ZoomLab® with integrated Nitrosamine Risk Assessment and Mitigation’ app

BASF has news for drug formulators! They introduced a new ‘Nitrosamine Risk Assessment and Mitigation’ app in ZoomLab®, their Virtual Pharma Assistant that helps you formulate faster. This new app allows users to do a risk assessment for nitrosamine drug substance-related impurities (NDSRIs) in their formulation.

The new app is available to all users free of charge for a test period. Generally it is a part of the ZoomLab® Premium Account portfolio.

NDSRIs are under increased regulatory scrutiny ever since N-Nitrosodimethylamin, a probable carcinogen, was found as an impurity in various batches of Valsartan in 2018. They can emerge as impurities during drug synthesis but can also form in a reaction with nitrite and a secondary or tertiary amine-structure within the active ingredient during drug product development and storage.

With their new app they offer a comprehensive approach that gives formulators access to the necessary tools to identify and mitigate the risk of NDSRI formation.

How does it work?

1. ZoomLab® helps you identify active ingredients that are susceptible to nitrosation and predict the most likely reaction products.
2. The acceptable intake of the predicted NDSRIs is then automatically assessed using the carcinogenic potency categorization approach (CPCA) introduced by global health regulators, such as EMA and FDA.
3. You can explore the potential impact of different formulations on nitrosamine formation directly within our app.

To get access to ZoomLab®, register here: https://zoomlab.com

Tutorial: Nitrosamine Risk Assessment

BASF’s Virtual Pharma Assistant ZoomLab® now includes two apps that help formulators assess the risk for nitrosamine formation in drug products.

The first app identifies active ingredients that are susceptible to nitrosation reactions and predicts the molecular structure of potential nitrosamine products. The predicted nitrosamines are then further assessed in a second app, which applies the carcinogenic potency categorization approach (CPCA) to determine an acceptable intake. Together with additional information about the drug product, such as the dose of the active ingredient, the tablet weight, the maximum daily dose, the nitrite content of the excipients and the overall tablet composition, the app estimates the contribution of each excipient to the potential nitrosamine intake. Different scenarios (e.g., direct compression or wet granulation) can be checked and compared to the previously defined acceptable daily intake.

Read more here and download the brochure here:

(click on the picture below)

Control nitrosamines with low nitrite excipients from BASF

More than 80 years ago, BASF invented PVPs, and we fully understand their chemistry. We have excipients with low
nitrites, particularly povidones (PVPs), copovidones and crospovidones.

Our povidones, copovidones and crospovidones have always been low nitrite grades with high lot-to-lot consistency.

You can continue using BASF excipients as-is:

• No efforts or costs in qualifying a new “low nitrite” or “controlled nitrite” grade.
• Assured supply chain resiliency since you can order povidone with low nitrites from any of our 3 global sites:
  USA, Germany and China.
• No need for costly reformulations.

We have measured, and not detected nitrites in our products.

Our LOQ and LODs are:

Povidones Kollidon® 30, 12 PF & 17 PF
LOQ = 0.1 ppm; Ion Chromatography

High molecular weight povidone Kollidon® 90 Evo,
copovidones (Kollidon® VA 64 & VA 64 Fine) and crospovidone Kollidon® CL grades
LOQ = 2 ppm and LOD < 0.7 ppm; Ion Chromatography

ABOUT NITROSAMINES

In pharma, nitrosamines are formed from the reaction of secondary or tertiary amines (usually from the API) with nitrites (from excipients or process impurities). There are two categories of nitrosamine impurities:

1. Nitrosamine Drug Substance-Related Impurities (NDSRIs) = formed from the API and its process impurities. Regulatory agencies have established acceptable intake (AI) limits for these. [1,2]
2. Nitrosamines from the formulation and drug product manufacturing process (impacted by water quality, high heat and humid processes, etc).

• Up to 40% of common APIs and 30% of API impurities can form NDSRIs. [3]
• Nitrites in excipients can lead to both types of nitrosamine impurities.
• As of 2023, the average nitrite

Read more here and download the full PDF here:

(click on the picture below)

Source: BASF

If you have any questions or need a sample of a product by BASF, please feel free to contact us at any time: