BBI

As European hospitals attempt to contain ever-increasing costs, the problem of reuse of disposable single-use medical devices has become widespread and is now close to the top of the European Union's medical device agenda.

The regulatory position, however, varies from country to country since this particular aspect is not dealt with in detail in the Medical Devices Directive (MDD). The directive as it stands can be interpreted in two ways – either allowing companies to state that a product cannot be reused because of scientifically proven risks (and having proof available to back up their claims), or requiring manufacturers to designate their product as single-use because they are not prepared to take legal responsibility for stating that a device can be reused (subject to validated proof of proper cleaning and sterilization procedures).

There are substantial worries already that devices such as endoscopes are less safe when reused, even when labeled for reuse and after correct sterilization procedures. Health authorities that have implemented DRG-type reimbursement procedures, as in Germany and Italy, are also concerned about the potential for fraud as physicians claim reimbursement for multiple devices where only one has been used.

The Belgian government has been proposing a decree requiring manufacturers to justify with scientific evidence their claims for single use. Publication of the decree in its present form seems unlikely, and the Belgian health ministry apparently is waiting for guidance from the European Commission (EC) following objections from several other European Union countries. However, the Belgian initiative has provided momentum for European action, and a European forum is planned to review the problem as part of the EC's five-year review of the MDD.

It is likely that manufacturers in the future may need to justify "single use" claims with risk assessment evidence or to ensure that information on reprocessing before reuse is accurate and clear.

Although no European country officially supports the reuse of disposable medical devices, Peter Schroer, quality manager at Ethicon Endo-Surgery (Norderstedt, Germany), said that in countries where the health authority has a policy against reuse, the practice is decreasing, while in countries without specific guidelines, it is increasing.

In Britain, the official National Health Service (NHS) position is that products labeled for single use should not be reused. In practice, many hospitals reuse disposables such as catheters. In France, reuse of single-use products has been banned since 1994. A court case last July resulted in a ruling that reuse of a single-use device constitutes a deception of the patient. In Portugal, the health ministry position is that reuse can compromise health to an unacceptable degree in the absence of documentation proving that essential requirements have been met.

Reuse of single-use products is legal in Germany, providing there is validated documentation on cleaning, disinfecting and sterilization and that all the potentially compromised performance characteristics of the device have been tested and validated. In Sweden, reused products, which would be classified as in-house manufactured products, must be processed in a facility that fulfills the essential requirements of the MDD. Documentation must be maintained for five years. Hopefully the European forum will find a way toward a standardized approach.

Drug delivery market set to double

As new technologies in research and development reach fruition and are commercialized over the next five years, global sales of drug delivery products are projected to exceed $100 billion, with the market today of $50 billion constituting only 12.5% of total world pharmaceutical sales.

Needle-free injection system sales are predicted to grow the fastest, from $400 million today to more than $1 billion by 2005, according to Informa Pharmaceuticals (London).

Disetronics' (Burgdorf, Switzerland) integrated diabetes management system, which is entering its final development stages prior to regulatory approval applications, is intended to be a further quantum leap in insulin-dependent diabetes treatment, according to the company, a rapidly growing drug delivery specialist. The i-DMS device combines a GlucOnline sensor for continuous monitoring of blood glucose levels with an insulin pump and special software in a device that, as a first step, monitors and displays blood glucose readings around the clock, warns the wearer if the level is too high or too low, and provides recommendations for the correct insulin dosage.

A Mark II version should be able to administer the insulin dosage required on a largely automatic basis and in permanent operation. In the middle of last year, a prototype GlucOnline sensor was presented in operation with a patient over a period of hours at the annual congress of the European Association for the Study of Diabetes (EASD).

Combined with Disetronics' Diaport percutaneous implantable port system, which delivers insulin directly to the liver circulation in a physiologically optimal way, faster response to insulin delivery will be obtained, resulting in more stable blood glucose levels.

Serono (Geneva, Switzerland) has signed an agreement with Bioject Medical Technologies (Portland, Oregon) giving Serono exclusive worldwide rights to Bioject's Vitaject 3 needle-free application system for all of Serono's current and future growth hormone products. These will compete with Pharmacia's (Peapack, New Jersey) growth hormone, which was launched in Japan last July using Disetronics' new-generation Genotropin Pen, which shows the dosage of growth hormone in milligrams, complying with the new World Health Organization (Geneva, Switzerland) guidelines.

Braun Melsungen (Melsungen, Germany) has developed a central monitor system for remote control of medical infusion in, for example, intensive care units. The new system controls up to 18 infusion pumps using a single selector knob. Automatic logging of the data of individual pumps connected to the system eliminates the need for subsequent analysis of delivery rate curves. With separate PC software, up to 300 medications can be edited, along with their parameters for a specific ward. These data are then available in a standard drug list that can be recalled in the same format at each patient's bedside.

UK neonatal hearing screening planned

The UK Department of Health (DoH) has gained applause and congratulations instead of its usual diet of complaints and brickbats as it prepares to introduce the first pilot neonatal hearing screening program in the middle of this year. A national program could be introduced by the end of 2002, according to the DoH.

The pilot project is in response to recommendations of the National Screening Committee, which sees clear benefits in national coverage but recognizes the need to assess how best to introduce the full program and its effects on the development of pediatric audiology services for neonates.

Presently, the infant distraction test is used in Britain for the detection of neonatal profound hearing impairment. Of 840 cases per year in Britain, this test fails to identify around 400 at 18 months and 200 by the age of 3 . Late diagnosis compromises a child's speech, language and communication abilities.

The DoH projects completion of the pilot test protocol and issue of tenders for equipment required by March. By April, 10 health authorities should be ready to start the pilot and another 10 by June. The pilot program is being organized by the Medical Research Council's Institute of Hearing Research.

Tinnitus diagnosis and therapy

Tinnitus is an incurable hearing problem affecting many older people and presenting a continuous background noise. Hortmann (Neckartenzlingen, Germany) has developed two devices to diagnose and treat tinnitus. Based on scientific concepts underlying habituation training and re-training therapy (TRT), the devices operate by incorporating the patient's tinnitus noise into a harmonious piece of music, so that patients are taught to selectively turn their attention away from their tinnitus noise.

The Tinnicur 4000 is the diagnostic and therapy unit used by the audiologist, and the Tinnicur 600 is a dedicated patient's unit for home therapy use. Tinnutus data (tone pitch, band width, lateral nature and volume) are determined using the Tinnicur 4000 and transferred to the home therapy unit.

Music therapy on a daily basis uses the relaxing benefits of listening to music to enable patients to re-train their attention away from the tinnitus noise to eventually perceive the noise as an integral part of daily background noise.

European business developments

The inhaler activities of Leiras Oy (Espoo, Finland), which was acquired by Schering (Berlin, Germany), have been spun off into Focus Inhalation Oy with the intention of selling it to an investment group. Schering also is planning to convert its biotechnology subsidiary, metaGen (also Berlin), into a separate company in 1Q01, aiming for an IPO on the German Neuer Markt at the end of 2002. Sales in the first nine months at Schering were up 32% in diagnostics and radiopharmaceuticals, and up 31% in therapeutics. Total revenues from U.S. operations were up 39% to $640 million. "The year 2001 will be much harder for Schering," said CFO Klaus Pohle.

Schering has named Hubertus Erlen as its new chairman as of April. He will take over from Guiseppe Vita, Schering's boss for the past 11 years. Vita is expected to join the supervisory board. Schering, whose shares obtained a NYSE listing last fall, has seen its shares rise 70% this year in Germany. "Our listing on the New York Stock Exchange is a key milestone in our efforts to broaden our shareholder base in the U.S.," Vita said.

Schering also has signed an exclusive marketing and distribution deal for Europe, North Africa and the near East with Syncor International (Chatsworth, California) for its Iodine-125 Seeds used in nuclear medicine therapy applications.

Fresenius Kabi (Bad Homburg, Germany), a major European dialysis therapy provider, has acquired for an undisclosed price Novamedical (Paris), which provides a similar service in France to more than 4,000 patients in both clinics and home therapy. 1999 revenues at Novamedical were $14 million.

Bracco (Milan), a European contrast media supplier, has signed an agreement with Dyax (Cambridge, Massachusetts) for exclusive global rights to Dyax's proprietary phage display technology to develop imaging products. Bracco is paying Dyax an initial $3 million plus, $3 million per year funding over the next three to six years, depending on achievement of milestones. Royalties will be payable on resultant marketed products. Phage display is a discovery method to label proteins, peptides and monoclonal antibodies that bind to diagnostic and therapeutic targets. The agreement also includes rights to develop and commercialise existing Dyax product leads in inflammation, cardiovascular and oncological imaging.

In 1998, BOC's (Windlesham, England) Ohmeda division was acquired in a three-way deal by Baxter International (Deerfield, Illinois), Becton Dickinson (Franklin Lakes, New Jersey) and Instrumentarium (Helsinki, Finland) in a deal masterminded by Instrumentarium's merchant bankers. The Ohmeda critical care and anesthesia sectors were merged by Instrumentarium into its Datex division. Instrumentarium's first nine months 2000 results include a payment from Baxter to Instrumentarium of $42 million as an adjustment of the purchase price allocation of the Ohmeda businesses. This has been treated by Instrumentarium as a reduction of goodwill resulting from the Ohmeda acquisition.

High-throughput screening takes off

DNA microarrays have proven to be powerful tools for understanding the functional relationships between the large sets of genes available from various genome databases. In spite of their utility in gene expression profiling, however, these microarrays provide no information about post-translational modifications, protein activity and protein-protein interactions.

Protein arrays are being developed to complement DNA microarrays. Ruud de Wildt and his group at the MRC Laboratory of Molecular Biology (Cambridge, England) and the UK Human Genome Mapping Project Center (also Cambridge) have created arrays for high-throughput screening of recombinant antibodies.

Protein arrays have evolved from 1 cm dot-blots (Western blot) on membranes, currently available from a number of diagnostic manufacturers, to biosensor surfaces like the BIAcore chips from BIAcore (Uppsala, Sweden). Since then, array formats have developed at a bewildering speed through 96- and 384-well ELISA trays to the high-density 18,342-cell array developed by de Wildt using a Protran nitrocellular filter from Schleicher & Schuell (Keene, New Hampshire).

A possible hybrid application of this technique may be to use established coupling chemistry developed for DNA chips to array protein-mRNA or protein-DNA complexes. A major drawback that will limit wider application of high-density protein arrays is the limited stability or lifetime of printed protein chips in comparison to DNA chips.