FDA and the Center for Research on Complex Generics (CRCG) will host a public workshop on June 15, 2023: Mitigation Strategies for Nitrosamine Drug Substance Related Impurities: Quality and Bioequivalence Considerations for Generic Products
Workshop Date and Time:
June 15, 2023; 8:30 a.m. – 5:30 p.m.
Registration:
Register now. Registration will close June 5 at 5:00 p.m. (ET) for in-person attendance and June 15 at 7:00 p.m. (ET) for virtual attendance.
The cost for in-person attendance is $250 and will cover event-related expenses. This workshop is free for virtual attendees.
For faculty and students from the University of Maryland, Baltimore; Universities at Shady Grove; and University of Michigan, the workshop is free for in-person attendance. Please contact us and indicate which workshop you are interested in.
Continuing education (CE) credits will not be provided for attending this workshop. A certificate of attendance will only be provided to individuals attending the workshop in-person.
About the Event:
The presence of N-nitrosamines in drug products can be a potential health concern. Some N-nitrosamines may increase the risk of cancer if people are exposed to them above acceptable intake limits and over long periods of time. Since the recent findings of N-nitrosamines in some types of drug products and considering their potential harmful effects to human health, regulatory agencies and drug manufacturers have been working continuously to understand the root causes of N-nitrosamine formation, assess the risks of N-nitrosamines, for human health, and take appropriate actions to reduce or prevent the presence of N-nitrosamines in active pharmaceutical ingredients (APIs) and drug products. N-nitrosamine drug substance related impurities (NDSRIs) are a class of N-nitrosamine sharing structural similarity to the API (having API or API sub-fragment in the chemical structures) that are receiving considerable attention among regulatory authorities.
The purpose of this workshop is to discuss the risks of forming NDSRIs in certain drug products, strategies to mitigate these risks, and considerations in assessing the safety risks of NDSRIs. The workshop will also discuss approaches to prevent or mitigate the formation of such impurities, for example, by adding a suitable antioxidant and/or pH modifier to drug products. Finally, the workshop will discuss the potential impacts of such reformulation on the bioequivalence of generic products, and strategies to efficiently address these issues.
Hybrid Experience:
The workshop will offer both in-person and virtual attendance options. The event will be held at the Universities at Shady Grove in Rockville, Maryland.
For those attending virtually, information on accessing the Zoom webinar can be found in the registration confirmation email or other emails from Zoom. If you have trouble accessing the virtual workshop, please email info@complexgenerics.org.
Workshop Topics:
- Reviewing the risk factors from APIs, excipients and/or manufacturing processes in the formation of NDSRIs and strategies to mitigate these risks
- Reviewing considerations in assessing the safety risks of NDSRIs
- Discussing the potential impacts of reformulation on the bioequivalence of generic products and strategies to efficiently address these issues
FDA and the Center for Research on Complex Generics (which is a collaboration between the University of Maryland School of Pharmacy and the University of Michigan College of Pharmacy) are dedicated to advancing programs that stimulate scientific dialogue, disseminate current insights about complex generics, and generate new knowledge in support of FDA’s mission to promote and protect the public health by increasing access to safe and effective generic medicines.
Audience:
This workshop is primarily for the generic drug industry and other involved collaborators, including consultants and contract research organizations that support generic drug applications.
Workshop Outline:
Introduction to the Workshop
The introduction to the workshop will be a brief overview on the interrelation of the risk of formation and possible mitigation approaches to prevent or mitigate NDSRIs, considerations in assessing the safety risks of NDSRIs, and the potential impact of reformulation on the bioequivalence of generic products.
- Presentation by expert from FDA
Session 1: Risk of Forming NDSRIs and Strategies to Mitigate the Risk
This session will discuss the risk factors from both the API and excipients in the formation of NDSRIs, and analytical methods used in the quantification of N-nitrosamines in pharmaceuticals. The speakers and panelists will also discuss the strategies to control impurities during the synthesis of the API and excipients, and other strategies to prevent the formation of NDSRIs in a drug product during its shelf-life.
- Presentations by experts from FDA and the generic drug industry
- Audience Q&A with panelists from FDA and the generic drug industry
Session 2: Safety & Risk Assessment of NDSRIs for Human Health
This session will focus on considerations in assessing the safety risks of NDSRIs. The speakers and panelists will discuss current efforts, by both the FDA and drug manufacturers, to assess the potential risk of NDSRIs for human health and to predict the activity and potency of NDSRIs by utilizing quantitative structure–activity relationship (QSAR) models or other relevant quantitative tools.
- Presentations by experts from FDA and the generic drug industry
- Audience Q&A with panelists from FDA and the generic drug industry
Session 3: Impact of Reformulation on the Bioequivalence of Generic Products and FDA Regulatory Perspectives on Reformulated Generics
This session will focus on the potential impact of reformulations (e.g., adding a suitable antioxidant to the existing formulation) on the bioequivalence of generic products and strategies to efficiently address these challenges. The speakers and panelists will discuss current and future research efforts to evaluate the effect of an antioxidant in the formulation on the absorption and/or the bioavailability of API and to utilize modeling and simulation approaches to assess the risk of potential bio-inequivalent scenarios in the event of a reformulation. The speakers and panelists will discuss regulatory perspectives relating to potential bioequivalence approaches for generic products that are reformulated to mitigate NDSRIs formation.
- Presentations by experts from FDA, academia, and the generic drug industry
- Audience Q&A with panelists from FDA, academia, and the generic drug industry
For more information: If you have any questions about this workshop please contact info@complexgenerics.org.
