International Regulatory Compliance

An Interdisciplinary Investigation of a Lake Ecosystem – Addressing Legal And Political Issues #1

Introduction

When I finished my PhD Dissertation a few years ago in July I took my first job as an Assistant Professor at a new interdisciplinary state university with an environmental focus. In particular, I looked forward to a brief respite from research and writing. Teaching would be a pleasure and a contrast from the intense concentration of completing graduate studies and writing a Dissertation. Upon arrival on campus in August I was contacted by another new Assistant Professor who wanted me to join a research team to investigate a problem on a Wisconsin lake in Marinette County near the Michigan border. I attempted to resist saying I wanted to settle into my new faculty position. However, my new colleague was persistent, so I decided to meet with his research team and learn more about their research concern.

As part of its mission, the new interdisciplinary University was committed to working with local communities and counties helping them  address environmental concerns. The issue on its face seemed to be fairly simple, but a closer analysis revealed a far more complex problem that I will discuss in several blogs. There are approximately 9,500 lakes in Wisconsin, most of them natural. The research concern in this case was a lake located in Northeastern Wisconsin. 

Lake Noquebay

The lake is approximately 2 miles by 4 miles with a surface area of 2,410 acres. The Lake Noquebay Dam constructed in 1929 slightly elevates the water level to between 666.2 feet and 664.95 feet. It is the largest Lake in the county and at that time contributed one-fourth of the tourist income to the county. The lake had a diverse fish population, bluegill,crappie,bass, walleye, northern pike, trout, rock bass, perch and muskellunge. In turn, tourism was a major industry for the county. The problem identified initially by the Agricultural Extension Agent and Marinette County leaders was “swimmer’s itch” and the concern was the negative impact it could have on the lake’s attraction as recreational area. 

Swimmer’s itch is a short-term immune reaction that occurs in the skin of humans who have been infected by water-borne parasites that enter the skin and raise red itchy bumps or welts that commonly occur within hours of infection and generally do not last more than a week. Basically, they are harmless but frightening to people who don’t know what they are and concerned about some kind of parasite infection – a potential disaster for the local tourist business.

The cycle of the parasite uses snails and ducks as hosts in their parasitic life cycle. During their life cycle the parasites enter the lake through duck feces and are eaten by water snails. Then the larvae of the parasite leave the snails and swim freely in the freshwater in search of water birds like ducks and accidentally come into contact with skin of swimmers. The larvae penetrate the skin and die immediately. The larvae cannot infect humans, but they cause an inflammatory immune reaction. The reaction causes itchy spots on the skin that will disappear in a week. Swimmer’s itch has been reported in lakes around the world.

The treatment that had been applied to control the snail population was to dump copper sulfate on the lake bottom as a molluscicide to kill the snails in swimming areas where swimmer’s itch was causing a problem. The efficacy of using copper sulfate was not clear, however, because offshore winds roil the water and easily dissipate the copper sulfate and move the snails across the bottom of the lake. An additional concern was the long term effect of copper sulfate on the Lake’s ecosystem.

Why me?

The leader of the research team was an aquatic biologist who earned his PhD at the University of Miami. While a graduate student he worked on a research project in Biscayne Bay that had been opposed by Florida Power & Light and became entangled in the politics of Dade County. He told me he vowed never to enter another research effort without having a lawyer and political scientist on the research team. Since I was both, he asked if I would work with him and his colleagues. I thought his point was interesting and so I agreed to work with the team. 

The team was composed of a PhD Aquatic Biologist, PhD Analytical Chemist, PhD Economist, PhD Leisure Scientist, PhD Vertebrate Ecologist, a Marinette County/University of Wisconsin Resource Development Agent and me – a JD Attorney and PhD Political Scientist. The political entities having jurisdiction over Lake Noquebay were Two Townships – (Middle Inlet and Lake), Marinette County and the State of Wisconsin. Since the Lake is not a navigable stream as defined by the Northwest Ordinance 1787, the federal government was not involved.

Defining The Lake Watershed

The first step was to identify the parameters of the Lake Noquebay watershed so that we could define the scope of our research project. Next we needed to examine the watershed itself. The lake watershed covered 54,000 acres. Approximately 85% of this land was forested. The remainder, interspersed over the watershed was agricultural cropland and pasture (or “open” land) and contained 66 farms. A County Forest and State wildlife area were located on the east side of watershed. The research team examined the flora and fauna of Lake Noquebay, tested the water chemistry and conducted a survey of residents and businesses around the lake.

The economy of the Lake Noquebay watershed was supported by agriculture, forestry, tourist and resort oriented business, with a recreation industry being predominant. There were nine resorts surrounding the lake with a total of 108 units. Including the resort units there were 301 living quarters on the lake of which 41 were year-round residences and 136 summer homes and cottages.

Potential Problems

The quality of the water was showing symptoms of accelerated eutrophication. The most serious symptom of management problems in the watershed was the proliferation of benthic weeds, particularly watermilfoil (Myriophyllum heterophyllum). The presence of the plant appeared to be associated with deep – one to ten feet – sedimentary deposits which were believed to consist primarily of partially decomposed organic matter, some of which indicated poorly conceived dredging and filling operations in the drainage basin. About 300 acres of the lake were affected with the excessive growth, amounting to an estimated biomass about 5000 tons (net weight).

To the best of the research team’s knowledge, this weed had not been previously reported as a problem in the Upper Great Lakes Region. The best information available about problem quantities of this type of vegetation was in the Tennessee Valley Authority reservoirs as well as in mucky areas of the southeastern United States. What started out as an effort to deal with swimmer’s itch evolved into a more pervasive problem affecting the lake that would become a major focus of the research team. 

Eutrophication already was a problem in a number of lakes in North Central and Northeastern Wisconsin, ranging from untreated sewage effluent and agricultural runoff to decomposed organic matter from forestry operations. In addition, there were new efforts to carve channels in marshy areas to build new homes with direct water access to the lake. Since the most severe form eutrophication can turn a lake into a bog killing the fish population, it destroys the lake as human recreational area. 

Legal-Political Problems

Legal and political analyses were undertaken to determine which governmental units were capable of influencing the management of body of water such as Lake Noquebay, and to indicate potential problems existing in the realm of overlapping or dual legal jurisdiction. During Phase I of the research program, a preliminary study of Marinette County zoning laws and the legal actions related to these laws was carried out. It was determined that the control of activities on the lake – such as boating – fell under the jurisdiction of the township governments. In the case of Lake Noquebay, this involved two townships (Middle Inlet Township and Lake Township). 

The control of water levels and the use of pesticides was under the jurisdiction of the Wisconsin Department of Natural Resources. Lakeshore zoning is a Countey responsibility. Since the legislation of 1965 and 1967 which created the Wisconsin Department of Natural Resources, considerable power over the management of waters in the State was concentrated in the DNR, necessitating a study of the lines of communication and administration and its regulatory and enforcement powers. 

Summary

Since my father chaired the Department of Geography at the University of Wisconsin-Eau Claire and taught Geomorphology, Geography of Wisconsin, Conservation, Environmental Management and also chaired the Scientific Areas Preservation Council for Wisconsin, much of what I learned about Lake Noquebay, was familiar to me. In turn, I was teaching courses on Environmental Policy and Environmental Law at my University. This provided a useful convergence of our backgrounds. Ironically, during the first summer of our research, “swimmer’s itch” was absent from the Lake, however, the proliferation of Myriophyllum Heterophyllum presented a significant problem to the future of the lake as a recreational area. 

I will return to the Lake Noquebay research project in several future blogs. It was an interesting case that illustrated the difficulties of addressing an environmental issue of interest to a population with diverse social and economic interests and concerns. It also highlighted the political and legal difficulties of trying to address these interests and concerns. 

My primary focus today is on International Regulatory Compliance, which includes both the requirements of regulatory authorities and the legal implications of compliance, non-compliance, documentation and sloppy attention to detail that could result in a lawsuit in a US Federal Court. I also focus on product safety and the steps necessary to create a safe product. If you have questions regarding ISO 9001 or CE Marking lawsuits you can contact me for a free preliminary consultation at my e-mail address jameskolka@gmail.com.  

IS FDA's 510(k) A Plausible Solution For the EU's CE Marking Problem With Silicon Breast Implants?

 

Introduction

The preceding four blogs discussed some of the problems I have observed with clients concerning private for-profit Notified Bodies and regulatory compliance with the three EU Medical Devices Directives. In the January 31, 2012 blog, I wrote the following paragraph concerning one possible alternative Notified Body approach to Medical Device approvals: 

“Something akin to an FDA 510(k) also should be created with device efficacy built in as major requirement. It isn’t a perfect solution because the 510(k) predicate device requirement doesn’t always avoid device defects in design and materials, but it is overseen by FDA not a private third party.”

The Mutual Recognition Agreement (MRA) signed between the US and EU in 1997, covered four areas, one being medical devices. The MRA provided for the creation of CABs (Conformity Assessment Bodies) approved by FDA to administer 510(k)s for selected Class II Medical Devices. Several of these CABs also are EU Notified Bodies. In this blog I want to return to the statement, “It isn’t a perfect solution because the 510(k) predicate device requirement doesn’t always avoid device defects in design and materials.”

US Politics Today 

Presently, there is a move in the US House of Representatives supported by some Senators to ease medical device regulations for Medical Device Manufacturers, hypothetically to encourage innovation and speed devices to the market. Even though the US has just begun to emerge from the disaster of deregulation of the US economy that allowed financial institutions to run amuck and create the worst financial crisis since the Great Depression, a convoluted ideology continues to appeal, i.e., regulation is bad, deregulation is good! Political ideology is a powerful force, uninformed by scientific knowledge and intelligence. Teddy Roosevelt and Abe Lincoln would have been appalled.  

The regulatory and enforcement problem afflicting CE Marking breast implant manufacturing and enforcement for the EU Medical DEvices Directives is different from the regulatory problem in the US, namely the weakness of the 510(k) approach. On February 1^st my wife received the following correspondence from Jim Guest, the President of Consumer Reports.

“It's a nightmare scenario. The implant that fixed your knee or your heart may actually be a ticking time bomb that could disable or kill you.
This isn't science fiction. Millions of medical devices including artificial hips, contact lens solution, heart stents, and pacemakers are being recalled - 700 different products a year.

And the vast majority of recalled products were never safety tested in humans, because the manufacturers claimed they were "similar" to products already on the market.

Tell Congress we don't want to be guinea pigs anymore!

Every new prescription drug must undergo rigorous testing on humans before it can be sold, even if it is similar to another drug already in use. Not so with medical devices. Because of this loophole in our safety laws, more than 90 percent of medical devices aren't safety tested before being sold nor are they routinely tracked afterwards to identify safety problems.

For example, a metal hip implant marketed by Johnson & Johnson was approved in 2005 without first undergoing clinical safety trials. It was recalled five years later after having a 1 in 8 failure rate in the UK, and releasing potentially toxic metals into the body. Countless patients had to undergo a second, painful 'revision' surgery.

It's time safety standards for medical devices are as strong as those for prescription drugs! E-mail your members now!

The device industry has unleashed an army of lobbyists and they don't want things to change. It will take a wave of consumers weighing in to make sure medical devices are safe and effective. Please take action, then forward this to friends and family. Thank you!

Sincerely,

Jim Guest
President, Consumer Reports

(Note: Consumer Reports is the largest and oldest independent non-profit testing and information organization in the US, serving only consumers since 1936.)

What are some of the problems with the 510(k)? 

Today the 35 year-old 510(k) System is used by FDA to review 90 percent of medical device applications each year. After numerous problems and ongoing billion dollar lawsuits concerning 510(k) approved medical devices, in 2009 FDA commissioned the Institute of Medicine (IOM) to study the problem and report back to FDA, which they did in August 2011.

The IOM report stated, “the process of using existing or “predicate” devices as the basis for evaluating the safety and effectiveness of a new device is “untenable.” The authors recommended that the FDA immediately stop using the protocol for Class III devices – considered to pose the highest potential risk to patients. “As devices have evolved and become more complex, our device-approval system has become incapable of assuring safety and effectiveness,” wrote New England Journal of Medicine executive editor Dr. Gregory Curfman and Dr. Rita Redberg, editor of the Archives of Internal Medicine. The system we use today was created 35 years ago in an era of much simpler and fewer devices and it is now outdated.

The New England Journal of Medicine editorial discussing the IOM report, specifically pointed out the ongoing problems with metal-on-metal hip implants including Johnson & Johnson’s DePuy ASR Acetabular System and DePuy ASR Hip Resurfacing System. The DePuy ASR XL Acetabular System was introduced in the US in 2005.

 The [DePuy] ASR was constructed by borrowing a metal alloy cup from a different hip device known as the [DePuy] ASR Hit Resurfacing System and retrofitting it onto a standard hip implant. The manufacturer successfully made the case that the reengineered implant was “substantially equivalent” to a predicate device. Its marketing clearance was therefore based not on trials or other clinical data but on bench testing in a laboratory, which was inadequate to simulate the stresses that would be placed on it in patients’ bodies. It soon became clear that the device failed at the astonishing rate of at least one in eight. (Brett Emerson, Injury Board.com, October 20, 2011) 

The metal-on-metal hip implants were found to shred minute metal particles into patients’ bloodstreams over time.

What Are The Institute of Medicine Recommendations? 

To begin the IOM, recommended that the agency (FDA) ditch the program entirely and replace it with an “integrated pre-market and post-market regulatory framework. It’s not clear that the 510(k) process is serving the needs of either the industry or patients, and simply modifying again will not help, said David Challoner who chaired the committee that wrote the report. The 510(k) Process cannot achieve its stated goals – to achieve innovation and make safe, effective devices available to patients in a timely manner – because they are fundamentally at odds with statutes that govern how FDA must implement the process.

Other IOM recommendations are:

• Boosting post-market surveillance and strengthening the FDA’s post-market authority;

• Ban all Class III devices, those of the highest risk, from the 510(k) fast-track process;

• Eliminate clearance using multiple predicate devices, by which a new device can be cleared by demonstrating equivalence to device that was also cleared through equivalence, forming a chain of devices that were never clinically tested, and 
• 
  
• Implement a formal post-market surveillance program.

The [IOM] report concluded that it was impossible for 510(k) clearance to assure safety and effectiveness, because it assesses neither, instead establishing only “substantial equivalence” to an existing device. 

 Summary 

As anticipated, the medical device industry rose up to complain about the reforms even though billion-dollar product liability lawsuits are working their way through the courts right now and will cost medical device companies a substantial amount of money. Not to mention that patients who suffer pain from the existing device and need to have the devices explanted and a new device inserted with no clear indication of how the surgical costs will be covered.

To return to the question about whether FDA’s 510(k) might serve as a model for EU regulation of its medical devices directives, the answer is no. The two regulatory systems face different issues:

• In the EU the issue is the competence of Notified Body device experts, the effectiveness of 70 for-profit Notified Bodies overseeing medical device manufacturers’ ISO 13485 Quality Management Systems, and the professional quality of oversight by 27 EU competent bodies.

• In the US the issue is a regulatory process that employs two strategies, (1) clinical trials for new high-risk device medical device, and (2) a 510(k) System focused “substantial equivalence” and expedience that doesn’t assure the safety and effectiveness of medical devices and consequently doesn’t focus on patient safety and product (device) safety.

Both the EU and US will have to work out their respective regulatory systems in the context of what presently exists but is not working. It’s not a simple process and it will take some work but it is essential that it be resolved in both the EU and US. Hopefully, private self-interest, political interference and intrusion won’t create a corrupted process that worsens what exists today.

My focus on International Regulatory Compliance has always included both the requirements of regulatory authorities and the legal implications of compliance, non-compliance, documentation and sloppy attention to detail that could result in compromised product safety and product liability lawsuits. In particular, I focus on product safety, patient safety and the steps necessary to create a safe product. I would be happy to help. If you have questions regarding CE Marking lawsuits you can contact me for a free preliminary consultation at my e-mail address jameskolka@gmail.com. 

FDA’s Quality System Regulation – Management With Executive Responsibility #2

Continuation

In the first part of this Blog I reviewed what FDA expects of Management with Executive Responsibility as spelled out in its Quality System Regulation and what FDA inspectors will be looking for in on-site inspections as spelled out in FDA’s Quality System Inspection Technique (QSIT). The regulatory emphasis is quite clear. 

Insurance Company Litigation Study

Next I want to review the observations about Management With Executive Responsibility from the unpublished findings of the litigation history of a Medical Device Insurance Company. A sample list of observations about management is quite interesting:

• Management failures frequently occurred due to noncompliance with FDA, EU Medical Devices Directives and other regulations and unawareness of the requirement for notification to the appropriate regulatory bodies and the attention that regulators would place on clinical studies

• Management staff of new emerging medical device companys selected to conduct clinical trials/studies often do not possess the appropriate expertise/experience with clinical investigations. They are very familiar with the research and development of the device under study, but often do not have the professional clinical competencies needed to manage a clinical study.

• Management often has shown a failure to use proper or adequate legal assistance to review, launch or be involved in clinical studies.

•  Management often shows a lack of indemnities/disclosure in the informed consent agreements between IRBs, sponsors and patients of clinical studies.

• There often are ethics issues regarding “conflicts of interest.”

• The study found that medical device manufacturers and their contract manufacturers often relied on the mistaken belief that they are immune from product liability because of their manufacturing relationships with each other. These are situations where no risk management techniques have been applied before beginning the manufacturing – actions that could have helped avoid potential exposure to product liability litigation.

• Contract manufacturers supplying a component part to device manufacturers often did not carry any product liability insurance coverage and this was not questioned by the device manufacturer.

• The study found management failure to comply with FDA Quality Management System regulations for contract manufacturing agreements.

• In this era of outsourcing, the study found that contract manufacturing agreements often were deemed unenforceable in foreign legal jurisdictions.

• Management often failed to create a product safety policy statement or reference patient or product safety in the company’s quality statements under the mistaken belief by top management that the quality statement alone is adequate on the subject.

• Management had philosophical conflicts in which members of management teams wanted to fight FDA and their “observations” or “warning letters”, rather than mutually cooperate in resolving implementation plan for integrating the observations into their manufacturing processes.

• Several product liability claims that were taken to jury trials mentioned the use of the company’s quality management system and quality manuals against the manufacturer – the company’s own quality processes were not being followed or audited.

• The study noted a lack of company management staff training on product safety and quality management systems and the documentation of this training.

• The study found that in most cases management teams were very lean in young medical device firms in early commercialization; untrained and unfamiliar with the basic principles of product liability avoidance.

• Management ego issues were noted as confused in regards to product liability risks when management teams decided to fight FDA citations/observations versus demonstrating a spirit of committed cooperation to correct or arbitrate observations.

• In many medical device companies that experienced product liability claims, executive management underestimated the amount of time and corporate resources that would be needed to defend the company against product liability litigation.

• The silence of senior management in regard to product liability litigation was seen as their acceptance of the behaviors that caused or led to the product liability litigation.

• A lack of general and specific training for managers concerning their product safety responsibilities was noted as a recurring problem in the management of product liability avoidance.

As noted earlier, this is sample drawn from a much larger list of observations. Each observation came as a cost to each of these companies resulting in increased litigation expenses to the companies above the amounts paid by their insurance companies, possible FDA fines and punitive damage losses. And of course, increased  premiums and an increased deductible. 

Warning Letters

Finally, I wanted to look at some FDA 483 Warning letters regarding Management With Executive Responsibility: 

August 5, 2011 – Failure of management with executive responsibility to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency to established principles to ensure the quality system satisfies the requirements of 21 CFR 820, as required by 21 CFR 820.40.

For example, according to your firm’s Executive Vice President your firm has not established management review procedures.

For example, according to your firm’s Executive Vice President there are no quality audit procedures and no quality audits have been performed. [The letter goes on t detail other failings of top management.] 

March 16, 2011 – Failure of management with executive responsibility to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of 21 CFR 820 and the manufacturer established quality policy and objectives as required by 21 CFR 820.20(c). For example, your firm has not conducted any management reviews of your quality system.

October 1, 2010 – Failure of management with executive responsibility to review the suitability of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of this part, as required by 21 CFR 820.20(c). For example, your firm failed to establish and implement written management review procedures. 

 November 24, 2010 – Failure of management with executive responsibility to review the suitability of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure the quality system satisfies the requirements of 21 CFR 820, as required by 21 CFR 820.20(c). For example, according to your firm’s management, the firm does not conduct management reviews and has not established management review procedures.

*Failure to establish quality system procedures and instructions, as required by 21 CFR 820.20(e). For example, according to you, your firm does not have quality system procedures.

* Failure of management with executive responsibility to establish its policy objectives for, and commitment to, qualities required by 21 CFR 820.20(a). For example, according to you, your firm has not established a quality policy. 

Conclusion 

The preceding are just a few statements concerning Management With Executive Responsibility contained in FDA Warning Letters sent to medical device manufacturers. The full letters are much more extensive detailing other concerns specific to these companies. My point is that FDA’s Quality System Regulation (QSR) places significant emphasis on the responsibilities of top management. The issue concerns the health and safety of the American public. 

I want to repeat what was written in the first Blog. I have worked with numerous medical device companies where Management’s understanding of FDA’s Quality System Regulation ranged from intelligent to clueless. I find the latter condition to be scary because it usually is accompanied by that wonderful combination, “arrogance and ignorance.” This is especially true when the company is owned by a single individual and driven by his ego and self-perceived brilliance. Not a healthy combination or work environment. Consultants need to consider carefully which companies and management they choose to work with.

As noted at the conclusion of the first Blog, my focus on International Regulatory Compliance has always included both the requirements of regulatory authorities and the legal implications of compliance, non-compliance, documentation and sloppy attention to detail that could result in a lawsuit in a Federal or State courtroom. I also focus on product safety and the steps necessary to create a safe product. If you have questions concerning medical device litigation, you can contact me for a free preliminary consultation at my new e-mail address jameskolka@gmail.com.

FDA’s Quality System Regulation – Management With Executive Responsibility #1

Introduction 

Not too long after FDA’s Quality Management System became the new Current Good Manufacturing Practice (CGMP), a colleague and I were asked by a client of our consulting firm to conduct a GAP Analysis to determine what needed to be done for them to comply with the Regulation and also to determine what needed to be done for all of their manufacturing plants and products to comply with CE Marking Requirements for the EU’s Medical Devices Directives. Since the company was (and is today) a major medical device manufacturer, our GAP Analysis audit took us to plants and operations throughout the US and Mexico. 

When we reported back our findings and recommendations to the CEO, he smiled and asked if they needed to comply with FDA’s new QSR. My colleague also smiled when she replied, "yes unless you think you look good in stripes!"

Of course this exchange occurred in good humor because FDA made it clear that they intended to hold Management With Executive Responsibility fully accountable for the implementation of the new QSR. “Good stripes” for bad management was and is a real possibility.

Today 

Since that friendly but intelligent exchange, I have worked with numerous medical device companies where Management’s understanding of FDA’s Quality System Regulation has ranged from intelligent to clueless. I find the latter condition to be scary because it usually is accompanied by that dangerous combination, “arrogance and ignorance.” This is especially true when the company is owned by a single individual and driven by his ego and self-perceived brilliance. Not a healthy combination and work environment. I think it is timely to review FDA’s definition of Management With Executive Responsibility in the QSR.

21 CFR Part 820 – Medical Device Quality System Regulation

§ 820.20 Management responsibility

(a) Quality Policy. Management with executive responsibility shall establish its policy and objectives for, and commitment to, quality. Management with executive responsibility shall ensure that the quality policy is understood, implemented, and maintained at all levels of the organization.

(b) Organization. Each manufacturer shall establish and maintain an adequate organizational structure to ensure that devices are designed and produced in accordance with the responsibilities of this part.

(1) Responsibility and authority. Each manufacturer shall establish the appropriate responsibility, authority, and interlation of all personnel who manage, perform, and assess work affecting quality, and provide the independence and authority necessary to perform these tasks.

(2) Resources. Each manufacturer shall provide adequate resources, including the assignment of trained personnel, for management, performance of work, and assessment activities, including internal quality audits, to meet the requirements of this part.

(3) Management representative. Management with executive responsibility shall appoint, document such appointment of, a member of management who, irrespective of other responsibilities, shall have established authority over and responsibility for:

(i) Ensuring the quality system requirements are effectively established and effectively maintain in accordance with this part; and

(ii) Reporting on the performance of the quality system to management with executive responsibility for review.

(c) Management Review. Management with executive responsibility shall review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure the quality system satisfies the requirements of this part in the manufacturer’s established quality policy and objectives. The dates and results of quality system review shall be documented. 

Enforcement

Another way to see how FDA views Management With Executive Responsibility is to examine the Guide To Inspections of Quality Systems that is used by FDA field staff to assess a manufacturers compliance with the Quality System Regulation and related regulations. It is also known as (QSIT) Quality System inspection Technique. Management with Executive Responsibility will be questioned about the Quality System at the beginning and at the end of an on site inspection. Page 18 of QSIT states:

Management Controls

Inspectional Objectives 

1.Verify that a quality policy, management review and quality audit procedures, quality plan, and quality system procedures and instructions have been defined and documented.

2.Verify that a quality policy and objectives have been implemented. 

3.Review the firm’s established organizational structure to confirm that it includes provisions for responsibilities, authorities and necessary resources.

4.Confirm that a management representative has been appointed. Evaluate the purview of the management representative.

5.Verify that management reviews, including a review of the suitability and effectiveness of the quality system, are being conducted.

6.Verify that quality audits, including re-audits of deficient matters, of the quality system are being conducted.

 At the conclusion of the inspection….

7.Evaluate whether management with executive responsibility ensures that adequate and effective quality system has been established and maintained. 

FDA field staff are guided through these inspectional objectives by a series of questions that are asked concerning each objective. Examples of the questions are,

• “ To determine what the firm’s organizational structure is, start by asking the authority and responsibility questions that are the start of every FDA inspection.”

• “ Determine whether personnel involved in managing, performing or assessing work affecting quality have the necessary independence and authority to perform those tasks.”

• “ Determine whether the appointed management representative actually has the purported responsibility and authority granted to him/her by the firm’s procedures or organizational structure.”

• “ Verify that the management representative is reporting back to the management with executive responsibility on the performance of the quality system. These reports should either be the subject of management reviews or at least provide a framework for those reviews.”

• “ Determine whether corrective action by upper management is being taken. Auditors may be asked if they observed any of the ongoing Quality System Regulation deficiencies during their prior audits (ongoing Quality System Regulation deficiencies may also be identified by reviewing prior FDA 483’s).”

• “ At this point in QSIT, you stop your review of the management system. You continue your inspection by evaluating the other subsystems. While you evaluate the other subsystems, keep thinking about what you are finding and whether it indicates that management is appropriately carrying out its responsibilities for providing adequate resources and overseeing the quality system to detect problems and address them.” 

Conclusion 

This, as they say, is only the tip of the iceberg. The on-site inspections are rigorous and a significant objective is to determine if Management With Executive Responsibility is actively engaged in overseeing the operation of the company’s quality management system. Egocentric executives who feel themselves above the day-to-day operations will be discovered and written up in a FDA 483 Warning Letter. If the behavior is too egregious, penalties can be levied and in the most extreme case criminal sanctions can be imposed. Therefore, the management of medical device company affecting the health and safety of the public is not treated lightly, nor should it be.

In the second Blog on this topic, I will examine some of the management observations by a medical device insurance company following an in-depth review of their insureds' litigation history. We will also look at a few published FDA warning letters on this topic. Holding executive management responsible for the operation of medical device and manufacturers is a significant step forward in addressing issues of safety. It requires continual vigilance.

My focus on International Regulatory Compliance has always included both the requirements of regulatory authorities and the legal implications of compliance, non-compliance, documentation and sloppy attention to detail that could result in a lawsuit in a Federal or State courtroom. I also focus on product safety and the steps necessary to create a safe product. If you have questions concerning medical device litigation, you can contact me for a free preliminary consultation at my new e-mail address jameskolka@gmail.com.  

Don’t Listen To Anyone Who Says You Don’t Have to CE Mark Your Product For The EU!

 

Introduction

I don’t know how many times I have heard words from distributors, buyers, politicians, clinics, etc. in the EU anxious to sell or buy new products saying, not to worry you don’t have to CE Mark your products for the EU. The first time was several years ago when the Mayor of a small town in Portugal wanted to assure a Michigan machinery manufacturer that he would take care of the CE Marking issue. Of course, he could not. The Mayor was so excited that a large US manufacturer was going to locate a new plant near his town he didn’t want anything to interfere with the process. The Michigan manufacturer had an order to deliver a machinery assembly line to manufacture fuel injection systems for an automobile plant. They were aware that CE Marking was required for machines.

Not too long before another Michigan manufacturer had shipped a non CE Marked machine to a plant they owned in Northern Ireland. A workman spotted the machine and reported it to his foreman as required by the EU Workplace Safety Act who then reported it to the British Government.

When the company was informed of their transgression, they said that it was their machine built in their Michigan plant and it was to be installed in their Northern Ireland plant so they asserted it didn’t have to be CE Marked. British authorities reminded the company that their plant was on sovereign British soil subject to UK & EU law. They gave the plant manager a six month suspended sentence under the Criminal Code, fined the company, told them to remove the machine until it complied with the Machinery Directive and said never do it again.

Placing A Product On The EU Market

The operative words in all EU New Approach Directives are very clear. For Example, the new Toy Safety Directive 2009/48/EC of 18 June 2009 states:

Chapter I

General Provisions

Article 1

Subject Matter

This Directive lays down rues on the safety of toys and on their free movement in the Community.

Article 2

Scope

1. This Directive shall apply to products designed or intended, whether or not exclusively, for use in play by children 14 years of age (hereinafter referred to as toys).

Article 3

Definitions

For the purposes of the Directive, the following definitions shall apply:

1. ’making available on the market’ means any supply of a toy for distribution, consumption, or use on the Community market in the course of commercial activities, whether in return for payment or free of charge. (emphasis added in bold print)

2. ’placing on the market’ means the first making available of a toy on the Community market. (emphasis added in bold print)

The same language can be found in all of the CE Marking new approach Directives. Any product that requires CE Marking, whether for payment or free, must be CE Marked. The liability for failing to CE Mark a product falls on the manufacturer, not the buyer. 

In the new Toy Safety Directive 2009/48/EC, the EU has set forth:

• Article 7, Obligations of distributors

• Article 8, Cases in which obligations of manufacturers apply to importers and distributors

• Article 9, Identification of economic operators

While its nice to see the EU set forth legal expectations for Distributors, Importers and Economic Operators, this does not take the “monkey off the back” of manufacturers. If a manufacturer places a non-marked product on the EU market that should have a CE Mark, that manufacturer is legally liable. 

What is the Legal Liability for Failing to CE Mark a Product? 

The new Toy Safety Directive spells out several steps that can be taken for placing a toy on the market that should be CE Marked;

• Chapter VI sets forth the “Obligations And Powers Of Member States” 

• Article 39 establishes the “Precautionary Principle”

• Article 40 establishes the “General Obligation To Organize Market Surveillance” in accordance with Articles 15 to 29 of Regulation (EC) No 765/2008 of 9 July 2008 setting out the requirements for accreditation and market surveillance relating to the marketing of products and Repealing Regulation (EEC) No 339/93

• Article 41 sets forth “Instructions to the notified body”

• Article 42, Procedure for dealing with toys presenting a risk at national level

• Article 43, Community safeguard procedures

• Article 44, Exchange of information – Community Rapid Information Exchange System

Finally, Article 45 defines what is meant by Formal non-compliance:

1.Without prejudice to Article 42, where a Member State makes one of the following findings, it shall require the relevant economic operator to put an end to the non-compliance concerned:

(a) that the CE marking has been affixed in violation of Article 16 [General principles of the CE marking] or 17 [Rules and conditions for affixing the CE marking];

(b) that the CE marking has not been affixed;

(c) that the EC declaration of conformity has not been drawn up;

(d) that the EC declaration of conformity has not been drawn up correctly;

(e) that the technical documentation is either not available or complete.

2. Where the non-compliance referred in paragraph 1 persists, the Member State concerned shall take appropriate measures to restrict or prohibit the toy being made available on the market, or shall ensure that it is recalled or withdrawn from the market. (emphasis added in bold print)

Summary

The reason I chose the Toy Safety Directive was a question this week from a client with whom I am working to CE Mark their products who was told by two distributors that their toy didn’t have to be CE Marked for sale in the EU. Whether the two distributors were incredibly ignorant, previously lucky in evading the law or duplicitous is beside the point they still try to persuade manufacturers to sell them non CE Marked toys. Fortunately, my clients were suspicious and suspected that the distributors were not telling the truth.

Finally, take a close look at Article 45 above, Formal non-compliance. Those of you who have been reading my recent Blogs, especially the last three posted on July 30, August 15 and August 17 respectively should recognize that the manufacturer who manufactured the machine that killed a worker in the UK and maimed another worker for life in the US did not satisfy any of these requirements! The Machinery Directive has the very same requirements as the Toy Safety Directive. 

The EU has adopted excellent legislation on Market Surveillance, however, I am still concerned with the quality of implementation. I think these types of steps are essential for effective Market Surveillance for the EU new approach Directives As noted previously, I would like to work with the EU to enforce market surveillance so that consumers aren’t injured or killed. I also would like to work with European manufacturers concerning steps  for them to take to reduce their liability exposure in the US market. It seems to fit the European philosophical approach to product safety and would help EU firms concerned about the litigious nature of the US marketplace. If anyone is interested in exploring these topics further, please contact me at jameskolka@gmail.com or  jim@jameskolka.com. 

Until Medical Device Manufacturers Conduct Product Safety & Product Liability Audits, Risk Management Does Not Exist!

Background

Several times since I began this blog in February 2009, I have mentioned a private “in-depth” litigation study conducted by a medical device insurance company of its litigation history. Since virtually all of their lawsuits have been settled out of court, there is no public record of mistakes to guide other medical device manufacturers, thereby allowing them to repeat the same mistakes over and over.

Quality Management Systems such as FDA’s Quality System Regulation (QSR), the EU’s Medical Devices Directives combined with ISO 13485:2003 Medical Devices – Quality will management systems – Requirements for regulatory purposes and Canada’s application of ISO 13485:20032 medical devices must be understood from a legal perspective.  They contain Quality Manuals and Quality Procedures developed by each company to comply with governmental regulatory requirements to manufacture a medical device. The system must be documented and must identify the processes that will be used to manufacture medical devices.

Quality system documents and records contain a wealth of information that can be obtained during discovery to determine if a company is satisfying governmental regulatory requirements and if a company is satisfying its own quality management procedures. Failure to follow regulatory requirements and/or follow the company’s quality management system requirements can be used against a company in litigation. Depending upon the seriousness of the regulatory failure, it could provide vital information to plaintiffs’ attorneys. 

Quality Manuals and Quality System Documents are intended to guide the operation of a company’s Quality Management System. Quality system documents are neither intended nor constructed to provide evidence of a company’s concern for patient safety and product safety. If a company wants to prove that it cares about patient safety and make safe products, it will have to build documentation to prove that point. 

Litigation

The three major areas of product liability litigation – Design, Manufacturing, and Post Sale Surveillance are specifically addressed by clauses in each regulatory Quality Management System. For example, to design a medical device using FDA’s Quality System Regulation (QSR), a company that wants to manufacture a Class III, Class II and certain Class I medical devices must follow 21 CFR 820.30 Design Controls. This means that there should be documents and records describing the stages of design development: 820.30 (b) Design and development planning, (c) Design input, (d) Design output, (e) Design review, (f) Design verification, (g) Design validation, (h) Design transfer, (i) Design changes, (j) Design history file. This means that records should exist documenting each of those stages, including risk analyses where and as needed. If records don’t exist, the device was not designed in accordance with FDA regulations 

All of this design information is available to plaintiffs’ attorneys in product liability lawsuits. Manufacturing a medical device follows its own set of QSR regulatory clauses. To be effective and not be blindsided by plaintiff’s allegations citing quality system breakdowns, corporate counsel and defense attorneys must understand regulatory Quality Management Systems in depth.

Quality Management Systems are audited internally following an audit protocol that visits each department at least once annually, more often if problems are found. Problems identified as nonconformities must be addressed by Corrective and Preventive Action CAPA). Departments are asked to make corrections following a timeline.  Internal audits, nonconformities and corrective actions are reviewed at least once annually (generally more often) by top management.  Management review minutes are kept. Internal audit records, nonconformities, corrective and preventive actions and management review minutes constitute a rich source of information for plaintiffs’ motions to compel. Consequently, corporate counsel and defense attorneys must understand what type of information and records are generated and be prepared to address these issues with their manufacturers.

What does this mean for product liability litigation?

The medical device insurance companies litigation study revealed several concerns regarding weaknesses of medical device manufacturers in product liability lawsuits. Remember the old saying, the question isn’t “if you are sued, will you be prepared” rather “when you are sued, will you be prepared!” A few of the findings are listed below:

• Several medical device manufacturers constructed Quality Management Systems to satisfy FDA and EU medical device regulatory requirements, but contained no documented methods, processes or procedures for communicating product safety concerns and/or incorporating those concerns into their business processes, thereby demonstrating no commitment to product safety.

• The study found a lack of internal processes and procedures in companies Quality Management Systems for escalating product safety concerns and a review of those concerns as well as a lack of any kind of cross functional committee to deal with product safety issues. Plaintiffs’ attorneys alleged that this demonstrated a lack of due care and concern for product and patient safety.

• The study found several instances of biotech firms failing to protect their documentation by asserting that attorney-client privilege prevented plaintiffs’ from examining their documentation during discovery, which assertion was not accepted by the court.

• The study found misconceptions by management of medical device manufacturers that compliance with FDA’s Quality System Regulation was enough to prevent product liability claims.

• The study found that management frequently continued to underestimate the risk of product liability litigation to the success and/or survival of their business.

• The study found that design research documents and agreements often contain hidden product liability exposures – the agreements were not reviewed by legal counsel familiar with clinical research or by insurers or brokers reviewing coverage limits and indemnification clauses.

• The study found a lack of qualified in-house personnel available to integrate product liability avoidance principles into the firm’s quality management system and establish an infrastructure for product safety, resulting in product liability post-production legal defense problems.

• The study found that company postproduction corrective and preventive actions were deemed to be inadequate for the degree of risk presented by individual complaint investigations resulting in both FDA regulatory actions and product liability lawsuits. 

Summary

These are but a few of the problems uncovered by the litigation study. The actual list is quite long and quite disturbing. The lack of training for product liability exposure is extraordinary. Virtually no firms conduct product liability audits or product safety audits of their operations. The assumption appears to be that compliance with FDA and EU regulations is sufficient. From my experience, quality managers do not see legal issues as their responsibility and therefore will pass them off to regulatory managers, corporate counsel and management. In turn regulatory managers do not focus on product liability exposure.

The focus on product safety and patient safety is inadequate and will continue to cause trouble. The maintenance of records often is poor. The wording of documents pays no attention to the legal consequences of what is said. Consequently, it appears that product liability lawsuits will continue to plague medical device manufacturers. There are steps that can be taken training personnel to conduct product liability audits, product safety audits and learn how to write documents so that the words don’t become minefields for litigation.

My wife has often told me that people don’t like to read they prefer getting their information in little word bites and sound bites. I generally respond that attorneys have always liked to read and will analyze what is said how it is said and use it in a court of law. If you have questions about product liability lawsuits and preventive steps such as product safety/product liability audits to reduce product liability exposure, you can contact me at my e-mail address jameskolka@gmail.com.

 

FDA Levies $ Billion Dollar Fines For Off Label Marketing Of Drugs

Background

A week ago yesterday, the Wall Street Journal reported that FDA is seeking $1 billion dollars from Johnson & Johnson to resolve a long running probe into the company’s marketing of an antipsychotic drug Risperal. The settlement of $1 billion would be among the largest in a string of settlements related to off-label marketing of drugs in recent years.  Since 2004 the federal government has been investigating whether J&J’s Janssen pharmaceutical unit improperly promoted Risperal for unapproved uses. The company said it set aside an unspecified amount of money for a potential settlement and it would likely face civil and criminal litigation if it didn’t settle.

Officials at J&J said they were surprised at the size of the sum that prosecutors are seeking. Prosecutors have been citing a benchmark $1.4 billion dollar settlement that Eli Lilly & Co. reached in 2009 to resolve a probe into alleged improper marketing of its antipsychotic drug Zyprexa. Lilly’s alleged off label marketing took place over a longer period of time. Under federal law, companies cannot market medicines for uses other than those approved by the Food and Drug Administration, although doctors can prescribe drugs for unapproved uses.

Prosecutors argue that Medicaid and other government programs are wasting tens of millions of dollars paying for medicines that drug makers encourage physicians to prescribe for uses that FDA hasn’t determined are safe and effective.  In 2009, Pfizer Inc. paid the pharmaceutical industry’s biggest settlement agreeing to pay $2.3 billion dollars to resolve an investigation into the marketing of the painkiller Bextra, which now has been withdrawn.

Since 2001, drug makers have paid more than $11 billion dollars in off-label marketing and other whistleblower fraud cases. The J&J case, like many others started as a whistleblower case. Company insiders (whistleblowers) can receive a portion of the settlement, if the government recovers money. Industry officials are upset about the millions of dollars that whistleblowers can earn from a successful case and argue that these people are often disgruntled employees whose allegations are taken out of context.

A guilty verdict could mean that medicines, e.g. drugs could no longer receive reimbursement from Medicaid and other government programs. Further, an unsuccessful court challenge by drug companies could result in expensive litigation brought by patients and might provoke some states, that don’t participate in the settlement, to seek reimbursement. While the allegations that prosecutors in Philadelphia and Washington DC are pursuing in the J&J case haven’t been disclosed, the FDA has approved Risperdal for treatment of schizophrenia and bipolar disorder. The agency, however, has warned that the drug should not be given to dementia related psychosis including elderly patients.

Off-Label Marketing of Drugs and Medical Devices

Off-label marketing has been an ongoing concern for FDA. The amount of money that drug and device companies can make from off-label marketing can run in the billions of dollars. It also can result in serious to fatal consequences for patients. Since Medicaid pays substantial amounts of money for these off-label abuses, the Federal Government has a dual interest in this problem, as a consumer and prosecutor. 

As a consequence, FDA and federal prosecutors are seeking to levy settlements to discourage companies from directly and indirectly encouraging off-label uses. FDA also has decided to take aim at corporate executives to rein in Pharma abuses. FDA warned in November 2010 and that it was resurrecting a 1970s legal doctrine to bring criminal charges against top executives.

The goal, said Eric Blumberg, FDA deputy chief counsel for litigation, was to ”change the corporate culture” at firms that have shrugged off $1 billion dollar penalties. “It is clear that fines are not working here”, Blumberg told a food and drug Law Institute meeting in Philadelphia. “We need to put something else on a scale to make people think twice, three times.” Blumberg was talking about illegal drug marketing.

FDA’s weapon of choice is the Park Doctrine, based on a 1975 case against Acme Markets president John Park. FDA charged Park personally with sanitation violations following multiple warning notices. The US Supreme Court agreed that Park as company president was ultimately responsible for ensuring compliance.

In 2007, three executives of Purdue Frederick Co. pled guilty to charges of misbranding OxyContin. The three paid $634.5 million to the Virginia Medicaid Fraud Unit and were barred from federal health care programs for 12 years.   

In 2010, four executives of Synthes pled guilty for off-label promotion of a bone cement. The four face fines of up to $10,000 each and a year in federal prison.

Other recent targets include former GlaxcoSmithKline vice president Lauren Stevens, indicted for making false statements and obstructing an FDA investigation into illegal marketing of Wellbutrin SR (buproprian sustained release) and former KV Pharmaceutical CEO and Chairman of the Board Marc Hamertin barred from participating in federal healthcare programs for 20 years.

Protecting the Nations Health

It is a remarkable when there is a push in Congress to ease up on regulations in the healthcare industry with the logic that it stifles innovation and slows delivery of new medicines to the market. It is understandable that the delivery of new medicines should be expedited as soon as possible, but not at the expense of patient safety and product safety.

It is difficult not to be cynical when there is a push in congress to ease up on regulating healthcare abuses. It is reminiscent of the words of Gordon Gekko, the main antagonist in Oliver Stone’s 1986 film Wall Street, when he said, “Greed, for lack of a better word, is good!” Apparently, that sentiment is alive and well in portions of America’s Healthcare Industry.

We read of medical mistakes in hospitals and hasty decisions by doctors that cause 100,000+ deaths each year. Compounding these problems with corporate greed is sad and troubling for the nation’s healthcare system. Unfortunately, it is nothing new. Prosecuting these abuses with adequate civil and criminal penalties appears to be the only way to dampen the onslaught.

Reducing regulations, while wildly popular among a few who dislike government oversight, enriches the few and hurts the many. If you have questions about healthcare abuses, product liability lawsuits and preventive steps such as product safety/product liability audits to reduce product liability exposure, you can contact me at my e-mail address jameskolka@gmail.com.