The Bracco Group: an history

Founded by the family whose name it carries and which has been at its helm for three generations, Bracco now heads a privately-owned international chemicals and pharmaceuticals and biomedical group which is a world leader in diagnostic imaging. The business was set up in 1927 as a result of a cooperation agreement between the Merck and Bracco families.
The company soon became established and Fulvio joined his father, Elio, its founder, in 1934. The post-war years marked a turning point in the company's history.
Fulvio Bracco decided to set up an independent industrial production and research company.
The Lambrate area on the outskirts of Milan was purchased for this purpose in the early 1950s. The Bracco head offices remain there to this day.

Strategic choices in research

The strategic decision to concentrate research in the specific field of diagnostic imaging was crucial in determining the company's future, as it made a name for itself in discovering original products which were highly competitive internationally and lead to genuine progress in the sector. The third generation of the family is represented by Diana Bracco, who joined the company in 1964. A graduate in chemistry, she went on to become General Manager in 1977, the Chairman and Managing Director of the company in 1999. A firm commitment to innovative and specialized research led to development of the iopamidol molecule, the first ever non-ionic contrast medium for urography and angiography, in the 1970s. Iopamidol was the result of forty years of painstaking research and was destined to change the face of the contrast medium market completely. It is now used in over 110 countries, and over 100 million examinations have been performed using iopamidol since 1981, the year of its launch.

Internationalization

Iopamidol met with resounding success on markets world-wide and Bracco went from strength to strength. Penetrating international markets was now vital to maintaining development as the company prepared to enter the next millennium. The internationalization plan kicked off with the purchase of Sintetica S.A. of Switzerland, that then became the Swiss branch of the Group. The year was 1987.
A series of events followed:
· Dibra-now Bracco Imaging- was set up in Ceriano Laghetto in 1988 for the production of fine chemicals exclusively for export. The company uses leading edge technological and ecological solutions;
· Bracco Research S.A. was set up in Geneva, next to the Battelle Park, in 1989;
· Bracco International was created in 1991 to offer scientific support to international marketing initiatives;
· Joint venture agreements were signed in 1991 and 1993 respectively with Eisai for Japan, and the German company Byk-Gulden for the countries of Central Europe;
· A huge leap forward came in 1994 with the United States. In August of that year, an agreement was signed for purchase by Bracco of the Diagnostic Division of Bristol-Myers Squibb. Bracco Diagnostics Inc. and Bracco Research USA were then created.
· On December 13,1999 the Bracco family announced the acquisition of the Merck KGaA (Darmstradt) stake in the imaging and pharmaceutical business of the Bracco Group.
· In 2000, Bracco undertakes a strategic alliance with Dyax, an American biopharmaceutical company.
· In June 2001 Acist Medical Systems Inc., a leading US company operating in the field of advanced injection systems for contrast media, became a part of Bracco Group.
· In February 2002 Bracco announced to have taken the control of Volume Interactions, a Singapore company specialized in the development of advanced software applications for the medical field and to have drawn an exclusive agreement for collaboration and licensing with Ikonisys, an American biomedical company specialized in non-invasive systems for prenatal diagnosis of the Down Syndrome.

The three research centers

With the three research centers in Milan, Geneva and Princeton, Bracco created a high-quality, international research network, to satisfy the sophisticated requirements of modern diagnostic techniques, including magnetic resonance imaging, nuclear imaging and ultrasound imaging. The centers work in close cooperation, but also specialize in different technologies. Geneva is specialized in drug delivery technology, including liposomes, microballoons and stabilized microbubbles. These find application mostly in X-ray and ultrasound imaging modalities. Princeton has special expertise in products for nuclear medicine and magnetic resonance imaging. The center in Milan, which is the largest of the three, is specialized mostly in X-ray and magnetic resonance products. Moreover, it is the corporate development site for new chemical entities.
The research program includes - in December of 1995 - Bracco's investment in Esaote, a leading biomedical company of which Bracco is now the major shareholder. In July of 1999, Bracco and Esaote found Ebit S@nità, an initiative aimed at providing integrated solutions for the use of communications and information technology in healthcare.
This network represents perhaps the largest single research structure in the world wholly dedicated to contrast media study and to the development of new products for the sophisticated demands of new diagnostic techniques such as magnetic resonance and sonography.

The structure of the Group

The Bracco Group is split into three types of units:
· The business units: the companies responsible for promotion, development and sale of company products (Bracco Spa, Bracco Diagnostics Inc., Bracco-Eisai, Bracco-Byk Gulden, Bracco International).
· The production units: the companies supplying the Group with products (the Bracco, Bracco Imaging and Spin plants).
· The research units (Milan, Geneva and Princeton, USA): these are strategic units which support the present and, most importantly, prepare for the future.

Pharmaceuticals division

Bracco is also growing in importance in the pharmaceuticals and OTC sector. The pharmaceuticals division has both its own brand of over-the-counter products and products under license from prestigious international partners. Bracco is present in the OTC sector with well-known brand names.

New research activities

Recently Bracco initiated a new line of research aimed at using monoclonal antibody fragments for targeting of in vivo diagnostic imaging agents. To this effect it instituted collaborations with groups at the Universities of Siena and Rome. A biochemical laboratory staffed with Bracco personnel was placed at the San Raffaele Biomedical Science Park. It is dedicated to the identification of suitable products and their preparation under regulatory conditions that allow early phases of clinical trials. Monoclonal antibodies hold the promise of exquisite specificity of target recognition. This property is maintained in fragments thereof, e.g. F(ab) fragments. Antibodies and their fragments can also be obtained with widely differing affinities, which strongly influence their pharmacokinetic properties. For imaging applications such antibodies or their fragments must transport to the chosen biological target in the body a signal-generating moiety, such as a radioactive atom for scintigraphy, a paramagnetic chelate or iron oxide particle for magnetic resonance imaging or a stabilized gas bubble for ultrasound imaging. Ways of conjugating such signal-generating moieties to antibodies and their fragments have been found which maintain the affinity and specificity of the latter. While intravascular targets allow imaging agents of considerable size, including stabilized gas bubbles with diameters up to several micrometers, extravascular targets can only be reached by much smaller entities. Thus the choice of the signal-generating moiety and antibody-based vehicle is strongly influenced by the location of the target.
Location of the target and the chosen signal-generating moiety are important factors determining desirable pharmacokinetic properties of the product. The affinity of the antibody or its fragment is one of the parameters that must be tailored to achieve desired pharmacokinetics. There exists a considerable literature on imaging agents of the described kind. For lack of their sufficiently complete characterization and for lack of production methods that satisfy regulatory requirements most of these agents are limited to demonstrations of the involved principles in animals. Only a few of these products, mostly scintigraphic agents, have been studied in man. Even fewer commercial products for human use have been developed. Their clinical performance leaves ample room for improvement. In addition many new applications are possible. Bracco intends to combine in the new antibody-based products preexisting proprietary technology regarding signal-generating moieties with innovative antibodies and their fragments developed in collaboration with the mentioned universities.