BBI

The diagnostics industry is rapidly moving toward multi-assay testing using a variety of biochip substrates, so that the reactivity of the serum can be simultaneously evaluated for a variety of analytes.

Euroimmun (Gross Gronan, Germany) has developed its Mosaic glass slide for immunofluorescence assays using four different individual chips. Its latest Mosaic slide for the detection of anti-neutrophil cytoplasmic antibodies (ANCA) makes possible differentiation between ANCA, antinuclear antibodies (ANA) and antibodies specific for myeloperoxidase (MPO). Differentiation between the two basic ANCA types, cANCA and pANCA can also be made.

Randox Laboratories (Crumlin, Northern Ireland) is engaged in final trials of its Biochip Array System which will carry out simultaneous multianalyte clinical chemistry testing. At the heart of the Randox system is a biochip manufactured using a variety of substrates, silicon, fused quartz or plastic, depending on the application. Individual biosensors on the biochip are produced using ion-etching, photolithographic and other microassay techniques to provide direct detection of a target analyte with the need for complex specimen processing.

The Randox system, which is planned for general release this year, incorporates a unique imaging system which enables accurate and rapid quantification of the signal at specific test sites. Specific and simultaneous profiling of biological markers seems to be the biggest advantage of the new Randox technology in clinical applications. It should simplify patient profiling and help clinicians to build more accurate diagnostic information.

A joint American and Russian research team has developed a biochip which can identify rapidly the strain of tuberculosis in a patient and, more importantly, whether it is resistant to certain drugs. The biochip used by the U.S. Department of Energy's Argonne National Laboratory (Chicago, Inninois) and the Russian Academy of Sciences' Engelhardt Institute of Molecular Biology (Moscow) is a glass slide with strands of genetic substrate embedded in gel sections.

Jonathan Cohen, head of infectious diseases at the Imperial College School of Medicine (London) said that biochip technology in particular has the potential to transform disease diagnosis. "It's being very rapidly developed and is potentially very robust. For example, it allows you to screen DNA to identify which patients are at risk of developing certain conditions."

Blood transfusion developments

The Swiss Red Cross Zentrallaboratorium (Bern, Switzerland) is the fifth-largest human blood processor worldwide after Centeon (Marburg, Germany), Baxter (Deerfield, Illinois), Bayer (Ludwigshafen, Germany) and Alpha Therapeutic (Los Angeles, California), with an annual throughput of around two million liters of plasma. The Swiss federal government has retained Warburg Dillon Read to investigate the potential commercialization of the Zentrallaboratorium (ZLB) operation so as to maximize its income producing capacity. With an income last year of $160 million the ZLB has seen 1997's growth rate of 29% fall to 9% in 1998 and a similar increase last year.

Much of the ZLB output is, however, currently supplied in bulk to pharmaceutical companies like Novartis (Basel, Switzerland) as immunoglobulins marketed under the Sandoglobulin label, or as albumin for the American Red Cross.

Plans are under way for production lines for a new fibrin surgical adhesive and for Rophylac Rh(D) antigen production during 2000 at a cost of almost $100 million.

In a separate announcement, the French blood bank agency Agence francaise du sang (AFS; Paris) and the French transplant agency have decided to set up a cord blood bank for use in pediatric stem cell transplantation procedures and as a potential alternative to bone marrow transplants.

The cord blood bank hopes to acquire and stock up to 5,000 cord blood donations of around 80 ml each collected in the Besancon, Bordeaux and Paris St Louis maternity units. After testing and acceptance, samples will be frozen in liquid nitrogen, with HLA typing and origin details available for interrogation by physicians from a new France-Greffe de Moelle (Bone marrow transplant) database.

A recent study from University Hospital Maastricht (Maastricht, the Netherlands) indicates that patients receiving blood transfusions during surgery had significantly greater inflammatory reaction and more post-operative complications than patients who were not transfused. The researchers suggest that the transfusion releases bioactive substances such as interleukin 6, an inflammatory mediator and protein which increases bacterial permeability. These agents amplify the systemic inflammatory responses triggered by the surgery, according to the study.

"This study provides evidence that the well-known inflammatory response to cardiac surgery, which historically has been attributed to the [heart/ lung bypass] procedure is strongly affected by the administration of packed red blood cells during surgery," the researchers said.

Commenting on the study, Howard Corwin, head of critical care medicine at Dartmouth-Hitchcock Medical Center (Lebanon, New Hampshire), said the evidence suggests that routine blood transfusions should be avoided and, if necessary, replaced by other ways of increasing hemoglobin levels – by using erythropoetin, for example.

Abbott and Matrix in anesthetic developments

Abbott Laboratories (Abbott Park, Illinois) has widened its line of anesthetic products by purchasing U.S. marketing rights to five products from Glaxo Wellcome (Brentford, United Kingdom). Abbott has acquired four of Glaxo's neuromuscular blockers – Nimbex, Mivacron, Nuromax and Tracrium – all of which are used as pre-operative muscle relaxants. It has also purchased rights for Ultiva, an ultra-short-acting analgesic. Sales in the United States for the five products amounted to $50 million in 1998.

Matrix Therapeutics (Leicester, United Kingdom) has started Phase II clinical trials of its novel general anesthetic agent, TO2. TO2 is a natural non-opioid compound combining anesthetic and analgesic activity, but without causing respiratory depression or lowering blood pressure. TO2 has been developed through a collaboration between Manchester University (Manchester, United Kingdom) and the University of California, Irvine (Irvine, California).

The Phase II trial is a first for Matrix, set up in 1988 by Manchester University's technology transfer unit, Manchester Innovation, and the Manchester office of venture capital company, 3i, which has provided seed funding.

Ian Rubin, CEO at Matrix, aims to license another six to 10 products over the coming months from academic groups, biotech and pharma companies. He anticipates a second round of financing to raise $17 million to $20 million in the first half of this year.

Needleless transfer device for hemophiliacs

Designed to eliminate the risk of needle-sticks in hemophilia drug delivery, a needleless transfer device has been developed by Medimop Medical Projects (Ra'anano, Israel). Freddy Zinger, president and CEO at Medimop, explained that the transfer device was developed to eliminate the need for transfer needles and filter needles in hemophilia drug therapy. "We've added features with the safety of the end-user in mind," he said. A flared rim guides vials into place, where they are automatically pierced. An embedded filter eliminates the risk of filter bypass.

Medimop has developed the device over two years of trials, and plans to supply it to pharmaceutical companies and to hemophilia treatment centers.

Early markers of cartilage breakdown

In rheumatoid arthritis, osteoarthritis and similar diseases the joint cartilage gradually disappears as the extracellular matrix (ECM) components break down. In the absence of objective biochemical measurements to assess cartilage breakdown, clinicians have to rely on indirect parameters such as clinical examination scores, pain, X-ray examinations or general inflammation markers.

Wieslab (Lund, Sweden) has developed two new tests for cartilage oligomeric matrix protein (COMP) and sulphated glycosaminoglycans (sGAG) which may become valuable tools in the evaluation of cartilage breakdown. Both tests can use synovial fluid or blood serum samples. While COMP measurements correlate with cartilage destruction levels in patients with rheumatoid arthritis and osteoarthritis, sGAG assays also give valuable indications of progress after trauma in, for example, knee injuries, by monitoring knee synovial fluid levels.

Early alert for Rhesus babies

Traditionally the prenatal diagnosis of Rhesus (Rh) incompatibility has relied on serological typing, which has required a fetal blood sample. Using PCR amplification, Qiagen (Hilden, Germany) has developed a technique using DNA obtained from amniotic cells, which can be obtained earlier and with a lower risk than fetal blood.

Although only very small numbers of amniotic cells are available for genetic testing, the use of Qiagen's QIAamp technology for DNA isolation has been proposed for RhD/CE typing. Rhesus blood group incompatibilities arise from the production of maternal antibodies against fetal Rh antigens. The Qiagen procedure allows a convenient and reliable determination of fetal Rh genotypes at an earlier stage in pregnancy, while also reducing risk to the unborn fetus.

Novo Nordisk gains rights to new insulin

Novo Nordisk (Bagsvaerd, Denmark) has negotiated exclusive world development and marketing rights to Flamel's (Lyon, France) long-acting basal insulin, Basulin. Under the agreement, Novo Nordisk is to fund clinical trials and product development, paying Flamel $5 million upfront and up to $37 million in milestone and royalty fees.

Currently in Phase I trials in Great Britain, Basculin is a long-acting once-daily formulation of human insulin based on Flamel's Medusa controlled-delivery system for the subcutaneous administration of therapeutic proteins and peptides.

Basulin provided 24-hour control of blood glucose levels in pre-clinical trials. Flamel claims this is twice as long as the coverage provided by other long-acting insulins. Basulin is the first of Flamel's products based on its Medusa delivery system.

Tumor blood flow reduction

Oxigene (Stockholm, Sweden, and Boston, Massachusetts) says that Phase I interim trial results on Combretastatin A4 Prodrug (CA4P) drug showed that this new anti-tumor-vasculature therapy does in fact significantly reduce blood flow to tumors in human cancer patients.

These trial results, presented at the Angiogenesis '99 conference in London, are the first clinical trials demonstrating an inhibitor effectively blocking blood flow within tumor-associated blood vessels. As compared to other anti-angiogenesis inhibitors currently in clinical development, CA4P acts on pre-existing tumor vasculature. Three Phase I trials of CA4P are currently unde rway in the U.S. and Great Britain.

Scotia plans PDT launch in U.S.

Scotia Holdings (Stirling, Scotland) has filed with both the FDA and the European Medicines Evaluation Agency (EMEA) for marketing approval for Foscan photodynamic therapy (PDT) agent as a palliative treatment for head and neck cancer. With Foscan undergoing fast-track review in the U.S., Scotia believes FDA approval could be granted by mid-2000, with approval in Europe in 4Q00.

Scotia is planning to develop Foscan for four additional cancer indications: palliative treatment of pancreatic or prostate cancers and bone metastases and non-palliative treatment of skin cancer. Phase Ib/II trials for all four indications are expected to begin in 2Q00, after successful completion of Phase Ia trials.

The company also plans to start clinical trials with a second photosensitizing agent, SQN400, for the treatment of primary and metastatic liver cancer.

French implants reimbursement to change

Payments for implants used in private clinics in France will change significantly with the French social security finance regulations for 2000. Although the law has been approved by the National Assembly, details will only be available when the decrees are published in two or three months time.

Until now, implants, including pacemakers and orthopedic implants used in private clinics, have been invoiced directly by the supplier to the patient, who then endeavored to obtain reimbursement from the social security system. Manufacturers have generally maintained buffer stocks at the clinics since, strictly speaking, they do not involve the clinic financially.

Under the new regulations, the clinic will become the purchaser. Since about 50% of health care spending on medical devices is in the private sector, this implies a substantial change in the market distribution structure, with the private clinics playing a much more important role in the future.

In addition, the new law introduces a dual reimbursement review system for medical devices – technical and medical aspects will be reviewed by the new French Agency for Healthcare Product Safety (AFSSAPS), while economic (reimbursement) factors will be the responsibility of the Healthcare Products Economic Committee of the Ministry of Solidarity and Labor. This dual system is similar to the existing French system for pharmaceutical reimbursement decisions.

Switzerland, European Union in MRA

Both chambers of the Swiss Parliament have agreed to the text of the Mutual Recognition Agreement (MRA) between Switzerland and the European Union. It has also been approved by the Federal Council and only needs now ratification by the European Parliament and Council.

Rainer Voelksen, head of the medical device department at the Federal Office of Public Health, said that implementation is targeted for January 2001. For medical devices, the MRA states that each party will accept results of each other's testing and certification bodies and will exchange vigilance information. Switzerland will have access to the European medical device regulatory database (EUDAMED).

Switzerland also plans to implement at the same date, January 2001, a new law introducing the European Union In Vitro Diagnostics (IVD) directive. If brought into force as scheduled, this would mean the IVD directive will come into force in Switzerland around six months after its June 7, 2000 deadline for the European Union. Switzerland already unilaterally recognizes the CE mark.

DMS acquires Apelem

Diagnostic Medical Systems (DMS; Perols, France) has acquired for an undisclosed price Apelem (Nimes, France). For DMS, best known for its Ubis ultrasound and Dexa bone densitometers, the acquisition of Apelem takes it into complementary sectors of radiography, fluoroscopy and angiography.

DMS/Apelem are developing a new techology to assess bone density with high-definition digitalised imagery.

Genset and CEA in collaboration

Genset (Paris) and the French Atomic Energy Commission (CEA; Gif-sur-Yvette, France) have signed a collaborative agreement to develop a large-capacity genotyping microprocessor. The two organizations already have filed patent applications on a number of technologies related to the program which, after validation in genotyping, will also be adapted for other applications like high-thruput screening, combinatorial chemistry, metabolic and toxicological studies.

Siemens Medical moves back into profit

Riding the effects of a strong U.S. dollar exchange rate, Siemens Medical (Erlangen, Germany) has declared a profit of $ 347 million on sales of $ 4.2 billion for the year ending September 30, a 7% increase over the previous year.