
[Federal Register Volume 78, Number 237 (Tuesday, December 10, 2013)]
[Notices]
[Pages 74146-74151]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-29394]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0853]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; 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 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 (the PRA).

DATES: Fax written comments on the collection of information by January 
9, 2014.

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 emailed 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: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 1350 Piccard Dr., PI50-400B, Rockville, 
MD 20850, PRAStaff@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 
Regulation--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

[[Page 74147]]

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 FD&C 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 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) 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) 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

[[Page 74148]]

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 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, 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 added design and purchasing controls, 
modified previous critical device requirements, revised previous 
validation and other requirements, and harmonized 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, 
or 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) re-packer, re-labelers, and contract 
sterilizer firms, which are subject only to requirements applicable to 
their activities. In addition, remanufacturers of hospital single-use 
devices (SUDs) are now to be considered to have the same requirements 
as manufacturers in regard to the regulation. The establishment, 
maintenance, and/or documentation of procedures, records, and data 
required by the regulation assists 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 25,986 respondents. 
A query of the Agency's registration and listing database shows that 
approximately 15,113 domestic and 10,873 foreign establishments are 
respondents to this information collection.\1\ These recordkeepers 
consist of manufacturers, subject to all requirements and contract 
manufacturers, specification developers, re-packers, re-labelers, and 
contract sterilizers, subject only to requirements applicable to their 
activities. Hospital remanufacturers of SUDs are now defined to be 
manufacturers under guidance issued by FDA's Center for Devices and 
Radiological Health, 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. 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 PRA burden placed on the 25,986 
establishments is an average burden.
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    \1\ Based on fiscal year 2012 data.
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    In the Federal Register of July 31, 2013 (78 FR 46347), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information to which one comment was received.
    The comment agreed that the information has practical utility but 
requested clarification regarding whether records gathered in 
electronic format will be made available outside of FDA.
    Disclosure of QS records is governed by the Freedom of Information 
Act (5 U.S.C. 552) and FDA's Public Information regulation at part 20 
(21 CFR part 20). Section 820.180(a) of the CGMP/QS regulation provides 
that records deemed confidential by manufacturers may be marked to aid 
FDA in determining what information may be disclosed under part 20. 
This applies to both paper and electronic QS records.
    Another part of the comment expressed a belief that ``the burden on 
industry of complying with FDA requests for information during an 
inspection is based on data FDA maintains on actual inspections; the 
estimates are averages'' and that ``it is unclear how FDA arrived at 
these estimates since they seem high when spread out across all 
registered device manufacturers.''
    The comment assumes that the burden estimate includes only the 
burden of responding to information requests during an inspection. 
However,

[[Page 74149]]

the estimates also include the burden of collecting, maintaining, and 
retaining the records. The comment's suggestion of 3.5 hours per year 
for ``responding to information requests during an inspection'' does 
not appear to include the burden of collecting, maintaining, and 
retaining the records and is based on the experience of only one 
segment of industry. 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 estimated 
burden is, therefore, an average burden.
    As a basis for its burden estimates, the Agency relied in part on 
certain information found in a study originally developed under FDA 
contract by Eastern Research Group, Inc., when the CGMP/QS regulation 
became final. The study was submitted to OMB as part of the original 
PRA approval and is part of the Federal docket. The Agency performs 
ongoing reviews of the information collection burden as required under 
the PRA for purposes of evaluating burden associated with its 
information collection requests and has done so for the purpose of 
extending the recordkeeping requirements associated with the CGMP/QS 
regulations. The commenter believes that the estimates the Agency 
provides are too high. However, the commenter does not offer an 
alternative methodology for estimating that the Agency may review. For 
these reasons we have not changed the hourly burden estimate.
    The comment also suggests that FDA did not make clear what was 
meant by the ``quality, utility, and clarity of the collected 
information'' in the 60-day notice requesting public comment on the 
information collection. ``Quality, utility, and clarity'' have the same 
meaning as in OMB's regulations at 5 CFR 1320.8(d)(1)(iii).
    Another part of the comment addressed concerns about the use of 
electronic means to fulfill the information collection requirements. 
The comment seems to assume that it would take additional time to 
provide electronic records at the request of an inspector because 
records that are not kept in electronic format would need to be scanned 
in order to fulfill the inspector's request. The comment also requests 
that FDA ``publish procedures for the use of any electronic submissions 
which may be contemplated'' to help the commenter allay concerns about 
misuse of photographs and electronic submissions.
    At this time, fulfillment of the information collection via 
electronic means is optional. We estimate that approximately 75 percent 
of respondents currently use some form of electronic recordkeeping to 
fulfill the information collection. Firms may use appropriate 
technology in accordance with FDA's ``Electronic Records; Electronic 
Signatures'' final rule (62 FR 13430; March 20, 1997) to comply with 
the CGMP/QS recordkeeping requirements. However, respondents may make 
the records available in paper format. There is no additional 
requirement that respondents convert existing paper records to an 
electronic format.
    The comment also requests an explanation regarding the citation of 
the standard ``ISO 9001'' in the 60-day notice for public comment, 
rather than ``ISO 13485.''
    In the notice, we included background information regarding the 
Quality System Regulation (part 820). We referenced ``ISO 9001: Quality 
Systems Model for Quality Assurance in Design/Development, Production, 
Installation, and Servicing'' because at the time the Quality System 
Regulation was issued and the preamble was written, ISO 9001 was the 
current standard.
    Additionally, the comment requests clarification regarding the 
Agency's contemplation of new submissions of information and includes 
suggestions related to such new submissions.
    At this time, there is no new requirement for submission of 
information under the QS regulations. Any future new requirements for 
information collection will be made available for public comment as 
required by 5 CFR part 1320.
    The Center for Devices and Radiological Health is proactive in 
ensuring that the medical device industry and other affected 
individuals are made aware of ongoing 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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                                                     Number of                        Average
     Activity/21 CFR Section         Number of      records per    Total annual     burden per      Total hours
                                   recordkeepers   recordkeeper       records      recordkeeping
----------------------------------------------------------------------------------------------------------------
Quality policy--820.20(a).......          25,986               1          25,986               7         181,902
Organization--820.20(b).........          25,986               1          25,986               4         103,944
Management review--820.20(c)....          25,986               1          25,986               6         155,916
Quality planning--820.20(d).....          25,986               1          25,986              10         259,860
Quality system procedures--               25,986               1          25,986              10         259,860
 820.20(e)......................
Quality audit--820.22...........          25,986               1          25,986              33         857,538
Training--820.25(b).............          25,986               1          25,986              13         337,818
Design procedures--820.30(a)(1).          25,986               1          25,986               2          51,972
Design and development planning--         25,986               1          25,986               6         155,916
 820.30(b)......................
Design input--820.30(c).........          25,986               1          25,986               2          51,972
Design output--820.30(d)........          25,986               1          25,986               2          51,972
Design review--820.30(e)........          25,986               1          25,986              23         597,678
Design verification--820.30(f)..          25,986               1          25,986              37         961,482
Design validation--820.30(g)....          25,986               1          25,986              37         961,482
Design transfer--820.30(h)......          25,986               1          25,986               3          77,958
Design changes--820.30(i).......          25,986               1          25,986              17         441,762

[[Page 74150]]

 
Design history file--820.30(j)..          25,986               1          25,986               3          77,958
Document controls--820.40.......          25,986               1          25,986               9         233,874
Documentation approval and                25,986               1          25,986               2          51,972
 distribution and document
 changes--820.40(a) and (b).....
Purchasing controls--820.50(a)..          25,986               1          25,986              22         571,692
Purchasing data--820.50(b)......          25,986               1          25,986               6         155,916
Identification--820.60..........          25,986               1          25,986               1          25,986
Traceability--820.65............          25,986               1          25,986               1          25,986
Production and process controls--         25,986               1          25,986               2          51,972
 820.70(a)......................
Production and process changes            25,986               1          25,986               2          51,972
 and environmental control--
 820.70(b) and (c)..............
Personnel--820.70(d)............          25,986               1          25,986               3          77,958
Contamination control--820.70(e)          25,986               1          25,986               2          51,972
Equipment maintenance schedule,           25,986               1          25,986               1          25,986
 inspection, and adjustment--
 820.70(g)(1) to (g)(3).........
Manufacturing material--                  25,986               1          25,986               2          51,972
 820.70(h)......................
Automated processes--820.70(i)..          25,986               1          25,986               8         207,888
Control of inspection,                    25,986               1          25,986               5         129,930
 measuring, and test equipment--
 820.72(a)......................
Calibration procedures,                   25,986               1          25,986               1          25,986
 standards, and records--
 820.72(b)(1) to (b)(2).........
Process validation--820.75(a)...          25,986               1          25,986               3          77,958
Validated process parameters,             25,986               1          25,986               1          25,986
 monitoring, control methods,
 and data--820.75(b)............
Revalidation--820.75(c).........          25,986               1          25,986               1          25,986
Acceptance activities--820.80(a)          25,986               1          25,986               5         129,930
 to (e).........................
Acceptance status--820.86.......          25,986               1          25,986               1          25,986
Control of nonconforming                  25,986               1          25,986               5         129,930
 product--820.90(a).............
Nonconforming product review/             25,986               1          25,986               5         129,930
 disposition procedures and
 rework procedures--820.90(b)(1)
 to (b)(2)......................
Procedures for corrective/                25,986               1          25,986              12         311,832
 preventive actions--
 820.100(a)(1) to (a)(7)........
Corrective/preventive                     25,986               1          25,986               1          25,986
 activities--820.100(b).........
Labeling procedures--820.120(b).          25,986               1          25,986               1          25,986
Labeling documentation--                  25,986               1          25,986               1          25,986
 820.120(d).....................
Device packaging--820.130.......          25,986               1          25,986               1          25,986
Handling--820.140...............          25,986               1          25,986               6         155,916
Storage--820.150(a) and (b).....          25,986               1          25,986               6         155,916
Distribution procedures and               25,986               1          25,986               1          25,986
 records--820.160(a) and (b)....
Installation--820.170...........          25,986               1          25,986               2          51,972
Record retention period--                 25,986               1          25,986               2          51,972
 820.180(b) and (c).............
Device master record--820.181...          25,986               1          25,986               1          25,986
Device history record--820.184..          25,986               1          25,986               1          25,986
Quality system record--820.186..          25,986               1          25,986               1          25,986
Complaint files--820.198(a),              25,986               1          25,986               5         129,930
 (c), and (g)...................
Servicing procedures and                  25,986               1          25,986               3          77,958
 reports--820.200(a) and (d)....
Statistical techniques                    25,986               1          25,986               1          25,986
 procedures and sampling plans--
 820.250........................
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............       9,043,128
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.



[[Page 74151]]

    Dated: December 3, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-29394 Filed 12-9-13; 8:45 am]
BILLING CODE 4160-01-P


