COMPANY BROCHURE

www.izotop.hu

Founded in 1959, the Institute of Isotopes of the Hungarian Academy of Sciences began to produce radioactive isotopes in 1964. It then became a major centre for the research, development and production of radioisotopes. With effect from 1993 a part of the former Institute has been operating as the Institute of Isotopes Co. Ltd.

OVERVIEW The company is divided into four major business units:

The main activities of the company cover the following fields: · Radiochemicals · Radiopharmaceuticals for diagnostic and therapeutical use · Cold kits for Tc labelling · Immunoassay kits available in a number of formats: RIA/IRMA, Kits for diagnostic purposes: thyroid assays, endocrinological assays, tumor markers, Down Syndrome, Kits for research purposes · Organic compounds labelled with 14C and 3H radioisotopes · Custom synthesis of 14C and 3H labelled compounds · Ir-192 and Co-60 sealed industrial sources · Irradiators, hot cells, hot-cell lines · Services in the field of radiation techniques

QUALITY AND SAFETY In accordance with our mission all activities are performed in compliance with ISO 9001 quality management system standard. The quality management system is certified by SGS Yarsley International Certification Services since 1998. In addition the production of in vivo pharmaceuticals is performed in compliance with requirements of GMP (Good Manufacturing Practice) which is regularly inspected by National Institute of Pharmacy and Nutrition/National Institute of Pharmacy. All in vitro diagnostic products have CE mark. PSA kits and kits for Down syndrome risk assessment are certified by notified body according to the relevant EU legislation. Immunoassay Business Line has certified quality management system according to ISO13485 standard for design, production and distribution of radioactive immunoassay kits. These certificates were issued by National Institute of Pharmacy and Nutrition/Directorate of Device Testing and Clinical Engineering. All our products, as well as their production, storage and delivery meet the strictest security requirements. Prevention of radioactive pollution of the environment is guaranteed by a multilevel safety system. Since 2012 we have IPPC licence and environmental management system is certified by SGS according to ISO 14001 standard as well.

SALES AND PURCHASE Institute of Isotopes distributes its products and services both to domestic and to export markets. Purchase of goods, raw materials needed for the production of import origin is also carried out here. Logistics, custom clearance, local door to door shipment and other related services are also arranged by us. Customer Service Telephone: +36 1 395-9081, +36 1 392-2577 · Fax: +36 1 395-9247, +36 1 392-2575 · [email protected]

www.izotop.hu

RADIOPHARMACY IN VIVO PRODUCTS FOR HUMAN DIAGNOSIS AND THERAPY IZOTOP's facility licensed for operating at a high level of radioactivity is located near to the Budapest research reactor. The level "A" isotope laboratory includes hot cell lines for the chemical and pharmaceutical processing of radionuclides. In addition, clean-room facilities in the radioactive and non-radioactive zones are available for production of radiopharmaceuticals and cold-kits, respectively. IZOTOP is a licensed company, possessing GMP Certificate for pharmaceutical preparation as well.

PRODUCTION OF RADIOISOTOPES

Radionuclides from neutron irradiation are mainly produced as raw materials for radiopharmaceuticals preparation (90Y, 125I, 131I, 153 Sm, 166Ho, 177Lu). These raw materials are also available as radiochemicals for various research purposes in life sciences and preclinical studies in pharmaceutical development.

IN VIVO RADIOPHARMACEUTICALS

The most often manufactured radiopharmaceuticals are the 131I sodium iodide solutions and capsules providing both the design of thyroid therapy and the thyroid treatment in hyperthyreosis as well as thyroid carcinoma. At the same time, 131I labelled metaiodo-benzyl-guanidin is used for the diagnosis and therapy of neuroendocrine tumours. 131I radiopharmaceuticals are produced on weekly basis. Cold kits for 99mTc-labelling fully meet the clinical requirements for studying renal, bone and hepatobiliary systems. DMSA provides excellent renal imaging as well as enabling the functional mass of kidneys to be determined. DTPA and EC (ethylene-L,L-dicysteine) are respectively used for studying the dynamics of the glomerular and tubular function. DTPA can also be used for liquor circulation studies. MDP is the most commonly used bone-seeking agent. Using IZOTOP's FYTON kit, the colloid which is formed in vivo enables both liver scintigraphy and the detection of internal bleeding. TECHIDA is a monitoring compound for studying the liver cell function and hepatobiliary excretion; PYRON is an agent for labelling red blood cells for blood-pool scintigraphy. PYRON is used for spleen scintigraphy, as well. EDTMP (Multibone) kit is manufactured for labelling either 90Y- or 153Sm-precursors to obtain agents for palliative therapy of painful bone metastases.

IMMUNOASSAY IN VITRO PRODUCTS FOR HUMAN DIAGNOSIS AND LIFE SCIENCE IZOTOP's Immunoassay business line is dedicated to develop, manufacture and supply high quality and cost effective products for clinical and research laboratory use. The first diagnostic tests developed by IZOTOP (at that time as a research institute of the Hungarian Academy of Sciences) were for pituitary hormones in the late 1970s. Some three decades on, our product range covers 50 different kinds of immunoassay kits and we have gained pride of place as Hungary's immunoassay producer. We produce broad range of immunoassay kits in RIA / IRMA formats covering assays in endocrinology, oncology and other fields of diagnostics. Our technology uses streptavidin coated surfaces (tubes and microplates) providing a simple, user-friendly separation method. Our in vitro diagnostic products are CE registered.

RADIOIMMUNOASSAY Tumor markers - This product group consists of assays for 11 different analytes. Total and free PSA IRMAs meet the most stringent requirements of experts in this field. These kits are certified by a notified body and CE marked according to European Directive on in vitro diagnostic medical devices, Annex II, List B requirements. CA 125, CA 19-9, CA 15-3, CYFRA 21.1 and CA 72-4 IRMA kits are newly developed by using Fujirebio gold-standard antibodies. Thyroid assays - These products represent the largest part of our immunoassay palette (TSH, FT3, FT4, T3, T4, TG, Calcitonin, T3Uptake, anti-TPO, anti-TG). As an example, we would call attention to our Turbo hTSH IRMA kit with an excellent functional sensitivity. Our competitive thyroid assays are robust, stable assays which don't require washing. Endocrinological assays - IZOTOP offers a great number of well-established endocrinological assays for measuring analytes such as GH, SHBG, C-peptide, Insulin, LH, FSH, Prolactin, Cortisol, Progesterone, DHEA-SO4. Prenatal screening – There are kits available for determination of biomarkers in first trimester (free βHCG, PAPP-A) and second trimester (direct total HCG, AFP, Unconjugated Estriol). These kits are certified by a notified body and CE marked according to European Directive on in vitro diagnostic medical devices, Annex II, List B requirements. Immunoassay kits for research – IZOTOP produces kits for determination of Rat Hormones. These are the following RIAs: rCorticosterone, rFSH, rGH, rLH, rPRL and rTSH. We produce also Rat Insulin and new developed Corticosterone ELISA kit. Solid phases – High binding capacity streptavidin coated products are available: 5 ml polystyrene tubes, magnetic particles, microtiter plates. Services – I-125 Labelling – Apart from immunoassay kits, we also offer I-125 labelling services for proteins and small molecules. Manufacturing – We can offer free capacity in the field of solid phase coating, component manufacturing. Developing – On the base of our experience we can offer our co-operation in assay/technology developing.

IZOTOP's Immunoassay Business Line focuses on what we do best: developing and manufacturing in vitro immunoassay kits of the highest quality.

SYNTHESIS CARBON-14 AND H-3 LABELLING Back to decades of activity on this field, more than thousand of organic compounds labelled with 14C or 3H radioisotopes have been synthesized for pharmacological, metabolism or environmental fate studies of drugs, pesticides, bioactive compounds, etc. Most of the labelled compounds synthesized during several decades are available as Catalogue items. A lof of C-14 labelled substances have also been produced as intermediates for other laboratories, some of them in large scale as well. Custom synthesis service of labelled compounds includes either the large-scale or the small-scale radiochemical total synthesis of the material with the required specification (position of labelling, specific activity, purity etc.) A detailed quality documentation and- upon agreement- the synthetic report are provided. A service for GMP syntheses of 14 C-labelled Active Pharmaceutical Ingredients (APIs or Drug Substances) and Investigational Medicinal Products (IMPs or Drug Products) will be available from the end of year 2015.

A Tritium Labelling Service is available to customers whose NRC license, facilities or safety concerns limit the amount of tritium that may be handled in their laboratories. The service includes the incorporation of tritium into target precursor, according to the customer's demand, the removal of catalyst and labile tritium from the crude product and the determination of total activity.

RADIATION TECHNIQUES · Manufacturing of radioactive sources, related services o Manufacturing of small and high activity Ir-192, Cs-137 and Co-60 sealed sources o Re-encapsulating of Ra/Be, Pu/Be, Am/Be sources · Manufacturing and servicing of the irradiators for the following purposes: o Multipurpose irradiators for commercial field o Research irradiators o Calibration irradiators o Manufacturing and servicing of NDT devices o Equipments for medical field o Manufacturing of PLC based control systems · Manufacturing of radiation protection systems o Manufacturing A and B(U) type transport containers for safe and secure transportation of radioactive material o Manufacturing of hot cells, storage boxes and whole body counters o Manufacturing of radiation protection walls, doors o Devices and systems for radiation protection · Radioactive Waste Management o Development of methods and technology o Preparation of feasibility studies, work plans o Environmental impact studies o Collection of radioactive waste, preparation for final deposition o Collection of disused radioactive sources · Irradiation test o Irradiation of samples (generally in the range of 0-5 MGy) o Morphology studies o Quality analyses o Examination of physical parameters · Transportation of radioactive materials o Transportation of small and high activity radioactive materials in specially designed containers of our company