Potential toxic chemicals and carcinogens in treatment drugs are one of the biggest problems to plague Active Pharmaceutical Ingredient (API) manufacturing. Because of this, one of the most important tasks of any manufacturer is to identify impurities before they impact the quality, efficacy and safety of drugs, as well as cause costly project delays.
Analyzing the levels of impurities and the physical, structural and behavioral attributes of these impurities in APIs helps to identify the potential cause of variations in the finished product during drug development and formulation. It’s also useful in spotting potential problems when evaluating new suppliers, changing or adding manufacturing sites, or scaling up production. Properly identifying impurities before making potentially critical manufacturing decisions will more often than not save time and money further down the line and help prevent API waste or prevent failure during clinical trials.
Definition
Impurities are chemical substances inside a confined amount of a sample which differ from the chemical composition of the material or compound of interest. Impurities are either naturally occurring or formed during the synthesis of a chemical compound. It is virtually impossible to have a molecular substance that is 100 percent pure and free of impurities. The goal for most manufacturers is to exceed the 99 percent range.
Impurities in raw materials
Impurities in Process Manufacturing
Another place where impurities can come from is in the process itself. Any impurities in the drug substance will then be introduced into the drug product.
The origin of the compound may also determine which guidelines to follow in the final evaluation of the drug impurity. Relevant guidelines include ICH Q3A (Impurities in New Drug Substances), ICH Q3B (Impurities in New Drug Products), ICH Q3C (Impurities: Guideline for Residual Solvents), and ICH M7 (Assessment and control of DNA reactive impurities in pharmaceuticals to limit potential carcinogenic risk).
According to ICH guidelines, if there are impurities in the range of .15 or higher, or compounds that are less than 98 percent pure, the impurities have to be identified and evaluated for potential toxicity.
If the presence of a compound – at the detected concentrations – would pose an unacceptable risk to the patient, or if it would seriously compromise the quality or efficacy of the drug product, it is clear that necessary steps should be taken to reduce, or eliminate the presence of this impurity.
In a lot of cases, however, the presence of the compound may not pose any safety, quality or efficacy issues for the drug product. In that case, proper documentation of the impurity (its identity, concentration, toxicological evaluation and quality impact) may be sufficient.
Identifying and eliminating as many impurities as possible is key to safe and successful product commercialization. Properly vetting suppliers and conducting testing throughout process manufacturing can identify impurity levels before they result in the loss of costly raw materials and the need to duplicate key steps.