4th Annual Conference 2018
22nd – 23rd October 2018
Boston, Massachusetts, USA


Conference Themes


Session 1 – Accelerated Stability

Session 2 – Forced Degradation

Session 3 – Physical Stability

Session 4 – Analytical Science


SOS 2018 Boston Agenda_FINAL

Current List of Speakers


  • Steven Baertschi, Ph.D. – Baertschi Consulting, LLC – 

    “The Remarkably Complex Degradation Chemistry of Drug X: Solving a Stubborn Mass Balance Problem”

  • Donald Clancy – Modeling Lead, GlaxoSmithKline –

    “Alternative Approaches to ASAPprime®”

  • Michael Dong, Ph.D. – Principal Consultant, MWD Consulting –

    “Developing Stability Indicating HPLC Methods: Case Studies”

    HPLC method development is an arduous and time-consuming process particularly for stability-indicating methods for drug substances and drug products. This seminar describes short cuts and tricks-of-the-trade to the separation scientist in rapid development of (u)HPLC methods (potency and ICH-compliant stability-indicating assays) using a 3-pronged method template approach and a universal generic gradient methodology. Method development case studies in pharmaceutical development including those for quality control of drug candidates with multiple chiral centers are used to illustrate these approaches.

    1. M. W. Dong and K. Zhang, UHPLC in method development, Trend in Anal. Chem., 63, 21-30, 2014.
    2. M.W. Dong, A Three-Pronged Template Approach for Rapid HPLC Method Development. LCGC North Am. 31(8), 612-621, 2013.

    Dr. Michael W. Dong is a principal consultant in MWD Consulting focusing on consulting and training services on HPLC/UHPLC, pharmaceutical analysis and drug quality. He was formerly Senior Scientist in Analytical Chemistry and Quality Control at Genentech, Research Director at Synomics Pharma, Research Fellow at Purdue Pharma, and Senior Staff Scientist at Applied Biosystems / Perkin-Elmer. He holds a Ph.D. in Analytical Chemistry from the City University of New York, and a certificate in Biotechnology from U. C. Santa Cruz. He has 100+ publications including a bestselling book on chromatography (Modern HPLC for Practicing Scientists, Wiley). He is an advisory board member of LCGC magazine, American Pharmaceutical Review, Connecticut Separation Science Council, and Chinese American Chromatography Association. He has been a columnist with LCGC North America since 2013 on “Perspectives on Modern HPLC”.

  • Shane Eisenbeis, Ph.D. – Associate Research Fellow, Pfizer –

    “Passivation of Carbohydrate -Containing Excipients via an Innovative Formulation Strategy: Proof of Concept”

    Thorough knowledge and control of impurities is an expectation for the registration of pharmaceuticals. It’s also well known that formation of API related impurities within formulated drug product are often related to decomposition of the excipients themselves. As an example formaldehyde and formic acid appear to be ubiquitous in many common excipients. Unfortunately these and other reactive species within formulations can lead to increasing impurity profiles which are often managed by the addition of additives. This presentation will report on a recent approach towards “passivating” carbohydrate based excipients in an effort to minimize not only the impact of excipient generated formaldehyde but also Maillard related impurities.
    Shane Eisenbeis1*, Todd Zelesky1, Greg Sluggett1, Robert North1 and Steven Baertschi2
    1. Pfizer Pharmaceuticals, Groton CT., 06340 USA
    2. Steven Baertschi Consulting, LLC, Carmel, IN., 46033 USA

  • Rachel Hemingway, Ph.D. – Senior Scientist, Lhasa Limited –

    “Zeneth Knowledge-Based System for the Prediction of Forced Degradation of Organic Compounds”

    Zeneth is an expert, knowledge-based system for the prediction of forced degradation of organic compounds. Features include the ability to predict the structures of degradants and the degradation pathways they undergo as well as a likelihood level for each degradant. The system generates predictions by using a library of chemical transformations. These transformations are researched and implemented by knowledge scientists using (mainly) publicly available literature. Zeneth can be used to aid the analysis of forced degradation experiments as well as to provide information to guide development of stability-indicating methods. The program is currently undergoing a period of redevelopment with the aspiration of providing faster and more accurate predictions. This is being achieved through implementation of new scientific features. Predicted degradants will now be given a ‘score’, which will be used in place of likelihood levels. This scoring system will add a level of granularity to predictions with the aim of generating fewer false positives. Plans to validate this methodology, a key aspiration, are in motion. The new software will also benefit from enhanced stereochemical behaviour. Calculating physicochemical properties is going to be an important part of the new software. A pKa calculator has been developed (in-house) and implemented with the aim of improving the accuracy of predictions for epimerisation reactions at various pH’s and a bond dissociation energy calculator is also in development.

    I graduated from the University of Hull in 2012 with a PhD in Chemistry. I studied Bioinorganic Chemistry in the Archibald group designing chemokine receptor antagonists appended to therapeutic porphyins for the targeted delivery of a drug to cancer cells overexpressing the chemokine receptor CXCR4. I then worked for a chemical manufacturer for 2.5 years as a research scientist in product development before joining Lhasa Limited. I have been part of the science team at Lhasa for 3 years, recently becoming a senior research knowledge scientist. During this time, I have worked almost exclusively on the Zeneth software. Zeneth is our expert knowledge-based system for the prediction of forced degradation of organic compounds.

  • Freneil Jariwala, Ph.D. – Senior Scientist, P&G Healthcare, R&D –

    “Feeling the Crunch: Accelerated Stability in the Land of OTC Drugs/Dietary Supplements”


    The global over-the-counter (OTC) drugs and dietary supplements markets are expected to be valued at $450B by 2024 with a compound annual growth rate (CAGR) of 9%. With the addition of novel dosage forms, such as chewable gels, and specialty nutraceutical/botanical blends, the speed of innovation and new product development is as important as the speed to market. Furthermore, regulatory bodies across the world are instituting ever more stringent regulations for these products. In this fast-paced environment, deep understanding of the products and their stability profiles is critical. And the analytical and stability scientists must play an essential role during development.

    In this pursuit, Procter & Gamble has adopted tools such as ASAPprime® as well as internally developed solutions for accelerated evaluations of stability profiles for a wide variety of active ingredients. These tools are utilized throughout the development cycle to aid in formulation development, specification limit settings, packaging options evaluations, and accelerating product launch. Several case studies will be presented wherein these tools were employed to provide critical insights in the stability of OTC drugs, vitamin supplements, and probiotics in varying dosage forms, such as tablets, capsules, chewable gels, and powders. Moreover, novel analytical approaches and experimental execution strategies will be discussed.

    Dr. Freneil B. Jariwala is a Senior Scientist at Procter & Gamble in the Personal Health Care division. He is currently leading analytical technology and method development for OTC drugs and dietary supplements products. He is also responsible for the strategy for identifying and deploying advanced analytical technologies, such as mass spectrometry.
    Previously, he was an Innovation and Entrepreneurship Doctoral Fellow at Stevens Institute of Technology (Hoboken, NJ, USA), where he received his Ph.D. in Analytical Chemistry (mass spectrometry) under Dr. Athula B. Attygalle. He completed his M.S. in Analytical Chemistry in 2010 at the same university. He is co-author on several peer-reviewed articles and recipient of multiple academic awards.

  • Dawen Kou, Ph.D. – Senior Scientist, Genentech –

    “Application of Accelerated Stability Assessment Programs to Facilitate Market Formulation Development of a Small Molecule Drug Product”

    Accelerated Stability Assessment Programs were extensively utilized to evaluate the stability of a small molecule drug product during market formulation development. The formulation contained a key acidic excipient as pH modifier to improve drug solubility and bioavailability, but it also increased the level of a degradant that is stability limiting. The effects of critical material attributes, formulation and process parameters, and packaging configurations on stability were investigated. The particle size of the excipient and the surface area of the API were found to have a major impact. When and how the excipient was introduced in the manufacturing process was also important. The final parameters were optimized to balance the stability, bioavailability, and manufacturability of the market formulation.

    Dr. Dawen Kou has over 15 years of experience in the pharmaceutical and biotech industry. He is currently a Senior Scientist and group leader in the department of Small Molecule Analytical Chemistry and Quality Control in Genentech at South San Francisco, CA. Prior to joining Genentech, he was a Senior Principal Scientist at Hoffmann La-Roche. He has a Ph.D. degree from a joint program of Rutgers university and the New Jersey Institute of Technology. He also holds a Mini-MBA diploma from Rutgers. Dr. Kou’s work focuses on analytical R&D for drug substance and drug product, with interest in biopharmaceutics, stability, chromatography, and new technologies. He has published extensively in scientific journals and book chapters.

  • Meng John Zhao, Ph.D. – Research Advisor, Eli Lilly –

    “Some Product Stability Findings When There is Little or No Degradation in Accelerated Stability Tests”

    Accelerated stability studies can help companies quickly quantify stability risks. Although little or no degradation during an accelerated test provides evidence that a product is stable, it does not discharge the risk of a low Ea mechanism. In addition, it can be difficult to estimate shelf life when some or even all of the accelerated test data are below the quantification limit. A Bayesian approach with weakly informative priors and zero order degradation kinetics allows one to make probabilistic statements about the degradation when stored at specified conditions for such situations. This Bayesian approach will be described and applied to hypothetical examples. Further, general implications for the design of accelerated tests will be given. Finally, an analagous Bayesian approach will be used to show how the stability of related drug substance campaigns can be compared and aggregated to provide more precise stability estimates and guide risk-based real-time stability tests.

    Meng J. Zhao is a Statistical Research with Scientist Eli Lilly & Company. He received his Ph.D. in Statistics in 2017.He also hold an MS in Statistics in the Department of Statistics at Virginia Tech and a masters in Biotechnology at Pennsylvania State University. His current research focuses in areas of liquid and solid pharmaceutical formulations development, as well as stability modeling of dosage potency.

  • Megan McMahon, Ph.D. – Associate Director, Global Regulatory CMC, Pfizer –

    “IQ Update: Lean Stability Perspectives Across Industry and Current Regulatory Feedback”

    Megan McMahon is a Director in Global CMC at Pfizer in Connecticut. Megan received her B.S. in Chemistry from Purdue University and M.S. in Regulatory Affairs/Quality Assurance from Temple University. Megan started her career at Pfizer in Chemical R&D as an analytical chemist and has worked in Regulatory CMC for the past 11 years. She is a member of Pfizer’s Impurity Council and Stability Council. Megan was a founding member of the AAPS Chemical and Biological API Focus Group in 2009 and served as chair in 2012 and 2013. Megan is currently an active member of the AAPS CMC Community steering committee and has taken a leading role on the AAPS Virtual Round Table series. In addition to her support of AAPS, Megan is an active member of the IQ Analytical Leadership Group, IQ Risk Based Predictive Stability Working Group, and leads the IQ Lean Stability Working Group.

  • Kausik K Nanda, Ph.D. – Associate Principal Scientist, Merck Research Laboratories –

    “Transition Metal Catalyzed Chemistry in Solid Oral Dosages”

    Oxidative degradation of API (Active Pharmaceutical Ingredient) is one of the common degradation pathways in drug products, and transition metal ions often play an important role in this process. Iron(III) is one of the most abundant metal ion impurities present in excipients and buffers. In drug degradation literature, iron(III) has been primarily shown as a catalyst in the oxidative process when hydroperoxides are present. However, the example of iron(III) in the absence of peroxides, acting as an oxidant is less common. This presentation will highlight the benzylic oxidation of drug molecules/drug fragments in the presence of iron(III) only. The formation of an aromatic cation radical is postulated as the key intermediate for the downstream oxidation.
    1. Kausik K. Nanda, William D. Blincoe, Paul Harmon, Leonardo R. Allain, W. Peter Wuelfing

    Kausik Nanda has more than 18 years of experience in the pharmaceutical industry. His expertise spans analytical, organic, organometallic and coordination chemistry. In his early career, Kausik had worked in discovery programs in the neuroscience, cardiovascular and infectious disease areas, where his team successfully developed lead identification, lead optimization and pre-clinical candidates. In his later career, Kausik’s work focused on solving multitude of problems in the development area, arising from chemical interaction in the drug product. The range of activities encompasses early development through commercial launch. His current research interest is in the field of novel drug degradation mechanism operating in the drug product. Kausik also represents the Drug Product area in the Merck Mutagenic Impurity Council, responsible for the policies related to mutagenic impurities in drug products and drug substances. He has authored more than 25 scientific articles in peer-reviewed journals and holds 13 patents.

  • Fenghe Qiu, Ph. D. – Senior Research Fellow, Boehringer Ingelheim Pharmaceuticals, Inc. –

    “Regulatory Update: IQ Risk-Based Predictive Stability Regulatory Sub-Team”

    Accelerated Predictive Stability (such as ASAP) can be used for a variety of applications during drug development. While some companies primarily use this approach for product development, many companies have been submitting Accelerated Predictive Stability data in regulatory submissions. The benefits of submitting Accelerated Predictive Stability data is twofold, it not only saves time which in turn can accelerates the clinical trial timeline and potentially shorten the time to deliver new therapies to patient, but also provides a more accurate prediction of the product stability than conventional approaches such as ICH approach. However, because Accelerated Predictive Stability is still relatively new, and has not been considered fully accepted by global regulatory agencies. It is for the benefits of both the industry and patients, the early adopters in the industry to work with agencies and each other to advance the acceptance of Accelerated Predictive Stability data in regulatory filings. This presentation provides an overview of the recent activities of the IQ RBPS regulatory sub-team in promoting the use of Accelerated Predictive Stability data in regulatory submissions, examples of success submissions, and at last the opportunities and challenges ahead of the industry.

  • Christopher Riley, Ph.D. – President, Riley and Rabel Consulting –

    “Complicated Solid-State Study and Analytical Challenging Case Study”

    AeroVanc is dry-powder inhalation product under development for the treatment of methicillin resistant S. Aureus (MRSA) infections in the lungs of cystic fibrosis patients. AeroVanc contains the antibiotic, vancomycin hydrochloride and L-leucine. Vancomycin, which is listed on the WHO’s List of Essential Medicine, is a complex glycopeptide derived from N. orientalis with significant analytical challenges, including the presence of at least 12 identified impurities and a similar number of unknown impurities1,2. Various HPLC methods are listed in USP, EP and the BP monographs for the assessment of vancomycin impurities; however, none of the compendial procedures provide acceptable separations for the determination of the impurities in vancomycin drug substance and in AeroVanc. Vancomycin has six ionizable groups and some of the impurities have seven. This presentation discusses the importance of design-of-experiments (DoE) combined with a good understanding of the physico-chemical properties of vancomycin (especially the relationship between the charge of the molecule and mobile phase pH) in the rational development of a robust analytical method for the separation of complex mixtures in a solid dosage form. A reversed HPLC column packed with a perfluorophenyl-C18 bonded phase from Phenomenex proved to be particularly suitable due to its high functional group selectivity and its ability to separate positional isomers. Design-of-experiments (DoE) involving the investigation of pH (2.5 – 7.0), and organic solvent composition (acetonitrile, THF and methanol) and concentration (0-100%) identified the optimum conditions, which involved isocratic elution for the separation of the peaks eluting before vancomycin and gradient elution for the peaks eluting after vancomycin. A DoE approach also proved very useful in defining the multi-dimensional relationship between the resolution of three critical pairs of peaks and the intrinsic variables (instrument type, flow rate, temperature, column age) and extrinsic variables (pH, solvent type and solvent composition).
    1. CM Harris, H Kopecka and TM Harris, J.Am.Chem.Soc., 1983, 105, 6915-6922
    2. AS Antipas, D Vander Velde and VJ Stella, Int.J.Pharm, 1993, 261-269

  • Gary Scrivens, Ph.D. – Senior Principal Scientist, Pfizer –

    “Prediction of the Long-Term Dissolution Performance of an Immediate-Release Tablet Using Accelerated Stability Studies”

  • Sabine Thielges, Ph.D. – Principal Scientist, Novartis –

    “ASAP for Parenteral Formulation Development – Solution and Lyophilisate”

  • Kenneth Waterman, Ph.D. – President, FreeThink Technologies, Inc. –

    “ASAPprime® Version 6 Algorithm-Based Data Analysis”

    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).

    Dr. Ken 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 worked 12 years at Polaroid (as a distinguished scientist) developing imaging products, then 13 years at Pfizer (as a Research Fellow) working on drug stability, drug delivery, biopharmaceutics and prodrugs. He is the author of over 70 publications and was made an AAPS Fellow in 2011. In 2011, he started FreeThink Technologies which both produces and licenses the accelerated stability software package ASAPprime® and is a CRO that has Connecticut-based laboratories specializing in stability for pharmaceuticals, generics, OTCs, nutraceuticals and consumer products.

  • Helen Williams, Ph.D. – Associate Principal Scientist, AstraZeneca –

    “Validating ASAP Predictions with ICH-Compliant Stability Data and Implementing GMP ASAP Studies”

    The application of ASAP studies during pharmaceutical development has been increasing within AstraZeneca over the last 5 years. As such just under one hundred ASAP studies have been completed during that time frame on our development portfolio, across drug substance, starting materials, intermediates and a range of drug product types. Over this ever-growing data set, real time ICH compliant stability data is now available for a number of the drug substances and products tested. Comparison of the ASAP predictions with the real-time stability data will be presented across a range of drug substances and products. Drug substances that are chemically stable and do not degrade during an ASAP study offer a particular challenge when setting an initial retest period. Real time ICH data for such drug substances will be presented, demonstrating that an initial retest period of at least 12 months can be supported when no degradation is observed during an ASAP study. A brief overview of the procedures followed to introduce GMP ASAP studies will also be presented.

    Helen graduated from Southampton University with a Masters of Chemistry degree in the summer of 1998 and started working for Zeneca a couple of months later. She has spent the last 20 years working as an analytical chemist within pharmaceutical development at AstraZeneca in Macclesfield, UK. She specialised as an expert in Electron Paramagnetic Resonance spectroscopy and more recently has spent the last 5 years focusing on Predictive Stability, as an Associate Principal Scientist. She is a member of the IQ Risk-Based Predictive Stability Working Group and became a Chartered Chemist with the RSC in 2014.

  • Manvi Hasija – Formulation and Stability Scientist, Sanofi

    “Forced Degradation Studies: An Essential Tool for the Formulation Development of Vaccines”

    Forced degradation studies are typically conducted during the early development phase of vaccine candidates to obtain information on potential degradation pathways, support analytical methods development, and identify potential vaccine stabilizers and optimal conditions for long-term storage. The regulatory guidelines for forced degradation regarding biologics have few to no procedural instructions on how to approach forced degradation studies. In my presentation, I will provide an overview of methods used to study forced degradation in vaccines, mechanisms of degradation, analytical methodology, forced degradation examples conducted for vaccine products.

    Manvi Hasija is Formulation and Stability Scientist at Sanofi, where she has managed the stability program for new vaccines in the BioProcessing Research and Development Division for over 13 years. Manvi has worked on the stabilization and characterization of a wide variety of new vaccine development projects. She manages a team of staff, and leads the development of new vaccine stability test and evaluation protocols. She interfaces with many different regulatory agencies regarding vaccine stability and has presented at various conferences. She holds an Masters of Biotechnology degree from University of Toronto and a B. Sc. (Hons) from the University of Calgary in Cellular, Molecular, Microbial, and Biology.