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In addition to physicochemical, content/activity, and other items, the quality standards for the full inspection of pharmaceutical excipients used in the production of biologics injections by biologics manufacturers should include routine safety tests, such as microbial limit or sterility tests, pyrogen and/or bacterial endotoxin tests, abnormal toxicity tests, etc.
Such excipients are biological products or sterile pharmaceutical preparations that have obtained marketing authorization, such as human serum albumin, heparin sodium, and sodium chloride injection.
Low-risk excipients
Such excipients are chemical APIs produced in accordance with the existing national drug standards, obtained the national drug Approval number and in accordance with the current Chinese Drug Production Quality Management Standard, such as various inorganic and organic chemical APIs.
Medium risk excipients
These kinds of auxiliary materials are non-animal-derived pharmaceutical auxiliary materials that are manufactured in accordance with the "Quality Management Standards for Pharmaceutical Auxiliary Materials" and obtained the approval number of national pharmaceutical auxiliary materials or managed according to the national record. Such as used as the diluent, buffer preparation of all kinds of chemical materials, used as a protective agent/stabilizer of all kinds of sugars, used as bacteriostatic thiomersal, and ointment matrix of single, double stearic acid triglyceride ester. Its quality control requirements should be higher than the first two grades of material.
High-risk excipients
Prior to the use of such excipients in the production of biological products, strict comprehensive quality tests shall be carried out and further treatment measures shall be taken if necessary, including:
(1) Improve the production process of auxiliary materials;
(2) Excipients are processed to improve the purity of excipients and inactivate and/or remove exogenous factors, pathogenic substances, or specific pollutants (such as animal viruses, prion proteins, etc.).
If there are several risk levels of the same excipient, the excipients with low-risk levels should be selected according to the characteristics of biological products and the production process.
For excipients of high-risk grade, the necessity of using these excipients should be evaluated early in product development and alternatives or alternative sources should be sought.
(1) The dosage of excipients in the formulation of biological products should be determined with the minimum dosage to play an effective role according to the safety and effectiveness research results of the preparation process and products.
(2) For excipients with clear functions that can be tested by appropriate methods, the addition of excipients in the formula should be considered comprehensively based on the performance test results of excipients, such as bacteriostatic efficacy test of bacteriostatic agents and antigen adsorption effect test of vaccine adjuvants.
(3) For excipients with toxic side effects or specific functions and other excipients that need to be controlled in biological products, the excipients content inspection items and limit requirements should be set in the finished product verification or appropriate intermediate product stage.
