[Federal Register Volume 64, Number 44 (Monday, March 8, 1999)]
[Notices]
[Pages 11018-11023]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-5523]


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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 Governale@OE@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]

BILLING CODE 4160-01-F

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[GRAPHIC] [TIFF OMITTED] TN08MR99.022



BILLING CODE 4160-01-C

[[Page 11022]]

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
----------------------------------------------------------------------------------------------------------------
 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?
----------------------------------------------------------------------------------------------------------------

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\
---------------------------------------------------------------------------

    \2\ ``Serious adverse health consequences'' are to have the same 
meaning as ``serious injury,'' which is defined in 
Sec. 803.3(aa)(1).
---------------------------------------------------------------------------

     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]
BILLING CODE 4160-01-F