Exclusive Interview with AbbVie's Continuous Processing SMEs
Interview Panel
Moiz Diwan, Head of Enabling Technologies
Presently, Moiz is leading Center of Excellence for Enabling Technology Development, a cross functional team of chemists, engineers and PAT scientists, impacting process development of various modalities such small molecules, antibody drug conjugates (ADCs), dermal fillers, etc. Moiz is also founder of FAST – Flow and Automation Strategy Team at AbbVie. FAST is a multi-disciplinary team of scientists and engineers from 13+ AbbVie sites across Discovery, Development, and Operations Manufacturing organization to efficiently share capabilities and resources, facilitate collaboration and provide strategic advancement on lab automation, plant automation, information management and continuous manufacturing technologies to maximize the impact.
Nandkishor Nere, Volwiler Research Fellow/Director
Nandkishor heads the critical cross-functional Center of Excellence (CoE) team and is responsible for API crystallization process development for the entire small molecule pipeline of AbbVie, Dr. Nere was the founder-leader of highly impactful AbbVie wide Cross-functional Modeling Forum (CMF). The CMF has been instrumental in developing various modeling platforms for the key CMC processes spanning small and large molecules.
Eric Moschetta, Senior Scientist II
Eric joined AbbVie in 2016 and is currently a senior scientist in Process Engineering in Process R&D. His current research interests include continuous extraction, photochemistry, kinetic modeling, flow chemistry, and crystallization.
Interviewer
Jennifer Small, Senior Program Director, CCP Summit
The 6th annual CCP Summit will be taking place in March 2022, and is the yearly meeting point for the strategical & scalable implementation of continuous processing across synthetic molecules & biologics in pharma. Built in collaboration with those at the forefront of this technology, the summit pairs technical case studies with stakeholder engagement and regulatory insights.
Opening Remarks
Moiz: The pharmaceutical process development pipeline is notoriously complex, intricate, and time consuming. Last year, as an industry, we spent over $60 billion dollars alone on Research and Development (R&D). The average time to market a new drug is 10 years with costs being at an all-time high. The major components of this long development timeframe have traditionally been lengthy clinical trials and stringent regulatory approval processes.
The pharmaceutical industry needs to:
In recent years, the adoption of novel technologies and scientific approaches, including predictive modeling, continuous manufacturing, automation, and advanced controls and informatics has accelerated to address these needs. The pharmaceutical industry and regulatory authorities have started to recognize the economic, environmental and safety benefits of continuous processing.
Jennifer: What is your vision for the future of the Flow and Automation Strategy Team at AbbVie? Do you think continuous processing will ever overtake batch for products at AbbVie?
Moiz: For the last two decades continuous manufacturing (CM) and flow chemistry have been constant topics of conversation in the pharmaceutical industry. Yet, despite environmental, economic, and time-to-market benefits, the adoption of CM technologies still faces resistance. Reasons for this include a lack of experience implementing CM processes, a natural propensity to stick with the status quo, build-up of appropriate infrastructure from lab to plant, and concerns around filing strategies. To address these constraints, we recently have endeavoured into developing end-to-end automated capability to screen and develop flow process. Idea is to democratize the adaption of these enabling technologies and have developed a strategy for evaluating, developing, and applying CM technologies across our small molecules and antibody-drug conjugate pipelines.
In cooperation with external vendors, we are developing a walk-up flow chemistry bench equipped with a variety of fluid dosing, reaction, and Process Analytical Technologies (PATs) that will enable chemists from across the company to easily evaluate multi-step continuous processes. The system will critically enable automated design space generation for flow processes, while also giving users the flexibility to interface with enabling technologies including photochemical and electrochemical synthesis. By combining advanced automation with data-driven experimentation, kinetic modeling, Artificial Intelligence (AI) process modeling and an intuitive yet robust interface, we plan to make flow chemistry process R&D accessible and harmonized within our organization.
Additionally, At AbbVie, we just completed setting up new laboratory and clinical manufacturing facility in North Chicago amenable for continuous process development and manufacture. Our vision and strategy is to develop these infrastructure and technologies in proactive manner and leverage them in timely manner. These facilities are ready and will play significant role in bring many unmet medical needs to patients faster and better. We will be sharing some of these newest capabilities at the upcoming CCP Summit.
Jennifer: We’re looking forward to your presentation Nandkishor on ‘Harnessing Modeling for Efficient Bio-Pharmaceuticals Process Development’. Do you feel that we utilize modelling enough in continuous processing? What more can be done to fully leverage technology?
Nandkishor: Experimentation for both the bench and commercial scales for continuous processes is highly intricate, expensive and can be time consuming. Modeling can certainly provide an inexpensive avenue of process understanding and optimization. However, it remains seldomly exploited. Development of easy to use robust integrated multiscale and multi-process models would be a key to fully leverage modeling technologies.
Jennifer: Eric, many pharmaceutical companies have ambitious sustainability goals; whilst continuous processing is often considered inherently ‘greener’ than batch, why is it essential that we still make a conscious effort to make our processes ‘greener’?
Eric: We are obligated to make our processes greener because it is imperative to reduce our industry’s impact on environmental and climate issues. We have a tremendous opportunity to shift the paradigm of commercial process development to include environmental impact as part of the overall approach.
As we make our processes greener earlier in development, we will instill better habits and practices that we can apply across process development and we will reap the benefits as we transition to commercial manufacturing.
Jennifer: Thank you for sharing your thoughts with us today and exciting work at the upcoming CCP Summit. Why do you feel that it is important that the community comes together to discuss the commercial implementation of continuous processing in Pharma?
Eric: Discussing our best practices and lessons learned as a community reduces the chances of “reinventing the wheel” across the industry. Sharing our experiences and knowledge allows us to align more easily with regulatory expectations and solving common technical challenges with continuous processing.
Moiz: Beyond what can be accomplished individually by each company, increased emphasis on industry academia collaborations, as well as pre-competitive collaborations among pharmaceutical companies will continue to drive greater scientific understanding and leveraging of collective resources to develop new tools and capabilities. We believe that companies that are proactively investing in technologies and in the development of talent that enable transformations will be better positioned for a sustainable future.
The successful adaptation of these enabling technologies relies on the ability of various scientists to work in a highly multidisciplinary and dynamic environment. Development of efficient and robust manufacturing processes requires cross functional expertise. Therefore, it is critical to facilitate cross-disciplinary collaboration not only among chemical engineers, but also synthetic organic chemists, analytical chemists, materials scientists, and pharmacists.
For example, robust reaction process design for small molecule APIs (active pharmaceutical ingredient) needs input from synthetic chemists for reaction mechanism and impurity identification, and from chemical engineers for reaction kinetics, mass transfer and scale-up considerations. Both chemists and chemical engineers are essential for developing innovative solutions required to translate challenging synthetic reactions into viable processes by using specialized reactor designs. Development of these solutions also requires appropriate online and offline data generation and analysis via PAT and other analytical methods.
To hear more details on the Team’s upcoming presentations at the 6th Annual Commercializing Continuous Processing in Pharma Summit download the full event guide, including primer workshops, ATMP focus day and site visit.