West Palm Beach Personal Injury Lawyer - Medical Devices & Implants

Daubert: Very Convoluted, Usually Confusing to Many, Nevertheless Elegant

Armand Rossetti — Thu, 06 Aug 2009 16:32:16 GMT

Pretrial Daubert hearings are essentially motions in limine that ultimately decide whether an expert is qualified, and whether that expert: 1) has based an opinion on sufficient facts or data; 2) will be able to testify using “reliable principles and methods,” and; 3) has applied the principles and methods reliable to the particular facts of a given case.

The Daubert factors are based Rule 702 of the Federal Rules of Evidence, which is used to examine an expert’s testimony as a whole. In addition under Rule 703, experts may reasonably rely on documents and information that may be inadmissible during trial. It is also Rule 703 that forms the basis for inquiry, concerning the reliability of any data that supports expert testimony. Furthermore, Rule 703 relaxes the requirement that experts need to acquire personal knowledge about the matter to which they testify. Finally, Rule 703 has little to do with whether an expert’s testimony, as a whole, meets Daubert standards. That determination rests with Rule 702.

Since a Rule 702 is more “holistic,” judges acting as gatekeepers should not require each document, or particular source of data that experts might use to form opinions, to be dispositive. In other words, Courts should not be conducting a Daubert inquiry on each and every document and deciding whether or not each document is qualified as being stand-alone reliable.

Instead, Judges should conduct a Rule 702 analysis in light of an expert’s reasoning and methodology in its entirety, or to analogize, judges should decide testimonial reliability under the totality of the medical, scientific and technical circumstances.

Daubert also requires that an expert witness has to assist and not to confuse the Trier of fact. If the Jury (Trier of fact) can understand whether a substance in particular is able to cause an injury and whether an injury resulted from that particular substance, an expert opinion would be redundant and unnecessary.

On the other hand, Rule 403 requires a Court to balance the probative value against the prejudicial effects of expert witness testimony. Courts should not confuse Rule 403 with Rule 703.

For example, experts do not necessarily need an epidemiological study with an internal control group or randomly selected participants to be able to show an association between exposure to a chemical and resulting bodily abnormalities. That is true because an association is not causation. While a case study might not be sufficient to show causation, it may be all that is necessary to show an association between presence of a toxic substance and a resulting injury.

However, if a Court mistakenly uses Rule 403 in place of Rule 703 to disqualify a source of information because that source in itself does not suffice in supporting causation, that Court has prematurely obviated the need to take all of the information, in the aggregate, and to perform a Rule 702 analysis to examine an experts methodology.

It is the expert in the first instance, and not the Court as gatekeeper, who is the judge of what recourses to choose to assist her in forming an opinion. It is the expert who will initially filter out prejudicial information as being irrelevant. The Court then uses Rule 703 to assure the reliability of evidence by vetting the bases that forms an expert’s testimony.

Let's take environmental asbestos infiltration an example, the fact that an air sampling study is an associational (or case) study affecting a few subjects, rather than a higher evidence based epidemiological study that affects several hundred subjects should not bar an expert from using the case study to inform her opinion about the dangers of asbestos release in the environment. The fact that a single case study published in a peer reviewed journal fails to establish causation under a Rule 703 review should go to the weight that the Jury will give such evidence, but it does not mean that an expert cannot eventually rely upon it in part to form an ultimate opinion.

Of course, if a single case study were the only source of evidence, then the Court might be reasonable in immediately performing a Rule 702 analysis to disqualify the entire testimony. However, the fact that an expert has relied upon several case studies to form an opinion, and has not used even one single epidemiological study should not in itself disqualify that expert’s testimony.

Rule 703 also addresses whether a study is of the type usually relied upon by experts in the field. Experts in different fields may rely upon different types of studies that span several different evidence based scientific levels. Certain professions might consider lower levels of scientific evidence as being adequate to enlighten the community about dangers inherennt in certain practices and procedures. In many instances, legal, ethical or moral considerations render higher evidence based, epidemiological studies forever unavailable.

For instance, the profession of orthopedic surgeons (community) may require only a certain number of evidence based medicine (EBM) level IV, peer reviewed case studies, instead of level I epidemiological studies, before that community decides to strongly recommend that surgeons discontinue using a certain procedure. In particular, the community may determine that a medical device, such as a pain pump that employs a medication, such as bupivacaine, is causing shoulder chondrolysis at a much higher than usual incidence. The community then conducts several different types of level IV EBM studies that expose the pump and anesthetic as being too dangerous for continued use in joints between bones. Just because it is unethical to conduct double blind, epidemiological studies, Courts should not consider the entire orthopedic decision making process to be less “scientific” than other such investigations.

If under Rule 703, Courts were to individually disqualify each and every level IV article as being insufficient and/or unreliable to base an association that might in light of additional studies, lead to causation, no orthopedic expert would be able to gather any evidence to form an opinion, and have a Court perform a Rule 702 analysis. That is the primary reason that many document-by-document decisions that have incorrectly occurred under Rule 703 have unfairly usurped the expert’s opportunity to undergo a required Rule 702 review under Daubert. This means that many plaintiffs and perhaps many defendants have not had their day in court. For a more comprehensive discussion, see US v. WR Grace.

Originally posted at InjuryBoard by Armand Rossetti

Curing Incontinence May Cause Greater Harm

Brenda Fulmer — Wed, 18 Feb 2009 16:41:59 GMT

The Food & Drug Administration recently issued warnings to patients and physicians regarding the rising tide of complaints related to surgical mesh products. Specifically, the medical devices that are used in surgeries for women suffering from bladder incontinence. Although the reports indicate that this is a new problem, it really is an old story. The complications reported in the latest news releases from the FDA include chronic infections, extrusion of the devices, abscess formation, and vaginal erosion. These are the very same complications reported years ago with Boston Scientific’s troubled ProteGen bladder sling. That sling was removed from the market in 1999. For years after that, the sling manufacturer was involved in lawsuits filed by hundreds of women who had suffered tragically catastrophic injuries due to the defective devices.

There has also been more recent litigation over the use of Mentor ObTape, a similar product utilized in incontinence surgeries. Unfortunately, the withdrawal of Mentor ObTape has not received a great deal of notice by the public and physicians. A number of lawsuits relating to Mentor ObTape are now coordinated by a federal court in Georgia.

The latest update from the FDA notes that it has received more than 1,000 reports of serious complications associated with the use of surgical mesh products in surgeries to repair bladder or vaginal prolapse and to treat stress urinary incontinence. These reports have come from nine different manufacturers, which certainly raises the question whether virtually all of these products are potentially defective or inappropriate for the recommended use in all patients.

Originally posted at InjuryBoard by Brenda Fulmer

I-Flow Corporation Versus the FDA: Touche!

Armand Rossetti — Fri, 13 Feb 2009 15:15:18 GMT

On December 22, 2008 the FDA sent a Warning Letter to I-Flow Corporation, manufacturer of the ON-Q pain pump. The Warning Letter stated numerous manufacturing and related violations, and the FDA informed the public of I-Flow's failure to respond sufficiently to a majority of the alleged violations.

The FDA uses a Warning Letter as a tool to ensure that manufacturers are aware of, and are complying with good manufacturing procedures (GMP) that will result in safe and effective medical device design and manufacture. The usual practice begins with an FDA establishment inspection, which results in an establishment inspection report (EIR). After the FDA reviews the EIR, if it finds evidence of substandard manufacturing practices or reporting procedures, it will issue a Warning Letter, containing details of the inspection and statements concerning insufficient GMP.

Thereafter, the FDA gives the manufacturer a period in which to respond, and if the manufacturer’s response is also insufficient, the FDA may allow a follow up response. However, if the FDA is not satisfied that the manufacturer has responded sufficiently, the next step would be termination of any and all manufacturing of violative medical devices destined for the US-American market.

The FDA’s December 2008 Warning Letter alleged that I-Flow had committed the following violations:

1) Failure to establish and maintain procedures for verifying the device design, as required by 21 C.F.R. 820.30(f).

2) Failure to establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 C.F.R. 820.30(i).

3) Failure to ensure that when results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 C.F.R. 820.75(a).

4) Failure to ensure that for validated processes, the monitoring and control methods and data, the date performed, and, where appropriate, the individual(s) performing the process or the major equipment used shall be documented, as required by 21 C.F.R. 820.75(b)(2).

5) Failure to ensure that when changes or process deviations occur, the manufacturer shall review and evaluate the process and perform revalidation where appropriate, as required by 21 C.F.R. 820.75(c).

6) Failure to identify the actions needed to correct and prevent recurrence of nonconforming product and other quality problems, as required by 21 C.F.R. 820.100(a)(3).

7) Failure to verify or validate the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 C.F.R. 820.100(a)(4).

8) 8) Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 C.F.R. 820.198 (1)(a) & (3)(d).

9) Failure to ensure that complaints involving the possible failure of a device, labeling, or packaging to meet any of its specifications were reviewed, evaluated, and investigated, as required by 21 C.F.R. 820.198(c), and failure to ensure that the record of the investigation included the dates and results of the investigation and any corrective action taken, as required by 21 C.F.R. 820.198(e)(6)-(7).

10) Failure to record and investigate the nature of the complaint, as required by 21 C.F.R. 820.198(e)(5).

11) Failure to establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 C.F.R. 820.30(i).

12) Failure to establish and maintain procedures for identifying valid statistical techniques required for establishing, controlling, and verifying the acceptability of process capability and product characteristics, as required by 21 C.F.R. 820.250(a).

13) Failure to establish and maintain procedures for rework, to include retesting and reevaluation of the nonconforming product after rework, to ensure that the product meets its current approved specifications, as required by 21 C.F.R. 820.90(b)(2).

14) Failure to establish and maintain acceptance procedures, where appropriate, to ensure that specified requirements for in-process product are met, as required by 21 C.F.R. 820.80(c).

15) Failure to establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 C.F.R. 820.80(d).

16) Failure to evaluate and select suppliers, contractors, and consultants on the basis of their ability to meet specified requirements, including quality requirements, as required by 21 C.F.R. 820.50(a)(1).

17) Failure to establish and maintain records of acceptable suppliers, contractors, and consultants, as required by 21 C.F.R. 820.50(a)(3).

18) Failure to maintain device history records, as required by 21 C.F.R. 820.184(d).

The Warning letter also listed numerous failures, concerning the sufficiency of I-Flow’s responses, and the FDA provided a host of examples of such failures.

In addition to issuing Warning Letters to medical device manufacturers, the FDA makes weekly Enforcement Reports available to the public. Those FDA Enforcement Reports contain information on actions taken in connection with Agency regulatory activities. In addition to providing the weekly Enforcement Reports, the FDA maintains a searchable website where it archives more than 20 years of those reports.

Here are some of I-Flow’s product recalls:

April 16, 2003:

PRODUCT
Homepump Eclipse Infusion Pump, Disposable Elastomeric Infusion System (100 ml x 50 ml/hr) Model E100500,
Part No. 5001065. Recall # Z-0687-03.
CODE
Lot 262074.
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA., by fax on March 4, 2003, and telephone on March 5, 2003. Firm initiated recall is ongoing.
REASON
Product infuses too fast at rate of 30 minutes instead of 2 hours. Component mix-up.
VOLUME OF PRODUCT IN COMMERCE
2,832 units.
DISTRIBUTION
CA, OH, WA,TX,UT, SC, MI, IL.

April 30, 2003:

PRODUCT
Paragon Administration Set (100 ml x 0.5 ml/hr) Part Number 5000936. Recall # Z-0709-03.
CODE
Lot numbers: 262111 (manufactured June 2002, expires May 2005); 282233 (manufactured August 2002, expires July 2005).
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA, by fax on March 5, 2003, and email on March 6, 2003. Firm initiated recall is ongoing.
REASON
Wrong component may result in over infusion of medications.
VOLUME OF PRODUCT IN COMMERCE
5,808 units.
DISTRIBUTION
NY, MA, and Internationally.

May 7, 2003:

PRODUCT
Easypump LT 6024 Easypump InfusionPump (60 ml x 22 ml/hr). Recall # Z-0741-03.
CODE
Lot numbers 04434366/2A2469 and 04434367/2A2470.
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA, by email on March 18, 2003. Firm initiated recall is ongoing.
REASON
Overinfusion due to misassembly.
VOLUME OF PRODUCT IN COMMERCE
2,638 units.
DISTRIBUTION
France.

January 21, 2004:

PRODUCT
Eclipse Infusion Pump, 250 ml X 250 ml per hour) Part
5001247. Recall Z-0312-04.
CODE
Lot 262073.
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA, by telephone on August 19, 2002 and by letter on August 27, 2002. Firm initiated recall is complete.
REASON
Slower than expected infusion of medications, such as antibiotics.
VOLUME OF PRODUCT IN COMMERCE
3,240.
DISTRIBUTION
Nationwide.

March 15, 2006:

PRODUCT
a) Easypump ST 100-1 infusion pump, Recall # Z-0584-06;
b) Easypump L T 60-24 infusion pump, Recall # Z-0585-06
CODE
a) Lot # 562791;
b) Lot # 562857
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest , CA , by letter dated January 17, 2006 , firm initiated recall is ongoing.
REASON
The sterile pack may contain the wrong infusion pump inside.
VOLUME OF PRODUCT IN COMMERCE
1,179 units
DISTRIBUTION
France

January 24, 2007:

PRODUCT
I-Flow ON-Q PainBuster (100 ml, 2 mI/hr) Pump, PM012, Recall # Z-0358-2007
CODE
Lot numbers: 662449 & 662742
RECALLING FIRM/MANUFACTURER
I-Flow Corp., Lake Forest, CA, by faxed letter on November 29, 2006. Firm initiated recall is ongoing.
REASON
The pump flow rate labeling may not match the package labeling. The label on filter may not match the label on the top of the pump or the package labeling.
VOLUME OF PRODUCT IN COMMERCE
3,475 units
DISTRIBUTION
Nationwide

October 17, 2007:

PRODUCT
ON-Q PainBuster with OnDemand (270 ml, 2 ml/hr + 5 ml bolus /60 min refill), Model PMB01, anesthetic/ narcotic medication pump. Recall # Z-0057-2008
CODE
6A4171 (exp. MAR 2009), 694133 (exp. FEB 2009), 654920 (exp. OCT 2008), 5A4732 (exp. MAR 2008), 584699 (exp. JAN 2008)
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA, by letter on March 27, 2007. Firm initiated recall is complete.
REASON
Misassembly: The ON-Q PainBuster PMB01 package may contain a Soaker catheter instead of a Non-Soaker catheter. As a result, the bolus button may remain latched in the down position which may cause the device to deliver continuously at 7 ml/hr instead of 2 ml/hr.
VOLUME OF PRODUCT IN COMMERCE
2,582 units
DISTRIBUTION
Nationwide and Internationally

September 24, 2008:

PRODUCT
ON-Q PainBuster Infusion Pump (270 ml, 5 ml/hr), REF PS6504, Part No. 5001260. The pump is indicated for continuous and/or intermittent delivery of medication (such as local anesthetics or narcotics) to or around surgical wound sites and/or close proximity to nerves for preoperative, perioperative and postoperative regional anesthesia and pain management. Routes of administration may be intraoperative, perineural, percutaneous and epidural. The ON-Q Pump is also intended to significantly decrease narcotic use and pain when used to deliver local anesthetics to or around surgical wound sites or close proximity to nerves when compared with narcotic only pain management. Recall # Z-1869-2008
CODE
Lot Number: 772166
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA, by letters on February 12, 2008. Firm initiated recall is ongoing.
REASON
The ON-Q PainBuster, REF PS6504 (lot number 772166), box may contain the wrong product, ON-Q PainBuster, REF PS6502. If the wrong product is used, patients would receive a 2 ml/hr infusion rather than a 5 ml/hr infusion, which could result in inadequate pain relief.
VOLUME OF PRODUCT IN COMMERCE
345 units
DISTRIBUTION
Internationally

Perhaps the FDA has used some or all of the I-Flow recalls as examples in its December 22, 2008 Warning Letter. However, given the prodigious number of I-Flow violations and recalls, and the FDA’s heavy handed propensity to redact identifying information, I will leave it to the reader to plow through this mess and to identify any pertinent connections between the two.

All in all, I-Flow has failed to provide sufficient responses, concerning the FDA's alleged GMP and adverse event reporting violations found in the FDA's December 22nd Warning Letter. In addition, the FDA's Enforcement Reports show that I-Flow has had to make numerous medical device recalls. The documents discussed above speak volumes about I-flow's laissez faire attitude toward medical device quality control and safety.

Originally posted at InjuryBoard by Armand Rossetti

After Recalling Complete MoisturePlus, AMO Recalls Healon D

Armand Rossetti — Tue, 13 Jan 2009 14:10:15 GMT

In 2007, Advanced Medical Optics (AMO) was in the headlines because the FDA had announced a recall of AMO's Complete MoisturePlus contact lens solution due to a high incidence of Acanthamoeba infections. This past week, the FDA announced a Class I recall on AMO’s Healon D ophthalmic viscosurgical device.

Reportedly, the FDA announced a Class I recall of AMO's new surgical device, which involved 4,439 units. Healon D is one of a family of a viscoelastic products, prepackaged in a syringe and applied in the eye during surgery to maintain spacial integrity and prevent collapse.

In its January 2, 2009 announcement, the FDA indicated that it had received 66 adverse event reports associated with the product, and that testing revealed elevated levels of endotoxin, which was associated with post operative intraocular inflammation and Toxic Anterior Segment Syndrome (TASS). Earlier in December 2008, AMO reported that it had retrieved 964 units and had accounted for most of the 1,450 units distributed in the United States.

It was only recently on October 8, 2008, that AMO received FDA Premarket Approval (PMA) for Healon D for use during cataract extraction, intraocular lens implantation, corneal transplant and glaucoma filtration surgery. By obtaining FDA approval, AMO received an opportunity to combination package Healon D with a higher molecular weight material called Healon GV, and existing standard Healon products.

In an effort to become a global leader in vision, Abbott has recently acquired AMO in principal for 2.8 billion dollars, and Abbott will be making a tender offer for AMO’s outstanding shares on January 26, 2009. Thereafter, AMO’s Chairman, Jim Mazzo, will be remaining with Abbott as AMO’s President.

Originally posted at InjuryBoard by Armand Rossetti

The FDA’s Approval of ProteGen Baffles the Mind

Armand Rossetti — Fri, 19 Dec 2008 14:21:29 GMT

Supple Peri-Guard was being used for the “repair of hernias and other intra-abdominal soft tissue defect or deficiency." However, Peri-Guard was not a true synthetic mesh.

patient’s own fascia or muscle to support periurethral tissue (autologous tissue graft), but that method was very invasive, and surgeons turned to using synthetic materials.

DePuy, Inc., submitted a 510(k) for its surgical mesh and listed equivalent devices, including Peri-Guard. In reviewing the DePuy 510(k), it is evident that Peri-Guard was manufactured from “SIS porcine small intestine submucosa,” and that surgeons had been using Peri-Guard for hernia repair, wound dressing, and as a mesh sling (the mesh is similar to this depiction of cross-linked porcine collagen).

caused an erosion rate that was 15 times that of natural slings that were either autologous (tissue taken from the same person), an allograft (human tissue taken from another person), or a xenograft (tissue taken from another species).

“…intended to reinforce soft tissue where weakness exists for the urological, gynecological and gastroenterological anatomy inclusive but not limited to the following procedures: pubourethral support, urethral and vaginal prolapse repair, colon and rectal prolapse repair, reconstruction of the pelvic floor, bladder support, and sacro-colposuspension.”

to view the entire patent, click on “Save Full Document”). Surgeons would use a drill guide to bore into either side of the pubic bone and then insert a left and right pin. Those pins were originally attached to suture material that led to either side of the urethra to support a “Bladder Neck Suspension” procedure. Boston Scientific later included the ProteGen sling as part of the Vesica System. The reason that Boston Scientific combined the two devices was due in part to corporate acquisitions, and ccertainly not because of extensive research.

Boston Scientific Corporation acquired Vesica and the Vesica System. Boston Scientific Corporation also acquired Meadox Medicals, Inc., which manufactured a bovine collagen covered polyester fabric called Hemashield, and that fabric was a tubular graft used in cardiovascular applications.

multicenter longitudinal study, (5 centers) investigators examined the records of patients who had ProteGen slings removed. Of the 34 patient records examined, 7 patients had isolated urethral erosion, 17 had vaginal extrusion, and 6 were associated with urethrovaginal fistulas (openings between two organs that usually do not connect). All of those slings required removal.

Surprisingly, however, materials experts in the medical arts have known, for decades, the reasons why different sling materials behave in specific ways.

dense inflammatory reaction. The previous linked figure depicts a strip of Mersilene (“filet de Mersilene”) with interspersed collagen fibers (“fibres de collagene”), giant cells (“cellule de geante”), and neutrophils (“polynucleaires”), which are all suggestive of ongoing inflammation.

in vitro and in vivo premarket studies. Third, everyone involved in producing sling devices should pay more attention to reviewing any and all available information about the chemical and physical makeup of materials destined to become a part of the device. Lastly, the FDA should take more time to investigate the compositions of all listed predicate devices and to determine whether or not those devices are actually "substantially similar" to the devices for which manufacturers are seeking approval.

Originally posted at InjuryBoard by Armand Rossetti

Shelhigh: Anatomy of an FDA Medical Device Products Seizure

Armand Rossetti — Wed, 03 Dec 2008 20:18:29 GMT

Usually, our discussions address how the FDA might have timely recalled defective and dangerous medical devices and drugs. However, this is a story about the way that the FDA seems to have overreacted in April 2007, when it ordered US Marshalls enter Shelhigh, Inc.’s New Jersey factory premises and seize every medical device that the company had manufactured and warehoused.

Shelhigh is a boutique medical device manufacturer known for its proprietary No-React® tissue products that utilize the widely accepted glutaraldehyde fixation process. Using its its proprietary know how, Shelhigh has managed to avoid the problems that accompany glutaraldehyde tissue processing.

These life saving No-React devices include the MitroFast mitral valve repair device, the BioMitral bicuspid valve, the BioRing annuloplasty ring, the BioConduit Stentless Valve, and Endura No-react Dura (photo unavailable).

It is hard to figure whether the joint FDA-US Marshalls strike on Shelhigh was an attempt by the FDA to show the world that it could regulate with impunity, or whether that strike was merely an arbitrary contest between a small manufacturer and a division within the FDA.

Amidst all of the action that was occurring between the FDA and Shelhigh in 2007, James Dickinson, an investigative reporter for Medical Device and Diagnostic Industry magazine (MD&DI), found that the FDA behaved differently toward small device manufacturers. He noticed that the FDA singled out small manufacturers for total facility shut down, and that those manufacturers were usually corporations with a single line of products and no other revenue stream.

According to Dickinson, the FDA’s Center for Devices and Radiological Health (CDRH) would review a small company’s documentation for evidence of deficiencies. And even when the CDRH could find no palpable evidence of product defects or risk to public health, it would demand remedial action that directly affected the entire line of devices; action that usually resulted in a total facility shut down.

Here is the general regulatory scenario. When the FDA mandated a total facility shut down, the typical small device company would realize that it had no choice and it would challenge the FDA because it was a matter of corporate life and death. The company would then attempt to discuss the merits of the FDA’s position, but something about the company’s aggressive stance (or desperation) would anger someone at the FDA. In response, the CDRH set about creating negative publicity that would damage the company’s sales, and bring the company to the threshold of bankruptcy.

The FDA would then penalize the small company for standing its ground, and the agency would refuse to discuss matters any further. Then the FDA would issue more damaging publicity and would become unresponsive to all substantive questions, whether from the company, its attorneys or the media. And it would do no good to launch a stepwise appeal to higher levels in the FDA, because the CDRH would just continue to stand by its original decisions.

Shelhigh’s predicament was not unique. Over the years, the FDA had challenged several small device companies, including TMJI in 2007, Utah Medical Products in 2004, Anderson Products in 1997, Myo-Tronics in 1994, Laedral in the same year, and Bioclinical Systems in 1988.

Of course, each of those device companies prevailed against the FDA in court, but they all had won what amounted to Pyrrhic victories, because their experience with the FDA led to bankruptcy, near bankruptcy or severe business interruption for nearly all of them. Let’s take a closer look at Shelhigh’s encounter with the FDA by starting with a few adverse events reports.

ADVERSE EVENTS ANALYSIS:

A search of the FDA’s MAUDE database date range [1/1/2003 - Present] revealed 17 Adverse Event Reports (AERs) that concerned one of Shelhigh’s devices, the Endura No-react Dura. Endura is a grafting material used as a substitute for the Dura mater, a tough sinuous sheet that covers the brain.

There were 58 reports for Shelhigh’s vast array of related tissue based devices. Among the 17 AERs for Endura, two reports fell within the date range [1/1/08 - Present]. Moreover, most of the 17 MAUDE reports involved Shelhigh’s distributor, Integra Lifesciences. That company filed several AERs just to report that Integra had received letters from the FDA regarding Endura No-react Dura. The first Shelhigh AER involving the Endura No-react Dura is dated March 10, 2003, and here is an excerpt from that report:

“Event Description [as submitted]

In 2003 this pt had brain surgery for malignant brain tumor. The dura was closed with durashield [sold as Endura] and a ventricular drainage catheter was placed. (could also be a source of contamination). One week post-op, the pt had cns symptoms and a lumbar puncture was performed to analyze their csf; was abnormal but found to be sterile. Subsequently the pt developed infection of the lumbar spine, and eventually grew Aspergillus fumigatas. Although rare, this hospital infection could be related to the lumbar puncture or to the procedure. The device was obviously sterile. Also, if this was device related, the infection would be central and not distally to the place of implantation.

Manufacturer Narrative

This fungal infection in the spine after brain surgery is very rare and unfortunate. The treating doctor wrote that they had no problem with the device. The patch was obviously sterile and infection could occur in any surgical procedure. The suspicion is that a contamination could occur via the lumbar puncture test, or via the drainage catheter. Enclosed are the sterility results. This is a procedure related complication and not device related.”

The next entry is dated November 18, 2004:

“Event Description

A 6x10 endura patch was implanted in a pt with chiary syndrome. Postoperatively, they developed a fever, steroid therapy was administered, and they responded well. After a week, the steroid therapy was discontinued, and the symptoms returned. The surgeon decided to remove the patch. Since the fever was of unk origin, the pt is now doing well. The neurosurgeon was not able to determine if there was a correlation between the patch and the fever.

Manufacturer Narrative

The neurosurgeon observed that the explanted patch was still soft and compliant with no inflammatory response. The explanted patch was sent for biological testing by the surgeon. The culture was negative. The neurosurgeon was not able to determine if there was a correlation between the patch and the fever. The patch was not returned to shelhigh, but rather discarded by the physician or hospital, therefore there can be no further studies on this patch. All shelhigh patches are sterilized using a validated method. Prior to release, the sterility results are reviewed for each production lot. There have been no patch failures related to product performance or sterility. Since shelhigh did not receive the lot or serial number of this patch, a review of the specific lot cannot be done. All lots of endura patches were reviewed for sterility documentation. All lots were found to be sterile.”

Most of the remaining AERs consisted of notifications, such as the following, that were not primary medical complaints:

“Event Description (February 6, 2008)

It has been reported by the patient's attorney, that the female patient underwent brain surgery in 2005 in which the reported device was used. It is alleged that due to imperfections in the product, the patient has suffered a severe brain infection that required additional hospitalization, medical bills and lost wages as well as much discomfort and pain.”

“Event Description (there were five similar reports listed for November 14, 2007)

“On 10/24/07, integra lifesciences received a letter from the fda indicating that a voluntary medwatch had been filed on the endura dural graft. The following info was reported, "incident date: 2005 craniotomy for intractable pain…”

“Event description (May 1, 2006), indicating that the graft was never removed:

… [T]he patient developed a post op wound infection twice since the operation to treat for syringomyelia. Infections were cultured on the same day and staphylococcus aureus was identified. Unknown if infection related to graft. Endura was never removed…”

After subtracting the number of reports from Integra Lifesciences and others like it (e.g., the AER from the attorney, and the graft that was never removed), there were relatively few actual injury cases, and none of those ruled out other sources, such as hospital infection. Yet on May 2, 2007, the FDA requested a Class I recall of all of Shelhigh’s products, including hospital inventories, because of sterility concerns.

Let’s take a closer look at the interplay between the FDA, Shelhigh and its distributor, Integra Lifesciences.

TIMELINE:

April 18, 2007:

Shelhigh issued a press release reporting that the FDA and US Marshalls had seized all implantable medical devices from Shelhigh, and that the company denied the FDA’s allegations that its manufacturing process compromised the safety and effectiveness of the devices.

April 19, 2007:

The FDA issued an alert entitled, Preliminary Advice for Patients: Possible Contamination and Malfunction of Heart Valves and Valve Conduits, Annuloplasty Rings, Surgical Grafts, Meshes and other Medical Devices Manufactured by Shelhigh, Inc. The alert made it clear that US Marshalls had seized Shelhigh’s medical devices because they were manufactured under conditions that may have contaminated the devices.

April 24, 2007:

Shelhigh issued a press release alleging that the FDA had “yelled FIRE in a crowded hospital,” and that hospitals were clearly confused by the recent FDA recall; Shelhigh was fielding a host of calls from hospitals about the recall. Shelhigh indicated that the company had assisted FDA inspectors and that the FDA had observed every aspect of Shelhigh’s operations over a 10 week period. In addition, Shelhigh had provided tens of thousands of documents to the FDA, including those related to raw materials, finished devises and distributed devices.

May 3, 2007:

Shelhigh responded to questions that the FDA had posted on its own website concerning the reasons for the recall, the locations where the FDA seized the devices, and whether the devices were safe to use. The FDA’s questions also addressed a shipment freeze, the basis for the seizure; whether Shelhigh even knew that the FDA was concerned with its manufacturing practices, what products were involved, and why those products were a serious risk. Shelhigh alleged that the FDA exhibited little or no expertise about the manufacture of the company’s products, and that the FDA had implemented an unnecessary abuse of its authority and responsibility, resulting in a denial of life-saving devices to patients in need.

Shelhigh also alleged that the FDA was ignoring repeated offers to meet and discuss any issues that might be surrounding the manufacture of the allegedly defective medical devices.

Also on May 3, 2007:

Shelhigh issued a press release that it had responded to the FDA’s recall request, indicating that it was the FDA’s first request, that it was unfounded, and that Shelhigh would not be recalling any products. Shelhigh stated that the FDA had misstated allegations that company records displayed a number of sterility test failures, and that the company’s testing and retesting procedures were not properly performed. Shelhigh then went on to mention that an independent ISO certified facility had performed the testing; the procedures had been in effect since 2000, and that numerous prior FDA inspections had not revealed any discrepancies.

May 7, 2007:

Shelhigh received a reply from the FDA concerning the company’s Freedom of Information Act request for reports on the AERs.

May 10, 2007:

Shelhigh received a reply from the FDA concerning the company’s Freedom of Information Act request for the Health Hazard Evaluations that the FDA allegedly compiled and used to justify the recall.

June 6, 2007:

Shelhigh released a position statement regarding the FDA’s actions, indicating that: 1) no entity or person had received any health hazard reports from the FDA; 2) the FDA was seeking to financially strangle the company; 3) the FDA had released a news program on its website promoting misleading allegations; 4) the FDA had not produced a Health Hazard Evaluation (HHE) as it must by law before issuing a recall; 5) the FDA needed actual described defects to draft an HHE and that it had none; 6) the FDA had posted misinformation on its website that went far beyond allegations contained in the complaint; 7) the FDA never discussed its observations with Shelhigh during the four months between the inspection and the complaint; 8) the FDA refused to verify Shelhigh’s responses to the inspection; 9) the FDA did not even have probable cause for the product seizure and that it had to fabricate justification; the FDA released trade secret information despite Shelhigh’s protests; 11) the FDA was trying to gather evidence after the fact to support its allegations; 12) Shelhigh was doing its best to resolve the confusion and misstatements that the FDA was making; 13) any prior warning letters (2000 and 2005) had nothing to do with the FDA’s present allegations; 14) the FDA was unsuccessful in using the unrelated warning letters to show a continued violation; 15) Shelhigh had refused to recall its products due to a complete lack of evidence of any safety hazard; 16) the FDA issued recall language for Integra to use in a distribution level recall, and it demanded that Integra recall all Shelhigh devices in distribution, and that the FDA had already issued its own separate recall days before; 17) Shelhigh asked what the real reason was for the recall, since it had a 10-year record of delivering safe devices; 18) the FDA was probably trying to save face, since it had made mistakes during the inspection and that supervisors had rubber stamped inspectors reports, and 19) the FDA should have presented its findings if it had any, instead of stating that Shelhigh’s devices “may” cause a health hazard.

Also on June 6, 2007:

Shelhigh issued a press release alleging that the FDA was refusing to disclose facts, and that neither the FDA nor Shelhigh had recalled any Shelhigh devices [the FDA had been dealing with Integra only].

June 25, 2007:

Shelhigh issued a press release indicating that the FDA and Shelhigh had reached an agreement to settle out of court. Both parties agreed that there had never been a Shelhigh based product recall; and that manufacturing procedures were in substantial compliance with FDA requirements. Some minor changes would have to be made to the manufacturing process, but they would be swiftly and easily implemented. The court had not ordered the agreement. Instead, the parties had reached an agreement of their own accord, which the court implemented in dispensing with the case in 2007.

What might have been a danger to the public, turned out to be a virtual tug of war between the FDA and Shelhigh. Meanwhile, well qualified attorneys who were standing by ready to help those who might have been injured later realized that there was no need to provide that assistance.

Originally posted at InjuryBoard by Armand Rossetti

Mentor ObTape Litigation Expands

Brenda Fulmer — Tue, 18 Nov 2008 13:37:32 GMT

On November 20, 2008, the Judicial Panel for Multidistrict Litigation will convene in Charleston to hear arguments on whether multi-district litigation should be established for the management of personal injury lawsuits filed by women who were harmed by Mentor ObTape. The petition filed by Mentor Corporation seeks to consolidate 22 individual lawsuits that were filed on behalf of women who were injured by this popular surgical mesh utilized in surgeries for stress urinary incontinence. The 22 lawsuits that are sought to be transferred were filed in federal courts in California, Florida, Georgia, Louisiana, Missouri, New Jersey, New York, Ohio, and Oklahoma. Mentor Corporation seeks the transfer and consolidation of these individual lawsuits in order to avoid corporate witnesses having to sit for multiple depositions and to provide the Defendant with consistency in discovery requests and legal rulings. The Defendant has suggested that the Mentor ObTape litigation be transferred to federal court in Oklahoma or the Northern District of Ohio. With this request for centralization of the litigation, it is anticipated that numerous additional individual lawsuits will be filed on behalf of women who were injured by the Mentor transobturator tape.

The Mentor ObTape surgical mesh product was first marketed in 2003. The product was withdrawn from the market after a number of women suffered severe complications associated with the device including: breakdown or erosion of vaginal tissue, chronic infections, extrusion of the mesh from the body, and other significant injuries.

Originally posted at InjuryBoard by Brenda Fulmer

The FDA Transvaginal Surgical Mesh Placement Complications Notification: Manufacturer Identification, and MAUDE Report Breakdown by Device

Armand Rossetti — Thu, 06 Nov 2008 11:50:43 GMT

On October 20, 2008, The FDA issued a dear healthcare practitioner notice, concerning complications associated with transvaginal placement of surgical mesh for certain procedures. The notification indicated that the FDA had received over 1,000 reports from nine surgical mesh manufacturers. However the FDA did not identify the manufacturers or devices, and the FDA did not provide time ranges for the MAUDE reports. Therefore, I have made an attempt to identify the manufacturers and to provide further information concerning the MAUDE reports. The following chart contains the information that I have found:

Manufacturer	Product Name (Device)	Number of MAUDE Events	Date Range

American Medical Systems	SPARC	65	02/21/2002 to 06/21/2007

Bard	Pelvicol	64	10/15/2001 to 05/08/2008
	Pelvisoft	1
Boston Scientific Scimed	Prefyx PPS	23	08/11/2006 to 9/3/2008
	Obtryx Curved Single	1	On 01/10/2006
	Obtryx Mesh Sling	62	08/24/2005 to 09/18/2008
	Advantage Sling System	29	07/25/2006 to 09/19/2008
	Prefyx System Mid U	23	08/11/2006 to 09/03/2008
	Mesh Sling System	78	08/19/2004 to 09/18/2008
Caldera	T-Sling	2	06/15/2004 to 11/26/2007

Ethicon	Gynemesh PS (K013718) a/k/a/ Prolift Pelvic Floor	123	04/14/2004 to 03/02/2008
	Prolene Polypropylene Mesh	72	01/28/2002 to 09/18/2008
Gynecare	Secur	1	Single Report on October 4, 2007
	TVT (See Ethicon, Inc. and Johnson & Johnson) (K974098)	4	07/21/2003 to 10/04/2007
Johnson & Johnson	Tension-Free Vaginal Tape (K974098) Also Medscand Medical Lab (Sweden), Ethicon, Inc., Ethicon Sarl (Switzerland),	495	05/12/1999 to 02/27/2007

Mentor	ObTape (K031767)	236	11/01/2002 to 10/19/2007

Sofradim	Uretex TO	64	10/23/2002 to 05/08/2008
	Avaulta Biosynthetic	0
	Uretex Pubovaginal Sling/support kit	27	10/24/2002 to 04/22/2008
	Bard Posterior Biosynthetic Support System	3	06/14/2007 to 09/14/2007
	Pelvetex Polypropylene Mesh	0

In the event that I have not reported information correctly, I welcome readers to email me with more accurate information if it is available.

Originally posted at InjuryBoard by Armand Rossetti

Tension Free Vaginal Tape (TVT or Vaginal Sling): What is it and how is it placed?

Armand Rossetti — Thu, 06 Nov 2008 08:41:39 GMT

Tension free vaginal tape (TVT) is a relatively narrow strip of propylene mesh tape [1.1 cm (1/2 inch) X 40 cm (14 inches)] with two stainless steel needles, one at each end that surgeons insert at the mid urethra. Here is another graphic depiction of the bladder and urethra. Note that females may use Kegel exercises to strengthen the external sphincter.

Let’s take a look at some pictures of normal and compromised sphincters. Normal sphincters display the following characteristics they are closed at rest (Fig. a), closed with stress maneuvers (Fig. b) and have an excellent guarding reflex (Fig. c). The second set of pictures shows type II stress urinary incontinence (SUI); the sphincter is closed at rest (Fig. a), remains open with stress maneuvers (Fig. b) and has a good guarding reflex (Fig. c). With type III SUI, the sphincter is open at rest (Fig. a), it remains open with stress maneuvers (Fig. b) and has a weak guarding reflex (Fig. c).

Surgeons perform the TVT placement operation by making two small abdominal incisions just above the pubic bone. The operation requires either local or general anesthesia. The surgeon then places a Foley catheter and inserts the rigid catheter guide into the Foley catheter. Then an assistant pivots the handle of the guide to the surgeon’s left side to expose the patient’s left endopelvic fascia. The surgeon then punctures the fascia with one TVT needle end and advances the needle through a space and to the anterior abdominal wall. The needle must hug the posterior wall of the pubic symphysis during this operation. Then the surgeon tents up the abdominal skin with the needle (pokes the needle making the skin look like a tent), then incises the top of the tented skin and allows the needle to come through. It looks like this (however, the surgeon still has to perform a contralateral procedure, see below).

To make certain that the bladder is free of punctures as a result of the operation, the surgeon then fills the bladder with 250 ml of saline, leaves the needle where it is and performs a cytoscopic examination, looking for bladder leaks. Then the surgeon repeats the procedure on the other (contralateral) side.

The tape must not twist during the insertion. The surgeon then cuts the needles at each end and removes them, leaving the tape in place. After that, the surgeon fills the bladder with saline and has the patient perform a coughing test. The surgeon pulls the tape up on each side until only a few drops of saline exit the urethra when the patient coughs. The tension test is the probably most important part of the procedure.

Although the tape is marketed as tension free, the surgeon must make sure that it is tension free by performing a proper tension test. Then the surgeon removes the protective plastic sheath from the tape and closes the vaginal and abdominal incisions.

For more comprehensive information, please visit this website. And for those who are interested in viewing the full, comprehensive and well-explained procedure, you may access the video here.

Originally posted at InjuryBoard by Armand Rossetti

Transmetallation: Which Gadolinium causes NSF, and What about Overexposure in Healthy Individuals Undergoing Multiple Scanning Procedures?

Armand Rossetti — Thu, 30 Oct 2008 11:24:37 GMT

All FDA approved gadolinium based contrast agents (GBCAs) combine a single atom of Gadolinium rare earth metal by chelating it with organic chemicals called ligands. More simply, chelation is the process of coating a less stable metal with more stable bio-friendly-type components to render the metal less reactive. The resulting lowering of the metal’s reactivity creates a more benign substance that can circulate through the body and not present a significant safety concern.

As previously discussed, individuals with kidney disease cannot clear the less toxic, chelated form of Gadolinium from the body before it loses its ligand coating, reacts with the body, and causes major problems, such as (Nephrogenic Systemic Fibrosis (NSF).

According to investigators, there are different categories of GBCAs:

Linear versus macrolytic structure;
Ionic versus non-ionic; and
Non-protein binding versus protein binding.

These three categories of Gadolinium contrast agents vary significantly in their propensity to release free Gadolinium, which is linked with NSF. Both the structure that makes up the particular form of coated Gadolinium and higher thermodynamic stability, or ability for the coated from to remain for longer periods in the body, will minimize the release of dangerous free (uncoated) Gadolinium that would remain in the body because the kidneys are not functioning to capacity to eliminate it.

Linear structures seem to be more reactive and macrolytic structures are more stable. That is because Release of gadolinium from a cyclic (macrolytic) chelate requires all four covalent bonds to be broken simultaneously.

Anecdotally, at least one patient, who has experienced multiple CAT scan procedures and who has received multiple GBCA injections during diagnostic treatment has reported actual pieces of metal, most likely Gadolinium, emerging through the skin. Evidently, the patient’s normal kidney function was not enough to handle the cumulative “overdosing” with Gadolinium, and that inability to handle Gadolinium elimination appears to be similar to situations where compromised kidneys are not able to handle a usual exposure of one or two injections during CAT scan diagnostic procedures.

To get a better understanding of what the chemistry and physics is all about; let’s look at the physical side of Gadolinium. The half life of Gadolinium chelates in patients with normal kidney function is 1.5 hours and more than 90% of a dose is excreted in 24 hours. Molecular weights of available GBCAs range from 558 to 1058 daltons. Free Gadolinium is up to 50 times more toxic than chelated (coated) Gadolinium GBCA.

Perhaps the following information is most important:

“Gadodiamide (Omniscan^®; GE Healthcare, Chalfont St Giles, Buckinghamshire, UK) has the shortest dissociation constant—30 seconds compared with 10 minutes and with 3 hours for gadopentetate dimeglumine (Magnevist^®; Bayer HealthCare Pharmaceuticals, Montville, NJ) and gadoteridol (ProHance^®, Bracco Diagnostics), respectively.”

As is evident, there is a wide variation between branded GBCAs, and the choice of what type of GBCA to brand may rest upon intellectual property protection considerations among manufacturers like GE, or Bracco. Each manufacturer tends to balance designing its product to avoid patent (IP) lawsuits, and then each deals with safety and effectiveness as those parameters will allow. Welcome to the fast paced and litigious IP world of competitive device manufacturing, which is not a bad thing at all, if the manufacturers are ethical, and the FDA is watching closely.

Originally posted at InjuryBoard by Armand Rossetti