Biotechnology Product Instability

A recent client experienced difficulties in stabilizing one of the products for almost 20 years. It gave indications occasionally for aggregations and instability. Nearly all of their products were sold abroad for many years. Still, the chemists have not been able to find a solution for this particular one. All employees, including salespeople, were very much concerned about it because it was indeed one of their best products.

Our first observations showed that the scaling up of the ingredients was not correctly done — all they have been estimated based on the gram, not mall calculations. Of particular importance was the estimation of the buffer substances, which was the main reason for instability in this specific case.

Going further, we figured out other details typical for the everyday practice observed in the industry. For example, in life science, we use raw materials for internal use with varying amounts of active ingredients (AIs). If we do not know the exact amount of the AI and the nature of the impurities, the probability of reproducing the original R&D product is very low. Often, the AI in the trade product exists under the same name, but the chemical formula is different.

Working in close cooperation with both external and internal suppliers and chemists in the company was one of the critical needs to overcome deviations of the product formulations. To this end, extensive training in chemistry fundamentals and QMS/QbD principles helps to understand the need to pay attention to specific details and thus avoid undesired inconsistency of the product from batch-to-batch. 

QbD fundamentals

Thousands of litres per batch have been lost for 20 years manufacturing the product. The costs of defects haven’t been calculated, as happens when a QMS/QbD program is not adopted in the house. QMS/QbD is still not considered as a regulatory requirement, but all its principles are applicable to get high-quality products at lower costs. Therefore, regulatory authorities gradually increase their focus on step-by-step QMS/QbD adoption in the industry-wide spectrum.