Drug Manufacturing and Stability Information based on European Drug Filings

dexmedetomidine hydrochloride with Brand Name Dexdor
made by Orion Corporation

Manufacturing info This Manufacturing process consists of the following steps: mixing and dissolution of ingredients, filtration, filing, terminal sterilization, inspection of ampoules/vials, assembly process (labeling and packaging).The critical steps of this particular manufacturing process have been identified and optimised during drug development. Satisfactory process validation data have been provided for the major steps of the manufacturing process. The batch analysis results show that the medicinal product can be manufactured reproducibly according to the agreed finished product. 2.2.3.3. Product specification The product specification is standard for concentrate for solution for infusion and contains tests with suitable limits for colour of solution (Ph.Eur), clarity of solution (Ph.Eur), particulate matter (Ph.Eur), extractable volume (Ph.Eur), pH (Ph.Eur), identification of dexmedetomidine (HPLC, UV), assay (HPLC), optical purity, impurities (HPLC), assay of sodium chloride, test for sterility (Ph.Eur) and bacterial endotoxins (Ph.Eur). Impurities and degradation products have been evaluated and found to be acceptable from the point of view of safety. All analytical procedures that were used for testing the finished product were properly described and satisfactorily validated in accordance with the relevant ICH guidelines. The batch analysis data for 5 production scale batches confirm that the concentrate for solution for infusion can be manufactured reproducibly according to the agreed finished product specifications. 2.2.3.4. Stability of the product Stability studies under ICH long-term and accelerated conditions (i.e. 25C/60% RH and 40C/75% RH) have been carried out for pilot and production batches covering all three proposed presentations (200 g/2 ml, 400 g/4 ml and 1000 g/10 ml). The results of the following tests were submitted: appearance (colour and clarity of solution), impurities, assay, pH, microbiological purity (Ph.Eur) and optical purity. The analytical methods used for the stability studies are identical with the methods proposed for routine testing of the finished product. During the stability studies the product did not show any significant change in its quality. All the results remained well within the specification limits during all the stability studies. A Photostability testing program was conducted in accordance with the recommendations of ICH guideline Q1B. The results were found to meet the specifications and the finished product does not require any special light protection. The stability of Dexmedetomidine 100 ?g/ml concentrate for solution for infusion has been evaluated on repeated freezing and thawing. The freeze-thaw study of Dexmedetomidine 100 ?g/ml concentrate for solution for infusion was carried out by storing 2 ml ampoules in a freezer at approximately -20 C at least for 24 hours. Freezing and thawing was carried out four times. All results complied with the specification confirming that repeated freezing and thawing does not have an impact on the quality and stability of the finished product. and Stability info Stability studies under ICH long-term and accelerated conditions (i.e. 25C/60% RH and 40C/75% RH) have been carried out for pilot and production batches covering all three proposed presentations (200 g/2 ml, 400 g/4 ml and 1000 g/10 ml). The results of the following tests were submitted: appearance (colour and clarity of solution), impurities, assay, pH, microbiological purity (Ph.Eur) and optical purity. The analytical methods used for the stability studies are identical with the methods proposed for routine testing of the finished product. During the stability studies the product did not show any significant change in its quality. All the results remained well within the specification limits during all the stability studies. A Photostability testing program was conducted in accordance with the recommendations of ICH guideline Q1B. The results were found to meet the specifications and the finished product does not require any special light protection. The stability of Dexmedetomidine 100 ?g/ml concentrate for solution for infusion has been evaluated on repeated freezing and thawing. The freeze-thaw study of Dexmedetomidine 100 ?g/ml concentrate for solution for infusion was carried out by storing 2 ml ampoules in a freezer at approximately -20 C at least for 24 hours. Freezing and thawing was carried out four times. All results complied with the specification confirming that repeated freezing and thawing does not have an impact on the quality and stability of the finished product.

dexmedetomidine with Brand Name Dexmedetomidine Accord
made by Accord Healthcare S.L.U.

Manufacturing info and Stability info Stability data from 3 commercial scale batches of finished product of each presentation stored for up to 12 months under long term conditions (25 C / 60% RH) and for up to 6 months under accelerated conditions (40 C / 75% RH) according to the ICH guidelines were provided. The batches of medicinal product are identical to those proposed for marketing and were packed in the primary packaging proposed for marketing. No significant changes have been observed on the data provided. Photostability studies for one batch were performed according to ICH Q1B. The testing was conducted on the final marketable product using the marketable pack. In accordance with EU GMP guidelines2, any confirmed out-of-specification result, or significant negative trend, should be reported to the Rapporteur and EMA. 26.32