Guest guest Posted May 25, 2004 Report Share Posted May 25, 2004 Greetings, esteemed hippies - That's quite a letter,eh? I work in analysis of clinical trial data, in a Biometry group, closely associated w/the Regulatory group, the folks who field such letters (God forbid that one should arrive!). My company is a biotech working on drug substances/products, and is into medical devices, but I think there is consierable crosstalk in industry regulations. So, I humbly offer a few observations - What would happen where I work were such a letter received? Certainly, there would be a terribly oppressive gloom followed by the irreducible wrath of Senior Management. Lapses in monitoring visits: these activities play into getting " clean " , " monitored " data that is essential to freezing the data and closing a trial. YOu'd think would be chomping at the bit to jump through the hoops, dot all the i's, and move as quickly as possible to clean submissible data. Protocol deviations happen, but generally these might pertain to inclusion/exclusion criteria that aren't central to the primary endpoints of the study. A protocol deviation that involves the use of a hip component other than the device the trial was done to evaluate? How odd. I would expect a protocol deviation to be signed off on by the CRA (clinical research associate, person who should be monitoring site compliance) and/or the Medical monitor, the lead medical person for a study on the WRight staff. This other component was approved? Missed visits: These happen. A study's sponsor doesn't expect 100% compliance in follow-up. There are ways to present such incomplete data. Unreported Serious Adverse Events (SAEs): Lapses here are a biggie. Sloppy work, for the clinical investigator at a site to give possible attribution to the device as cause of an SAE, and then not have that be submitted? I'm thinking that maybe used a CRO to manage the study and study data. A CRO is a clinical research organization, and a device or drug company that doesn't have the appropriate staff can hire a CRO to essentially run the study. The CRO's agents would be exepcted to make site visits and interact with site staff to assure compliance w/protocol. But even if a shabby CRO were involved here, appears at least not to have done a careful audit of the CRO's work. Just a few thoughts. Necessary disclaimers: I know nothing of this situation other than what was stated in the May 14 FDA letter. Absolutely nothing that I say reflects in any manner any opinion of my employer. I do not portray myself as an expert on the subject, and these statements are just my own opinion and not intended by me to represent reliable testimony of any sort. Anyway....surf on, Resurfers! I have a 6'10 " and two 7'4 " s sitting getting dusty that I hope to use again someday! - Bob > Hey hippies, we're all adults here. But that doesn't needfully mean > we can all manage the intricacies of the internet and government > postings. SO...IF YOU DON'T WANT TO READ THE FDA LETTER TO WRIGHT, > DON'T READ ANY FARTHER. It is not at all clear what devices they may > be talking about, since those parts are REDACTED...which means, > you're not permitted. And the letter mentions a couple of serious non- > hip issues. > > Read carefully. And know that it is block-copied from the FDA > warning letters website without change of any kind. In some cases, > the lines didn't " justify " , as they say in the newspaper trade. (It > only means some margins may be odd.) But I didn't even want to > change those oddities, so there would be no question about the > authenticity of the copy. > > Hobble on,hippies...unless you've already run you 10k on the &^% $*$# > Conserve+ that my insurance now almost certainly won't pay for. > > Alan > > Public Health Service > Food and Drug Administration > > Center for Devices and > Radiological Health > 2098 Gaither Road > Rockville, MD 20850 > > > > MAY 14 2004 > > WARNING LETTER > > Via Federal Express > > > W. Churinetz > Senior Vice President > Medical Technology, Inc. > 5677 Airline Rd. > Arlington, TN 38002-0100 > > Dear Mr. Churinetz: > > This Warning Letter informs you of objectionable conditions found > during a Food and Drug Administration (FDA) inspection conducted at > Medical Technology, Incorporated. This letter also requests > that you implement prompt corrective actions. Ms. E. , an > Investigator from FDA's New Orleans District Office, conducted the > inspection from January 20 through January 29, 2004. The purpose of > the inspection was to determine if your activities as a Sponsor of > the study for the [redacted], and [redacted], complied with > applicable FDA regulations. The products used in the study are > devices as defined in Section 201 (h) of the Federal Food, Drug, and > Cosmetic Act [21 U.S.C. 321(h)]. > > The FDA inspection was conducted under a program designed to ensure > that data and information contained in requests for Investigational > Device Exemptions (IDE), Premarket Approval Applications (PMA), and > Premarket Notification [510(k)] submissions are scientifically valid > and accurate. The program also ensures that human subjects are > protected from undue hazard or risk during the course of scientific > investigation. > > Our review of the inspection report and related documents submitted > by the New Orleans District Office revealed serious violations of > Title 21, Code of Federal Regulations, (21 CFR), Part 812 - > Investigational Device Exemptions, and Section 520(g) of the Act [21 > U.S.C. 360j(g)]. At the close of the inspection, Ms. discussed > deviations observed during this inspection with Brown, Kate > Garretson, and Becky Fortner. The deviations noted during the > inspection and our subsequent inspection report review are discussed > below: > > Failure to ensure proper monitoring of the investigation and failure > to secure investigator compliance [21 CFR 812.40 and 46(a)]. > > Examples of these failures include but are not limited to the > following: > > The Investigational Plan you submitted to the FDA under [redacted] > stated that " Monitoring visits will be conducted as needed but at > least annually. " Your records showed that, of the ten study sites > participating in the study, four have not received a monitoring visit > since 2002. Specifically: > > [redacted], Site [redacted]---the last monitoring visit was June 3- 5, > 2002. > [redacted], Site [redacted]---the last monitoring visit was February > 15, 2002. > [redacted], Site [redacted]---the last monitoring visit was December > 5, 2002. > [redacted], Site [redacted]---the last monitoring visit was February > 4, 2002. > All four of these clinical investigators are continuing to collect > safety and efficacy study data from enrolled subjects, even though > the study may be closed to active enrollment. Responsibilities of > Sponsors include ensuring proper monitoring of the investigation [21 > CFR 812.40] in order to secure compliance with the investigational > plan [21 CFR 812.46(a)]. In addition, since these clinical sites have > not been monitored since 2002, the study data reported to the FDA in > your PMA submission, [redacted] have not been verified against the > subjects' case histories maintained by the clinical investigators. > > A sponsor who discovers that an investigator is not complying with > the signed investigator agreement, the investigational plan, the > requirements of applicable FDA regulations, or any conditions of > approval imposed by FDA or the reviewing Institutional Review Board > (IRB) must promptly either secure compliance or discontinue shipments > of the device to the investigator and terminate the investigator's > participation in the investigation [21 CFR 812.46]. > Your records contained documentation of several protocol deviations > by clinical investigators participating in the study for [redacted] > yet you failed to secure investigator compliance. Examples of these > failures include the following: > > [redacted] (site [redacted] deviated from the protocol by not using > the test article in at least three subjects. Two of these subjects, > [redacted] and [redacted] received a hip component from another > company's device and are included in the primary efficacy data > analysis reported to the FDA in your PMA submission ([redacted]) > > [redacted] ([redacted]) and Dr. [redacted] (site [redacted] each > enrolled at least one subject who did not meet eligibility criteria. > Both of these subjects, [redacted] and [redacted] are included in the > primary efficacy data analysis reported to the FDA in your PMA > submission ([redacted]). > > Dr. [redacted] (site [redacted]) enrolled eleven patients whose range > of motion efficacy data had to be deleted from the database because > there was no record that Dr. [redacted] had actually seen the > patients. > > There were numerous instances across several clinical sites of study > patients with missed post-surgical follow-up visits and follow-up > evaluations. > There were no records to demonstrate that your firm obtained prompt > correction and subsequent compliance by the clinical investigators in > question, or that your firm terminated the clinical investigator's > participation in the study to prevent the recurrence of serious > protocol deviations or regulatory violations. > > Failure to report all adverse events that occurred during the study > to the FDA as required by 520(g) of Act. > > An example of this failure includes but is not limited to the > following: > > A requirement of the IDE approval that you received for this device > study is that you make reports to the FDA of data obtained as a > result of the investigational use of the device during this study. > This includes reporting adverse events. This information assists the > FDA in determining compliance with the conditions granted, reviewing > the progress of the investigation, and evaluating the safety and > effectiveness of the device. The Investigational Plan you submitted > to the FDA under IDE [redacted] stated that all adverse events and > complications that occurred at the study sites would be reported to > the FDA. However, at least four serious adverse events that occurred > at Clinical Study site [redacted] between 2001 and 2003 were not > reported to the FDA: > > [redacted] : Dislocation of the device requiring closed reduction on > [redacted]. This event was considered to be possibly related to the > study device by the clinical investigator. > > Pt. [redacted]: Grade II - III heterotopic ossification of the right > hip, diagnosed [redacted] and Grade III heterotopic ossification of > the right hip diagnosed on [redacted]. These events were recorded at > the subject's follow-up visits, but were not reported on an Adverse > Event Form as required by the study protocol. > > Pt [redacted] Cardiac catheterization and insertion of stents for > treatment of coronary artery disease on [redacted]. This event was > considered to be unrelated to the study device by the clinical > investigator. > > Pt. [redacted]: Surgical removal of tonsils and section of uvula for > treatment of obstructive sleep apnea on [redacted]. This event was > considered to be unrelated to the study device by the clinical > investigator. > The above-described deviations are not intended to be an all- > inclusive list of deficiencies that may exist in this clinical study. > It is your responsibility as a sponsor to assure adherence to each > requirement of the Act and all pertinent federal regulations. > > Within 15 working days after receiving this letter, please provide > written documentation of the specific steps you have taken or will > take to correct these violations and prevent the recurrence of > similar violations in current or future studies. Any submitted > corrective action plan must include projected completion dates for > each action to be accomplished. Failure to respond to this letter and > take appropriate corrective action could result in the FDA taking > regulatory action without further notice to you. Send your response > to: > > Food and Drug Administration > Center for Devices and Radiological Health, Office of Compliance > Division of Bioresearch Monitoring, Program Enforcement Branch II, > HFZ-312 > 2094 Gaither Road, Rockville, land 20850 > Attn: Mr. Levering Keely, Consumer Safety Officer. > > We are also sending a copy of this letter to FDA's New Orleans > District Office, Food and Drug Administration, 22201 23rd Drive SE, > Bothell, WA 98021. We request that you also send a copy of your > response to that office. If you have any questions, please contact > Mr. Keely by phone at , ext. 142, or by e-mail at > Levering.Keely@f... > > Sincerely yours, > > /s/ > > A. Ulatowski > Director > Office of Compliance > Center for Devices and > Radiological Health Quote Link to comment Share on other sites More sharing options...
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