
[Federal Register: October 18, 2010 (Volume 75, Number 200)]
[Notices]               
[Page 63834-63838]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18oc10-61]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-N-0273]

 
Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Current Good 
Manufacturing Practice Quality System Regulations

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

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 
November 17, 2010.

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: 202-395-7285, or e-mailed to oira_submission@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: Daniel Gittleson, Office of 
Information Management, Food and Drug Administration, 1350 Piccard Dr., 
PI50-400B, Rockville, MD 20850, 301-796-5156, 
Daniel.Gittleson@fda.hhs.gov.

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 FD&C 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 current good 
manufacturing practice (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/quality system (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 FD&C 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

[[Page 63835]]

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 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 quality system 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, and 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

[[Page 63836]]

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, require 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, 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 8,924 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 there manufacture 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 Control Number 
0910-0073, which still provides valid base line data.

Explanation of Recordkeeping Burden Estimate

    FDA estimates respondents will have a total annual recordkeeping 
burden of approximately 3,105,552 hours. This figure also consists of 
approximately 143,052 hours spent on a startup basis by 734 new firms.
    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. Additional factors considered in 
deriving estimates included the following:
     Establishment type: Query has been made of CDRH's 
registration/listing databank and the current count was 7,748 domestic 
firms subject to CGMPs. It was also calculated that each year, the 
number of new domestic firms subject to CGMPs is 734. The average 
amount of firms therefore subject to CGMPs over the 3 years is 
therefore 8,924 and this figure has been used to calculate the total 
burden. 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.
     During the last report it was estimated that this number 
was 8,963. When the last set of numbers was calculated, FDA was still 
using a paper based system to register and list firms. On October 1, 
2007, FDA switched to an electronic system for registration and 
listing. Also at that time the Food and Drug Administration Amendments 
Act of 2007 instituted an establishment registration fee for some types 
of facilities. FDA believes that during the fiscal year 2008 annual 
registration cycle, establishments that had previously registered but 
were not required to do so, removed themselves from inventory of active 
establishments. FDA believes that the current figures reported by the 
electronic system more accurately reflect the inventory of registered 
establishments.
     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 
subpart C, Design Controls. The type of firm

[[Page 63837]]

subject to each requirement was identified by the 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 Control Number 0910-
0073. It was approved by OMB on July 16, 1992, and expired on June 30, 
1995. The methodology used is different than that used by ERG in 
estimating incremental tasks when the new CGMP/QS became final 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 8,924 respondents), which 
compensates for differences in methodology.
    In the Federal Register of June 24, 2010 (75 FR 36092), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received two comments, however only one 
was regarding the information collection. One part of the comment 
questioned a technical reference found within the 60-day notice, 
stating not that the reference was incorrect, but that it may be 
somewhat misleading since the reference is updated on a regular basis 
and this was not communicated in the notice. While the commenter is 
correct that ISO 9001 is on version 2008 and ISO/DIS 13485 is on 
version 2003, the standard ISO 9001 and ISO/DIS 13485 are referenced 
because they are the standard regardless of version.
    Another part of the comment maintains that the term ``collect'' is 
misleading as it pertains to recordkeeping requirements because 
relevant documents are only submitted if requested; however, the 
comment agrees that the information collection is necessary. Under the 
PRA regulations, records retention is considered ``information 
collection,'' as defined by the PRA 5 CFR 1320.3
    A third part of the comment stated that it was not clear to whom 
the regulations applied based on the statement, ``[e]xcept for 
manufacturers, not every type of firm is subject to every CGMP/QS 
requirement.'' FDA believes the scope of the regulations found at part 
820.1 makes it clear to whom the requirements are applicable.
    The commenter questioned the validity and availability of a study 
that was conducted by the ERG in 1996, claiming that without benefit of 
the study itself, comments regarding burden estimates were too 
difficult to make. As a basis for its burden estimates, the agency 
relied in part on certain pieces of information found in the 1996 study 
and recommends that FDA make this document part of the docket. The 
study was submitted to OMB as part of the original PRA approval and is 
part of the Federal docket.
    The commenter states that FDA assumes that the burden for each firm 
is the same, i.e., each of the 8,924 firms has exactly the same burden. 
The flexibility of the system suggests that the ``one size fits all'' 
approach in the Federal Register is not appropriate. The PRA burden 
placed on the 8,924 firms is an average burden on respondents.
    The commenter believes that the estimates the agency provides are 
too low, but does not offer an alternative methodology for estimating 
that the agency may review. The comment goes on to suggest, however, 
that a new analysis similar to the 1996 study be conducted and serve as 
the basis for future burden estimates because our estimates have not 
changed in several years. While FDA agrees that additional analysis is 
always helpful in determining burden, the agency does perform ongoing 
reviews of the burden associated with PRA burden as required under the 
PRA for purposes of evaluating burden associated with its information 
collection requests, and has done so for purposes of renewing these 
CGMP/QS regulations.
    Finally, the commenter suggests that the agency's regulation 
regarding electronic signatures found at part 11 (21 CFR part 11) is 
overly cumbersome to many firms. Part 11 is a separate regulation from 
part 820, and it is only mentioned for reference purposes in the 
preamble. The record keeping for part 11 is not within the scope of 
this paperwork analysis.
    Also, CDRH is proactive in ensuring that the medical device 
industry and other affected individuals are made aware of on-going 
issues relating to the CGMP/QS regulations. FDA's Medical Device GMP/QS 
experts have participated in numerous conferences and seminars relating 
to the CGMP/QS regulatory requirements. During these sessions, our GMP/
QS experts share information through speeches and panel discussions 
that provide a forum for open discussion. During these discussions 
guidance and direction is often given to the audience to help them 
understand their regulatory responsibilities under the GMP/QS 
regulation. In addition, issues are sometimes identified by the 
audience that provides the agency areas that we may need to clarify to 
affected individuals.
    FDA estimates the burden of this collection of information as 
follows:

                                                   Table 1--Estimated Annual Recordkeeping Burden \1\
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                                                                                       Annual
                          CFR section                               Number of       frequency per     Total annual        Hours per        Total hours
                                                                  recordkeepers     recordkeeping        records           record
--------------------------------------------------------------------------------------------------------------------------------------------------------
820.20(a).....................................................             8,924                 1             8,924                 7            62,468
820.20(b).....................................................             8,924                 1             8,924                 4            35,696
820.20(c).....................................................             8,924                 1             8,924                 6            53,544
820.20(d).....................................................             8,924                 1             8,924                10            89,240
820.20(e).....................................................             8,924                 1             8,924                10            89,240
820.22........................................................             8,924                 1             8,924                33           294,492
820.25(b).....................................................             8,924                 1             8,924                13           116,012
820.30(a)(1)..................................................             8,924                 1             8,924                 2            17,848
820.30(b).....................................................             8,924                 1             8,924                 6            53,544
820.30(c).....................................................             8,924                 1             8,924                 2            17,848
820.30(d).....................................................             8,924                 1             8,924                 2            17,848
820.30(e).....................................................             8,924                 1             8,924                23           205,252
820.30(f).....................................................             8,924                 1             8,924                37           330,188
820.30(g).....................................................             8,924                 1             8,924                37           330,188
820.30(h).....................................................             8,924                 1             8,924                 3            26,772
820.30(i).....................................................             8,924                 1             8,924                17           151,708
820.30(j).....................................................             8,924                 1             8,924                 3            26,772

[[Page 63838]]


820.40........................................................             8,924                 1             8,924                 9            80,316
820.40(a) and (b).............................................             8,924                 1             8,924                 2            17,848
820.50(a)(1) through (a)(3)...................................             8,924                 1             8,924                22           196,328
820.50(b).....................................................             8,924                 1             8,924                 6            53,544
820.6.........................................................             8,924                 1             8,924                 1             8,924
820.65........................................................             8,924                 1             8,924                 1             8,924
820.70(a)(1) through (a)(5)...................................             8,924                 1             8,924                 2            17,848
820.70(b) and (c).............................................             8,924                 1             8,924                 2            17,848
820.70(d).....................................................             8,924                 1             8,924                 3            26,772
820.70(e).....................................................             8,924                 1             8,924                 2            17,848
820.70(g)(1) through (g)(3)...................................             8,924                 1             8,924                 1             8,924
820.70(h).....................................................             8,924                 1             8,924                 2            17,848
820.70(i).....................................................             8,924                 1             8,924                 8            71,392
820.72(a).....................................................             8,924                 1             8,924                 5            44,620
820.72(b)(1) and (b)(2).......................................             8,924                 1             8,924                 1             8,924
820.75(a).....................................................             8,924                 1             8,924                 3            26,772
820.75(b).....................................................             8,924                 1             8,924                 1             8,924
820.75(c).....................................................             8,924                 1             8,924                 1             8,924
820.80(a) through (e).........................................             8,924                 1             8,924                 5            44,620
820.86........................................................             8,924                 1             8,924                 1             8,924
820.90(a).....................................................             8,924                 1             8,924                 5            44,620
820.90(b)(1) and (b)(2).......................................             8,924                 1             8,924                 5            44,620
820.100(a)(1) through (a)(7)..................................             8,924                 1             8,924                12           107,088
820.100(b)....................................................             8,924                 1             8,924                 1             8,924
820.120(b)....................................................             8,924                 1             8,924                 1             8,924
820.120(d)....................................................             8,924                 1             8,924                 1             8,924
820.130.......................................................             8,924                 1             8,924                 1             8,924
820.140.......................................................             8,924                 1             8,924                 6            53,544
820.150(a) and (b)............................................             8,924                 1             8,924                 6            53,544
820.160(a) and (b)............................................             8,924                 1             8,924                 1             8,924
820.170(a) and (b)............................................             8,924                 1             8,924                 2            17,848
820.180(b) and (c)............................................             8,924                 1             8,924                 2            17,848
820.181(a) through (e)........................................             8,924                 1             8,924                 1             8,924
820.184(a) through (f)........................................             8,924                 1             8,924                 1             8,924
820.186.......................................................             8,924                 1             8,924                 1             8,924
820.198(a) through (c)........................................             8,924                 1             8,924                 5            44,620
820.200(a) and (d)............................................             8,924                 1             8,924                 3            26,772
820.25........................................................             8,924                 1             8,924                 1             8,924
                                                               -----------------------------------------------------------------------------------------
    Totals....................................................  ................  ................  ................  ................         3,105,552
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital or operating and maintenance costs associated with this collection of information.


    Dated: October 12, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-26102 Filed 10-15-10; 8:45 am]
BILLING CODE 4160-01-P

