documenting that certain requirements are performed and in
recordkeeping.  We used an estimated annual batch production of 1,408
batches per year to estimate the burden of requirements that are related
to the number of batches produced annually, such as final § 111.260,
“What must batch production record include?”.  The estimate of 1,408
batches per year is near the midpoint of the number of annual batches
reported by survey firms.

The length of time that CGMP records must be maintained is set forth in
final § 111.605.  Tables 18 and 19 reflect the estimated burdens for
written procedures, record maintenance, periodically reviewing records
to determine if they may be discarded, and for any associated
documentation for that activity for records that will be required under
part 111.  We have not included a separate estimate of burden for those
sections that require maintaining records in accordance with final §
111.605, but have included those burdens under specific provisions for
keeping records.  For example, final § 111.255(a) requires that the
batch production records be prepared every time a batch is manufactured,
and final § 111.255(d) requires that batch production records be kept
in accordance with final § 111.605.  The estimated burdens for both §
111.255(a) and (d) are included under final § 111.260 (what the batch
record must include).

The information collection provisions of this final rule have been
submitted to OMB for review.

Prior to the effective date of this final rule, we will publish a
document in the Federal Register announcing OMB’s decision to approve,
modify, or disapprove the information collection provisions in this
final rule.  An agency may not conduct or sponsor, and a person is not
required to respond to, a collection of information unless it displays a
currently valid OMB control number.

HHS/FDA-Internal-Deliberative–Confidential

Final PRA 9-28-05, 6-26-06

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