[Federal Register Volume 72, Number 130 (Monday, July 9, 2007)]
[Notices]
[Pages 37235-37239]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-13152]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2007N-0229]


Agency Information Collection Activities; Proposed Collection; 
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 an 
opportunity for public comment on the proposed collection of certain 
information by the agency. Under the Paperwork Reduction Act of 1995 
(the PRA), Federal agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed extension of an existing information 
collection, and to allow 60 days for public comment in response to the 
notice. This notice solicits comments on recordkeeping requirements 
related to the medical devices current good manufacturing practice 
(CGMP) quality system (QS) regulation (CGMP/QS regulation).

DATES: Submit written or electronic comments on the collection of 
information by September 7, 2007.

ADDRESSES: Submit electronic comments on the collection of information 
to: http://www.fda.gov/dockets/ecomments. Submit written comments on 
the collection of information to the Division of Dockets Management 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. All comments should be identified with the 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: Under the PRA (44 U.S.C. 3501-3520), Federal 
agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed extension of an existing collection of information, 
before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.

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 
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 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 devices intended for human use. The authority for this 
regulation is covered under sections 501, 502, 510, 513, 514, 515, 518, 
519, 520, 522, 701, 704, 801, and 803 of 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 the 
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 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 the following 
topics: (1) The quality policy; (2) the organizational structure; (3) 
the quality plan; and (4) 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 respective 
order, the establishment, maintenance, and/or

[[Page 37236]]

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, respectively, require 
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), and (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) and (b), and 820.170(a) and (b), respectively, require the 
establishment, maintenance, and/or documentation of 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: (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 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) 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) through (d), 
respectively, require the establishment, maintenance,

[[Page 37237]]

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, which 
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, remanufacturers 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 that 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 (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 carry-over requirements. The carry-over 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.
    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     Total Annual
  21 CFR Section     Recordkeepers    per Recordkeeping        Hours        Hours per  Record     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
----------------------------------------------------------------------------------------------------------------
820.20(d)                      8,963                  1              8,963               9.89             88,644
----------------------------------------------------------------------------------------------------------------
820.20(e)                      8,963                  1              8,963               9.89             88,644
----------------------------------------------------------------------------------------------------------------
820.22                         8,963                  1              8,963              32.72            293,269
----------------------------------------------------------------------------------------------------------------
820.25(b)                      8,963                  1              8,963              12.68            113,651
----------------------------------------------------------------------------------------------------------------
820.30(a)(1)                   8,963                  1              8,963               1.75             15,685
----------------------------------------------------------------------------------------------------------------
820.30(b)                      8,963                  1              8,963               5.95             53,330
----------------------------------------------------------------------------------------------------------------
820.30(c)                      8,963                  1              8,963               1.75             15,685
----------------------------------------------------------------------------------------------------------------
820.30(d)                      8,963                  1              8,963               1.75             15,685
----------------------------------------------------------------------------------------------------------------
820.30(e)                      8,963                  1              8,963              23.39            209,645
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[[Page 37238]]

 
820.30(f)                      8,963                  1              8,963              37.42            335,395
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820.30(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)                   8,963                  1              8,963              21.90            196,290
 through (a)(3)
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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)                   8,963                  1              8,963               1.85             16,582
 through (a)(5)
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820.70(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)                   8,963                  1              8,963               1.43             12,817
 through (g)(3)
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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               8,963                  1              8,963               1.43             12,817
 (b)(2)
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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              8,963                  1              8,963               4.80             43,022
 (e)
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820.86                         8,963                  1              8,963               0.79              7,081
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820.90(a)                      8,963                  1              8,963               4.95             44,367
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820.90(b)(1) and               8,963                  1              8,963               4.95             44,367
 (b)(2)
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820.100 (a)(1)                 8,963                  1              8,963              12.48            111,858
 through (a)(7)
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820.100(b)                     8,963                  1              8,963               1.28             11,473
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820.120(b)                     8,963                  1              8,963               0.45              4,033
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820.120(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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820.140                        8,963                  1              8,963               6.34             56,825
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820.150(a) and                 8,963                  1              8,963               5.67             50,820
 (b)
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820.160(a) and                 8,963                  1              8,963               0.67              6,005
 (b)
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820.170(a) and                 8,963                  1              8,963               1.50             13,445
 (b)
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[[Page 37239]]

 
820.180(b) and                 8,963                  1              8,963               1.50             13,445
 (c)
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820.181(a)                     8,963                  1              8,963               1.21             10,845
 through (e)
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820.184(a)                     8,963                  1              8,963               1.41             12,638
 through (f)
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820.186                        8,963                  1              8,963               0.40              3,585
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820.198(a)                     8,963                  1              8,963               4.94             44,277
 through (c)
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820.200(a) and                 8,963                  1              8,963               2.61             23,393
 (d)
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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 the 
following:
     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 that 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 single-use medical devices 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: 
(1) 40 percent goes to requirements dealing with manufacturing 
specifications, process controls, and the DHR; (2) 20 percent goes to 
requirements dealing with components and acceptance activities; (3) 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 28, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-13152 Filed 7-6-07; 8:45 am]
BILLING CODE 4160-01-S