Process-related impurities are undesirable substances found in biopharmaceutical samples. These chemicals can be cell substrates, come from the production process (e.g., nutritional medium, initiators of protein production and selection, chemicals utilized in further purification), or be the result of chemical alterations to the product.
Process-related impurities can be separated into three categories:
1. Impurities formed from cell substrates, such as host cell protein (HCP) or DNA.
2. Impurities from cell culture, including inducers, antibiotics, serum, and medium components.
3. Impurities from downstream processes, such as enzymes, reagents, and solvents.
Process Impurities, often referred to as Process-Related Impurities (PRIs), are substances that are introduced into a pharmaceutical product during the manufacturing process. They can originate from a variety of sources, including:
Raw Materials
Reaction Intermediates
Solvents and Reagents
Manufacturing Process
PRIs are frequently identified and quantified during the process development and quality control phases. Identifying and controlling these contaminants is crucial for guaranteeing pharmaceutical product purity and adhering to the ICH's regulatory standards.Quality control in biopharmaceutical manufacturing is mainly reliant on process-related impurities. Impurities introduced during the manufacturing process can have a significant impact on the quality, safety, and efficacy of pharmaceutical products.
Impurities can be formed during the bio-manufacturing process as a result of product degradation, starting materials and reagents, byproducts, storage conditions, and contamination. Process-related contaminants can have a negative impact on patients if not detected and quantified correctly. Some contaminants can be found at extremely low quantities, making identification and measurement challenging. Specialized procedures, such as pre-concentration and derivatization, may be required to increase the sensitivity of an analytical approach. Technologies must be selective enough to discriminate between contaminants and other components in a sample matrix. Such selectivity can impair the performance of an analytical procedure.
Matrix effects can interfere with the separation and detection of contaminants, needing additional processes to overcome them. Analytical validation procedures must be verified in order to assure accuracy, precision, and reliability. Validation processes are time-consuming, resource-intensive, and may necessitate the use of reference materials or standards. The lack of established procedures for identifying and measuring process-related contaminants might make it difficult to compare data from various laboratories and research. Standardizing methods and reference materials can assist laboratories enhance technique consistency and accuracy.