North Jersey Chromatography Group



NJCG 2023
Annual Symposium

The Role of Chromatography in Upholding Pharmaceutical Quality

October 12, 2023
12:00-6:00 PM

Double Tree Hotel
Mirabelle Room
200 Atrium Drive
Somerset, NJ

Cost: Free
Please Register Below




Thursday, October 12, 2023


Presentation/Activities


12:00 PM


Registration


Vendor Show and Posters

___________


12:50 PM


Welcome and Introduction


Qian Zhang, NJCG Chair

BMS


Isabelle Vu Trieu

Waters Corportation

__________


1:05 PM


Nitrosamine Risk Assessment and

Control of Pharmaceutical Products


Dr. Jinjian Zheng

Merck

____________


1:40 PM

​

Analytical Methodology for the Detection and

Quantitation of N-Nitroso-Propanolol Using

Liquid Chromatography and

Tandem Mass Spectroscopy


Dr. Marian Twohig

Waters Corporation


_____________


2:10 PM


NJ-ACS Overview


Justyna Sikorska

NJ-ACS Chair

Merck​

______________


2:20 PM


Adanced Modeling from Highly

Accelerated Stability Testing (ASAP)

to Determine Drug Product

Shelf Life


Kenneth C. Waterman


FreeThink Technologies

______________


2:50 PM


Break


Vendor Show and Posters


Open Bar (Sponsored by Waters Corp.)

_____________


3:50 PM


A Novel UHPLC-UV-CAD-HRMS

Mutli-Detector Platform to Address Analytical

Uncertainty Challenges During Extractables

and Leachables Analysis


Dr. Chongming Liu

SGS Health Science

____________________


4:20 PM


Medical Device Extractables/Leachables

Study: Analytical Challenges

and Case Studies


Dr. Yijun Lu

Ethicon, Johnson and Johnson

​___________


4:50 PM


Vendor Show and Posters


Cocktail Hour (Sponsored by

Waters Corp.)

____________


​5:50 PM


Raffle


Roger Hsu, NJCG Treasurer

Insmed


Closing Remarks


Nimisha Thakur, NJCG Secretary

Merck

​



PRESENTATION ABSTRACTS



nitrosamine risk assessment and control in pharmaceutical products



Dr. JinJian Zheng (Presenter)
In this presentation, I will give an overview of recent update on regulatory guidance especially on recommendation of acceptable limit based on Carcinogenic Potential Categorization Approach. I will then share the strategies to perform nitrosamine risk assessment for small molecule pharmaceutical products. Analytical development to support nitrosamine risk assessment will be discussed including 1) testing for trace level vulnerable amines in drug substances 2) testing for nitrite in excipients and 3) testing for nitrosamines in drug products. Several case studies will be used to demonstrate how to establish control strategies based on the outcome of risk assessment.


Analytical Methodology for the Detection and Quantitation of N-Nitroso-Propranolol using Liquid Chromatography and Tandem Mass Spectrometry



Dr. Marian Twohig (Presenter)

The discovery of N-nitrosamines in drug products has been causing global safety concerns in the Pharmaceutical Industry since their unexpected discovery in 2018. This has led to multifaceted risk mitigation strategies to ensure patient safety. N-nitroso compounds have been designated as a cohort-of-concern by the ICH M7 guidelines because some of the compounds that have been tested in this class have demonstrated carcinogenicity in rodent bioassays. In addition to concerns about the alkyl nitrosamines, including N-nitrosodimethylamine (NDMA), there are also concerns about the formation of Nitrosamine Drug Substance Related Impurities (NDSRI). NDSRI, are a class of nitrosamines that are structurally related to the active pharmaceutical ingredient (API). Propranolol is a β-blocker that is widely used and considered a safe medication. However, it can form a nitrosated derivative, N-nitroso-propranolol. In this work we present analytical methodology for the detection and quantitation of N-Nitroso-propranolol in drug substance..



Advanced Modeling from Highly Accelerated Stability Testing (ASAP) to Determine Drug Product Shelf Life



Dr. Kenneth C. Waterman (Presenter)

ASAP employs isoconversion (time to hit the specification limit at each condition) with designed temperature/RH conditions (based on a humidity-corrected Arrhenius equation) to build a model for degradant formation or potency loss for drug products and drug substances. Once the model is built, the shelf-life inside packaging can be determined based on the calculated RH inside the packaging. These methodologies provide for far better predictions of shelf-life (expiry) than previously possible at a significantly reduced time frame (2-3-weeks). ASAPprime® employs this science in combination with statistical tools to enable accurate estimations of shelf-life with many factors determined computationally (e.g., packaging, storage conditions, storage excursions). ASAPprime® has now been successfully used in regulatory filings in many countries to reduce time and lengthen allowed shelf-lives.



A Novel UHPLC-UV-CAD-HRMS Multi-detector Platform to Address Analytical Uncertainty Challenges during Extractables and Leachables Analysis



Dr. Chongming Liu (Presenter)

LC/MS, often hyphenated with UV detection, is commonly used to detect and annotate the non-volatile fraction of compounds in Extractables & Leachables (E&L) studies. Industry guidance and regulatory requirements indicate an analytical evaluation threshold (AET), above which the identification of the compounds in question is necessary for toxicological risk assessment. The use of AET requires semi-quantitation of compounds during the identification process, which is commonly carried out with surrogate standards. However, MS signal intensity can vary significantly between different compounds. UV detection is often used as an alternative, however it requires that the analyte contains a chromophore. To overcome these limitations and lower the uncertainty of the concentration estimate of unknowns, charged aerosol detection (CAD) has been proposed as an orthogonal detector of non-volatile compounds. One benefit of this detector is that when constant mobile phase composition is maintained, the signal response is more universal, thus enabling the surrogate quantitation of unknown compounds with lower uncertainty than using MS. Here, we demonstrate the combination of the three detection techniques in one system to allow the concurrent measurement of UV absorption, CAD signal and high resolution-accurate mass (HRAM) mass spectra from one injection. The performance of this system for extractables analysis is evaluated in the analysis of an Extractable & Leachable (E&L) standard mixture. Additionally, the application to the analysis of extractable samples and the workflow for identification of compounds prioritized based on CAD response

is highlighted








Medical Device Extractables/Leachables Study: Analytical Challenges and Case Studies



Dr. Yijun Lu (Presenter)

Ethicon is part of Johnson & Johnson Medtech and is a world leading manufacturer of innovative surgical care products such as sutures, mesh devices, hemostats, breast implant, drug/device combination products, energy and mechanical devices. These diverse product lines are manufactured using a wide range of materials with a variety of processes. Suitable analytical chemistry techniques and critical in-house expertise are crucial for chemical evaluation of the raw materials, the device components, and the finished devices in support of new product development and product life cycle management.


In this presentation, two case studies will be presented to illustrate how we utilize different analytical techniques to characterize medical device extractables/leachables (E/L) per ISO-10993 guidance documents. First case study relates to the identification of an unknown extractable compound from a new filter used in biopharmaceutical manufacturing process. Additional analysis by orthogonal analytical technique to mass spectrometry, such as NMR, plays a critical role in structure elucidation. Second case study focuses on the analysis of semi-volatile extractables of breast implant made from silicone elastomer. Technical challenges associated with liquid and gas chromatography techniques will be highlighte








DR. Jinjian Zheng



Senior Principal Scientist
Analytical Commercialization Technology
Merck



Dr. Jinjian Zheng joined Schering-Plough/ Merck in 2003, and is currently a Sr. Principal Scientist at Analytical Commercialization Technology, Merck Manufacturing Division. Dr. Zheng has provided analytical support for both drug substance and drug product across different stages from development, commercialization to supply. He is a subject matter expert on chromatography at Merck. Currently, he teaches a short course on systematic HPLC method development and lead a chromatography study forum to facilitate chromatographic method development and trouble shooting. Dr. Zheng has received several awards including Merck Commercialization Award, Merck Manufacturing S&T Innovation Award. He is currently leading the analytical development efforts at Merck to support nitrosamine risk assessment and control for small molecule products.



Dr. Marian twohig



Principal Scientist
Discovery and Development Group
Waters Corporation



Dr. Marian Twohig has over 20 years of experience supporting quantitative and qualitative applications in the pharmaceutical, food and environmental and materials science industries. She works as a Consultant Scientist for Waters Corporation where she has previously held several Senior Scientist positions. Currently, the focus of Marian’s work is in the development of quantitative analytical methods to meet the needs of the pharmaceutical industry. She is particularly interested in chromatographic separations and the application of combining low- and high-resolution mass spectral data with other chemical information for identification of unknown chemical entities. Marian holds a Ph.D. in Analytical Chemistry from Munster Technological University, Cork, Ireland.



DR. Kenneth C. Waterman



Founder and President
FreeThink Technologies, Inc.



Dr. Kenneth Waterman received his B.S. degree with honors in Chemistry from UCLA, his Ph.D. in Physical Organic Chemistry from UC Berkeley and conducted post-doctoral studies in physical and photo-chemistry as an NIH Research Fellow at Columbia University. Dr. Waterman’s distinguished scientific career includes 12 years as a scientist at Polaroid working to develop imaging products, and 13 years as a Research Fellow at Pfizer working on drug stability, drug delivery, biopharmaceutics and prodrugs. He is the author of over 75 publications/patents and was made an AAPS Fellow in 2011. In 2011, he began FreeThink Technologies, Inc. with laboratories located in Connecticut. FreeThink’s laboratories have unique expertise in stability, formulation development and new drug delivery platform development. In addition, FreeThink produces and licenses its advanced accelerated stability software, ASAPprime®.



Dr. Chongming liu



Supervisor
Extractables and Leachables
SGS Health Science



Dr. Chongming Liu serves as a Supervisor in the Extractables and Leachables (E&L) team at SGS Health Science in Fairfield, NJ. At SGS, his daily responsibility is to oversee the team members in performing E&L testing on pharmaceutical containers and medical devices, serve as a technical expert in resolving analytical challenges, assist laboratory maintenance as well as instrument troubleshooting, and to elucidate structures for unknown organic compounds of interest based on high-resolution GC-FID/MS and LC-PDA/MS data. Prior to his current role, Chongming joined the E&L team at SGS as an Instrumentation Chemist, and obtained experience in hands-on analytical techniques, study design and technical writing. During his graduate study, Chongming got the opportunity to immerse into extensive training in modern mass spectrometric techniques and obtained a Ph.D. degree in Analytical Chemistry from Stevens Institute of Technology. Prior to that, he held a B.Sc. degree in Chemistry from University of Science and Technology of China (USTC).



Dr. Yijun Lu



Associate Director
Analytical Characterization
Ethicon R&D, Johnson & Johnson



Dr. Yijun Lu currently serves as Associate Director for Analytical Characterization in ETHICON R&D supporting MedTech sector in Johnson & Johnson. Yijun leads the structure elucidation, polymer characterization, and chromatography & wet chemistry labs. She also oversees extractable/leachable studies for medical implants, biologics, and device/drug combination product, and analytical characterization of breast implant.


Yijun has over 20 years’ experience in chemical and medical device industries and has been with Johnson & Johnson for 20 years. Yijun is a J&J representative and accredited US expert on AAMI/BE Biological Evaluation Committee (US TAG for ISO/TC 194) and a key technical leader in WG 14 (Material characterization).


Yijun is the co-chair for A.S.I.A employee resource group (ERG) at ETHICON, Johnson & Johnson. She has been actively involved in J&J’s diversity and inclusion initiatives and leading efforts to develop & advance A.S.I.A. members. Yijun also proactively develops and builds strong collaborations within J&J ERGs & with external Asian professional associations.


Yijun received her Ph.D. in Food Chemistry from Rutgers University, her Master degree in Polymer Chemistry from Rensselaer Polytechnic Institute, and her Bachelor degree in Applied Chemistry from Peking University.



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