Medical Device Warning Letter Draft Pilot; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98N-0645]

Medical Device Warning Letter Draft Pilot; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is planning to initiate

a pilot program involving the medical device industry that is a

continuation of the ``medical device industry initiatives.'' This draft

pilot concerns the issuance of warning letters for quality system,

premarket notification submission (510(k)), and labeling violations.

This draft pilot is intended to optimize resource utilization, enhance

communication between industry and FDA, and provide firms with

incentives to promptly correct violations or deficiencies. The draft

pilot includes eligibility criteria and procedures for the issuance of

warning letters and will not be implemented until after the public

comment period has expired.

DATES: Written comments on the draft pilot may be submitted by October

13, 1998.

ADDRESSES: Submit written comments on the draft pilot to the Dockets

Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers

Lane, rm. 1061, Rockville, MD 20852. Comments should be identified with

the docket number found in brackets in the heading of this document.

See the Supplementary Information section for electronic access to the

draft pilot.

FOR FURTHER INFORMATION CONTACT:

Device quality system warning letter draft pilot: Jeffrey B.

Governale, Division of Compliance Policy (HFC-230), Office of

Regulatory Affairs, Food and Drug Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301-827-0411, FAX 301-827-0482.

Premarket notification (510(k)) and labeling warning letter draft

pilot: Chester T. Reynolds, Office of Compliance (HFZ-300), Center for

Devices and Radiological Health, Food and Drug Administration, 2098

Gaither Rd., Rockville, MD 20850, 301-594-4618, FAX 301-594-4610.

SUPPLEMENTARY INFORMATION:

I. Background

During recent FDA/medical device industry grassroots forums,

several issues were discussed concerning FDA's interaction with the

medical device industry. After considering these issues, the agency

plans to initiate a pilot program that will last for 18 months, and

then be formally evaluated. The draft pilot includes procedures for the

issuance of warning letters for quality system (21 CFR part 820),

510(k) (part 807, subpart E) (21 CFR part 807, subpart E), and labeling

(e.g., 21 CFR part 800, subpart B; part 801, and part 809, subparts B

and C) violations. This draft pilot is currently restricted to the

medical device industry and is a continuation of the medical device

industry initiatives.

FDA currently maintains contracts with the States of California,

Colorado, and Texas that will expire on September 30, 1998, to conduct

medical device inspections on behalf of FDA. This draft pilot does not

include those inspections done under State contract for FDA. However,

noncontract medical device inspections done by FDA personnel in these

States will be eligible for this draft pilot.

The purpose of this draft pilot is to optimize resource

utilization, enhance communication between the medical device industry

and FDA, and provide firms with incentives to promptly correct

violations or deficiencies. Implementation of this draft pilot will not

impact on violative situations where enforcement action is necessary to

protect the public health.

The medical device warning letter draft pilot is being issued as a

guidance document and represents the agency's current thinking on the

subject. It does not create or confer any rights for or on any person

and does not operate to bind FDA or the public. An alternative approach

may be used if such approach satisfies the applicable statute,

regulations, or both.

The agency has adopted good guidance practices (GGP's) that set

forth the agency's policies and procedures for the development,

issuance, and use of guidance documents (62 FR 8961, February 27,

1997). This pilot is being issued as a draft level 1 guidance

consistent with GGP's.

The draft pilot consists of two parts that are described as

follows:

I. Device Quality System Warning Letter Draft Pilot

Dates: (insert initiation and ending dates 18 months apart)

This draft pilot is restricted to the medical device industry

and is a continuation of the medical device industry initiatives.

Following a domestic device quality system inspection which

finds current good manufacturing practice (CGMP) deficiencies

(situation 1, compliance program (CP) 7382.830--part V) that warrant

a warning letter, the establishment is to be given 15 working days

to respond from the issuance date of the list of inspectional

observations (FDA-483). If the firm's written response to the FDA-

483 is deemed to be satisfactory by the district office, then a

warning letter should not be issued.

This draft pilot does not apply to:

1. Nonquality system inspections such as mammography,

radiological health, and bioresearch inspections;

2. Establishments that manufacture devices as well as other FDA

regulated products;

3. Establishments that manufacture devices that are regulated by

the Center for Biologics Evaluation and Research (CBER);

4. Recidivous establishments as defined in CP 7382.830;

5. An inspection that uncovered CGMP, premarket notification

submission (510(k)), or labeling deficiencies that may cause serious

adverse health consequences;

6. A compliance followup inspection when the previous inspection

resulted in a warning letter or regulatory action for quality

system, 510(k), or labeling violations;

7. An inspection that disclosed other significant device

violations (e.g., medical device reporting or premarket approval) in

addition to quality system, 510(k), or labeling violations which

warrant the issuance of a warning letter or regulatory action; or

8. A situation where the firm's management failed to make

available to FDA personnel all requested information and records

required by regulations or laws enforced by FDA.

If the district is essentially satisfied with the written

response to the FDA-483 but needs further clarification, it may seek

additional information via untitled correspondence, meetings, or

telephone.

If the firm fails to respond to the FDA-483, a warning letter

should be sent to the establishment once the 15 working day period

has expired. If the district receives a response to the FDA-483

within 15 working days, the district has 15 working days from the

receipt date to determine whether the response is satisfactory. If

it is necessary for the district to consult with the Center for

Devices and Radiological Health's Office of Compliance for technical

assistance, the latter office has 15 working days to respond to the

district and then the district has 15 working days to respond to the

establishment. If the written response to the FDA-483 is determined

to be unsatisfactory, the district should send a warning letter to

the establishment.

When no warning letter is issued by the district office due to

the firm's satisfactory written response, the postinspectional

notification letter (see attachment 1 of this

[[Page 45822]]

document) should be sent to the establishment.

When a decision is made not to send a warning letter due to a

satisfactory written response from the firm, the inspection should

be classified as voluntary action indicated (VAI) and the profile

should be designated as acceptable.

When no warning letter is issued, as described previously, and

the next inspection discloses situation 1 CGMP deficiencies, then

FDA personnel should proceed as if a warning letter had been issued

for the previous inspection and consider appropriate enforcement

action. (See the graphic for the device quality system warning

letter draft pilot as attachment 2 and table 1 for attachment 3.)

This draft pilot will be evaluated by FDA at the end of the 18-

month period.

Copies of all domestic warning letters that include a device

CGMP adulteration charge (section 501(h) of the Federal Food, Drug,

and Cosmetic Act (21 U.S.C. 351(h))) for inspections that are

initiated between (insert initiation date) and (insert date 18

months after start date) should be forwarded to the Division of

Compliance Management and Operations (DCMO)/Office of Enforcement

(OE) (HFC-210) with a cover page. (See attachment 4 for a copy of

this cover page.)

When warning letters are not issued for situation 1 CGMP

deficiencies under this draft pilot, copies of the postinspectional

notification letters issued for the inspections initiated between

the above dates should be sent to Jeffrey B. Governale, Division of

Compliance Policy (DCP)/OE (HFC-230).

Any questions concerning this draft pilot should be directed to

Jeffrey B. Governale via telephone (301-827-0411), facsimile (301-

827-0482), or electronic mail (Jeffrey Governale@OE@FDAORAHQ).

Attachments: As stated

Attachment 1--Model Postinspectional Notification Letter for Device

Quality System Warning Letter Draft Pilot

[Name and title of most responsible individual]

[Establishment's name and address]

Dear ____________________ :

The Food and Drug Administration (FDA) conducted an inspection

of your firm's [description] facility at [address] on [date]. The

inspection covered the following devices:

[list devices and their profile classes]

At the end of the inspection, the FDA investigator left a list

of inspectional observations (FDA-483) at your firm. We have

received your firm's written response, dated [date] to that FDA-483.

Copies of this response and the FDA-483 are enclosed.

While this inspection found deficiencies of your quality system

that would warrant a warning letter if not corrected, your written

response has satisfied us that you either have taken or are taking

appropriate corrective actions. At this time, FDA does not intend to

take further action based on these inspectional findings. The agency

is relying on your commitment regarding corrective actions and,

should we later observe that the deviations from the quality system

regulation have not been remedied, future regulatory action (e.g.,

seizure, injunction and civil penalties) may be taken without

further notice.

Based upon your corrective action, the deficiencies noted during

FDA's inspection will not affect applicable pending premarket

submissions or export certificates for devices manufactured at your

facility that were specifically inspected. This information is

available to Federal agencies when they consider awarding contracts.

There may be other devices and operations of your firm for which the

conclusions from this inspection are not applicable. The agency may

separately inspect your firm's facilities to address the quality

system regulation in these areas.

Your firm has an ongoing responsibility to conduct internal

self-audits to assure you are continuing to maintain conformance

with the quality system regulation.

For further information, please contact the following individual

at this office:

[name and telephone number]

Sincerely,

District Director

______________ District Office

Enclosures

bcc:

HFC-230 (Governale)

(district office internal distribution)

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[[Page 45824]]

Attachment 3--Device Quality System Warning Letter Draft Pilot

Important

If one or more of your answers to any of the questions are

different than those found in the answer column of this Table, then

this pilot does not apply to your situation. You should follow FDA's

normal standard operating procedures instead.

Table 1

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Number Question Answer

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1............ In addition to devices, does the establishment manufacture other FDA No

regulated products?

2............. Does the establishment manufacture devices that are regulated by No

CBER?

3............. Is the establishment a recidivous firm per CP 7382.830? No

4............. Did the inspection uncover CGMP, 510(k), or labeling deficiencies No

that may cause serious adverse health consequences?

5............. Was this a compliance followup inspection to a warning letter or No

regulatory action for quality system, 510(k), or labeling

violations?

6............. Did the inspection disclose other significant device violations in No

addition to quality system, 510(k), or labeling violations which

warrant the issuance of a warning letter or regulatory action?

7............. Did the firm's management make available to FDA all required Yes

information that was requested?

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Attachment 4--Cover Page for the Device Quality System Warning Letter

Draft Pilot

To: FDA/ORA/OE/DCMO (HFC-210)

(mailing address: 5600 Fishers Lane, Rockville, MD 20857-001)

From: ____________________

________District (HFR-______)

Establishment's name and address:

Date inspection was initiated:

(This cover page should be attached to each warning letter that

includes a device CGMP adulteration charge (under section 501(h) of

the act). Please refer to the device quality system warning letter

pilot before filling out this cover page.)

The attached warning letter was issued for device CGMP

deficiencies for one or more of the following reasons. Please check

the appropriate reason(s):

______ The establishment did not respond to the FDA-483 within

15 working days.

______ The establishment provided an unsatisfactory response to

the FDA-483 within 15 working days.

______ The establishment manufactures devices as well as other

FDA regulated products.

______ The establishment manufactures devices that are

regulated by CBER.

______ The inspection uncovered CGMP, 510(k), or labeling

deficiencies that may cause serious adverse health consequences.

______ The inspection disclosed other significant device

violations (e.g., medical device reporting or premarket approval) in

addition to quality system, 510(k), or labeling violations which

warrant the issuance of a warning letter or regulatory action.

______ The firm's management failed to make available to FDA

personnel all requested information and records required by

regulations or laws enforced by FDA.

Please record any comments that the district may have concerning

this pilot on the back of this cover page.

II. Premarket Notification (510(k)) and Labeling Warning Letter Draft

Pilot

Dates: (insert initiation and ending dates 18 months apart)

A. Background

The impetus for this draft pilot has its origins in FDA

grassroots meetings with the medical device industry. During these

meetings warning letters, for both premarket notification submission

(510(k)) and labeling violations, were identified as topics for

discussion. Manufacturers contend that:

1. They are often unaware of the agency's concerns about 510(k)

and labeling issues until they receive a warning letter;

2. Information about these concerns is often available at the

time of the inspection; and

3. If notified during the inspection manufacturers would have an

opportunity to respond, and perhaps resolve, the concerns identified

by the investigators.

Consequently, this draft pilot has been developed in response to

the device industry's concerns. The purpose of this draft pilot is

to determine if notifying firms about 510(k) and labeling issues, in

lieu of a warning letter, will result in the efficient resolution of

the issues.

B. Draft Pilot Procedures

The 510(k) and labeling warning letter draft pilot does not

apply to the following situations:

1. Advertising and promotion issues;

2. Establishments that manufacture devices as well as other FDA

regulated products;

3. Establishments that manufacture devices that are regulated

by the Center for Biologics Evaluation and Research (CBER);

4. An inspection that uncovered CGMP, 510(k), or labeling

deficiencies that may cause serious adverse health consequences;

5. A compliance followup inspection when the previous inspection

resulted in a warning letter or regulatory action for quality

system, 510(k), or labeling violations;

6. An inspection that disclosed other significant device

violations (e.g., medical device reporting or premarket approval) in

addition to quality system, 510(k), or labeling violations which

warrant the issuance of a warning letter or regulatory action;

7. A situation where the firm's management failed to make

available to FDA personnel all requested information and records

required by regulations or laws enforced by FDA;

8. Devices that were never cleared by FDA via a 510(k) and were

not exempted from this requirement (Sec. 807.81(a)(1) or (a)(2));

9. A major change or modification in the intended use of the

device (Sec. 807.81(a)(3)(ii)); or

10. Electronic products that emit radiation as defined in 21 CFR

1000.3.

Domestic device inspection reports, with endorsements, that

identify possible 510(k) violations of Sec. 807.81(a)(3)(i) (a

change or modification in the device that could significantly affect

the safety or effectiveness of the device) and/or possible labeling

violations should be forwarded to the Office of Compliance (OC),

Center for Devices and Radiological Health (CDRH), HFZ-306. If CDRH

believes that a warning letter situation exits, OC will notify the

establishment via an untitled letter within 30 working days. The

untitled letter will inform the establishment of the need to correct

the violation by submitting either a new 510(k) or an appropriate

labeling change. CDRH will send a copy of this letter to the home

district. If a warning letter situation/correction is not warranted,

OC will notify the district by memorandum, facsimile, or electronic

mail. The district will inform the establishment, in writing, that

no correction is required.

Firms will have 15 working days from the date of a CDRH untitled

letter to respond. CDRH will have 30 working days to evaluate the

firm's response. An exception to this timeframe may occur if CDRH

has to consult with the district and/or the firm. If CDRH determines

that a firm's response is satisfactory, a warning letter should not

be issued. If CDRH is essentially satisfied with the firm's response

but needs further clarification, it may seek additional information

via telephone or untitled correspondence.

If a firm fails to respond to CDRH's untitled letter, a warning

letter should be sent to the establishment by CDRH when the 15

working day timeframe has expired. If CDRH receives a response to

the untitled letter within 15 working days, CDRH has 30 working days

from the receipt date to determine whether the response is

satisfactory. If the written response is determined to be

unsatisfactory, CDRH should send a warning letter to the

establishment.

When no warning letter is issued by CDRH due to a firm's

satisfactory written response, a postinspectional notification

letter should be sent by CDRH to the establishment, with

[[Page 45825]]

a copy to the home district, which includes the following language:

``While this inspection found deficiencies concerning (insert

`premarket notification (510(k)),' `labeling,' or both as

appropriate] that would warrant a warning letter if uncorrected,

your written response has satisfied us that you either have taken or

are taking appropriate corrective actions. At this time, FDA does

not intend to take further action based on these inspectional

findings. The agency is relying on your commitment regarding

corrective actions and, should we later observe that these

deficiencies have not been remedied, future regulatory action (e.g.

seizure, injunction and civil penalties) may be taken without

further notice.''

When a CDRH decision is made not to send a warning letter due to

a satisfactory written response from the firm, the district should

classify the inspection as VAI and the profile as acceptable for the

labeling or 510(k) issues.

When no warning letter is issued, as described previously, and

the next inspection of the firm discloses significant 510(k) and/or

labeling deficiencies, then FDA personnel should proceed as if a

warning letter had been issued for the previous inspection and

consider appropriate enforcement action.

C. Administrative

Copies of all warning letters will be forwarded to the Division

of Compliance Management and Operations (DCMO), Office of

Enforcement (OE)(HFC-210). When Warning Letters are not issued for

510(k) or labeling deficiencies under this pilot, copies of the

postinspectional notification letters issued for inspections that

are initiated between (insert initiation date) and (insert date that

is 18 months after the initiation date) should be sent to Jeffrey B.

Governale, Division of Compliance Policy (DCP)/OE, HFC-230.

CDRH's OC will monitor the warning and postinspectional

notification letters and evaluate the pilot 1 year after it begins.

Any questions about this pilot should be directed to Chester T.

Reynolds, OC/CDRH, HFZ-300.

II. Request for Comments

Interested persons may, on or before October 13, 1998, submit to

the Dockets Management Branch (address above) written comments on the

draft pilot. Two copies of any comments are to be submitted, except

that individuals may submit one copy. Comments are to be identified

with the docket number found in brackets in the heading of this

document. The agency will review all comments, but in issuing a final

pilot program need not specifically address every comment. The agency

will make changes to the draft pilot in response to comments, as

appropriate. Copies of the draft pilot and received comments may be

seen in the Dockets Management Branch (address above) between 9 a.m.

and 4 p.m., Monday through Friday.

III. Electronic Access

A copy of the draft pilot may also be downloaded to a personal

computer with access to the World Wide Web (WWW). The Office of

Regulatory Affairs (ORA) and the CDRH home pages include the draft

pilot and may be accessed at ``http://www.fda.gov/ora'' or ``http://

www.fda.gov/cdrh'', respectively. The draft pilot will be available on

the compliance references or compliance information pages for ORA and

CDRH, respectively.

Dated: August 20, 1998.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 98-23027 Filed 8-26-98; 8:45 am]

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