[Federal Register: February 28, 2001 (Volume 66, Number 40)]
[Notices]               
[Page 12798-12802]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28fe01-69]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 01N-0063]

 
Agency Information Collection Activities; Proposed Collection; 
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 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 collection of 
information, and to allow 60 days for public comment in response to the 
notice. This notice solicits comments on information collection 
requirements related to the medical devices current good manufacturing 
practice (CGMP) quality system (QS) regulation.

DATES: Submit written comments or electronic comments on the collection 
of information by April 30, 2001.

ADDRESSES: Submit electronic comments on the collection of information 
to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.accessdata.fda.gov/scripts/oc/dockets/edockethome.cfm. 
Submit written comments on the collection of information to the Dockets 
Management Branch (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: Peggy Schlosburg, Office of 
Information Resources Management (HFA-250), Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-1223.

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: (1) Whether the proposed collection of information 
is necessary

[[Page 12799]]

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 (CGMP) Quality 
System (QS) Regulation--21 CFR Part 820 (OMB Control No. 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 has the authority to prescribe regulations 
requiring that the methods used in, and the facilities and controls 
used for, the manufacture, preproduction 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 in part 820 (21 CFR part 820) of the Code 
of Federal Regulations 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. 
Section 820.20(a) through (e) requires management with executive 
responsibility to establish, maintain, and/or review: 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: Procedures to control design of class III and class II devices, and 
certain class I devices as listed therein; plans for design and 
development activities and updates; procedures identifying, 
documenting, and approving design input requirements; procedures 
defining design output, including acceptance criteria, and 
documentation of approved records; procedures for formal review of 
design results and documentation of results in the design history file 
(DHF); procedures for verifying device design and documentation of 
results and approvals in the DHF; procedures for validating device 
design, including documentation of results in the DHF; procedures for 
translating device design into production specifications; procedures 
for documenting, verifying and validating approved design changes 
before implementation of changes; and the records and references 
constituting the DHF for each type of device.
    Section 820.40 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 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) through (e), and (g) through (i) requires the 
establishment, maintenance, and/or documentation of: Process control 
procedures; procedures for verifying or validating changes to 
specification, method, process, or procedure; procedures to control 
environmental conditions and inspection result records; requirements 
for personnel hygiene; procedures for preventing contamination of 
equipment and products; equipment adjustment, cleaning and maintenance 
schedules; equipment inspection records; equipment tolerance postings; 
procedures for utilizing manufacturing materials expected to have an 
adverse effect on product quality; and validation protocols and 
validation records for computer software and software changes.
    Sections 820.72 and 820.75(a), (b), (b)(2), and (c) require, 
respectively, the establishment, maintenance, and/or documentation of: 
Equipment calibration and inspection procedures; national, 
international or in-house calibration standards; records that identify 
calibrated equipment and next calibration dates; validation procedures 
and validation results for processes not verifiable by inspections and 
tests; procedures for keeping validated processes within specified 
limits; records for monitoring and controlling validated processes; and 
records of the results of revalidation where necessitated by process 
changes or deviations.
    Sections 820.80 and 820.86, respectively, require the 
establishment, maintenance, and/or documentation of: Procedures for 
incoming acceptance by inspection, test or other verification; 
procedures for ensuring that in-process products meet specified 
requirements and the control of product until inspection and tests are 
completed; procedures for, and records that show, incoming acceptance 
or rejection is conducted by inspections, tests or other verifications; 
procedures for, and records that show, finished devices meet acceptance 
criteria and are not distributed until device master (DMR) activities 
are completed; records in the device history record (DHR) showing 
acceptance dates, results and equipment used; and the acceptance/
rejection identification of products from receipt to installation and 
servicing.
    Sections 820.90 and 820.100 require, respectively, the 
establishment, maintenance and/or documentation of: Procedures for 
identifying, recording, evaluating, and disposing of nonconforming 
product; procedures for reviewing and recording concessions made for, 
and disposition of, nonconforming product; procedures for reworking 
products, evaluating possible adverse rework effect and recording 
results in the DHR; procedures and requirements for corrective and 
preventive actions, including analysis, investigation, identification 
and review of data, records, causes and results; and records for all 
corrective and preventive action activities.
    Sections 820.120(b) and (d), 820.130, 820.140, 820.150, 820.160, 
and 820.170, respectively, require the establishment, maintenance, and/
or documentation of: Procedures for controlling and recording the 
storage, examination, release and use of labeling; the filing of 
labels/labeling used in the DHR; procedures for controlling product 
storage areas and receipt/dispatch authorizations; procedures for 
controlling the release of products for distribution; distribution 
records that identify consignee, product, date and control numbers; and 
instructions, inspection and test procedures that are made available, 
and the recording of results for devices requiring installation.

[[Page 12800]]

    Sections 820.180(b) and (c), 820.181, 820.184, and 820.186 require, 
respectively, the maintenance of records: 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; 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; that are contained in DHR's, 
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 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: Complaint files and procedures for receiving, 
reviewing, and evaluating complaints; complaint investigation records 
identifying the device, complainant, and relationship of the device to 
the incident; complaint records that are reasonably accessible to the 
manufacturing site or at prescribed sites; procedures for performing 
and verifying that device servicing requirements are met and that 
service reports involving complaints are processed as complaints; and 
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 (International Organization for Standardization) 
9001:1994 ``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 burdens upon finished device manufacturer firms, 
which are subject to all recordkeeping requirements, and 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 final 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 9,229 respondents. These 
recordkeepers consist of 7,229 original respondents and an estimated 
2,000 hospitals that remanufacture or reuse single use medical devices. 
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 single use medical devices 
(SUD's) are now defined to be manufacturers under guidelines issued by 
the Center for Devices and Radiological Health's (CDRH's) 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 (October 7, 1996, 61 FR 52602) 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 Paperwork 
Reduction Act submission No. 0910-0073. This still provides valid 
baseline data.
    FDA estimates respondents will have a total annual recordkeeping 
burden of approximately 3,167,670 hours (shown as 3,167,670 in table 1, 
of this document, of this justification statement due to rounding). 
This figure also consists of approximately 114,882 hours spent on a 
startup basis by 650 new firms. Table 1 below identifies burden 
estimates per sections of the regulation.
    FDA estimates information collection burdens imposed as follows:

                                                   Table 1.--Estimated Annual Recordkeeping Burden\1\
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                                                                  Annual
               21 CFR Section                     No. of       Frequency per   Total Annual      Hours per         Total Hours        Total Operating &
                                               Recordkeepers   Recordkeeping      Records      Recordkeeper                           Maintenance Costs
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820.20(a)                                       9,229               1           9,229               6.58          60,727
820.20(b)                                       9,229               1           9,229               4.43          40,884
820.20(c)                                       9,229               1           9,229               6.17          56,943
820.20(d)                                       9,229               1           9,229               9.89          91,275

[[Page 12801]]


820.20(e)                                       9,229               1           9,229               9.89          91,275
820.22                                          9,229               1           9,229              32.72         301,973
820.25(b)                                       9,229               1           9,229              12.68         117,024
820.30(a)(1)                                    9,229               1           9,229               1.75          16,151
820.30(b)                                       9,229               1           9,229               5.95          54,913
820.30(c)                                       9,229               1           9,229               1.75          16,151
820.30(d)                                       9,229               1           9,229               1.75          16,151
820.30(e)                                       9,229               1           9,229              23.39         215,866
820.30(f)                                       9,229               1           9,229              37.42         345,349
820.30(g)                                       9,229               1           9,229              37.42         345,349
820.30(h)                                       9,229               1           9,229               3.34          30,825
820.30(i)                                       9,229               1           9,229              17.26         159,293
820.30(j)                                       9,229               1           9,229               2.64          24,365
820.4                                           9,229               1           9,229               8.91          82,230
820.40(a) and (b)                               9,229               1           9,229               2.04          18,827
820.50(a)(1) to (a)(3)                          9,229               1           9,229              21.9          202,115            $1,181,925
820.50(b)                                       9,229               1           9,229               6.02          55,559
821                                             9,229               1           9,229               0.32           2,953
821                                             9,229               1           9,229               0.67           6,183
820.70(a)(1) to (a)(5)                          9,229               1           9,229               1.85          17,074
820.70(b) and (c)                               9,229               1           9,229               1.85          17,074
820.70(d)                                       9,229               1           9,229               2.87          26,487
820.70(e)                                       9,229               1           9,229               1.85          17,074
820.70(g)(1) to (g)(3)                          9,229               1           9,229               1.43          13,197
820.70(h)                                       9,229               1           9,229               1.85          17,074
820.70(i)                                       9,229               1           9,229               7.5           69,218
820.72(a)                                       9,229               1           9,229               4.92          45,407
820.72(b)(1) to (b)(2)                          9,229               1           9,229               1.43          13,197
820.75(a)                                       9,229               1           9,229               2.69          24,826
820.75(b)                                       9,229               1           ,9229               1.02           9,414
820.75(c)                                       9,229               1           9,229               1.11          10,244
820.80(a) to (e)                                9,229               1           9,229               4.8           44,299
820.86                                          9,229               1           9,229               0.79           7,291
820.90(a)                                       9,229               1           9,229               4.95          45,684
820.90(b)(1) and (b)(2)                         9,229               1           9,229               4.95          45,684
820.100 (a)(1) to (a)(7)                        9,229               1           9,229              12.48         115,178
820.100(b)                                      9,229               1           9,229               1.28          11,813
820                                             9,229               1           9,229               0.45           4,153
820.120(b)                                      9,229               1           9,229               0.45           4,153
820.120(d)                                      9,229               1           9,229               0.45           4,153
820.130                                         9,229               1           9,229               0.45           4,153
820.140                                         9,229               1           9,229               6.34          58,512
820.150(a) and (b)                              9,229               1           9,229               5.67          52,328
820.160(a) and (b)                              9,229               1           9,229               0.67           6,183
820.170(a) and (b)                              9,229               1           9,229               1.5           13,844
820.180(b) and (c)                              9,229               1           9,229               1.5           13,844
820.181(a) to (e)                               9,229               1           9,229               1.21          11,167
820.184(a) to (f)                               9,229               1           9,229               1.41          13,013
820.186                                         9,229               1           9,229               0.4            3,692
820.198(a) to (c)                               9,229               1           9,229               4.94          45,591
820.200(a) and (d)                              9,229               1           9,229               2.61          24,088
820.250                                         9,229               1           9,229               0.67           6,183
Totals                                                                                                         3,167,673            $1,181,925
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\1\ There are no capital costs associated with this collection of information.

    Burden (labor) hour and cost estimates were developed under FDA 
contract by the 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 data bank and has counted 7,229 domestic firms 
subject to CGMP's. They were then grouped as: Manufacturers (5,463), 
contract manufacturers (204), specification developers (960), 
repackers/relabelers (574), remanufacturer (21) and contract 
sterilizers (7). In addition, hospitals that

[[Page 12802]]

reuse or remanufacture devices are now considered manufacturers under 
new FDA guidance. It is 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. Thus, the number of 
manufacturers will increase from 5,463 to 7,463 making the total number 
of firms subject to CGMP's 9,229.
     Potentially affected establishments: Except for 
manufacturers, not every type of firm is subject to every CGMP/QS 
requirement. For example, all are subject to quality policy 
(Sec. 820.20(a)), document control (Sec. 820.40), and other 
requirements, whereas only manufacturers and specification developers 
are subject to part 820 Subpart C--Design Controls. 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, 
under OMB Paperwork Reduction Act submission No. 0910-0073. It was 
approved by OMB on July 16, 1992, and it 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 a final rule. 
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 9,229 respondents), which 
compensates for differences in methodology.
    FDA estimates that some 650 ``new'' establishments (marketing 
devices for the first time) will expend some 114,882 ``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--to requirements dealing with manufacturing specifications, 
process controls and the DHR; 20 percent--to requirements dealing with 
components and acceptance activities; 25 percent--to requirements 
dealing with equipment, records (the DMR and QSR), complaint 
investigations, labeling/packaging and reprocessing/investigating 
product nonconformance; and 15 percent--to quality audit, traceability, 
handling, distribution, statistical, and other requirements.

    Dated: February 22, 2001.
William K. Hubbard,
Senior Associate Commissioner for Policy, Planning, and Legislation.
[FR Doc. 01-4850 Filed 2-27-01; 8:45 am]
BILLING CODE 4160-01-F