@Naiffer_Host
Hi Naiffer,
Though the title of this thread is Most burning challenge for API manufacturers, we are discussing about Nitrosamines in excipients which is a challenge for MAHs since many excipient suppliers are unable to provide this information. I tried if it was possible to edit the title but was unable to locate the option.
The approach that is being adopted is multidimensional since MAHs are not excipient mfrs and do not possess the knowledge of the excipient process and related controls , moreso many excipients are obtained from natural sources so assessing for Nitrosamines in them is also a challenge, nevertheless this needs to be done.
1)This requires extensive collaboration, knowledge sharing and sensitising the excipient manufacturers with respect to significance of assessing Nitrosamines in excipients . It also requires availability of resources like SMEs, Analytical capabilities at excipient mfrs end. This consumes time yet suppliers have started working on these aspects. Some of them are subcontracting the Analytical testing activities to a third party
2)Till date there’s no guidance document from any Regulatory agency on this topic. IPEC Europe n Americas have guidance documents available on this topic and these are being used as the basis of evaluating Nitrosamines risk assessments by suppliers. BASF has an Online link available for accessing this information , this is an excellent example of a proactive approach to collaborate with MAHs
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From the mfrs perspective, it is important rather mandatory to include evaluation of Nitrosamines in the Drug substance, product in the product development phase as a part of Quality by design approach to avoid expensive Product Recalls later especially in today’s times in a pandemic where drug supply chain shortages owing to these issues can prove detrimental to public health. Excipients and Primary pkg materials need to be evaluated for the information on Nitrosamines from the mfrs or suppliers before taking a decision on selecting them. The Nitrosamine assessment approach should also be performed for products in the market post approval where ICH Q12 concepts can be applied in context of Lifecycle mgt of Products n methods.
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Assessment of including Nitrosamine evaluation is being included in vendor qualification programmes by MAHs. Inability to provide this info by excipient n primary pkg material suppliers will eventually translate into loss of business because a MAH would not wish to collaborate with a supplier who is unable to provide assurance of the presence/absence of Nitrosamines in their products.
Since this is an evolving n emerging area for Industry wrt evaluation of Nitrosamines and the Analytical Technologies being employed , probably it would take some time for Industry to have a complete package available but it’s not impossible. What is needed at this time is collaboration between Regulators & Industry to have a comprehensive approach for assessment, testing not only in APIs n products but also extended to excipients and primary pkg materials. IPEC and Excipact collaborations can aid in achieving thos goal as these bodies govern the excipient mfrs and inclusion of Nitrosamine assessment n controls in Excipact certification pr9grammes can help immensely
The agencies are doing an excellent job of educating the Industry in terms of assessing Nitrosamines in substances and products. EDQM recently concluded a very detailed training programme on Impurities that also had presentations on Nitrosamines n mutagenic Imps and Interpretation of ICH M7