• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

  • Print
  • Share
  • E-mail

David C. Hoffman, D.D.S. 19-Mar-08

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration

 

9200 Corporate Boulevard
Rockville, Maryland 20850


Mar 19 2008

WARNING LETTER

VIA FEDERAL EXPRESS

David C. Hoffman, D.D.S.
256-C Mason Ave
Staten Island, NY 10305-3408

Dear Dr. Hoffman:

This Warning Letter is to inform you of objectionable conditions observed during the Food and Drug Administration (FDA) inspection conducted at your clinical investigational site from November 11, 2007 through Dec 12, 2007, by an investigator from the FDA New York District Office. The purpose of this inspection was to determine whether your activities as a clinical investigator of the clinical study of the [redacted] sponsored by [redacted] complied with applicable federal regulations. The [redacted] is a device as that term is defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h). This letter also requests prompt corrective action to address the violations cited.

The inspection was conducted under a program designed to ensure that data and information contained in requests for Investigational Device Exemptions (IDE), Premarket Approval (PMA) applications, and Premarket Notification submissions (510(k)) are scientifically valid and accurate. Another objective of the program is to ensure that human subjects are protected from undue hazard or risk during the course of scientific investigations.

Our review of the inspection report prepared by the district office revealed violations of Title 21, Code of Federal Regulations (21 C.F.R.) Part 812 -- Investigational Device Exemptions, Part 54-Financial Disclosure by Clinical Investigators, and Section 520(g)(21 U.S.C. 360j(g)) of the Act. At the close of the inspection, the FDA investigator presented an inspectional observations FORM FDA 483 for your review and discussed the observations listed on the form with you. The deviations noted on the FDA 483 and our subsequent review of the inspection report are discussed below:

1. Failure to ensure that an investigation is conducted according to the signed agreement, investigational plan, and applicable FDA regulations. [21 CFR 812.100 and 812.110(b)]

The investigational protocol requires that subjects be evaluated [redacted] Follow-up includes [redacted] and a [redacted] and then [redacted]. Review of the subjects' records identified that follow-up examinations were not performed as required by the protocol.

As reported in Table 8 of the 2006 Annual Report, the following did not have follow-up examinations as required by the protocol:

No Follow-up:

Since 09/29/2003

Since inception of Study

[redacted] eligible subjects

[redacted] eligible subjects

[redacted] eligible subjects

[redacted] eligible subjects

[redacted] eligible subjects

[redacted] eligible subjects

[redacted] eligible subjects

[redacted] eligible subjects

[redacted] eligible subjects

[redacted] eligible subjects

[redacted] eligible subjects

[redacted] eligible subjects

Totals [redacted]

[redacted]

Investigator non-compliance with the study protocol was previously observed during your last inspection in 2002, and cited in the letter issued to you on May 12, 2003. In your previous response letter to FDA dated August 26, 2003, you stated that you would be taking the following corrective action: "I will recommend that [redacted] send a letter to the FDA requesting a change in protocol and that patients not be seen at the listed predetermined times during the first [redacted] year other than that they be seen within the [redacted] and then with arrangements with a local [redacted] for follow-up with [redacted] taken at [redacted] and yearly intervals if there are no symptoms. Symptomatic patients will obviously be followed on a more comprehensive basis, as their clinical situation requires." As listed above, many subjects missed their protocol required follow up visits which indicates your corrective action was not implemented adequately.

2. Failure to maintain accurate, complete, and current records of each subject's case history and exposure to the device. [121 CFR 812.140(a)(3)]

[redacted] forms failed to identify any [redacted] part by part number or lot serial number as required in the case report forms for the following subjects: [redacted]

The dates of [redacted] in the subject listing you supplied to the FDA investigator in the [redacted] document did not correspond with some subjects identified in [redacted] document. Further, they did not correspond with the 2006 annual report date of [redacted], as follows:

[redacted]

2006 annual report

[redacted]

Adverse event page

[redacted]

[redacted]

[redacted]

[redacted]

In addition, the [redacted] identified in Table 8 of the 2006 Annual Report for the following subjects did not agree with either the [redacted] or the [redacted] document:

[redacted]

2006 annual report

[redacted]

[redacted]

[redacted]

[redacted]

Please provide copies of policies, procedures, and training with expected completion dates that are being developed and implemented to ensure case histories for this investigation and any other investigations in which you participate will be complete, current, and accurate. Please include a plan to evaluate and correct the case histories for the current investigation.

3. Failure to prepare and submit complete and accurate and timely reports of unanticipated adverse device effects.[21 CFR 812.150(a)(1)]

An investigator shall prepare and submit complete, accurate and timely reports to the sponsor and to the reviewing IRB of any unanticipated adverse device effect occurring during an investigation as soon as possible but in no event later than 10 working days after the investigator first learns of the effect. You failed to adhere to the above-stated regulation. Examples of this failure include but are not limited to the following:

a. Several subjects' [redacted] reportable adverse effect letters did not have a subject identification number, date of [redacted] or date of the adverse effect.
b. One letter failed to identify an accurate date of the adverse effect [redacted]
c. Several letters outside of the date or reporting timeframe of 10 days [redacted]

There were also several inaccuracies in reportable adverse effects as follow:

In a FDA letter [redacted] received dated August 10, 2007, regarding the 2006 Annual report (Tables 2, 3, and 4), FDA requested additional information concerning adverse effects, [redacted], and [redacted] identified in those tables. Your office response to this FDA inquiry identified [redacted] subjects with adverse effects.

During the November - December 2007 inspection, the FDA investigator requested documentation of adverse effects that your office reported to the IRB. When compared, the adverse event reports given to the FDA and IRB did not match. For example:

a. The list provided to the IRB contained 4 reports which did not appear on the list provided by [redacted]
b. The list provided by [redacted] contained [redacted] subjects not on the list in the computer identified as IRB documentation of adverse effect reporting.

4. Failure to maintain accurate, complete and current records of receipt, use or disposition of a device. [21 CFR 812.140(a)(2)]

You failed to maintain records relating to the quantity of the device, dates of receipt, batch or other identifying numbers; names of persons receiving, using or disposing of the device; and identification of disposition of the devices.

Inadequate record maintenance was previously observed during your last inspection in 2002, and cited in the letter issued to you on May 12, 2003. In your August 2003 response you stated that you would be taking the following corrective actions: "A specific office log and file will be created with just the information pertaining to patients in the FDA study. In addition, [redacted] This information will be kept in both [redacted] and patient's chart." Additionally, you stated, With regard to all patients enrolled in the study to date, [redacted] A further corrective action with regards to the overall study will be undertaken to delineate our clinical coordinator who does exist and she will be brought up-to-date on all the information relating to this study. We will look for an appropriate course on conducting an FDA study for our clinical coordinator as well as for myself as principle investigator to take, as this will bring us further familiarity with conducting an appropriate study or future studies."

You failed to maintain a specific office log or fill in the [redacted] traceability section of the case report form requesting part, lot, or serial numbers. There was no record or accountability of [redacted] that were [redacted] to [redacted] which indicates that your corrective action is inadequate.

5. Failure to submit progress reports on the investigation to the sponsor and IRB at regular intervals but in no event less often than yearly. [21 CFR 812.150(a)(3)]

There was no documentation of any annual report submitted to the IRB or sponsor.

6. Failure to submit a complete and accurate certification of financial disclosure as required by 21 CFR 54 [21 CFR 812.110(d)]

A clinical investigator shall disclose to the sponsor sufficient accurate financial information to allow the applicant to submit complete and accurate certification of disclosure statements. The investigator shall promptly update this information if any relevant changes occur during the course of the investigation.

During the inspection of 2002, [redacted] provided documentation to the FDA investigator with a copy to you dated 10/24/2002 stating that there were no Financial Disclosure Forms signed by you. During this current inspection you produced an Investigator's Agreement Form dated 10/30/2001, (pre-dating the statement given to the previous investigation that no financial disclosure was signed) which contained some language and elements regarding financial disclosure, There remains no documentation that you ever filled out the financial disclosure Form FDA 3455 as required and you have failed to complete a detailed description of the disclosable financial arrangements and interests regarding the proprietary interests you have in the product.

The violations described above are not intended to be an all inclusive list of problems that may exist with your clinical study. It is your responsibility as a clinical investigator to ensure compliance with the Act and applicable regulations. These violations are reflective of bioresearch monitoring review of the clinical study investigation.

Please provide copies of policies, procedures, and training that are being developed and implemented to ensure that this investigation and any other investigations in which you participate will be conducted in accordance with the signed investigator agreement, investigational plan, and applicable FDA regulations. Please identify the expected completion dates for all policies, procedures, training, and other corrective actions.

Within fifteen (15) working days of receiving this letter, please provide written documentation of the actions you have taken or will take to correct these violations and prevent the recurrence of similar violations in current or future studies for which you are the clinical investigator. Failure to respond to this letter and take appropriate corrective action could result in the FDA taking regulatory action without further notice to you. In addition, FDA could initiate disqualification proceedings against you in accordance with 21 C.F.R.812.119.

You will find information to assist you in understanding your responsibilities and planning your corrective actions in the FDA Information Sheets Guidance for Institutional Review Boards and Clinical Investigators, which can be found at http://www.fda.gov/oc/ohrt/irbs/. Any submitted corrective action plan must include projected completion dates for each action to be accomplished.

Send your response to:

Food and Drug Administration,
Center for Devices and Radiological Health
Office of Compliance, Division of Bioresearch Monitoring
9200 Corporate Boulevard, HFZ-311
Rockville, Maryland 20850
Attention: Doreen M. Kezer, Branch Chief

A copy of this letter has been sent to the New York District Office, 158-15 Liberty Ave, Jamaica, NY, 11433. Please send a copy of your response to that office.

If you have any questions, please contact Ms. Doreen Kezer, BSN, MSN, at 240-276-0125, or email, Doreen.Kezer@fda.hhs.gov.

Sincerely yours,

/S/

Timothy A. Ulatowski
Director
Office of Compliance
Center for Devices and
Radiological Health

cc:
PURGED COPY: [redacted]