Regulatory Aspects of a cGMP Continuous Drug Substance Process and Contrasts with Continuous Drug Product
Continuous drug substance processes were run in a new building that won the International Society for Pharmaceutical Engineering 2019 Facility of the Year Award for Innovation. The talk focuses on the benefits of continuous drug substance processing, regulatory aspects, and contrasts with continuous drug product. There was no startup transition waste 10 out of 13 unit operations. Three different continuous reactions all started with a planned amount of startup transition waste, but product collection started before steady state for all of them. The continuous extractions, evaporations, crystallization, semi-continuous filtration, and one of the reactions all started in a controlled procedural manner without diverting any material to waste. Processes were designed for ease of stop/restart with no diverting to waste. Run time in the plant (>1 month) was longer than in development. Surge tanks decoupled upstream and downstream continuous sections, and also facilitated the use of rolling average approach for quantifying acceptable magnitude and duration of disturbances. PAT frequency was less than DP CM, enabled because of long mean residence times and broad RTDs. High specificity of on-line HPLC was more important than high frequency of spectroscopic probes. PAT was used for the continuous reactions, but only parametric control was used for workup and isolation, including continuous crystallization. Continuous crystallization was needed for kinetic rejection of a key quinoline dimer impurity which could not be rejected thermodynamically. PAT and parametric control both informed divert and return from divert. Batch size ranged from 4 kg to 18 kg API, taking advantage of the flexible batch size benefits of CM. RTD Modeling quantified lot genealogy. Cleaning frequency was adjustable. It was left to the judgment of the cGMP operations and technical staff to decide when it was time to stop for a cleanout, rather than specifying a fixed time duration. It is anticipated that each subsequent run will get longer than the previous before cleanout because of the gained understanding of fouling mitigation over time. Parametric control was used for several continuous processing sections. Development scale was 200X-1000X smaller than manufacturing scale.

Emerging Technologies in Drug Delivery Combustion Products: Drivers and Limiters
Presentation will review the key combination product drug delivery device technology trends to meet the future needs of biopharmaceutical users, and what are the key elements that are accelerating or limiting the maximization of these technologies.

Achieving Decarbonization & Resilience with Microgrids
Amgen and AlphaStruxure will co-present ongoing initiatives to achieve carbon neutrality and enhance energy resilience at Amgen’s largest manufacturing facility in Juncos, Puerto Rico. Judith Velazquez, Executive Director of Engineering at Amgen, will present an overview of facility processes/infrastructure, sustainability goals, and energy drivers unique to Puerto Rico as well as results, benefits, and lessons learned from real-world energy optimization and generation projects. Philippe Bouchard, VP of Development at AlphaStruxure, will present evaluation and conceptualization of a fully integrated microgrid – including solar PV, battery storage, and cogeneration – as well as emerging technologies such as green hydrogen, carbon capture and biomass gasification to achieve carbon neutrality.

Building an In-House Cell and Gene Therapy Manufacturing Facility during the Pandemic
The impact and disruption caused by the COVID-19 pandemic added an unprecedented level of risk and complexity for companies like Expression Therapeutics who were in the midst of constructing a new manufacturing facility. By taking a flexible project execution approach including pre-fabricated cleanrooms, the company was able to adapt to the situation and overcome the challenges ultimately resulting in the successful completion of the project on time and under budget. The project case study will be presented.

Precision in Time: Delivering Results in Urgency
o The world handed our industry an urgent and paramountly important need for precise medicine, with considerably zero warning. When the COVID-19 pandemic reached the world and became more than a regional concern, life as we knew it came to a screeching halt, lives were lost at unprecedented rates, and many more were at risk every day. Within the Pharmaceutical Industry, we had an Urgent need to deliver precision in time. The COVID-19 Vaccine was developed, tested, and available for global public use faster than any other vaccine, or drug product, in history. This presentation dives into some of the background, development tactics, project management, and the facilities of the future, that tie together to prepare our industry for the next Urgent need, the next pandemic, and the next vaccine that will help save countless lives.

ElevateBio BaseCamp: Redefining Biomanufacturing and Agile Scaling of Operations
This presentation will provide an overview of the design and operations of BaseCamp in Waltham, discuss lessons learned, and our approach to scaling and operations of additional facilities in the future.