Florida Personal Injury Blog - Medical Devices & Implants

Troubling Ghostwriting Survey Prompts New Medical Journal Policies

Don Greiwe — Tue, 06 Oct 2009 08:48:02 GMT

A survey released by The Journal of the American Medical Association (JAMA) concludes that six of the top medical journals in the U.S. published a “significant number” of ghostwritten articles in recent years, reports the NY Times. Ghostwriting in the medical profession generally means that the research or conclusions were not written by the credited author. A dangerously common practice in the medical industry is for a pharmaceutical company to pay a group of professional writers to produce papers, and then pay scientists or physicians to attach their names to these articles. Ghostwriting has been common for years, but has received harsh media attention, especially recently. In late July, a federal judge ordered the unsealing of confidential court documents revealing that the pharmaceutical giant Wyeth orchestrated dozens of ghostwritten articles to promote their line of hormone replacement drugs.

According to the anonymous survey of 630 published medical papers, 11% of the articles in the New England Journal of Medicine were ghostwritten. Likewise, 7.9% of the articles in JAMA, 5% of the articles in The Annals of Internal Medicine, and 2% of the articles in Nature Medicine were ghostwritten. In reality, these statistics may actually be much higher, because ghostwriting is difficult to track due to its covert nature.

Many are calling for medical journals to step up enforcement of anti-ghostwriting policies. In an article written in response to the survey, PLoS Medicine editors have made a call to the industry to institute a zero tolerance policy – identifying and retracting any ghostwritten articles and banning those authors from future publications. There’s been swift congressional support too, with Senator Chuck Grassley (R – IA) telling reporters “objective research is really at the heart of public trust in medicine.” Senator Grassley has led the Congressional charge against ghostwriting in Congress, and strongly encourages medical journals to adopt strong anti-ghostwriting policies.

Supporters of ghostwriting say that it allows articles to be released much sooner than otherwise, thus potentially getting medically sound data to the public as soon as possible. However, this data cannot, and should not, be relied upon to make medical decisions if there is a fundamental conflict of interest. The only way medical journals can protect their integrity is to take a very firm stance against ghostwriting, and institute strict policies to identify and combat it.

Originally posted at InjuryBoard by Don Greiwe

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

Medtronic Class I Recall of Kappa and Sigma Series Devices

C. Todd Alley — Mon, 22 Jun 2009 12:51:35 GMT

Medtronic, in conjunction with the FDA, has issued Class I recall – the most serious type of recall classification reserved for products whose continued use could lead to serious illness or death - of the following lines of pacemakers:

· Medtronic Kappa Series 600/700/900

· Medtronic Sigma Series 100/200/300

The recall has been issued because of a serious risk of operational failure. These devices may fail due to a separation of wires that connect the electronic circuit to other pacemaker components, such as the battery. Patients with malfunctioning pacemakers may experience a return of symptoms associated with abnormal heart rate, such as fainting or lightheadedness. Pacemaker-dependent patients may experience serious injury or even death. Most of the pacemakers affected by this recall have been implanted in patients for five years or longer.

Alley, Clark & Greiwe has been involved with Medtronic litigation for years, and our attorneys have been directly involved with other Medtronic recalls (including Medtronic Sprint Fidelis Leads and Medtronic Implantable Cardioverter Defibrillators (ICD) devices). While it’s unfortunate that another model line has been recalled, it is not particularly surprising. Please contact our office and we will help you determine if a particular pacemaker is part of this recall.

Originally posted at InjuryBoard by C. Todd Alley

Medtronic Defibrillator Lead Linked to 13 Deaths

Eddie Farah — Sat, 04 Apr 2009 01:08:00 GMT

An independent panel of physicians now says the death count from the Medtronic Sprint Fidelis cardiac wire is closer to 13, more than the five deaths the company previously revealed.

Last month, the company told doctors about the increased number of patient deaths and suggested that leaving the lead intact was perhaps the best choice for the majority of patients. Four of the patient deaths resulted from removing the defective lead.

The defective lead was in the heart of about 270,000 patients when Medtronic pulled the device in October 2007.

Patients have filed lawsuits over the Sprint Fidelis lead which delivered either too many shocks or didn’t deliver an appropriate shock to steady a heartbeat. The cases charge product liability, negligence, fraud, and breach of contract, among other charges.

Patients can ensure they are safe from defective medical devices and drugs only when their makers fully and openly disclose the side effects. It sounds simple and reasonable, but unfortunately litigation, or the threat of litigation provides a strong incentive for companies to avoid design defect or failure-to-warn lawsuits.

The Medical Device Safety Act of 2009 returns to consumers the ability to hold a company accountable for a defective product that the company, in some cases, knowingly markets to the public.

The public can sign on to support the Act in an online petition.

Once you’ve been injured, filing a lawsuit helps you recover what it might cost you for a lifetime of medical care, but it does not reverse the harm. Forcing transparency with the threat of a lawsuit might, and let's not forget it's an American right.

It’s too bad that companies don’t just do the right thing and insist on the highest standard of safety to minimize harm, but clearly they don’t.

Originally posted at InjuryBoard by Eddie Farah

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

$16.6 Million Duragesic Pain Patch Trial Ends

Eddie Farah — Mon, 24 Nov 2008 22:59:00 GMT

The trial of a woman who died from an overdose of the drug delivered through the Duragesic pain-killing patch is over. The jury awarded her husband and three children $16.6 million.

The Chicago area woman, Janice DiCosolo, 38, died in February 2004. DiCosolo was the mother of three children who suffered constant pain from a neurological condition, reflex sympathetic dystrophy for which she used the patch.

The narcotic, fentanyl, is the pain killing main ingredient in the patch, made by Alza Corp, owned by Johnson & Johnson. Fentanyl is 100 times more powerful than morphine. The pain patches are supposed to be worn 72 hours and then thrown out.

DiCosolo was wearing one when she died. The amount of the fentanyl contained in the patch is enough to kill 10 men weighing 300 pounds each, said her lawyer Jim Orr.

One lot of the Duragesic patches was recalled in February 2004 because the adhesive on the back of the device was improperly sealed. DiCosolo died the next day, the patch she wore was from that lot.

This represents the fourth pain-patch loss for J &J in two years.

Duragesic generated $1.16 billion in sales last year, according to Bloomberg.

Her case began last October, one day after a Sanford Florida jury awarded $13.3 million to the family of Susan Hodgemire, a 34-year-old mother of five who was recovering from back surgery. She too died when a Duragesic patch failed in 2002, flooding her system with the narcotic. In the middle of the night Hodgemire began vomiting violently, then lapsed into a coma and stopped breathing.

Last year, a West Palm Beach, Florida man’s family was awarded $5.5 million after dying from an overdose of prescription patch painkiller. Adam Hendelson was 21 and shattered his hip in a car accident in 1996. Because of constant pain, he was prescribed the Duragesic patch in 2003. He died at the age of 28, from an overdose of fentanyl.

Meanwhile there may be as many as 100 of these cases waiting to have their day in court.

J & J says it may appeal the latest case. #

Originally posted at InjuryBoard by Eddie Farah