Information on production material imported from the Republic of Korea in 2013
Based on the newly received information, upon the Customs Office reported about infliximab, imported from the Republic of Korea, the Agency for Medicinal Products and Medical Devices (HALMED) hereby would like to provide information related to the production material from the Republic of Korea in 2013, that attracts great interest from the Croatian public and media and is being incorrectly associated to the revocation of the Zagreb Institute of Immunology’s manufacturing license.
There were no finished medicinal products or human vaccines to be used in Croatian patients, or any other alternative to products of the Zagreb Institute of Immunology, but an intermediate product for manufacturing , was imported, more precisely the active substance infliximab that has never been manufactured by the Zagreb Institute of Immunology. The biological substance infliximab is a monoclonal antibody used in manufacturing of a new generation so called "clever” biological medicines and cannot be in neither way associated with the products by the Zagreb Institute of Immunology, hence this manufacturer has never been producing neither this substance nor medicinal products or any other medicinal product intended to treat patients with the same indication as infliximab. Therefore, we are highlighting once again that the import of blood products from the Republic of Korea in 2013, that attracted great interest from the public, has not been associated with the revocation of the Zagreb Institute of Immunology’s manufacturing license.
The active substance infliximab is used for manufacturing biological medicinal products required by the European legislation to be authorised for all Member States centrally. This centrally authorised procedure results in one authorisation valid in all Member States and is carried out by the European Medicines Agency and the European Commission.
So, the large amount of the imported active substance from the Republic of Korea was not imported for the needs of the Croatian health sector, but for the needs of the entire European Union and it was imported to Croatia, where a part of the manufacturing process for the whole EU takes place. Namely, the intermediate product with the active substance infliximab is imported in the Republic of Croatia by the manufacturer that performs one part of the manufacturing, thereafter, the manufacturing of the finished medicinal product ready for human use is continued in another EU Member State and the manufacturer with a seat in another Member State is responsible for batch release on the European market.
For import of this intermediate product, no approval from Croatian institutions was needed, as under the current legislation, manufacturers of pharmaceuticals and vaccines may import the starting material necessary for further production based on the valid manufacturing license and they do not need individual additional licenses for import of individual starting materials or intermediate products. Under Article 128 of the Medicinal Products Act, for partial manufacturer of intermediate products or medicinal products by licensed manufacturer in the Republic of Croatia, no HALMED’s import/enter approval is needed. However, all starting material used in pharmaceutical manufacturing must be adequately controlled, but not through issuing of approval for import of stating material or intermediate products, but through inspection of manufacturing sites and assessment of the entire registration dossier before authorisation of every single medicinal product (as finished product from starting material) as well as by quality control testing before batch release and a number of additional off-shelf controls. In this case, the European Medicines Agency carries out a very strict control of quality, efficacy and safety of this biological medicine and all its components, including, of course, the active substance.
The active substance infliximab is a so called monoclonal antibody against tumour necrosis factor α (TNFα), the substance causing a strong inflammation in the body when secreted in large amounts. Therefore, infliximab is found as active substance in medicinal products for treatment of rheumatic diseases (i.e. rheumatic arthritis, spondiloarthropathy, psoriatic arthritis), chronic inflammatory gut disease (Crohn’s disease, ulcerative colitis), inflammatory skin diseases (i.e. psoriasis) and inflammatory diseases of other tissues and organs and only in those patients where conventional medicines may not achieve satisfactory result. It is evident, that the substance infliximab may not be substitute for products that the Zagreb institute of Immunology ceased to produce (human albumin, vaccine against tetanus, vaccine against diphtheria and tetanus, human immunoglobulin, human immunoglobulin against tetanus).
After the expiry of the Zagreb Institute of Immunology ‘s manufacturing license for production of medicinal products from human blood or plasma, animal sera and bacterial vaccines, HALMED informed the public on its webpages, on the caution assumption, on the possible shortage of medicinal product that are not any longer produced by the Zagreb Institute of Immunology. However, neither of these medicinal products has been imported from the Republic of Croatia and therefore HALMED repeatedly emphasized that the import from the Republic of Korea is not associated with the revocation of the Zagreb Institute of Immunology’s manufacturing license.
HALMED informed earlier that this import of blood products from the Republic of Korea in 2013 that attracted a great interest from the public did not refer to finished medicinal products or vaccines for use in patients in Croatia. In the meanwhile, newly received information confirm the import of starting material for the entire EU needs and not an import of finished medicinal products intended for the Croatian healthcare system.