Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Preparation of a specification and description of the process validation on the manufacturing process of biological active substance streptokinase as part of the drug master file for the EU ***

Nicola Leven (Abschlußjahr: 2023)

Summary
Language: English
Streptokinase is produced by BBT Biotech GmbH as an API for low regulated markets. Since on the one hand the requirements of the authorities in the non-regulated countries are currently increasing significantly and are becoming more and more similar to the European regulations and on the other hand the demand for thrombolytics from regulated countries is increasing, it is necessary to adapt the approval documents. In order to meet the requirements of the EU both from a GMP and regulatory point of view and to be able to obtain approval in European countries, a prospective process validation was performed on three consecutive batches of streptokinase API according to the described guidelines. Streptokinase is a thrombolytic which converts human plasminogen non-pro-teolytically to plasmin. Plasmin is a key enzyme in the human coagulation cascade that dissolves fibrin and consequently lyses an existing blood clot.
Since the first upstream steps are done by the Japanese supplier, only the manufacturing steps (downstream) carried out at BBT Biotech GmbH were considered and validated. A specification containing all CQAs was defined according to European Pharmacopoeia as well as ICH guidelines. Moreover, all CPPs were also defined on the basis of a risk analysis in form of a FMEA. Possible impurities were also addressed and these were also considered during validation.
The validation was carried out against a validation plan and all results were summarised in a validation report. The validation was successfully conducted. All CPPs as well as CQAs were within the predefined specification limits.
Pages: 52
Annexes: 3, Pages: 50