IN PERSON
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Maurizio Suppo, PhD, is vice president |
Small and medium-sized international IVD companies have found the current European diagnostic market an encouraging environment since the approval of the IVD Directive in July 2003. Often faced with a laborious and financially consuming regulation process in the United States, smaller diagnostic manufacturers are turning to the European industry to establish a market presence. The regulation process in Europe is not without its hurdles, however, and only the IVD companies that manage to navigate the upcoming modifications in regulation and medical vigilance will successfully maintain their position.
To learn more about the opportunities, challenges, and regulatory changes in the burgeoning European market, IVD Technology editor Richard Park spoke with Maurizio Suppo, PhD, vice president of regulatory affairs, quality systems, and environment, health, and safety at Siemens Healthcare Diagnostics (Eschborn, Germany). In this interview, Suppo discusses coordinating regulatory compliance efforts, the details of risk classification management, and the IVD Directive’s effect on the European IVD market. He also talks about increasing competition in the European market, the advantages and disadvantages of multiple state authorities, and the role of individual member states in postmarket surveillance and medical vigilance.
IVD Technology: What are the primary challenges that IVD companies encounter in their regulatory compliance efforts in Europe?
Suppo: There has been an enormous increase in attention to regulatory compliance from European health authorities throughout European member states. There also has been an enormous increase in medical vigilance and postmarket surveillance. The French health authorities always have been active in medical vigilance and have reemployed civil servants to increase medical vigilance efforts, particularly with the coming of CE mark registration guidelines. Additionally, there’s been a dramatic increase in the attention given to incidents and near-incidents by Irish, German, Spanish, and Portuguese health authorities. Italy has dedicated resources
exclusively for medical vigilance as well.
Regarding IVDs, the recent increase in attention in medical vigilance combined with the lack of coordination across European member states creates a particularly challenging situation in which industry has to explain technical issues related to vigilance cases to each national authority regardless of product availability. For example, if a safety corrective action is announced in Country A and it is not notified in Country B because the company doesn’t sell the product there, the manufacturer often will receive calls from Country B requesting an explanation regarding the safety corrective action noted on the company Web site for Country A. So IVD companies have to invest resources to deflect any negative reactions associated with procedures that differ from country to country.
How do IVD companies address challenges such as medical vigilance in Europe?
European IVD manufacturers have to address challenges like medical vigilance by adding additional resources to their organizations. Unfortunately, adding resources in a central office location alone is not enough because when authorities follow up on an IVD product, they are only focused on their country’s state authorities and procedures. Manufacturers must have competent people working locally in different countries who are able to interact with authorities to appease their concerns and explain the company’s processes. The internal contacts must have a constant line with the product experts at the manufacturing facilities throughout the United States and Europe as well.
At the moment, every time a company issues a field safety corrective action, the authorities are very focused on the manufacturer’s evaluation of the risk posed to the user and patients. In particular, the authorities focus on the need to conduct “look-back” tests in order to make sure patient results were correct. Companies, therefore, have to adapt their procedures when conducting corrective actions. The scientific and technical detail in a field corrective action letter will be scrutinized by panels of experts from the various member states’ health authorities. European member states are not effectively coordinating on IVD medical vigilance, so each country’s authority is conducting a separate evaluation. This practice can be problematic because the authority of Country A may be primarily focused on pregnancy, while authorities from Country B may be more focused on infectious disease.
European IVD companies also have to address challenges such as postmarket surveillance, which is a broader concept than medical vigilance. The process includes monitoring adverse events, scientific papers, and, most notably, external quality-assessment schemes (EQAS). EQAS are country-specific proficiency tests submitted by governmental organizations or independent third-party organizations to all laboratories. There are also EQAS for specific markers.
The EQAS process usually involves third-party companies or governmental organizations sending samples to several laboratories. The labs test the samples and report the results to the organizers that publish them. Such information is important for the authorities because it is necessary to monitor the quality of laboratories, as well as identify whether laboratories using specific products or tests of a certain brand have issues or concerns.
What do you consider to be the cause of the lack of coordination amongst the various European member states and regulatory authorities?
The single European IVD market has been successfully achieved by the CE mark. Unfortunately, medical vigilance and postmarket surveillance have been left in the hands of the individual countries’ health authorities. In other words, the single market created by the IVD Directive (IVDD) is sufficient until the postmarket surveillance and medical vigilance processes begin. After the product has been distributed, manufacturers have to work with the individual member states because they are solely responsible for insuring and defending the health of their citizens, and, therefore, the member states’ authorities are also responsible for enacting medical or pharmaco vigilance policies.
Consider for a moment the issue of diagnostic test or medical device reimbursement. In theory, it’s a sound medical practice for a country’s government to subsidize the use of diagnostic tests, medical devices, or drugs. Such products are intended to protect and improve the health of the citizens and, therefore, avoid the higher costs of hospitalization and disease. However, there is no coordination in Europe on what constitutes an effective medical reimbursement practice, so government reimbursement of IVD tests (as well as medical devices and drugs) differs widely among the various EU member states.
Do specific interests such as medical vigilance and postmarket surveillance add a new level of regulatory challenges for an IVD company in each European country?
Absolutely. For example, French IVD manufacturers may conduct postmarket evaluations on specific tests that focus on different aspects compared with Irish medical authorities. We are witnessing a continuing trend in which more countries are imitating other national authorities and following their procedures closely. Overall, medical vigilance is a much heavier burden on the IVD industry now than it was five years ago.
Maintaining European Standards
What are the primary challenges that IVD companies encounter in their efforts to maintain their quality systems to meet European standards?
IVD manufacturers must have a quality system in place in order to comply with the IVD Directive. The system requires commitment, time, and resources to meet the internationally acknowledged standard for quality systems of the medical device industry included in the ISO 13485. From a manufacturing perspective, without ISO 13485, diagnostic companies are unable to place the CE mark on their products. This concept extends to the countries’ commercial organizations as well. Companies selling highly technological IVDs and sophisticated equipment must have commercial organizations in the various countries capable of assuring a high level of customer support in order to maintain such sophisticated test equipment in top performing order.
Technical maintenance is not as essential for low-tech products and rarely presents a problem for postmarket surveys in this type of low-tech industry. However, quality service maintenance and technical support is one of the key factors for success and often differentiates companies in the IVD market. Logistically, it is a country-specific process for the IVD industry overall. How manufacturers ship products in China can be quite different from how manufacturers ship products in Canada. Attention to different geographical and temperature environments and local ground transportation patterns can play an important role in the success of an IVD company. The industry leader will be the IVD company with top-quality products that is also committed to providing an excellent range of services to its customers by having its country’s commercial organizations operating according to robust quality systems officially certified.
How has the IVD Directive affected IVD companies’ abilities to do business in Europe?
The IVDD has dramatically affected the ability of manufacturers to do business in Europe in a positive way. The diagnostic industry has recognized that the IVDD has been very successful. There are some outstanding issues, but, by and large, it has been a success. The directive has allowed the industry to introduce the newest technology on the European market much earlier than other market regions.
For some companies, the IVDD allows them to release their products only in the European market due to the cumbersome regulatory process in the United States, which requires small and medium-sized manufacturers to undergo a lengthy process they cannot afford. The European market is more affordable and IVD companies can get product approval and registration quickly. If manufacturers look at the process from the user’s point of view (for example, the clinical or laboratory directors), the European market is healthier than in other countries because there is more competition and the latest technology is more rapidly available.
Planning for the Future
What other regulations for IVDs does the European Commission plan to implement?
In May, the European Commission sent a consultation document on the medical device directives to all medical device manufacturers. It raises some fundamental questions regarding the simplification of the logistical framework for medical devices. The European Commission is enquiring on the potential value of establishing one primary authority responsible for medical devices instead of the multiple-authorities regulation system currently in place. The proposal is an attempt to address the disadvantages of dealing with multiple European authorities when conducting procedures such as postmarket surveillance.
The IVD industry is still assessing the pros and cons of this proposal because it would have an enormous impact on the operational processes and resources put in place to address the current regulatory environment. For example, a central agency for medical devices would be responsible not only for the premarket approval of certain categories of IVDs but also for the postmarket vigilance. Industry is unsure whether such an agency would regulate all devices or only devices with the highest risk assessment. Today, the notified bodies are responsible for premarket activities that involve eventually granting the CE mark to IVD products.
Essentially, there are many considerations on the table, and the industry is very cautious about supporting significant changes to the current directive framework. However, there may be some justification in having more European coordination on postmarket surveillance and medical vigilance. The IVDD is primarily dedicated to products that are classified according to a list. There are four levels of IVDs in the IVDD: Annex 2 List A, Annex 2 List B, self-test products, and others IVD products.
The European Commission and some of the member states’ authorities may have determined that the current list-based classification of IVDs too rigid because it does not allow product reclassification based on different or changed risk criteria of given tests. Currently, any addition or reclassification to the IVDD lists would require a change of the IVDD itself, a difficult and extensive process. The consultation document is enquiring about the benefits of replacing the list-based classification with a rules-based risk classification for IVD products and medical devices as a solution.
Many industry professionals can foresee a certain rationale in adopting rules instead of lists. However, the European Diagnostic Manufacturers Association (EDMA) is willing to adopt the Global Harmonization Task Force rules that have been published specifically for the IVD industry, as opposed to reinventing rules that may make the classification process inhomogeneous with products around the world. The EDMA projects that in a few years there will be a total reassessment of IVD classification regardless of whether the European Commission continues to employ the list-based classifications or moves to a rules-based reclassification. Products will be reassessed and reclassified, which will mean an additional increase of industry regulation because many products will be moved to another, possibly higher, risk classification.
What areas are the European Commission interested in revising and updating in the IVD Directive?
In addition to rules-based risk classification, the European Commission has expressed interest in examining the industry position on issuing the new classification procedure in the form of a regulation instead of a directive. The current legislation—Medical Devices Directive, Active Implantables Directive, and the IVDD, are all explicit directives, which are not laws themselves. In order to become a law of a member state, the directive has to be transposed into the legislative framework of each member state. Directives allow for some flexibility and discretion by the member states during the transposition process.
A European regulation, on the other hand, is a law that is immediately enforceable and does not have to be transposed into the logistical framework of the member states. The nature of the regulation is that, as a law, it is subject to interpretation by the courts. For example, the current directive allows each member state to determine whether IVD manufacturers will be required to use the national language of each country for IVD products for professional use. With a European regulation, the decision to use English or the national language of each member state would no longer be subject to interpretation, but would have to be clearly specified in the text of the law. In this case, the concern of the IVD industry is that this would result in a dramatic escalation of language requirements which would take away the little flexibility IVD manufacturers have today. Such issues will have to be specified in the regulation language.
To circumvent the considerable financial burden of translation costs, the IVD industry would like to push for clearer and more open acceptance for the supply of instructions for use (IFUs) by other means (e.g., access via company Web sites, new versions of IFUs “wired” to analyzers permanently connected to the Web, fax-back services, hard-copy manuals, etc.). It can be particularly costly for manufacturers to supply IFUs in all the languages in Europe, let alone the world.
What have been the major developments in IVD regulation in major markets around the world? What is the current status and latest development in the effort to move industry toward global harmonization of IVD regulations?
Regulations are on the rise everywhere, particularly in the Asia-Pacific region. European IVD companies are facing new or more-strict regulations in many countries (e.g., Singapore, China, Malaysia, etc.) and international authorities are increasing their level of attention on IVDs. It’s interesting to see health authorities of developing countries tackle IVD regulation according to risk assessment, which is similar to the approach used in the United States and Europe. Australia, Turkey, and countries throughout Eastern Europe not yet part of the European market are in the process of establishing specific regulations for IVDs. For the diagnostic industry, the regulatory scenario is clearly on the rise worldwide.
