Heberkinasa: recombinant streptokinase.

I would like to comment about Heberkinasa (recombinant streptokinase): one of the preparations included in the article written by Dr Hermentin et al. 1 The quality control system of the Center of Genetic Engineering and Biotechnology has been successfully evaluated by the World Health Organization and another International Regulatory Organizations. The biological activity of the Heberkinasa batch 80010 was approved by our quality control laboratory with a value of 688 773 IU, using the clot lysis assay described in the British Pharmacopoeia of 1998 for the determination of potency of streptokinase. A secondary standard of recombinant strep-tokinase previously calibrated against the Second International Standard for the strep-tokinase (code 88/826) was used. We participated in the International Collaborative Study organized by the NIBSC for the establishment of the Third International Standard for Streptokinase (laboratory number 4). Our results 2 were similar to the ones obtained by the rest of the participant laboratories. We have compared a batch of streptase and kabikinase and a batch of Heberkinasa using the method described in the Pharmacopoeia and all the cases fulfil the established specification (potency is not less than 90% and not greater than 111%). Using other methods described in the literature to determine potency of several plasminogen activators, clear clot 3 and the chromogenic substrate (it does not use fibrin in the assay and for this reason it is considered as an indirect method), we have determined the biological activity of two different preparations of recombinant strep-tokinase (one of them Heberkinasa) and streptase. The Third International Standard for streptokinase was used for both the methods. Heberkinasa and streptase fulfil the specification of the British Farmacopea (90–111%) using the method of clear clot, unlike the other recombinant streptokinase. The same batches were evaluated with the chromogenic substrate and contradictory results were obtained with the recombinant streptokinase. With this method, Heberkinase does not pass; however, the other product containing recombinant streptokinase and streptase passes satisfactorily. Our conclusions are as follows: a recom-binant protein although differing by only one amino acid from the sequence of a natural protein is considered to be another product; therefore, it should be evaluated against standards of the same origin calibrated previously against the international standard using direct methods. The discrepancies between the potency claimed and that measured for several strep-tokinase preparations in the results published in this article are due to the employment of a method that uses as standard …