Development of Positron Emission Tomography (PET) precursor.

Project’s background: Positron emission tomography/Computed Tomography (PET/CT-scanning) is becoming the most versatile diagnostic tool for early/metastatic cancer detection as well as examination of Parkinson and Alzheimer patients. Nuclear medicine procedures are capable of mapping physiological function and metabolic activity and thereby giving specific information about the organs. The Project partners TBD-Biodiscovery and PharmIdea have acquired all the competence and experience necessary to enter the PET diagnostic market: production of active ingredients and final dosage drug forms. Both partners are business-driven enterprises with a mission, focusing on both rewarding sales to the customers and making the product available for end-users — oncology and neurology patients in Estonia and Latvia. The outcome of the Project is final dosage form of the PET-product with all the documentation package, necessary for its implementation in nuclear medicine centers and hospitals. After the first Product is developed and marketed, TBD and PharmIdea plan to continue the cooperation and develop the next PET-products for oncology studies, studies of Alzheimer and Parkinson disease and seek the marketing channels to reach the hospitals worlwide. Project’s cross-border nature: Application of PET-radiopharmaceuticals for use in patients is subject to strict legislation. In the European Union, all steps in the manufacturing of PET-products are to be produced under Good Manufacturing Practices regulations. The PET-product is to be manufactured in two parts: firstly the chemical steps and then the production of final dosage drug form. TBD-Biodiscovery has all the necessary competence in GMP-manufacturing of chemicals and is also the only company in Estonia with the GMP certificate for the production of pharmaceutical ingredients. TBD does not have any facility for the production of final dosage drug forms. Vice versa, PharmIdea is a Latvian contract manufacturer of final dosage drug forms under GMP regulations and in sterile environment, but Pharmidea does not perform the chemical steps. The alliance between two companies is very natural. The outcome of the Project is the PET-product (final dosage form) with all necessary documentation package, ready to be implemented firstly in the brand new Latvian Centre of Nuclear Medicine and also Tallinn North-West Hospital Radiology department.

The Project has significant added value: it will increase the level of medicine services in Baltic region. The oncology and neurology patients will be provided with all necessary medical investigations at home country with no need to travel abroad. During the Project, new jobs will be created in Latvia and Estonia.

The common benefit of both partners is to have long-term contracts with Baltic hospitals, increasing turnovers and companies’ profits. Project’s objectives: The main objective of the Project is to develop a PET-product used in Positron emission tomography-computer tomography (PET-CT) for cancer, Alzheimer or Parkinson diagnostics. This Product will be created as a result of very tight cross-border cooperation between Estonian and Latvian companies TBD-Biodiscovery and PharmIdea. The second objective of the Project is to manufacture the Product ready for marketing and commercialization. The Estonian and Latvian hospitals are considered to be the first and the most valuable partners for implementation of the PET-product. Both partners realize that there are more than 30000 cancer patients in Estonia and 75000 in Latvia, and hope to address a significant portion of those patients, making the modern diagnostic tools more available and cheaper. The highest challenge here is to reduce the mortality for the cancer patients, especially for the ones having already metastatic cancer: the efficient treatment of small tumors is impossible without having good approach to diagnostics. The third objective of the Project is to fully explore cooperation between Estonian and Latvian partner. After the Project is completed, TBD and PharmIdea plan to continue their cooperation and develop a set of PET-products for oncology and neurology diagnostics. The current Project is a start of a much bigger collaboration on international level with special attention to the needs of Latvia and Estonia. Project’s main activities: To select the most promising PET-product, partners have to perform market studies and patent research. After the product is selected, TBD will immediately undertake the technology development. The goal is to obtain general method of manufacturing and to be ready to go to GMP level (Good Manufacturing Practice) at the next stage. PharmIdea will develop the quality control methods for PET-product. TBD will proceed with the GMP-validation of the manufacturing process with support of PharmIdea in quality controls. PharmIdea will also develop the final dosage form of the PET-product, followed by GMP-validation of this process. These activities will ensure the quality of the PET-product. GMP-documentation such as ASMF (Active Substance Master File) will be compiled by both partners. During the stability studies a lot of information on the real durability of both the pharmaceutical substance (PET precursor) and its final dosage form (lyophilized in vial) will be obtained. As a result of the activities, partners will select, develop and manufacture PET-product with full package of documentation, ready to be implemented in hospitals.

Positron emission tomography/computed tomography (PET/CT-scanning) is becoming the most versatile diagnostic tool for early/metastatic cancer detection as well as an examination of Parkinson and Alzheimer's patients. The project partners TBD-Biodiscovery (Estonia) and PharmIdea (Latvia) have the competences and experience necessary to enter the PET diagnostic market: production of active ingredients and final dosage drug forms. The aim of the project was to develop technology for the production of the PET precursor for diagnostics. This molecule can be used for the early diagnosis of prostate cancer, one of the most common cancers in men in Europe and worldwide. In addition to early diagnosis, PET prcursor could be used in patient health control for remission (after chemotherapy or radiation therapy) and for the diagnosis of small metastatic tumors in advanced cancer. TBD-Biodiscovery was responsible for the development of the production method and GMP validation, and PharmIdea continued to develop quality control methods and stability studies. The outcome of the project is the final dosage form of the PET-product with the package of supporting documentation, necessary for its implementation in nuclear medicine centers and hospitals. Achievements of the project: Collection of the market, patent, and scientific data in close cooperation of partners, Final selection of PET-product, which has full freedom to operate in the European Union and worldwide and preparation of several intermediates and building blocks for the synthesis of PET precursor, Synthesized first samples of the PET-product, used for early diagnostics of prostate cancer, and fully identified structure using modern analytical methods, Successful process validation and development of an analytical method for both the PET-product and its drug form, Successful technological process development and validation for the production of PET products which can be implemented for routine production in the future, Successful compilation of CTD Module 3 documentation, Starting and continuing the stability studies, both short term, and long term, Organization of the biotech/pharma matchmaking event in Riga (Latvia). To reach the general public, TBD-Biodiscovery contacted multiple hospitals, science centers, and research facilities and different unions (e.g. cancer societies, doctor societies), in total 200 different facilities were contacted. Also, both partners have actively looked for innovative companies already active in the area of nuclear medicine or developing new products/methods for PET-diagnostics and big pharma companies looking for new products with high added value.

The objective of the Project is to jointly develop the PET-product for diagnostics of oncology or neurology diseases, using competences and strengths of two companies, TBD-Biodiscovery and PharmIdea. In the WP1, TBD and PharmIdea will select the best PET-product to develop. The contributions of both partners are needed: e.g. TBD will perform the market/patent research and analyze the synthetic methods. PharmIdea will consult TBD on the market study and pharmaceutical requirements and will also contact the doctors from Latvian Centre of Nuclear Medicine. According to EU legislation, PET radiopharmaceuticals are considered to be drugs. A series of regulatory and legal aspects have to be followed prior to release for human application. Production of PET-products by chemical synthesis and manufacturing of final dosage form have to be performed in full compliance with very strict GMP regulations. Both partners are needed to complete the Project. Immediately the precursor is selected, the experimental work will be launched. TBD will develop and manufacture the PET-product in accordance with GMP guidelines while PharmIdea will develop analytical methods necessary to ensure the quality of the product. In the WP2 PharmIdea will develop the final dosage form. The GMP-development and GMP-validation will be performed by TBD and Pharmidea. TBD will focus on the manufacturing process using the chemical synthesis and Pharmidea will assist TBD in the quality issues and analytical validations. After validation batches of PET-product are produced by TBD, PharmIdea will use them for the validation of final dosage manufacturing process. In the WP3 both partners will compile the GMP-documentation, which requires cooperation of production and quality specialists from both sides. Therefore, both the technology development and pharmaceutical documentation require specific competences and equipment that can be provided only by joining resources of both project partners.