Medical Device Warning Letter Pilot

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98N-0645]

Medical Device Warning Letter Pilot

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is initiating a pilot

program involving the medical device industry that is a continuation of

the ``medical device industry initiatives.'' This pilot concerns the

issuance of warning letters for quality system, premarket notification

submission (510(k)), and labeling violations. This 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 pilot includes eligibility criteria and

procedures for the issuance of warning letters.

EFFECTIVE DATES: Initiation date March 29, 1999. Termination date

September 8, 2000.

ADDRESSES: Submit written comments on the 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

pilot.

FOR FURTHER INFORMATION CONTACT:

Device quality system warning letter 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 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 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 is

initiating a pilot program that will last

[[Page 11019]]

for 18 months, and then be formally evaluated. The pilot includes

procedures for the issuance of warning letters for quality system (21

CFR part 820), 510(k) (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 pilot is currently restricted to the medical device

industry and is a continuation of the medical device industry

initiatives.

The purpose of this 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 pilot will not impact on violative

situations where enforcement action is necessary to protect the public

health.

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). In the Federal Register of August 27, 1998 (63 FR 45821), FDA

published a notice of availability of the draft pilot as a Level 1

guidance document consistent with GGP's. FDA received comments on the

draft from a medical device trade association and three individual

firms. FDA evaluated these comments and made revisions to the guidance

as appropriate.

The medical device warning letter 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 pilot consists of two parts that are

described below:

I. Device Quality System Warning Letter Pilot

Effective Dates: Initiation date March 29, 1999. Termination

date September 8, 2000.

This 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.

The device quality system warning letter 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. Any inspection that uncovers CGMP, premarket notification

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

adverse health consequences;\1\

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\1\ ``Serious adverse health consequences'' are to have the same

meaning as ``serious injury,'' which is defined in Sec. 803.3(aa)(1)

(21 CFR 803.3(aa)(1)).

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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. Any inspection that discloses 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

promptly 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,

following receipt of the Center's response, to respond to the

establishment. In this situation, the agency should not exceed 30

working days from the receipt date of the written response to the

FDA-483.

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 document) should be

sent to the establishment. The inspection should be classified as

voluntary action indicated (VAI) and the profile should be

designated as acceptable.

When no warning letter is issued, following a satisfactory

written response, 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 pilot as attachment 2 and table 1 for

attachment 3.)

This 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 March 29, 1999, and September 8, 2000, should be

forwarded by the districts 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 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) by the districts.

Any questions concerning this pilot should be directed to

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

827-0482), or electronic mail (Jeffrey [email protected]@FDAORAHQ).

Attachments, as stated:

Attachment 1--Model Postinspectional Notification Letter for Device

Quality System Warning Letter 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

[[Page 11020]]

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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[GRAPHIC] [TIFF OMITTED] TN08MR99.022

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Attachment 3--Device Quality System Warning Letter Pilot

Important: If one or more of your answers to any of the

questions are different than those found in the answer column of

Table 1, 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 No

manufacture other FDA regulated products?

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

regulated by CBER?

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

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

deficiencies that may cause serious adverse health

consequences?

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

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

or labeling violations?

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

violations in 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 promptly available to FDA Yes

all required information that was requested?

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

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. Please check all of the following statements that

apply:

______ 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 promptly 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 Pilot

Effective Dates: Initiation date March 29, 1999. Termination

date September 8, 2000.

A. Background

The impetus for this 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 pilot has been developed in response to the

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

determine whether notifying firms about 510(k) and labeling issues,

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

of the issues.

B. Pilot Procedures

The 510(k) and labeling warning letter 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. Any inspection that uncovers CGMP, 510(k), or labeling

deficiencies that may cause serious adverse health consequences;\2\

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\2\ ``Serious adverse health consequences'' are to have the same

meaning as ``serious injury,'' which is defined in

Sec. 803.3(aa)(1).

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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. Any inspection that discloses 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

promptly 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 with a 510(k) and

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

(a)(2)) (21 CFR 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 or untitled letter 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

[[Page 11023]]

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 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 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 March 29, 1999, and September 8, 2000, 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 18 months after it

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

T. Reynolds, OC/CDRH, HFZ-300.

II. Comments

Interested persons may, at any time, submit to the Dockets

Management Branch (address above) written comments regarding this pilot

program. Two copies of any comment 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.

Comments will be considered in determining whether to revise, revoke,

or adopt this pilot program on a permanent basis. Received comments may

be seen in the office above between 9 a.m. and 4 p.m., Monday through

Friday.

III. Electronic Access

A copy of the 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 pilot and may be

accessed at ``http://www.fda.gov/ora'' or ``http://www.fda.gov/cdrh'',

respectively. The pilot will be available on the compliance references

or program areas/compliance information pages for ORA and CDRH,

respectively.

Dated: March 1, 1999.

William K. Hubbard,

Acting Deputy Commissioner for Policy.

[FR Doc. 99-5523 Filed 3-5-99; 8:45 am]

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