[Federal Register: June 14, 2004 (Volume 69, Number 113)]
[Notices]
[Page 33035-33040]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr14jn04-89]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2004N-0034]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Medical Devices;
Current Good Manufacturing Practice Quality System Regulation
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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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
[[Page 33036]]
(OMB) for review and clearance under the Paperwork Reduction Act of
1995.
DATES: Fax written comments on the collection of information by July
14, 2004.
ADDRESSES: OMB is still experiencing significant delays in the regular
mail, including first class and express mail, and messenger deliveries
are not being accepted. To ensure that comments on the information
collection are received, OMB recommends that comments be faxed to the
Office of Information and Regulatory Affairs, OMB, Attn: Fumie Yokota,
Desk Officer for FDA, FAX: 202-395-6974.
FOR FURTHER INFORMATION CONTACT: Peggy Robbins, Office of Management
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-1223.
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.
Medical Devices; Current Good Manufacturing Practice (CGMP) Quality
System (QS) Regulations--21 CFR Part 820 (OMB Control Number 0910-
0073)--Extension
Under section 520(f) of the Federal Food, Drug, and Cosmetic Act
(the act) (21 U.S.C. 360j(f)), the Secretary of the Department of
Health and Human Services (the Secretary) has the authority to
prescribe regulations requiring that the methods used in, and the
facilities and controls used for, the manufacture, pre-production
design validation (including a process to assess the performance of a
device but not including an evaluation of the safety and effectiveness
of a device), packing, storage, and installation of a device conform to
CGMP, as described in such regulations, to assure that the device will
be safe and effective and otherwise in compliance with the act.
The CGMP/QS regulation implementing the authority provided by this
statutory provision is found at part 820 (21 CFR part 820) and sets
forth basic CGMP requirements governing the design, manufacture,
packing, labeling, storage, installation, and servicing of all finished
medical devices intended for human use. The authority for this
regulation is covered under the act (21 U.S.C. 351, 352, 360, 360c,
360d, 360e, 360h, 360i, 360j, 360l, 371, 374, 381, and 383). The CGMP/
QS regulation includes requirements for purchasing and service
controls, clarifies recordkeeping requirements for device failure and
complaint investigations, clarifies requirements for verifying/
validating production processes and process or product changes, and
clarifies requirements for product acceptance activities quality data
evaluations and corrections of nonconforming product/quality problems.
Requirements are compatible with specifications in international
quality standards, ISO (International Organization for Standardization)
9001 entitled ``Quality Systems Model for Quality Assurance in Design/
Development, Production, Installation, and Servicing.'' CGMP/QS
information collections will assist FDA inspections of manufacturer
compliance with quality system requirements encompassing design,
production, installation, and servicing processes.
Section 820.20(a) through (e) requires management with executive
responsibility to establish, maintain, and/or review these topics: The
quality policy, the organizational structure, the quality plan, and the
quality system procedures of the organization. Section 820.22 requires
the conduct and documentation of quality system audits and reaudits.
Section 820.25(b) requires the establishment of procedures to identify
training needs and documentation of such training.
Section 820.30(a)(1) and (b) through (j) requires, in the following
respective order, the establishment, maintenance, and/or documentation
of these topics: (1) Procedures to control design of class III and
class II devices, and certain class I devices as listed therein; (2)
plans for design and development activities and updates; (3) procedures
identifying, documenting, and approving design input requirements; (4)
procedures defining design output, including acceptance criteria, and
documentation of approved records; (5) procedures for formal review of
design results and documentation of results in the design history file
(DHF); (6) procedures for verifying device design and documentation of
results and approvals in the DHF; (7) procedures for validating device
design, including documentation of results in the DHF; (8) procedures
for translating device design into production specifications; (9)
procedures for documenting, verifying validating approved design
changes before implementation of changes; and (10) the records and
references constituting the DHF for each type of device.
Section 820.40 requires manufacturers to establish and maintain
procedures controlling approval and distribution of required documents
and document changes.
Section 820.40(a) and (b) requires the establishment and
maintenance of procedures for the review, approval, issuance and
documentation of required records (documents) and changes to those
records.
Section 820.50(a)(1), (a)(2), (a)(3), and (b) requires the
establishment and maintenance of procedures and requirements to ensure
service and product quality, records of acceptable suppliers, and
purchasing data describing specified requirements for products and
services.
Sections 820.60 and 820.65 require, respectively, the establishment
and maintenance of procedures for identifying all products from receipt
to distribution and for using control numbers to track surgical
implants and life-sustaining or supporting devices and their
components.
Section 820.70(a)(1) through (a)(5), (b) through (e), (g)(1)
through (g)(3), and (h) and (i) requires the establishment,
maintenance, and/or documentation of these topics: (1) Process control
procedures; (2) procedures for verifying or validating changes to
specification, method, process, or procedure; (3) procedures to control
environmental conditions and inspection result records; (4)
requirements for personnel hygiene; (5) procedures for preventing
contamination of equipment and products; (6) equipment adjustment,
cleaning and maintenance schedules; (7) equipment inspection records;
(8) equipment tolerance postings; procedures for utilizing
manufacturing materials expected to have an adverse effect on product
quality; and (9) validation protocols and validation records for
computer software and software changes.
Sections 820.72(a) and (b)(1) and (b)(2) and 820.75(a) through (c)
require, respectively, the establishment, maintenance, and/or
documentation of these topics: (1) Equipment calibration and inspection
procedures; (2) national, international or in-house calibration
standards; (3) records that identify calibrated equipment and next
calibration dates; (4) validation procedures and validation results for
processes not verifiable by inspections and tests; (5) procedures for
keeping validated processes within specified limits; (6) records for
monitoring and controlling validated processes; and (7) records of the
results of revalidation where necessitated by process changes or
deviations.
Sections 820.80(a) through (e) and 820.86, respectively, require
the establishment, maintenance, and/or documentation of these topics:
(1) Procedures for incoming acceptance by inspection, test or other
verification; (2) procedures for ensuring that in-process
[[Page 33037]]
products meet specified requirements and the control of product until
inspection and tests are completed; (3) procedures for, and records
that show, incoming acceptance or rejection is conducted by
inspections, tests or other verifications; (4) procedures for, and
records that show, finished devices meet acceptance criteria and are
not distributed until device master record (DMR) activities are
completed; (5) records in the device history record (DHR) showing
acceptance dates, results and equipment used; and (6) the acceptance/
rejection identification of products from receipt to installation and
servicing.
Sections 820.90(a), (b)(1), (b)(2), and 820.100 require,
respectively, the establishment, maintenance and/or documentation of
these topics: (1) Procedures for identifying, recording, evaluating and
disposing of nonconforming product; (2) procedures for reviewing and
recording concessions made for, and disposition of, nonconforming
product; (3) procedures for reworking products, evaluating possible
adverse rework effect and recording results in the DHR; (4) procedures
and requirements for corrective and preventive actions, including
analysis, investigation, identification and review of data, records,
causes and results; and (5) records for all corrective and preventive
action activities.
Section 820.100(a)(1) through (a)(7) states that procedures and
requirements shall be established and maintained for corrective/
preventive actions, including the following: (1) Analysis of data from
process, work, quality, servicing records; investigation of
nonconformance causes; (2) identification of corrections and their
effectiveness; (3) recording of changes made; and, (4) appropriate
distribution and managerial review of corrective and preventive action
information.
Section 820.120 states that manufacturers shall establish/maintain
procedures to control labeling storage/application; and examination/
release for storage and use, and document those procedures.
Sections 820.120(b) and (d), 820.130, 820.140, 820.150(a) and (b),
820.160(a) and (b), and 820.170(a) and (b), respectively, require the
establishment, maintenance, and/or documentation of these topics: (1)
Procedures for controlling and recording the storage, examination,
release and use of labeling; (2) the filing of labels/labeling used in
the DHR; (3) procedures for controlling product storage areas and
receipt/dispatch authorizations; (4) procedures controlling the release
of products for distribution; (5) distribution records that identify
consignee, product, date and control numbers; and (6) instructions,
inspection and test procedures that are made available, and the
recording of results for devices requiring installation.
Sections 820.180(b) and (c), 820.181(a) through (e), 820.184(a)
through (f), and 820.186 require, respectively, the maintenance of
records: (1) That are retained at prescribed site(s), made readily
available and accessible to FDA and retained for the device's life
expectancy or for 2 years; (2) that are contained or referenced in a
DMR consisting of device, process, quality assurance, packaging and
labeling, and installation, maintenance, and servicing specifications
and procedures; (3) that are contained in DHRs, demonstrate the
manufacture of each unit, lot or batch of product in conformance with
DMR and regulatory requirements, and include manufacturing and
distribution dates and quantities, acceptance documents, labels and
labeling, and control numbers; and (4) that are contained in a quality
system record (QSR) consisting of references, documents, procedures and
activities not specific to particular devices.
Sections 820.198(a) through (c) and 820.200(a) and (d),
respectively, require the establishment, maintenance and/or
documentation of these topics: (1) Complaint files and procedures for
receiving, reviewing and evaluating complaints; (2) complaint
investigation records identifying the device, complainant and
relationship of the device to the incident; (3) complaint records that
are reasonably accessible to the manufacturing site or at prescribed
sites; (4) procedures for performing and verifying that device
servicing requirements are met and that service reports involving
complaints are processed as complaints; and (5) service reports that
record the device, service activity, and test and inspection data.
Section 820.250 requires the establishment and maintenance of
procedures to identify valid statistical techniques necessary to verify
process and product acceptability; and sampling plans, when used, that
are written and based on a valid statistical rationale, and procedures
for ensuring adequate sampling methods.
The CGMP/QS regulation amends and revises the CGMP requirements for
medical devices set out at part 820. It adds design and purchasing
controls; modifies previous critical device requirements; revises
previous validation and other requirements; and harmonizes device CGMP
requirements with quality system specifications in the international
standard, ISO 9001:1994 entitled ``Quality Systems--Model for Quality
Assurance in Design, Development Production, Installation and
Servicing.'' The regulation applies neither to manufacturers of
components or parts of finished devices, nor to manufacturers of human
blood and blood components subject to 21 CFR part 606. With respect to
devices classified in class I, design control requirements apply only
to class I devices listed in Sec. 820.30(a)(2).
The regulation imposes burdens upon finished device manufacturer
firms, which are subject to all recordkeeping requirements, and also
upon finished device contract manufacturer, specification developer,
repacker and relabeler, and contract sterilizer firms, which are
subject only to requirements applicable to their activities. Due to
modifications to the guidance given for remanufacturers of hospital
single-use devices, reusers of hospital single-use devices will now be
considered to have the same requirements as manufacturers in regard to
this regulation. The establishment, maintenance and/or documentation of
procedures, records and data required by this regulation will assist
FDA in determining whether firms are in compliance with CGMP
requirements, which are intended to ensure that devices meet their
design, production, labeling, installation, and servicing
specifications and, thus are safe, effective and suitable for their
intended purpose. In particular, compliance with CGMP design control
requirements should decrease the number of design-related device
failures that have resulted in deaths and serious injuries.
If FDA did not impose these recordkeeping requirements, it
anticipates that design-related device failures would continue to occur
in the same numbers as before and continue to result in a significant
number of device recalls and preventable deaths and serious injuries.
Moreover, manufacturers would be unable to take advantage of
substantial savings attributable to reduced recall costs, improved
manufacturing efficiency, and improved access to international markets
through compliance with CGMP requirements that are harmonized with
international quality system standards.
The CGMP/QS regulation applies to some 8,254 respondents. These
recordkeepers consist of 8,188 original respondents and an estimated 66
hospitals which remanufacture or reuse single use medical devices. They
include manufacturers, subject to all requirements and contract
[[Page 33038]]
manufacturers, specification developers, repackers/relabelers and
contract sterilizers, subject only to requirements applicable to their
activities. Hospital remanufacturers of single use medical devices
(SUDs) are now defined to be manufacturers under guidelines issued by
FDA's Center for Devices and Radiological Health's (CDRH) Office of
Surveillance and Biometrics. Respondents to this collection have no
reporting activities, but must make required records available for
review or copying during FDA inspection. The regulation contains
additional recordkeeping requirements in such areas as design control,
purchasing, installation, and information relating to the remanufacture
of single use medical devices. The estimates for burden are derived
from those incremental tasks that were determined when the new CGMP/QS
regulation became final as well as those carry-over requirements. The
carry-over requirements are based on decisions made by the agency on
July 16, 1992, under OMB control number 0910-0073. This still provides
valid baseline data.
FDA estimates respondents will have a total annual recordkeeping
burden of approximately 2,833,020 hours. This figure also consists of
approximately 143,052 hours spent on a startup basis by 650 new firms.
FDA estimates information collection burdens imposed as follows:
Table 1.--Estimated Annual Recordkeeping Burden1
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Total Operating
CFR Section Number of Annual Frequency Total Annual Hours per Total Hours and Maintenance
Recordkeepers of Recordkeeping Hours Recordkeeper Cost
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820.20(a) 8,254 1 8,254 6.58 54,311 ---------
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820.20(b) 8,254 1 8,254 4.43 36,565 ---------
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820.20(c) 8,254 1 8,254 6.17 50,927 ---------
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820.20(d) 8,254 1 8,254 9.89 81,632 ---------
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820.20(e) 8,254 1 8,254 9.89 81,632 ---------
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820.22 8,254 1 8,254 32.72 270,071 ---------
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820.25(b) 8,254 1 8,254 12.68 104,661 ---------
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820.30(a)(1) 8,254 1 8,254 1.75 14,445 ---------
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820.30(b) 8,254 1 8,254 5.95 49,111 ---------
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820.30(c) 8,254 1 8,254 1.75 14,445 ---------
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820.30(d) 8,254 1 8,254 1.75 14,445 ---------
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820.30(e) 8,254 1 8,254 23.39 193,061 ---------
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820.30(f) 8,254 1 8,254 37.42 308,865 ---------
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820.30(g) 8,254 1 8,254 37.42 308,865 ---------
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820.30(h) 8,254 1 8,254 3.34 27,568 ---------
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820.30(i) 8,254 1 8,254 17.26 142,464 ---------
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820.30(j) 8,254 1 8,254 2.64 21,791 ---------
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820.4 8,254 1 8,254 8.91 73,543 ---------
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820.40(a)-(b) 8,254 1 8,254 2.04 16,838 ---------
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820.50(a)(1)-(a)(3) 8,254 1 8,254 21.9 180,763 $1,181,925
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820.50(b) 8,254 1 8,254 6.02 49,689 ---------
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820.60 8,254 1 8,254 0.32 2,641 ---------
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820.65 8,254 1 8,254 0.67 5,530 ---------
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820.70(a)(1)-(a)(5) 8,254 1 8,254 1.85 15,270 ---------
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820.70(b)-(c) 8,254 1 8,254 1.85 15,270 ---------
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820.70(d) 8,254 1 8,254 2.87 23,689 ---------
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820.70(e) 8,254 1 8,254 1.85 15,270 ---------
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[[Page 33039]]
820.70(g)(1)-(g)(3) 8,254 1 8,254 1.43 11,803 ---------
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820.70(h) 8,254 1 8,254 1.85 15,270 ---------
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820.72(a) 8,254 1 8,254 4.92 40,610 ---------
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820.70(i) 8,254 1 8,254 7.5 61,905 ---------
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820.72(b)(1) to (b)(2) 8,254 1 8,254 1.43 11,803 ---------
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820.75(a) 8,254 1 8,254 2.69 22,203 ---------
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820.75(b) 8,254 1 8,254 1.02 8,419 ---------
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820.75(c) 8,254 1 8,254 1.11 9,162 ---------
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820.80(a)-(e) 8,254 1 8,254 4.8 39,619 ---------
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820.86 8,254 1 8,254 0.79 6,521 ---------
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820.90(a) 8,254 1 8,254 4.95 40,857 ---------
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820.90(b)(1)-(b)(2) 8,254 1 8,254 4.95 40,857 ---------
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820.100(a)(1)-(a)(7) 8,254 1 8,254 12.48 103,010 ---------
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820.100(b) 8,254 1 8,254 1.28 10,565 ---------
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820.120 8,254 1 8,254 0.45 3,714 ---------
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820.120(b) 8,254 1 8,254 0.45 3,714 ---------
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820.120(d) 8,254 1 8,254 0.45 3,714 ---------
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820.130 8,254 1 8,254 0.45 3,714 ---------
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820.140 8,254 1 8,254 6.34 52,330 ---------
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820.150(a)-(b) 8,254 1 8,254 5.67 46,800 ---------
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820.160(a)-(b) 8,254 1 8,254 0.67 5,530 ---------
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820.170(a)-(b) 8,254 1 8,254 1.5 12,381 ---------
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820.180(b)-(c) 8,254 1 8,254 1.5 12,381 ---------
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820.181((a)-(e) 8,254 1 8,254 1.21 9,987 ---------
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820.184(a)-(f) 8,254 1 8,254 1.41 11,638 ---------
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820.186 8,254 1 8,254 0.4 3,302 ---------
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820.198(a)-(c) 8,254 1 8,254 4.94 40,775 ---------
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820.200(a) and (d) 8,254 1 8,254 2.61 21,543 ---------
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820.250 8,254 1 8,254 0.67 5,530 ---------
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Totals ................. ................. ................. ................. 2,283,020 $1,181,925
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Burden (labor) hour and cost estimates were originally developed
under FDA contract by Eastern Research Group, Inc. (ERG), in 1996 when
the CGMP/QS regulation became final. These figures are still accurate.
Additional factors considered in deriving estimates included:
[[Page 33040]]
Establishment type: Query has been made of CDRH's
registration/listing databank and has counted 8,188 domestic firms
subject to CGMPs. In addition, hospitals which reuse or remanufacture
devices are now considered manufacturers under new FDA guidance. During
the last report, it was estimated that out of the 6,000 hospitals in
the United States, one third of them (or 2,000 hospitals) will reuse or
remanufacture single use medical devices. After investigations of many
hospitals and the changes in enforcements of FDA's requirements for
hospitals, the number of reuse or remanufactures of single-use medical
devices have decreased from the estimated 2,000 to an estimated 66
hospitals. Thus, the number of manufacturers will increase from 7,229
to 8,188, but the total number of firms subject to CGMPs will decrease
from 9,229 to 8,254.
Potentially affected establishments: Except for
manufacturers, not every type of firm is subject to every CGMP/QS
requirement. For example, all are subject to FDA's quality policy
regulations (Sec. 820.20(a)), document control regulations (Sec.
820.40), and other requirements, whereas only manufacturers and
specification developers are subject to FDA's design controls
regulations (Sec. 820.30). The type of firm subject to each
requirement was identified by ERG.
FDA estimated the burden hours (and costs) for the previous CGMP
regulation in 1992. That estimate was submitted to OMB on May 4, 1992.
It was approved by OMB on July 16, 1992, and expired on June 30, 1995.
The methodology used is different than that used by ERG in estimating
incremental tasks when the new CGMP/QS became final. Nevertheless, the
agency believes its 1992 estimate adequately represents labor hours
(and costs) needed to comply with previous CGMP requirements carried
over into the new CGMP/QS regulation. The 1992 estimate used 9,289
respondents (rather than 8,254 respondents), which compensates for
differences in methodology.
FDA estimates that some 650 ``new'' establishments (marketing
devices for the first time) will expend some 143,052 ``development''
hours on a one-time startup basis to develop records and procedures for
the CGMP/QS regulation.
FDA estimates that annual labor hours are apportioned as follows:
40 percent goes to requirements dealing with manufacturing
specifications, process controls and the DHR; 20 percent goes to
requirements dealing with components and acceptance activities; 25
percent goes to requirements dealing with equipment, records (the DMR
and QSR), complaint investigations, labeling/packaging and
reprocessing/investigating product nonconformance; and 15 percent goes
to quality audit, traceability, handling, distribution, statistical,
and other requirements.
Dated: June 4, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-13212 Filed 6-10-04; 8:45 am]
BILLING CODE 4160-01-S