Mutual recognition, but step by step

BBI Newsletter, The, Nov, 1997

The Mutual Recognition Agreement (MRA) frame-work document initialled by the FDA and the European Commission earlier this year probably will take at least a year to achieve ratification. In the meantime, manu-facturers and authorized certification organizations, known as conformity-assessment bodies, are feeling their way through existing complexities and potential problem areas.

For example, even though the U.S. Quality System Regulation program is nearly identical to the ISO 9000 standard, it is still necessary to have both quality sys-tem certifications. At least under the MRA, one confor-mity assessment testing house will be able to provide both certifications. Afurther difficulty with the MRA is likely to be its connection to the FDA's third-party review pilot pro-gram, which was initiated last year. The program, which borrows from the European Union (EU) system, allows designated testing houses, similar to Europe's notified bodies, to certify a range of low-risk Class I and Class II devices for compliance with FDA requirements. Of a total of 37 organizations expressing an interest in being designated as third-party reviewers, only seven were initially selected. The only testing house admitted to the program which did not have a U.S. operation was the British Standards Institute (BSI; London). The program initially covered about 220 Class I and 30 Class II devices, with more Class II devices to be added as the FDA completes the necessary device-spe-cific review guidance. According to Peter Walker, who heads the program at BSI, "European manufacturers have expressed some interest, but mostly for devices which are not covered by the pilot scheme." Walker said that in evaluating the original applications to join the pilot program, the FDA was most cautious about ethical questions and conflicts of interest. It wanted proof that testing houses were independent, had no arrangements with manufacturers and could vouch for the integrity of their personnel. U.S. manufacturers are concerned over confidentiality and tend to trust the FDAwith trade secrets more than a contracted assessor. However, the MRA includes provisions for the protec-tion of confidential data and for the availability of infor-mation within the scope of public interest. The MRA, as currently framed, will open up the program to permit all European notified bodies to review 510(k)s against U.S. requirements and to submit the reviews to the FDA for final action. The MRA will run for an initial three-year trial period, after which a consensus review will establish which EU-notified bod-ies have established their ability to carry out reviews in accordance with FDA requirements. On a more upbeat note, the mutual recognition agreement does represent a major step forward. EU and FDA regulatory bodies currently spend large sums of money carrying out transatlantic inspections each year and the MRA should make that unnecessary. In any case, as Walker noted, this practice has not been effective anyway, because it simply was not economi-cal for the FDA to visit manufacturers of low-risk devices. EU manufacturers also have been spending much time and money retesting their products after arrival in the U.S. The MRA should eventually enable manufacturers to use a single notified body to perform certifications to enable both U.S. and European market entry. In addi-tion, the MRA includes the basis of a cross-Atlantic early warning system to simplify and encourage the exchange of product vigilance reports. Implementation of the harmonized ISO 10993 bio-compatibility standard is already simplifying for man-ufacturers the preparation and review of design dossiers and technical documentation. Effectively a manufacturer merely will have to demonstrate that the device has been tested and found to comply with ISO 10993. Presentation to a standard format will also, of course, simplify for the physician or surgeon the com-parison of data on competing products. Stanford blazes 'biocomputational' trail A new center that will emphasize the merger of medicine and computer technology has been estab-lished at Stanford University School of Medicine (Palo Alto, California). Yet to be named, the facility will be a "national biocomputation center," exploring leading-edge mergers of computers and medical knowledge, such as the development of "virtual med-icine." While first centering on the use of virtual reality in medicine,the center will include a wide range of other projects merging biology and computer science with national applications and implications, according to the center's director, Dr. Stephen Schendel, professor and chair of functional restoration at the university's med-ical school. The center was officially launched in September ceremonies at NASA's Ames Research Center at Moffett Field, and the space agency has agreed to pro-vide $500,000 in yearly funding over the next five years. The project was launched by two researchers who developed a virtual-surgery workbench enabling sur-geons to visualize a complex surgery in a 3-D environ-ment before entering the operating room. The new endeavor has been described as being developed as a "center-without-walls" in which scientists at Stanford and other institutions will collaborate to push state-of-the- art techniques and seek other partners from both academia and private industry. NASAneuroscientist Dr. Muriel Ross said the tech-nology to be developed is expected to be applied in diagnosing and treating trauma victims, in visualizing damage to the heart and blood vessels and in treating neurological disorders, among other problems. "We haven't begun to scratch the surface, she said. "A lot of it is going to depend on the creativity of the physi-cians." Additionally, the center is expected to capitalize on computer approaches to the Human Genome Project, requiring computer analysis of large amounts of data. Feds charge researchers falsified data U.S. government authorities have charged research-ers at a California testing lab with falsifying clinical study data, making it necessary for the FDA to review studies for a so-far-undetermined number of drugs. A U.S. attorney in Los Angeles filed charges against Dr. Robert Fiddes, the owner and principal researcher at American Pharmaceutical Research (Whittier, Califor-nia), formerly known as Southern California Research Inc. Charges also were filed against two other study coordinators at the company, Laverne Charpentier and Delfina Hernandez. The firm conducted a variety of studies for products to treat a broad range of medical conditions and diseases, including birth control, hyper-tension, diabetes, asthma, sinusitis, vaginitis, menopause, and others. The companies for which American Pharmaceutical Research did tests included Rhone-Poulenc Rorer, SmithKline Beecham plc, Bayer AG, Roche Holding AG, Pfizer, Glaxo Wellcome plc, Akzo Nobel NV, and others. The government officials charged that the researchers used a variety of false and inaccurate techniques which failed to meet approved testing criteria. In one case, for instance, the company reported that it had used 25 patients in testing a drug for vaginal yeast infection when, in fact, only one patient was involved. Some of the practices allegedly were carried out over a period of six years, according to authorities, who said they were made aware of the problems by former employees who reported "irregularities" in testing practices. California news media have reported that the three charged have signed plea agreements preliminary to entering guilty pleas in the cases. Under the plea agree-ment, the company has agreed to pay $270,268 to Rhone-Poulenc Rorer; $269,981 to SmithKline Beecham; $139,000 to Pfizer; $50,320 to Pharmaco-Organon; $50,000 to Roche; $45,918 to PPD-Zambon; $29,279 for CTMS/Glaxo; and $18,000 to Bayer.