Agency Information Collection Activities; Submission for OMB Review; Comment Request

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98N-0357]

Agency Information Collection Activities; Submission for OMB

Review; Comment Request

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that the

proposed collection of information listed below 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: Submit written comments on the collection of information by July

15, 1998.

ADDRESSES: Submit written comments on the collection of information to

the Office of Information and Regulatory Affairs, OMB, New Executive

Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn:

Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: Margaret R. Schlosburg, Office of

Information Resources Management (HFA-250), Food and Drug

Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-1223.

SUPPLEMENTARY INFORMATION: In compliance with section 3507 of the PRA

(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 (CGMP) Quality

System (QS) (21 CFR Part 820)--(OMB Control Number 0910-0073--

Reinstatement)

Under section 520(f) of the Federal Food, Drug, and Cosmetic Act

(the act) (21 U.S.C. 360j(f)), the Secretary of the Department of

Health and Human Services (the Secretary) has the authority to

prescribe regulations requiring that the methods used in, and the

facilities and controls used for, the manufacture, pre-production

design validation (including a process to assess the performance of a

device but not including an evaluation of the safety and effectiveness

of a device), packing, storage, and installation of a device conform to

CGMP, as described in such regulations, to assure that the device will

be safe and effective and otherwise in compliance with the act.

The CGMP/QS regulation implementing the authority provided by this

statutory provision is found in part 820 of the Code of Federal

Regulations (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. 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 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

[[Page 32668]]

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 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

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.

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 final CGMP/QS regulation amended and revised the CGMP

requirements for medical devices set out at part 820. The final rule

added design and purchasing controls; modified previous critical device

requirements; revised previous validation and other requirements; and

harmonized 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 imposed 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. 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

[[Page 32669]]

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.

FDA estimates information collection burdens imposed by the

addition, modification and revision of CGMP requirements in the final

rule as follows:

[[Page 32670]]

Table 1.--Annual Recordkeeping Burden

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Total Hours\1\

Number of Annual Total Annual Hours per (incremental Total Hours\2\ Total Operating &

21 CFR Section Recordkeepers Frequency of Records Recordkeeper increase in (prior continuing Maintenance Costs

Recordkeeping burdens) burdens)

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820.20(a) 7,237 1 7,237 10.96 79,386 ------- -------

820.20(b) 7,237 1 7,237 6.38 35,285 10,885 --------

820.20(c) 7,237 1 7,237 10.28 74,364 ------- -------

820.20(d) 7,237 1 7,237 16.49 119,305 ------- -------

820.20(e) 7,237 1 7,237 16.49 119,305 ------- -------

820.22(a) 7,237 1 7,237 53.53 376,507 10,885 -------

820.25(b) 7,237 1 7,237 21.13 152,896 ------- -------

820.30(a)(1) 7,237 1 7,237 2.92 21,162 ------- -------

820.30(b) 7,237 1 7,237 9.91 71,718 ------- -------

820.30(c) 7,237 1 7,237 2.92 21,162 ------- -------

820.30(d) 7,237 1 7,237 2.92 21,162 ------- -------

820.30(e) 7,237 1 7,237 38.98 282,115 ------- -------

820.30(f) 7,237 1 7,237 62.37 451,342 ------- $27,363,204

820.30(g) 7,237 1 7,237 62.37 451,342 ------- -------

820.30(h) 7,237 1 7,237 5.56 40,236 ------- -------

820.30(I) 7,237 1 7,237 28.77 208,173 ------- -------

820.30(j) 7,237 1 7,237 4.40 31,848 ------- -------

820.40 7,237 1 7,237 13.61 85,081 13,420 -------

820.40(a) and (b) 7,237 1 7,237 2.04 ------- 14,748 -------

820.50(a)(1) through (a)(3) 7,237 1 7,237 34.34 225,240 23,251 $898,500

820.50(b) 7,237 1 7,237 10.04 72,679 ------- -------

820.60 7,237 1 7,237 0.54 3,914 ------- -------

820.65 7,237 1 7,237 0.67 ------- 4,839 -------

820.70(a)(1) through (a)(5) 7,237 1 7,237 1.85 ------- 13,420 -------

820.70(b) and (c) 7,237 1 7,237 1.85 ------- 13,420 -------

820.70(d) 7,237 1 7,237 4.11 22,335 7,374 -------

820.70(e) 7,237 1 7,237 1.85 ------- 13,420 -------

820.70(g)(1) through (g)(3) 7,237 1 7,237 1.43 ------- 10,347 -------

820.70(h) 7,237 1 7,237 1.85 ------- 13,420 -------

820.70(i) 7,237 1 7,237 11.26 68,092 13,420 -------

820.72(a) 7,237 1 7,237 7.26 42,165 10,347 -------

820.72(b)(1) through (b)(3) 7,237 1 7,237 1.43 ------- 10,347 -------

820.75(a) 7,237 1 7,237 3.81 20,172 7,374 -------

820.75(b) 7,237 1 7,237 1.02 ------- 7,374 -------

820.75(b)(2) 7,237 1 7,237 1.17 1,096 7,374 -------

820.75(c) 7,237 1 7,237 1.17 1,096 7,374 -------

820.80(a) through (e) 7,237 1 7,237 4.80 ------- 34,721 -------

820.86 7,237 1 7,237 0.79 ------- 5,735 --------

820.90(a) 7,237 1 7,237 7.39 44,217 9,272 -------

820.90(b)(1) and (b)(2) 7,237 1 7,237 7.39 44,217 9,272 -------

820.100(a)(1) through (a)(7) 7,237 1 7,237 20.50 145,144 3,226 -------

820.100(b) 7,237 1 7,237 1.28 ------- 9,272 -------

820.120 7,237 1 7,237 0.45 ------- 3,226 -------

820.120(b) 7,237 1 7,237 0.45 ------- 3,226 -------

820.120(d) 7,237 1 7,237 0.45 ------- 3,226 -------

820.130 7,237 1 7,237 0.45 ------- 3,226 -------

820.140 7,237 1 7,237 10.12 68,418 4,839 -------

820.150(a) and (b) 7,237 1 7,237 9.45 68,418 ------- -------

820.160(a) and (b) 7,237 1 7,237 0.67 ------- 4,839 -------

820.170(a) and (b) 7,237 1 7,237 1.50 ------- 10,885 -------

820.180(b) and (c) 7,237 1 7,237 1.50 ------- 10,885 -------

820.181(a) through (e) 7,237 1 7,237 1.21 ------- 8,783 -------

820.184(a) through (f) 7,237 1 7,237 1.41 ------- 10,240 -------

[[Page 32671]]

820.186 7,237 1 7,237 0.40 ------- 2,873 -------

820.198(a) through (c) 7,237 1 7,237 6.42 26,850 19,644 -------

820.200(a) through (d) 7,237 1 7,237 4.35 31,459 ------- -------

820.250 7,237 1 7,237 0.67 ------- 4,839 -------

Totals 7,237 1 7,237 3,527,901 375,268 $28,261,704

Grand Totals\3\ 3,903,169 $28,261,704

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\1\ Incremental increase in burden hours to achieve compliance with additional requirements in revised regulation.

\2\ Recordkeeping hours for prior requirements carried over into revised regulation, as approved by OMB on July 16, 1992, and expired on June 30, 1995

(OMB No. 0910-0073).

\3\ Note: Totals may not add due to rounding.

[[Page 32672]]

Under OMB information collection 0910-0073, Current Good Manufacturing

Practices (CGMP) for Medical Devices, there were 375,266 hours approved

for recordkeeping information collections contained in part 820. These

hours included 114,882 burden hours as a one time start up expenditure

for 650 new firms. The additional requirements contained in Current

Good Manufacturing Practice; Quality system (CGMP/QS) regulation will

add 3,527,901 burden hours to the burden, resulting in a total

recordkeeping burden of 3,903,169 hours. The 3,527,901 burden hours

includes 1,433,579 burden hours for a one time start up expenditure for

7,237 manufacturers and 2,094,321 burden hours expended annually by

7,237 manufacturers.

The recordkeeping estimate includes approximately 9.6 times as many

manufacturers with a one time start up expenditure, due to the addition

of the design control requirements. Further, the recordkeeping burden

hour calculations were estimated using a complex methodology involving

the estimated noncompliance ratio for small, medium, large, and very

large manufacturers multiplied by the number of manufacturers in each

category. These calculations factor in a rate of product innovation for

new products, including 510(k) devices.

Approximately 85 percent of the additional burden hours for CGMP/QS

regulation originate from the following four subparts of part 820: (1)

Subpart B--Quality System Requirements; (2) Subpart C--Design controls;

(3) Subpart E--Purchasing Controls; and (4) Subpart J--Corrective and

Preventive Action. Over 45 percent of the 3,527,901 burden hours are

attributed directly to the addition of design control requirements. The

purchasing control requirements and the respective recordkeeping burden

are approximately 8 percent of the additional recordkeeping burden.

Dated: June 8, 1998.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 98-15812 Filed 6-12-98; 8:45 am]

BILLING CODE 4160-01-F