NITROSAMINE

IMPURITIES

29 - 30 June 2021

Mitigating Nitrosamine Impurities in Pharmaceuticals -

Current Challenges & Future Perspective

LIVE
VIRTUAL
FORUM
 Industry
Landscape:
Nitrosamines, or more correctly N-nitrosamines, refer to any molecule containing the nitroso functional group. These
molecules are of concern because nitrosamine impurities are probable human carcinogens. Although they are also
present in some foods and drinking water supplies, their presence in medicines is nonetheless considered
unacceptable.
To ensure the safety of the U.S. drug supply, FDA has launched the availability of a guidance for industry, entitled
“Control of N-Nitrosamine Impurities in Human Drugs.” This guidance recommends steps manufacturers of active
pharmaceutical ingredients and drug products should take to detect and prevent objectionable levels of nitrosamine
impurities in pharmaceutical products. The guidance also describes root causes that may introduce nitrosamine
impurities.

The European Medicines Agency (EMA) has assessed the risk of nitrosamine formation or presence during the
manufacture of human medicines and has provided guidance to marketing authorization holders to avoid the presence
of nitrosamine impurities. EMA finalized a review under Article 5(3) of Regulation (EC) No 726/2004 in June 2020 to
provide guidance to marketing authorization holders on how to avoid the presence of nitrosamine impurities in human
medicines.
Companies are required to have appropriate control strategies to prevent or limit the presence of these impurities and,
where necessary, to improve their manufacturing processes. The 2nd edition of Nitrosamine Impurities Forum
scheduled on 29-30 June 2021 will discuss on the current challenges & future perspective.

Why this forum?

The second edition of Nitrosamines Impurities Forum will focus on the challenges to any molecule containing the
nitroso functional group while discussing on the below:

• Understanding current regulatory requirement to tackle with Nitrosamine Impurities concerns

• How to calculate & derive on acceptable intake limit?
• Gain clarity on choosing correct analytical methods & tools to address these impurities
• How nitrosamines are formed – Chemical mechanism behind this?
• How to stop condition reaction of forming nitrosamine impurity
• How to restrict these impurities at the process or R&D stage?
Who will Attend
Pharmaceuticals Life sciences
Industries /
Categories
API Bio-
Manufacturers Pharmaceuticals

Designation: Departments:
• Vice Presidents • Quality Assurance
• Associate Vice Presidents • Quality Control
• Directors • R&D
• Associate Directors • Production & Manufacturing
• Heads/Plant Heads • Analytical
• Deputy General Managers • Regulatory
• General Managers • Packaging
• Senior Managers
• Managers
• Assistant Managers
• Senior Executives

Why attend?
To understand chemistry and risk assessment
in formulated products

Learn to choose correct analytical Techniques

& methods to evaluate and assess
nitrosamines

Ensuring quality & mitigation strategies to

control nitrosamines from manufacturing
stage to finish product

Educate your employees to do risk analysis

and stay updated with complex changes in
nitrosamines

Understand the importance of supplier

qualification
Speakers
Dr. BM Rao
Dr. Andrew Teasdale
Head - QA for Emerging Markets,
Senior Principal Scientist Impurity
CQC & ASAT (Analytical Science
Management and External Advocacy
& Technology)
AstraZeneca
Dr. Reddy's Laboratories

Mr. Chander Mani Dr. David Elder

Application Engineer-LCMS Principal Consultant
Agilent Technologies David P Elder Consultancy

Dr. Ganapathy Mohan Dr Giorgio Blom

Executive Director Senior Scientist
Merck AstraZeneca (Supported by
Thermo Fisher Scientific)

Dr. George Johnson Dr. Kevin P. Cross

Professor VP Product Engineering &
Swansea University Production, Leadscope &
Medical School, UK Principal Investigator
USFDA Collaborations

Dr Mark Harrison
Senior Scientist Naiffer Romero
AstraZeneca (Supported Sr. Manager Scientific Affairs
by Thermo Fisher Scientific) US Pharmacopeia (USP)

Dr. Raphael Nudelman

Dir. Chemical & Dr. Steven W. Baertschi
Computational Toxicology President
Teva Pharmaceuticals Baertschi Consulting LLC

Dr. Tom van Wijk Dr. Ulrich Rose

Principal Scientist Head of Division A, Deputy Head
Analytical Science &Technology European Pharmacopoeia
for Established Pharmaceuticals Department,
Abbott Healthcare Products B.V. EDQM, Council of Europe
 CONFERENCE SCHEDULE
Day 1: 29th June 2021
14.15 (IST)/12.45 (GST)/ Registration & Networking
10:45 CEST
14:45 (IST) /13:15 (GST)/ Opening Remarks by Informa Markets in India
11:15 CEST
Updated Guidelines on Nitrosamine Impurities by FDA & EMA
• Guidelines for API & Drug Products
15.00 (IST) /13:30 (GST)/ • Risk Assessment
11:30 CEST • Analytical Methods & Acceptable Intake Limits
15.20 (IST) /13:50 (GST)/ Break
11:50 CEST
Nitrosamines Impurities, USP’s Response – Tools & Resources
The nitrosamine impurities crisis prompted regulators around the world to increase
their scrutiny of drug manufacturing processes even further. In the future, this
15.30 (IST) /14:00 (GST)/ greater scrutiny may lead to the discovery of nitrosamine impurities in other
12:00 CEST medicines. For this reason, manufacturers need to understand which medicines are
likely to form nitrosamines, how and at what levels nitrosamine impurities are
forming, and how to control nitrosamines.
In the following seminar we will explore how USP responded to the nitrosamine
impurities crisis with a proposed general chapter on nitrosamine impurities that
provides a risk assessment strategy, methods for detecting and measuring
nitrosamine impurities, along with physical reference standards against which
manufacturers can compare their test results. Additionally, USP have create a whole
suite of resources and tools for stakeholders to effectively face the challenges of
Nitrosamine Impurities.
Mr. Naiffer Romero, Sr. Manager Scientific Affairs, US Pharmacopeia (USP)
16:00 (IST) /14:30 (GST)/ Break
12:30 CEST
16:10 (IST) /14:40 (GST)/ European Pharmacopoeia response to Nitrosamine Contamination:
12:40 CEST • New general chapter providing analytical procedures to control the relevant N-
nitrosamine impurities
• Revisions of monographs and preparation of general texts
• Rapid implementation of the revised sartan monographs
Dr. Ulrich Rose, Head of Division A, Deputy Head, European Pharmacopoeia
Department at the EDQM, Council of Europe
16:40 (IST) /15:10 (GST)/ Break
13:10 CEST

Information Classification: General

 N-Nitrosamines: Chemistry and Risk Assessment in Formulated Products
This presentation will provide an overview of the fundamental chemistry involved in
the most common pathways for formation of N-nitrosamines in formulated drug
16:50 (IST) /15:20 (GST)/ products. Mechanistic insights will be provided with a focus on strategies for
13:20 CEST limiting and controlling the formation of nitrosamines during both manufacturing
and throughout the shelf-life. Guidance will also wbe provided for assessing the risk
of nitrosamine formation in formulated products in the context of the risk to the
patient
• Chemistry of the N-nitrosation reaction
• Structure and reactivity of N-nitrosamines
• Risks of formation in formulated products
• Strategies for controlling using chemical insights
Dr. Steven W. Baertschi, President, Baertschi Consulting LLC
17:20 (IST) /15:50 (GST)/ Break
13:50 CEST
Root Causes of Nitrosamine Impurities in Drug Substances & Drug Products
• Sources of secondary, tertiary, and quaternary amines that forms Nitrosamines
• Vendor-sourced raw materials, recovered materials & quenching process
17:30 (IST) /16:00 (GST)/ • Excipients and chemical degradation
14:00 CEST • Lack of supplier qualification
• Risk of formation of nitrosamines during storage throughout its shelf life
• Lack of process optimization and control
18:00 (IST) /16:30 (GST)/ Networking Break
14:30 CEST
Analytical Method Development and Optimization for Nitrosamines in API and
18:20 (IST) /16:50 (GST)/ Pharmaceutical Products)
14:50 CEST Dr Giorgio Blom, Senior Scientist, AstraZeneca (Supported by Thermo Fisher
Scientific)
19:00 (IST)/17:30 (GST)/ Break
15:30 CEST
Panel Discussion
Ensure Quality & Mitigation Strategies to Control Nitrosamines from
Manufacturing stage to Finish Product
- How to streamline processes to avoid nitrosamine impurity in drug substance &
drug products?
- Implement best risk analysis and risk evaluation strategies to avoid nitrosamine
impurities
- Development of a systematic risk-based approach
- Review on certain conditions which periodically form nitrosamines
- Implement Good Documentation Practices to trace back & identify root causes of
nitrosamines
19:10 (IST)/ 17:40 (GST)/ Moderator: Dr. Ganapathy Mohan, Executive Director, Merck
15:40 CEST Panelist:
• Dr. Andrew Teasdale, Senior Principal Scientist Impurity Management and
External Advocacy, AstraZeneca

Information Classification: General

 • Dr. BM Rao, Head - QA for Emerging Markets, CQC & ASAT (Analytical Science
& Technology), Dr. Reddy's Laboratories
• Dr. Kevin P. Cross, VP Product Engineering & Production, Leadscope &
Principal Investigator, USFDA Collaborations
• Dr. Ulrich Rose, Head of Division A, Deputy Head, European Pharmacopoeia
Department at the EDQM, Council of Europe

End of Conference Day 1

Day 2: 30th June 2021

14.15 (IST)/ 12.45 (GST)/ Registration & Networking
10:45 CEST
14:30 (IST)/ 13:15 (GST)/ Opening Remarks by Informa Markets In India
11:15 CEST
The Complexity of Nitrosamines for the Generics Industry
15:00 (IST)/ 13:30 (GST)/ • Small alkyl nitrosamines vs "complex" nitrosamines
11:30 CEST • Is read-across feasible for "complex" nitrosamines?
• De-risking of "complex" nitrosamines
o Are all nitrosamines part of the CoC?
o Ames test analysis of "complex" nitrosamines
o MW adjustment of AIs
Dr. Raphael Nudelman, Dir. Chemical & Computational Toxicology, Teva
Pharmaceuticals
15:30 (IST)/ 14:00 (GST)/ Break
12:00 CEST
15:40 (IST)/ 14:10 (GST)/ Nitrosamine Methodology: How low is too low?
12:10 CEST • An overview: How did global regulatory agencies rapidly develop "fit for
purpose" methodologies for nitrosamine detection and control?
• Analytical target profile - disconnect between AIs, dose, and method LOQs
(EU/FDA requirements - Feb 2021)
• How do we prevent false positives/negatives - some of the analytical
pitfalls?
• Global capacity for routine ppb methodologies - is it adequate?
• Is this a proportionate response for drugs -nitrosamines are everywhere,
food, water, environment, tobacco (they are even formed
endogenously)?
• Conclusions
Dr. David Elder, Principal Consultant, David P Elder Consultancy
16:10 (IST)/ 14:40 (GST)/ Break
12:40 CEST

Information Classification: General

 16:20 (IST)/ 14:50 (GST)/ Challenges in the Analysis of Nitrosamines
12:50 CEST
• Methodologies for the determination of nitrosamines
• Compound specific method selection
• Analytical method assessment (case study)
Dr. Tom van Wijk, Principal Scientist, Analytical Science &Technology for
Established Pharmaceuticals, Abbott Healthcare Products B.V.
16:40 (IST)/ 15:10 (GST)/ Networking Break
13:10 CEST
17:10 (IST)/ 15:40 (GST)/ Sponsorship Topic: Highly Sensitive and Robust LC-MS/MS Quantification
13:40 CEST Method for Nitrosamine Impurities in Drug Substances & Drug Products
17:40 (IST) / 16:10 (GST)/ Break
14:10 CEST
17:50 (IST) / 16:20 (GST)/ How to deal with Nitrosamine Impurities in API?
14:20 CEST The regulators earlier investigations led to industry-wide recalls of valsartan
and other “sartan” (losartan, irbesartan) angiotensin II receptor blockers
(ARBs). More recently, the nitrosamine impurities findings have been extended
to ranitidine, nizatidine, and metformin, leading to recalls of these drug
products. This presentation will highlight how API and drug product
manufacturers consider the ways nitrosamines form and evaluate the risk for
nitrosamine contamination or formation in their products, prioritizing
evaluation of APIs and drug products based on factors such as maximum daily
dose, duration of treatment, therapeutic indication, and number of patients
treated & evaluate synthetic route including regulatory starting materials and
solvents
Dr. George Johnson, Professor, Swansea University Medical School, UK
18:20 (IST) / 16:50 (GST)/ Break
14:50 CEST
18:30 (IST) / 17:00 (GST)/ Implementing ICH M7 principles to deal with nitrosamine impurity
15:00 CEST
19:00 (IST) / 17:30 (GST)/ Break
15:30 CEST
ss Panel Discussion: Supported by ‘Thermo Fisher Scientific’
Risk Assessment Strategy to Avoid Nitrosamine Impurities
- What is acceptable by regulators while conducting risk assessment?
- Identify challenges in assessing risk in Raw Materials, API, Drug products &
Packaging Materials
19:10 (IST)/ 17:40 (GST)/ - How to calculate acceptable intake limit which is set by regulatory
15:40 CEST authorities?
- How to choose suitable analytical methods to meet the acceptance intake
limit?
- 3-Step Approach to implement Risk Assessment with real case examples with
lessons learned during the process
Moderator: Dr. David Elder, Principal Consultant, David P Elder Consultancy
Panelist:
• Dr. George Johnson, Professor, Swansea University Medical School, UK

Information Classification: General

 • Dr. Kevin P. Cross, VP Product Engineering & Production, Leadscope &
Principal Investigator, USFDA Collaborations
• Dr Mark Harrison, Senior Scientist, AstraZeneca (Supported by Thermo
Fisher Scientific)
• Dr. Tom van Wijk, Principal Scientist, Analytical Science &Technology for
Established Pharmaceuticals, Abbott Healthcare Products B.V
End of Conference

Information Classification: General

 Platinum Partner

Silver Partner

Contact
For Delegate Registration
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M: +91 88280 65252 | E: sailee.patne@informa.com

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For Speaking and Exhibit Opportunities:

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