Risk-based approach to assessing the content of elements with undefined permitted daily exposure in biological origin drugs

When evaluating the risk of elemental impurities for which no permitted daily exposure (PDE) has been established, but which are present in a medicinal product, it is necessary to comply with requirements regarding the permitted content of such elements as specified in the relevant regulatory documents. The elements with undefined PDE are characterized by reference exposure doses (RfD), exceeding which is associated with a non-carcinogenic risk.

Objective - based on a generalization of requirements from regulatory documents of manufacturers of human albumin, blood clotting factors and insulin, to permissible content of elements with undefined PDE, assess the non-carcinogenic risks of their negative effects on the human body.

Materials and methods. The object of the study is the regulatory documentation of manufacturers of human albumin, blood clotting factors and insulin, materials from national and regional pharmacopoeias, the State Register of Medicines. The work used an information-analytical research method.

Results. An analysis and generalization of the requirements of regulatory documentation from manufacturers regarding the permissible content of elements with undefined PDE (K, Na, Al for albumins; Ca, Na, Al - for human blood clotting factors; Zn - for insulins) and corresponding methods for their determination was conducted. An assessment of non-carcinogenic risks of adverse effects was carried out for Al and Zn.

Conclusion. It was established that the impact of Al and Zn on human health when consuming maximum therapeutic doses of these drugs is characterized as acceptable and does not pose a risk of developing non-carcinogenic effects. The use of a pharmacopoeial method for determination of Al in albumin leads to the risk of obtaining false negative results.

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