[Federal Register Volume 72, Number 182 (Thursday, September 20, 2007)]
[Notices]
[Pages 53774-53778]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-18582]


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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 [email protected]. 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