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Navigating nitrosamine risk mitigation with confidence
Many research groups are investigating possible root causes of nitrosamine contamination in human drug products and potential mitigation strategies. The latest data includes a large in silico study that demonstrates the risk of contamination in drug products may be more common than previously thought, with 40.4% of active pharmaceutical ingredients (API) and 29.6% of API impurities presenting as potential nitrosamine precursors. Similarly, another research group found a new impurity known as NTTP (Nitroso-STG-19), which was detected above the acceptable intake limit in sitagliptin (anti-diabetic) medicines.
What’s more? Scientists have uncovered an additional root cause of nitrosamine impurities, beyond the API. The nitrocellulose primer in lidding foil can act as a nitrosating agent, and nitrosamines can transfer directly from the foil to the drug product during packaging. In addition, other nitrosating agents or nitrosamine precursors like nitrites have been found in excipients. Such emerging science, regulatory changes and additional documentation requirements can make it challenging for drug formulators and manufacturers to keep pace and develop optimized nitrosamine mitigation strategies.
Partnering for success
An effective nitrosamine mitigation strategy requires robust formulation, analytical, technical and regulatory expertise. However, many pharmaceutical companies may lack the infrastructure or experience to tackle nitrosamine risk mitigation alone. Therefore, a partnership can be the best time- and cost-efficient solution to bring safer formulations to market. Whether you require help throughout your nitrosamine mitigation journey, or specialized support for certain steps, the right partner can provide you with customized solutions to succeed in this complex landscape. So what should you look for in a partner?
Superior understanding of nitrosamine mitigation strategies
All companies must assess the risk of nitrosamine contamination in their drug products, as failure to do so could result in drug recalls, and potentially increase the risk of patients not receiving critical medication. If help is needed to assess nitrosamine risk, it is important to choose a partner that deeply understands the mitigation strategy you are aiming to implement.
Advanced formulation and technical expertise
Adapting the manufacturing process to formulate – or reformulate – new or existing drugs, requires extensive expertise. This is not something that can be learnt overnight, and therefore partnering with an expert that already has the knowledge and capabilities to assist your company is a valuable strategy. For instance, dsm-firmenich has the advanced formulation expertise to help manufacturers find an effective mitigation strategy according to their individual portfolio.
Established mitigation strategy
A partner offering a proven mitigation strategy means there is no need to reinvent the wheel when it comes to creating safer drug products. Various routes of nitrosamine risk mitigation exist, such as using antioxidants as excipients, which is a valuable and safe option to lower nitrosamine formation. Results from important studies have demonstrated that the antioxidants ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) can be leveraged to successfully mitigate nitrosamine formation. An added benefit of this strategy is that the antioxidants help stabilize and protect the API from degradation.
Formulators looking to use antioxidants to lower nitrosamines in drug products to below the accepted level require access to high-quality, pharma grade, GMP-certified antioxidant ingredients. With over 70 years of experience in manufacturing the secure supply of vitamins as APIs and excipients, dsm-firmenich has the right solution for your antioxidant needs. Beyond ingredients, dsm-firmenich can also support with pioneering solutions for reformulation, based on proprietary research.
Global regulatory insight
A global issue needs a global partner. To navigate the requirements of multiple regulatory agencies in various countries, as well as evolving legislations around nitrosamines, partnering with a worldwide company that can manage the necessary documentations and market entry registration processes helps companies enter the market with confidence.
Finding a reliable partner that can provide the technical guidance required to reformulate existing products or develop new formulations is key to the successful implementation of a proven nitrosamine risk mitigation strategy.
Anne-Cecile Bayne is the global science and innovation lead, pharma and medical nutrition at DSM-Firmenich.
Filed Under: Drug Discovery and Development, Regulatory affairs
