Spectroscopy in Pharmaceutical Analysis

A joint virtual conference presented by Spectroscopy magazine, the Society for Applied Spectroscopy, and the Coblentz Society

This event is now available on demand.

Register for the event to gain free access to all sessions.

Event Overview:

What are the latest capabilities of spectroscopic techniques in pharmaceutical analysis? What is the current state of implementation of these techniques? How do the latest techniques and applications fit into the current regulatory context? Join us for this insightful two-day virtual symposium—presented jointly by Spectroscopy, the Society for Applied Spectroscopy, and the Coblentz Society—to get the answers to these questions and more, as we look at the application of a range of spectroscopic techniques for different types of analyses in the pharmaceutical industry, from early R&D through manufacturing. And ask your own questions during the live question-and-answer sessions with the speakers.

Each day, there will be a morning session and an afternoon session. The morning sessions will provide a series of 30-minute talks, followed by an interactive question-and-answer (Q&A) and discussion period with all the speakers. In the afternoon sessions, leading instrument suppliers will give 20-minute talks discussing troubleshooting, tips-and-tricks, and applications.
We wish to extend a special thank you to our symposium committee, of members and officers of the Society for Applied Spectroscopy and the Coblentz Society, for developing this program:

Benoit Igne of Vertex Pharmaceuticals
Larry McDermott of Vertex Pharmaceuticals
Brandye-Smith Goettler of Merck
John Wasylyk of Bristol Myers Squibb
Ellen V. Miseo, a consultant
Andrew Whitley of Horiba Scientific
Adam Hopkins of Metrohm USA, Inc.

Who Should Attend:

Anyone using spectroscopy techniques to solve practical problems in the pharmaceutical industry—from early R&D through manufacturing.

Key Things You Will Learn About:

Innovative uses of spectroscopic tools
The still large potential for more uses of spectroscopic techniques when combined with contemporary computing power and artificial intelligence
The combination of mid-IR, Raman, and focused beam reflectance measurements as a “smart” system to optimize crystallization processes
The full context of spectroscopic techniques in the tests and procedures of the USP-NF
The verification of USP compendial procedures and validation of alternative procedures
Using NIR spectroscopy to characterize multiple direct compression (DC) blends, complementing existing formulation development tools
How machine learning and hyperspectral imaging are advancing biocatalysis
The current state of the art and near future of application-driven PAT innovation
Best practices in managing the lifecycle of approved PAT methods
Using the unique chemical fingerprints of drug products obtained with Raman, IR and NIR spectroscopy to identify counterfeits or authenticate legitimate products
The role of low-frequency Raman spectroscopy in solid-state characterization of pharmaceuticals, as an alternative to XRPD

For any technical questions please contact Jordan Ramesh:
jramesh@mjhlifesciences.com

Symposium Agenda:

Wednesday, November 30
Morning session: 9:30 am – Noon EST

Spectroscopy in Pharmaceutical Analysis I

9:30 am EST
The Use of Spectroscopic Techniques in Pharmaceutical Analysis
Stephen Hammond, Steve Hammond Consulting LLC

Spectroscopy plays a huge and vital role in analysis of pharmaceutical processes and products. Every step of the manufacturing path uses different types of spectroscopies, from the acceptability of raw materials through to control of processing steps for active ingredient and drug product; the quality assessment of final products; and in the area of packing operations. If these techniques are used in manufacturing, then they also played an important role during research and development. Many of the applications have become commonplace, for example the use of infrared and Raman handheld spectrometers for raw material identification and conformance. The combination of mid-IR, Raman, and focused beam reflectance measurements are used extensively in active ingredient process development and manufacturing. In this presentation a case study will be used to describe the use of these technologies as a “smart” system to optimize crystallization processes. The steady migration to manufacturing of drug product using continuous systems, and the desire for real time release (RTR) has driven the development of more sophisticated measurement systems that can operate in a dynamic environment. The interfacing and use of fast scanning near-infrared (NIR) probe–based instruments in manufacturing equipment will be presented as a case study to illustrate this new capability. This talk will review some newer innovative uses of spectroscopic tools and illustrate the still huge potential for even more uses of these techniques when combined with contemporary computing power and artificial intelligence.

10:00 am EST
Applications of Spectroscopy Analytical Techniques in the USP–NF
Edmond Biba (presenter) and Horacio Pappa, the United States Pharmacopeial Convention (USP)

The presentation covers the use of spectroscopic techniques in the tests and procedures of USP-NF compendia. A historical summary of the evolution of spectroscopy techniques in the general chapters of USP–NF will be presented first, followed by a brief discussion of USP general chapters for individual techniques. Then the talk will focus more on the use of vibrational spectroscopy and revisions and updating of the respective general chapters. The components of spectroscopy chapters numbered below 1000 and above 1000, as well as the respective rationale, will be discussed. General consideration regarding the verification of compendial procedures and validation of alternative procedures as included in respective general chapters also will be addressed.

10:30 am EST
Development of a Near Infrared (NIR) Spectroscopy–Based Characterization Approach for Inherent Powder Blend Heterogeneity in Direct Compression Formulations
Zhenqi Shi (presenter and corresponding author), Kallakuri Suparna Rao, Prajwal Thool, Robert Kuhn, Rekha Thomas, Sharyl Rich, and Chen Mao (corresponding author), Genentech Inc.

With the advent of the continuous direct compression (CDC) process for pharmaceutical manufacturing, it becomes increasingly desirable to characterize inherent powder blend heterogeneity at a small batch scale for a robust and CDC-amenable formulation. To accomplish this goal, a near infrared (NIR) spectroscopy–driven characterization approach was developed and implemented on multiple direct compression (DC) blends in this study, with the intended purpose of complementing existing formulation development tools and making it possible to build an early CMC data package for late-phase process analytical technology (PAT) method development. Three fumaric acid DC blends, designed to harbor varied degrees of inherent blend heterogeneity, were employed. Near-infrared spectral data were collected on a kilogram-scale batch blender via both time- and angle-based triggering modes. The time-triggered data were used to investigate the blending heterogeneity with respect to rotation angles, while the angle-triggered data were used to provide blending variability characterization and compare against offline HPLC-based results. The time-triggered data revealed that the greatest blend variability was observed between revolutions, while the blending variability within a single revolution stayed relatively consistent with respect to rotation angles. The angle-triggered data showed that there is a consistent trend between NIR spectroscopy and HPLC-based methods on characterizing blend heterogeneity across different estimated sample sizes for individual blends, and across the three blends at a given sample size. This study contributes to establishing NIR spectroscopy as a potential characterization approach for inherent powder blend heterogeneity for early R&D. It also highlights the promise of continuous characterization of inherent powder blend heterogeneity from gram scale to mini-batch CDC scale.

11:00 am EST
Machine Learning and Hyperspectral Imaging for Enzyme Immobilization Analysis: Advancing Biocatalysis for Pharmaceutical Applications
Joseph P. Smith, Merck

Biocatalysis has rapidly become an essential tool within pharmaceuticals for the development of efficient, safe, and sustainable chemical syntheses. Immobilization of the biocatalyst, typically an engineered enzyme, offers significant advantages, including increased enzyme stability, improved resistance to environmental change, and enhanced reusability. Determination of the spatial distribution of the immobilized enzyme is key for proper functionality; however, currently available analytical tools are frequently inadequate. Machine learning, in the form of multivariate curve resolution, with Raman hyperspectral imaging, is presented here as a methodology for investigating the spatial and chemical distribution of evolved pantothenate kinase immobilized onto two diverse, microporous resins. An exhaustive analysis indicates that this proposed technology can successfully resolve, both spatially and spectrally, all chemical species involved in enzyme immobilization, including the enzyme of interest, both resins, and other key components. Quantitation of the spatial coverage of immobilized enzyme, a key parameter used for biocatalytic process development, was successfully accomplished. Optimal analytical parameters were elucidated, including evaluation of different excitation wavelengths. Exploratory chemometric approaches, including principal component analysis, were utilized to investigate the chemical species embedded within the data sets. The totality of this information can be utilized for an enhanced understanding of enzyme immobilization processes and can thus enable improved implementation of biocatalysis within the scientific and pharmaceutical communities.

11:30 am EST
Question-and-answer period with all the speakers in the session

Afternoon session, 2:00–4:00 pm EST

Spectroscopy in Pharmaceutical Analysis: Applications, Tips, and Best Practices from Our Sponsors
2:00–4:00 pm   Leading instrument suppliers give educational 20-minute talks addressing applications, tips, and best practices in the use of spectroscopy in pharmaceutical analysis

2:00 pm EST New NIR Spectrometers Using Fourier Transform Technique
John Gilmore, Business Development Manager, Hamamatsu Corporation

John D. Gilmore has been characterizing leading-edge photonic devices for over three decades. He has developed sophisticated test and measurement capabilities, enabling precise characterization of image sensors and spectrometers. In addition, he has vast knowledge of the operation, optimization, and practical use of photonic devices, with particular emphasis on image sensors, spectrometers, and Raman modules. He received his B.S. degree in electronic engineering technology (EET) from Capital Institute of Technology, in Laurel, Maryland, in 1986, and received his M.S. degree in electrical engineering with a concentration in solid state devices and material processing from the New Jersey Institute, in Newark, New Jersey., in 1993. He joined Hamamatsu Corp. in September of 1986 and is currently the spectrometer business development manager. He is currently involved with the development of application-specific inspection equipment, general spectrometer marketing, and advanced field technical support.

2:20 pm EST Raman Spectroscopy and Imaging in Life Sciences and Pharmaceutical Research
Ievgeniia Iermak, Application Scientist, Witec GmbH

Raman imaging microscopy is a versatile, label-free and nondestructive chemical characterization method based on an energy shift in light scattered by molecules. It can provide high-resolution information about the composition and spatial distribution of materials. The technique is well suited for studies of pharmacological formulations and their interactions with cells and tissues, as well as for quality control, drug discovery and counterfeit product identification. This presentation will provide an overview of Raman imaging microscopy, describe recent developments in its associated technology, and offer several vivid examples of its application in life sciences and pharmaceutical research.

2:40 pm EST Overcoming Analytical Bottlenecks for Batch and Continuous Manufacturing in a GMP Environment with Raman Spectroscopy
Justin Moretto, Product Manager, Endress+Hauser

Many of the challenges facing manufacturers of pharmaceutical products can be attributed to the rigorous and resource-intensive testing at various unit operations in order to ensure the highest quality products. The FDA has recently demonstrated increased confidence in spectroscopic techniques, and Raman specifically, as a tool for the monitoring of continuous pharmaceutical manufacturing. Interesting opportunities for monitoring and automation in the areas of multi-layer coating, granulation CQAs, crystallization, and content uniformity at concentrations under one percent will be discussed through the lens of GMP implementation and regulatory opinions.

3:00 pm EST Fast Tablet Imaging Using FTIR and QCL Microscopy
Thomas J Tague Jr, Ph.D., Applications Manager, Bruker Scientific, LLC

Thomas Tague is the Applications Manager for Bruker Corporation. He is also a member of the Visiting Advisory Committee of the Metropolitan Museum of Art in New York and the Advisory Board of Amplified Sciences. Dr. Tague received his Ph.D. from the University of Utah in Chemistry and his B.S., also in Chemistry, from the University of Texas at San Antonio. He conducted his postdoctoral research at the University of Virginia working with Professor Lester Andrews. He is a member of the American Chemical Society, Society for Applied Spectroscopy, American Physical Society, and the Optical Society of America. Dr. Tague is active in developing new methods and instrumentation with the goal of improving the sensitivity and detection limits of spectroscopy related applications. Tom has more than 90 publications and 5 Patents.

Thursday, December 1
Morning session: 9:30 am – Noon EST
Spectroscopy in Pharmaceutical Analysis II

9:30 am EST
Application Driven PAT Innovations: Some Already Available But Not Yet Widely Adopted, the Current State of the Art, and the Not-Too-Distant Future
Martin Warman, Martin Warman Consultancy Ltd

Focusing on the needs of the application often gives opportunities around deploying instruments with a higher capability in development and early commercial manufacturing (whilst establishing process understanding) but then deploying a simpler and higher sensitivity application-specific “sensor” once the causes of variance in the process are better understood—possibly coupled with offline analysis using an instrument that has a lower frequency but much higher capability to verify that process understanding is current. This presentation will give examples of where small modifications in configurations of existing technology can drastically improve application specificity but also where an instrument with wider or narrower capability can be appropriately selected, dependent on the degree of process understanding, and how this approach is driving new technology development to meet those needs.

Further, defining a comprehensive PAT-enabled control strategy that enables in-process control (IPC) and real-time release (RTR) is challenging, but the real-world execution of such a strategy is another level. Here we will discuss some of the technical and operational challenges of first establishing that a process is in a state of control and then ensuring that it stays within a state of control, such that we can ensure the quality of the finished product. This includes establishing, justifying, and operating a strategy for periods when PAT data are not available for in-process control but also to ensure appropriate data are evaluated for real-time release, as well as the generation for batch reports including these data for product disposition.

10:00 am EST
Lifecycle Management of Approved PAT Methods
Larry McDermott, Vertex Pharmaceuticals

Process analytical technology (PAT) systems such as spectroscopic analyzers utilizing multivariate models play an integral part in most pharmaceutical continuous manufacturing lines. During the lifecycle of the product, changes to the process or to process analytical methods must be handled through the company’s pharmaceutical quality management system, with critical attention to any regulatory agency commitments. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q12 guideline on technical and regulatory considerations for pharmaceutical product lifecycle management provides a framework to facilitate the management of post-approval chemistry, manufacturing, and controls (CMC) changes in a more predictable and efficient manner. Model performance must be monitored through the lifecycle of the product through an active continued process verification (CPV) program. Trending is conducted to ensure processes and analytical methods remain stable and perform within a validated state. This presentation will provide examples of lifecycle management and effective change management of models including model updates performed to enhance model robustness over time for models used on a near infrared (NIR) spectrometer installed in-line on an oral solid dosage continuous manufacturing line that has been in use since approval in 2019.

10:30 am EST
Suspect and Counterfeit Drug Screening Using Various Analytical Techniques
Ravi Kalyanaraman, Bristol-Myers Squibb

Counterfeit drugs are potentially dangerous and serious threats to patients globally. It is estimated that approximately 10 to 20% of the world’s pharmaceutical drugs are counterfeited. Even in countries that are generally considered to have a more regulated environment, such as the USA, the UK, and Canada, counterfeit medicines have entered the legitimate supply chain due to increasing international trade and sales via the internet. Due to this infiltration, pharmaceutical manufacturers and health authorities have found ways to authenticate and identify their product by various technologies. These technologies include covert and overt features along with serialization added to the packaging material and authenticating the suspect drug product for these features. One of the effective ways to authenticate and verify the chemical contents in a pharmaceutical product is by using Raman, infrared (IR) and near infrared (NIR) spectroscopy and by obtaining a unique chemical fingerprint of the drug product using these techniques. Using these product fingerprints, for the past 15 years we have shown that it is possible to test a suspect sample and identify if it is a counterfeit and to authenticate if it is a legitimate product. Solid dosage forms (tablets and capsules) and liquid dosage forms (biologics) were analyzed in a non-destructive manner with little or no sample preparation. This talk will feature specific examples of screened counterfeit drugs using spectroscopy and other analytical techniques.

11:00 am EST
Low Frequency Raman Spectroscopy for Evaluation of Crystallinity in Ritonavir
Huzeyfe Yilmaz (presenter), Manolya Kukut Hatipoglu, and Daniel Willett, U.S. Food and Drug Administration (FDA), Division of Complex Drug Analysis, Center for Drug Evaluation and Research, St. Louis, Missouri, USA

Ritonavir is a protease inhibitor used for the treatment of acquired immunodeficiency syndrome (AIDS). More recently it has been used for treatment of coronavirus disease (COVID-19) where ritonavir is co-packaged with nirmatrelvir as Paxlovid under an emergency use authorization by the U.S. FDA. The drug was marketed as a semi-solid capsule in 1996 and was discontinued in 1998 because of a failure to meet dissolution requirements due to the presence of a second crystalline polymorph. In 2010, an amorphous ritonavir formulation produced through hot melt extrusion (HME) was approved by the FDA. The current reference listed drug (RLD) and generic products for ritonavir should possess minimal to “none-detected” levels of ritonavir in its crystalline form in immediate release (IR) tablets. Traditionally, crystallinity and polymorph analysis for active pharmaceutical ingredient (API) is performed using X-ray powder diffraction (XRPD). Emerging technologies in solid state characterization of pharmaceuticals, such as low-frequency Raman spectroscopy, offer alternatives to XRPD with similar level of sensitivity and minimal sample preparation.

11:30 am EST
Question-and-answer period with all the speakers in the session

Afternoon session, 2:00–3:00 pm EST

Spectroscopy in Pharmaceutical Analysis: Applications, Tips, and Best Practices from Our Sponsors
2:00–3:00 pm   Leading instrument suppliers give educational 20-minute talks addressing applications, tips, and best practices in the use of spectroscopy in pharmaceutical analysis

Speakers