Control of Classification and Limits of Biological Products Manufacturing Excipients

For the production of biological products injections by biological product manufacturing enterprises, medicinal excipients are used. In addition to the items such as physical and chemical properties, content and activity in its quality standards, routine safety checks should be included such as microbiological or sterility checks, pyrogen and/or bacterial endotoxin checks, and abnormal toxicity checks.

The first level of excipients is of relatively low risk

This type of excipient is a sterile bio product or pharmaceutical preparation that has been granted market approval, such as human serum albumin, heparin sodium and sodium chloride injection solution and other buffered electrolyte salts excipients.

The second level of excipients is of low risk

This type of excipient is a chemical raw material that meets the national drug standards, has obtained a national drug approval number, and is produced in accordance with China's current "Drug Production Quality Management Regulations," such as various inorganic and organic chemical raw materials.

The third level of excipients is of moderate risk

This type of excipient is produced in accordance with the "Quality Management Regulations for Pharmaceutical Excipients," with a national pharmaceutical excipient approval number or a non-animal source pharmaceutical excipient record managed by the state. Such as chemical materials used as diluents, buffering agents, various sugars used as maintainers/stabilizers, thiomersal used as antimicrobial agent and monostearate/di-stearate glycerides used as ointment matrices, etc. Their quality control requirements should be higher than those of the first two levels of materials.

The fourth level of excipients is of high risk

This type of pharmaceutical excipients wholesale should be subjected to strict and comprehensive quality testing before being used in the production of biological products, and necessary processing measures should be taken, including:

• Improvement of the production process of excipients;

• The excipients should be processed to increase the purity, inactivate and/or remove external factors, pathogenic substances, or specific contaminants (such as animal viruses, prions, etc.).

When there are several risk levels of the same excipient, excipients with lower risk levels should be selected according to the characteristics of the biological product and its production process.

For high-risk level excipients, in the early stage of product development, it is necessary to evaluate the use of these excipients and search for alternative materials or sources.

Control of excipient restrictions

• The addition of excipients in the formulation should be determined based on the results of studies on the production process and safety and effectiveness of the biological product, with the minimum effective dose being used.

• For excipients that have a specific function and whose performance can be tested appropriately, the amount of excipients added to the formulation should be considered in combination with the performance test results of the excipient, such as antimicrobial efficacy testing for antimicrobial agents or antigen adsorption testing for vaccine adjuvants, etc.