The Challenges for the US of Regulating Compliance and Quality on a Global Scale

Bob Rhoadesdiscusses the problems faced by US regulators and industry in ensuring the safety of imported devices and device components manufactured overseas.

Bob Rhoadesis the director of the quality systems and compliance practice at Becker Consulting in Washington, DC. Email: [email protected]. Website: www.becker-consult.com.

With scrutiny and criticism of the US Food and Drug Administration increasing in recent months, in particular with regard to the issue of contaminated heparin from China, the medical industry is slowly awakening to the potential domestic effects of global events such as these. Though much of the current public spotlight is focused on drugs and their safety, an equally important discussion awaits with respect to medical devices manufactured around the world and exported to the US.

An increasingly aware and savvy marketplace will undoubtedly begin to question the source of the products their healthcare dollar goes toward, and demand more information and proof that the drugs and devices on which they depend are safe and effective.

In many ways, we are seeing a throwback to the early 1900s, when serious crises involving health products moved Congress to create the Federal Food, Drug, and Cosmetic Act, and in turn created the FDA. More than a century later, the organisation charged with policing and protecting the public health has been outstripped by the incredible growth of a world economy fueled by extraordinary medical innovation, coupled with the inevitable thirst for profitable business ventures. This combination has pushed many industries to search out low-cost production opportunities around the world. As events of the last couple of years have shown, it also leaves a door open to substandard manufacturing practices, quality systems that do not measure up and an inspection scheme that cannot adequately monitor the processes and factories producing the goods that consumers around the world use every day.

Consider for a moment the complexity of today's medical device manufacturing environment. Firstly, the devices themselves are more intricate (eg computer-controlled electromechanical devices used in life-saving procedures and therapies) and some employ novel software or radiofrequency technologies. Secondly, their assembly may involve high precision hand-assembly or highly automated equipment. Lastly, the source of the components that are used is vast and difficult to trace.

As medical device firms strive to bring these advanced technologies to the healthcare system, the opposing pressures of business and cost of healthcare - with its added convolution of insurance and reimbursement - make it increasingly challenging to make a profit. Simply stated, manufacturers seek to reduce costs by finding cheaper ways to produce component parts and cheaper places to assemble final products. In a global marketplace, a given medical device may be produced anywhere and have components sourced from various parts of the world.

As the media elevates concerns about where our medical products come from, wary consumers are told they are now at ever-increasing risk whenever they take a drug, or undergo a medical procedure. As consumers, we place a great deal of trust in the makers of those products. Perhaps more so, we have placed a tremendous amount of trust on a regulatory agency to guarantee that products are of sound design and are safe and effective before they are commercialised. That same agency is responsible for assuring the public that the factory continues to manufacture products under a quality system that ensures a commitment to the safety of every device and of every dose.

At a Global Harmonization Task Force conference in October 2007¹, FDA commissioner Andrew von Eschenbach said: “We will face, particularly in the world of devices, an increasing realisation that there is no such thing as ‘Made in America’.” Dr von Eschenbach added: “It is much more likely to be ‘Assembled in [America]’ as parts or pieces will more and more likely be coming from a wide variety of sources and countries, and that will continuously challenge us to be able to define and harmonise our regulatory experience and our regulatory responsibility.”

FDA wrestles with inspection explosion

As the FDA's inspection dilemma has come to light over the heparin contamination and other crises of the past two years, the magnitude of the problem has been borne out in a host of newspaper and magazine articles. None, however, has been quite so dramatic as the reports the Government Accountability Office issued in November 2007 (on drugs)²and in January 2008 (on devices)³on weaknesses in the FDA's inspection programme for foreign producers.

The FDA is currently under fire specifically for lapses related to the heparin contamination issue. In its report on drug safety, the GAO stated that while there are an estimated 3,000 facilities in China now producing drugs, the FDA has only managed to perform current good manufacturing practice inspections in about 10 to 20 of those facilities each year for the last few years. In fact, the FDA is struggling with its legally specified obligation of inspecting domestic producers once every two years. The calculations of available resources versus current producers in China alone would take nearly 30 years to inspect each facility once - and those estimates do not include other countries like India, now the second-largest producer of active pharmaceutical ingredients, nor do they include other products.

Medical device inspections on foreign soil are an equally daunting challenge for the FDA. The GAO report on devices states that there are about 10,600 registered device manufacturers (producing Class II or Class III devices), with nearly half of those based outside US borders. The report further says that during the period 2002 to 2007, the FDA has managed to inspect an average of 247 foreign establishments each year, or only about 5% of the total. With the recent focus on concern relating to goods coming from China, it is interesting to note that over the same six-year period, China had the lowest rate of inspection (64 inspections over the six years for almost 700 registered establishments).

Dr von Eschenbach, during testimony before the House Subcommittee on Oversight and Investigations, Committee on Energy and Commerce, on 23 April, stated after repeated questioning regarding the FDA's oversight on foreign inspections from committee chairman John Dingell (Democrat - Michigan) that he believed that giving the agency more resources to perform more inspections would only be part of the solution. In fact, the FDA has also been criticised for not being more diligent in upgrading antiquated data management systems that have been cited as inaccurate and incomplete. Multiple data systems, created for different purposes at different times over the past two decades, are hindering the FDA's ability to respond effectively to a growing number of far-reaching public health issues.

Impact on the future

The drug and medical device industries are increasingly complex in nature, and the processes that are used to make the end products have expanded under an expansive global economy. Previous ideas and revamped approaches to the foreign inspection issue have fallen short of expectations, and the recent crises and their impact on patients worldwide have created new dynamics to which the FDA and US legislators must react. Previous attempts to increase the use of third-party inspections, or to utilise the reporting of audits conducted by foreign authorities as monitoring mechanisms, have missed the mark for a variety of reasons.

The current call from Congress to simply increase resource appropriations for inspecting firms that import to the US is also short-sighted. Regulatory policing is an important factor for ensuring compliance, but it can never be the whole answer. Pressure from an increasingly discerning public will force new thinking and new priorities. Over the next three to five years, we can expect a number of reactions, including the following:

• the FDA will, in the short term, yield to pressure from Congress and increase inspection activity, both in number and severity;
• Congress will consider additional appropriations to grant the FDA more opportunities to strengthen the enforcement system, both through resources and technology;
• Congress will likely consider new legislation, once again, to elevate the power and authority of the FDA to take stronger legal actions against companies that are proven to have deficiencies in their products and their processes, with more attention to their ability to control quality upstream in their supply chain; and
• global regulators will respond in kind and continue to strengthen harmonised approaches to the inspection question, in terms of both quantity and severity.

Companies must respond positively and proactively to these trends by establishing not only strong internal quality systems, but also by extending the responsibility of product quality to the suppliers of their raw materials and component parts. Supplier selection and surveillance will, by necessity, become a core business competency that companies must embrace. If they do not, they will suffer the perils that may now be hiding undetected deep within their finished products.

References

1. Global Harmonization is Key to Import Safety - Andrew von Eschenbach, 5 October 2007, www.fda.gov/ola/2007/foreigndrugs110107.html

2. US GAO, Preliminary Findings Suggest Weaknesses in FDA's Program for Inspecting Foreign Drug Manufacturers, GAO-08-224T, 1 November 2007, www.gao.gov/new.items/d08224t.pdf

3. US GAO, Challenges for FDA in Conducting Manufacturer Inspections, GAO-08-428T, 29 January 2008, www.gao.gov/new.items/d08428t.pdf