- Posted October 9, 2013 by
- MORGAN LEWIS RESPONSE TO THE SENATE FINANCE COMMITTEE CONFIRMING THE FACT THAT THE OUTCOMES REGISTRY HAD NOTHING TO DO WITH THE MYXO ETLOGIX CLINICAL TRIAL
- 150 years later, newspaper retracts editorial panning Gettysburg Address
- OHRP FDA REGULATIONS FOR INFORMED CONSENT CLASSIFIES INVESTIGATIONAL DEVICES SUCH AS THE MYXO ETLOGIX MODEL 5100 UNDER THE LAWS WHICH REQUIRE FULL INFORMED CONSENT:
- FDA CONGRESSIONAL OFFICE ON JULY 16, 2009 OFFICIALLY CATAGORIZES THE MYXO ETLOGIX MODEL 5100, MANUFACTURED BY EDWARDS LIFESCIENCES AS INVESTIGATIONAL AND OF SIGNIFICANT RISK
- Northwestern University and Northwestern Memorial Hospital Elements of Informed Consent : HIPPA WAIVER DOES NOT APPLY TO FDA STUDIES subject to the FDA regulations at 21 CFR 50
EDWARDS LIFESCIENCES FAILS TO REPORT HEART ATTACK TO FDA DURING COMPLIANCE REVIEW OF THE MYXO ETLOGIX RING AS DOCUMENTED IN LETTER TO HONORABLE SENATOR RICHARD LUGAR
NOV 0 5 2009
Dear Senator Lugar:
Thank you for your letter of August 4, 2009, regarding a situation brought to your attention by Dr. Nalini Rajamannan involving the status with the Food and Drug Administration (FDA or the Agency) of the model 5100 McCarthy Myxo dEtlogix Annuloplasty Ring, manufactured by Edwards Lifesiences (Edwards) LLC, for use in heart valve repair. The material you enclosed included a copy of a July 16, 2009, letter FDA had sent to a patient from Illinois, Ms. Atonista Vlahoulis, who had expressed concern about the use of the Myxo valve product by a surgeon who implanted this device in her. Below are responses FDA has made in reply to several follow-up questions the Agency received to the July 16, 2006, letter addressed to Ms. Vlahoulis .
1. The Agency says that sponsors are "encouraged to contact the Agency if they have questions regarding the appropriateness of a 510(k)." Ifthere are no disincentives for making the wrong determination, why would manufacturers seek advance input from the Agency or submit a new 510(k) rather than wait for the FDA to request one?
FDA believes that sponsors have disincentives to make the wrong determination. However, FDA has determined that its guidance to industry entitled "Deciding When to Submit a 51O(k) for a Change to an Existing Device" is not sufficiently clear in describing when a sponsor must submit a 5IO(k) to FDA. For example, the changes Edwards made to its device were not clearly described as requiring the submission of a 510(k).
Inrecognition of the rapid rate of device evolution, FDA's regulations provide that manufacturers need to submit a new 51O(k) only when a change or modification , or the sum of incremental changes or modifications, could significantly affect the safety or
effectiveness of the device. This standard is contained in 21 CFR 807.81(a)(3). In our
guidance document entitled "Deciding When to Submit a 51O(k) for a Change to an Existing Device," the Agency provided guidance on the types of labeling, technology, performance and material changes that may cross this threshold . We state in the
guidance that if a firm, after consulting the guidance, still has questions on whether or not a new 51O(k) is needed, they should contact our premarket review offices.
In that guidance FDA also advised manufacturers that design control requirements applicable to all Class II and III devices, and to certain Class I devices, are required to identify, document, validate, review and approve design changes before their implementations . The device history file must contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and quality system requirements. See 21 CFR 820.30(i), (j). FDA has access to the device history file upon inspection.
A manufacturer has strong incentives to comply with these 51O(k) and design control requirements. Significant consequences flow from noncompliance. Ifa manufacturer implements a change or modification without submitting a new 51O(k), and FDA subsequently determines the change required clearance of a new 51O(k) before device marketing, FDA considers the unapproved device to be in violation of the Act, may advise the manufacturer to recall the product or take other measures to correct products already in distribution, and may take additional compliance action against the manufacturer and the product. In assessing the appropriate response in a particular situation, FDA must assess the risks to public health, and determine whether the company made a good faith effort to determine if the changes could significantly affect the safety and effectiveness of the device. FDA would consider the significance of the changes made and possible implications to the patient, whether a manufacturer had appropriate rationale and/or documentation to support its decision, and whether or not the manufacturer is taking steps to come into compliance. The manufacturer's interest in avoiding such compliance actions provides strong incentive for diligence and good faith in making that initial determination.
There are additional incentives that apply outside the FDA regulatory scheme, such as the incentive to avoid private lawsuits and other negative interactions with patients and the health care community.
FDA is planning to update existing guidance in this area. We plan to take the lessons learned from these events and take the opportunity to communicate more clearly on these issues.
2. Did the FDA review any data on the patients who already had the device implanted prior to clearance by the FDA for marketing? Ifnot, why not?
Yes, an overview of the clinical experience to date was reviewed in the 51O(k) submission. This included a paper entitled "Initial Clinical Experience with Myxo ETlogix Mitra! Valve Repair Ring," (J Thorac Cardiovasc Surg 2008:1-9) published by McCarthy et al., information from Edwards Lifesciences' in-house registry, and a review of the Center for Devices and Radiologic Health's (CDRH or the Center) Manufacturer and User Facility Device Experience (MAUDE) database.
The McCarthy paper describes a two-surgeon, single-institution experience with 100 Myxo ETlogix (dETlogix) implants for repair ofmyxomatous mitral regurgitation over 18 months. The authors reported no postoperative mortality, infection, myocardial infarction, or renal failure. There was one reoperation for bleeding and one stroke. Ninety-eight percent of patients showed no residual regurgitation on intraoperative echocardiogram, with a mean transvalvular gradient of 3.0 mmHg. At hospital discharge (average 5.6 days later), 93.9 percent of patients had no regurgitation and 6.1 percent had
Follow-up was reported for an unknown number of patients with a total of 338 echocardiograms over an average time of 6.1 months (range unknown). Mitral regurgitation (MR) of 1+ was found in 18 percent of the Myxo ETlogix patients; it is stated that there was no statistical difference between discharge MR and follow-up MR, and that no patient had MR > 2+. Persistent, obstructive systolic anterior motion was not seen. The safety and effectiveness outcomes reported in this manuscript are similar to what one would expect for mitral valve repair operations involving an annuloplasty ring.
In the 51O(k) the sponsor provided a summary of the data included in their in-house registry. The sponsor reported that a total of 667 units had been distributed with 10 observations. Four were complaints, including two cases of suture pull-out, one case of a systemic rash responding to steroids, and the fourth, a possible cause of "inflammatory response." The sponsor reported that there were six device explants. Four devices were explanted during the procedure, but without report on whether the device was replaced with a different ring or by valve replacement. Details for the remaining two explants were not available....."
The Agency also reviewed medical device reports (MDRs) submitted to the MAUDE database during our review of the 51O(k). This database search returned five entries for four events (it appeared that the first two entries were for the same event). Three of the four events occurred on the date of implant for suture pulling through the annulus or for "unknown reasons." The fourth event was patient death and took place approximately six months after implant. The cause of death was not reported.
Regarding our review of Edwards' in-house registry data and the MDRs submitted for the dETlogix device, the Agency felt that the frequency and type of complaints and adverse events reports were consistent with the expected outcomes in this patient population...."
Assistant Commissioner for Legislation
Permission to use figure from the patient as per the Myxo File Part VII.