[Federal Register: September 20, 2007 (Volume 72, Number 182)]
[Notices]
[Page 53774-53778]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr20se07-51]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2007N-0229]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Medical Devices:
Current Good Manufacturing Practice Quality System Regulations
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 (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.
DATES: Fax written comments on the collection of information by October
22, 2007.
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: 202-395-6974, or e-mailed to baguilar@omb.eop.gov. All comments
should be identified with the OMB control number 0910-0073. Also
include the FDA docket number found in brackets in the heading of this
document.
FOR FURTHER INFORMATION CONTACT: Denver Presley, Jr., Office of the
Chief Information Officer (HFA-250), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-1472.
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 Quality System
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
current good manufacturing practices (CGMPs), as described in such
regulations, to assure that the device will be safe and effective and
otherwise in compliance with the act.
The CGMP/Quality System (CGMP/QS) regulation implementing authority
provided by this statutory provision is found under 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
[[Page 53775]]
devices intended for human use. The authority for this regulation is
covered under the act , i.e. 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
Standards, ``ISO 9001: ``Quality Systems Model for Quality Assurance in
Design/Development, Production, Installation, and Servicing.'' The
CGMP/QS information collections will assist FDA inspections of
manufacturers for compliance with QS 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 the following
topics: (1) The quality policy, (2) the organizational structure, (3)
the quality plan, and (4) the QS procedures of the organization.
Section 820.22 requires the conduct and documentation of QS audits
and re-audits.
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 respective
order, the establishment, maintenance, and/or documentation of the
following 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), (h), and (i) requires the establishment, maintenance,
and/or documentation of the following 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), (b)(1), and (b)(2) and 820.75(a) through (c)
require, respectively, the establishment, maintenance, and/or
documentation of the following 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 require, respectively,
the establishment, maintenance, and/or documentation of the following
topics: (1) Procedures for incoming acceptance by inspection, test or
other verification; (2) procedures for ensuring that in-process
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
the following 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)
[[Page 53776]]
and (b), and 820.170(a) and (b), respectively, require the
establishment, maintenance, and/or documentation of the following
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 that are: (1) 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) contained or referenced in a DMR
consisting of device, process, quality assurance, packaging and
labeling, and installation, maintenance, and servicing specifications
and procedures; (3) contained in a DHR and demonstrate the manufacture
of each unit, lot or batch of product in conformance with DMR and
regulatory requirements, include manufacturing and distribution dates,
quantities, acceptance documents, labels and labeling, control numbers;
and (4) 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) through (d),
respectively, requires the establishment, maintenance and/or
documentation of the following 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 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 under part 820. The regulation adds design and
purchasing controls; modifies previous critical device requirements;
revises previous validation and other requirements; and harmonizes
device CGMP requirements with QS specifications in the international
standard, ``ISO 9001: Quality Systems Model for Quality Assurance in
Design/Development Production, Installation and Servicing.'' The rule
does not apply 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) of the regulation. The rule imposes burden upon: (1)
Finished device manufacturer firms which are subject to all
recordkeeping requirements; (2) finished device contract manufacturers;
specification developers; and (3) repacker, relabelers and contract
sterilizer firms, which are subject only to requirements applicable to
their activities. In addition, re-manufacturers of hospital single-use
devices (SUDs) 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.
The CGMP/QS regulation applies to approximately 8,963 respondents.
These recordkeepers consist of 8,945 original respondents and an
estimated 18 hospitals which remanufacture or reuse SUDs. They include
manufacturers, subject to all requirements and contract manufacturers,
specification developers, repackers, relabelers and contract
sterilizers, subject only to requirements applicable to their
activities. Hospital remanufacturers of 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 SUDs. The estimates
for this burden are derived from those incremental tasks that were
determined when the new CGMP/QS regulation became final as well as
those carryover requirements. The carryover requirements are based on
decisions made by the agency on July 16, 1992, under OMB clearance
submission 0910-0073, which still provides valid baseline data.
FDA estimates respondents will have a total annual recordkeeping
burden of approximately 3,076,370 hours. This figure also consists of
approximately 143,052 hours spent on a startup basis by 650 new firms.
In the Federal Register of Monday, July 9, 2007, FDA published a
60-day notice soliciting public comments on the information collection
requirements for the proposed extension of this collection of
information. In response to that notice, no comments were received.
FDA estimates the burden for this collection of information as
follows:
Table 1.--Estimated Annual Recordkeeping Burden\1\
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No. of Annual Frequency of Total Annual Hours Per
CFR Section Recordkeepers Recordkeeping Hours Recordkeeper Total Hours
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820.20(a) 8,963 1 8,963 6.58 58,977
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820.20(b) 8,963 1 8,963 4.43 39,706
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820.20(c) 8,963 1 8,963 6.17 55,302
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[[Page 53777]]
820.20(d) 8,963 1 8,963 9.89 88,644
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820.20(e) 8,963 1 8,963 9.89 88,644
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820.22 8,963 1 8,963 32.72 293,269
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820.25(b) 8,963 1 8,963 12.68 113,651
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820.30(a)(1) 8,963 1 8,963 1.75 15,685
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820.30(b) 8,963 1 8,963 5.95 53,330
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820.30(c) and (d) 8,963 1 8,963 1.75 15,685
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820.30(e) 8,963 1 8,963 23.39 209,645
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820.30(f) and (g) 8,963 1 8,963 37.42 335,395
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820.30(h) 8,963 1 8,963 3.34 29,936
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820.30(i) 8,963 1 8,963 17.26 154,701
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820.30(j) 8,963 1 8,963 2.64 23,662
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820.40 8,963 1 8,963 8.91 79,860
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820.40(a)and (b) 8,963 1 8,963 2.04 18,285
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820.50(a)(1) through (a)(3) 8,963 1 8,963 21.90 196,290
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820.50(b) 8,963 1 8,963 6.02 53,957
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820.6 8,963 1 8,963 0.32 2,868
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820.65 8,963 1 8,963 0.67 6,005
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820.70(a)(1) through (a)(5), (b), and (c) 8,963 1 8,963 1.85 16,582
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820.70(d) 8,963 1 8,963 2.87 25,724
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820.70(e) 8,963 1 8,963 1.85 16,582
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820.70(g)(1) through (g)(3) 8,963 1 8,963 1.43 12,817
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820.70(h) 8,963 1 8,963 1.85 16,582
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820.70(i) 8,963 1 8,963 7.50 67,223
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820.72(a) 8,963 1 8,963 4.92 44,098
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820.72(b)(1) and (b)(2) 8,963 1 8,963 1.43 12,817
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820.75(a) 8,963 1 8,963 2.69 24,110
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820.75(b) 8,963 1 8,963 1.02 9,142
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820.75(c) 8,963 1 8,963 1.11 9,949
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820.80(a) through (e) 8,963 1 8,963 4.80 43,022
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820.86 8,963 1 8,963 0.79 7,081
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820.90(a), (b)(1), and (b)(2) 8,963 1 8,963 4.95 44,367
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820.100 (a)(1) through (a)(7) 8,963 1 8,963 12.48 111,858
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820.100(b) 8,963 1 8,963 1.28 11,473
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820.120(b) and (d) 8,963 1 8,963 0.45 4,033
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820.130 8,963 1 8,963 0.45 4,033
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[[Page 53778]]
820.140 8,963 1 8,963 6.34 56,825
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820.150(a) and (b) 8,963 1 8,963 5.67 50,820
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820.160(a) and (b) 8,963 1 8,963 0.67 6,005
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820.170(a) and (b) 8,963 1 8,963 1.50 13,445
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820.180(b) and (c) 8,963 1 8,963 1.50 13,445
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820.181(a) through (e) 8,963 1 8,963 1.21 10,845
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820.184(a) through (f) 8,963 1 8,963 1.41 12,638
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820.186 8,963 1 8,963 0.40 3,585
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820.198(a) through (c) 8,963 1 8,963 4.94 44,277
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820.200(a) and (d) 8,963 1 8,963 2.61 23,393
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820.25 8,963 1 8,963 0.67 6,005
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Totals 3,072,337
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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:
Establishment Type: Query has been made of CDRH's
registration/listing databank and has counted 8,963 domestic firms
subject to CGMPs. In addition, hospitals which reuse or remanufacture
devices are now considered manufacturers under new FDA guidance. After
investigations of many hospitals and the changes in enforcements of
FDA's requirements for hospitals, the number of reuse or remanufactures
of SUDs have decreased from the estimated 66 to an estimated 18
hospitals. Because the total number of registered firms is not static,
the number of respondents will fluctuate from year to year resulting in
slight changes to the overall burden. Currently, there are 8,963 firms
subject to the CGMPs; an increase from the last renewal of 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 estimates the burden hours (and costs) based on the last
approved renewal for this information collection.
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: September 14, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-18582 Filed 9-19-07; 8:45 am]
BILLING CODE 4160-01-S