End to end CDMO services for the importation, encapsulation and distribution of T3S and Placebo for the LIONNS-D2 Trial

Tender description

The School of Medicine successfully applied for a UKRI grant to investigate in a randomised controlled trial (RCT), a new IMP (investigational medicinal product) called Triiodothyronine sulphate (T3S) in hypothyroid subjects with a gene difference in a thyroid related enzyme called deiodinase 2 (D2).<br />We are looking for a CDMO to (i) Import and QP sign off T3S and matched placebo tablets obtained from Ardena, Pamplona, Spain who will manufacture these to GMP standards; (ii) over encapsulate commercially secured L-thyroxine (LT4 ) and matched placebo capsules; (iii) store T3S and matched placebo obtained from Ardena, and over encapsulated LT4 and matched placebo; (iv) label T3S, LT4 and respective placebo packs for distribution to trial subjects; (v) distribute T3S and matched placebo and over encapsulated LT4 and matched placebo packs to trial pharmacy (Royal Glamorgan Hospital, Wales).<br /><br />Context of research<br />Hyopothyroidism, affecting 3-5% of the population, is usually treated with LT4 to which the vast majority respond. However, about 13-15% of them continue to have symptoms and a poor quality of life despite LT4 treatment. They have a deficiency of triiodothyronine (T3), the active thyroid hormone, at tissue level and should benefit from the addition of synthetic T3 called liothyronine (LT3). But current LT3 preparations are short acting, unphysiological and are clinically inappropriate. Therefore all 16 randomised clinical trials (RCT) hitherto of LT3, using short acting LT3, have been inconclusive. We believe this new preparation, T3S which is a long acting LT3, is a more physiological and better option and wish to try this in a randomised controlled trial (RCT) in a group of hypothyroid subjects with the D2 gene difference which makes them better responsive to LT3 treatment. <br />Unfortunately, at present there is no commercial producer of T3S. We have had extensive advanced discussions with CDMOs (companies that produce drugs for clinical use) who are able to manufacture this drug if the Investigator’s Brochure (IB) and Investigational Medicinal Product Dossier (IMPD) are available from the original producers of this drug, Bracco Ltd. Following these discussions we have identified a company named Ardena NV, Pamplona, Spain, who are able to produce <br />(i) the active pharmaceutical ingredient (API) and <br />(ii) the investigational medicinal product (IMP), and <br />(iii) the finished drug formulation (FDF) i.e. they are able to manufacture the drug from raw materials to the finished product ready for clinical use. <br />They are also able to package the FDF in blister packs for use by participants in the LIONNS-D2 RCT. All these activities will be done to GMP standards. <br />Ardena is able to <br />i) source raw materials from an existing supplier <br />ii) manufacture the API (Active Pharmaceutical Ingredient) to GMP compliance status and <br />iii) manufacture the IMP (Investigational Medicinal Product) to GMP compliance and QP regulatory status.<br />We now require a CDMO able to handle the activities detailed in paragraph 2, after Ardena have manufactured and packed T3S and matched placebo, ready for importation to the UK.<br />