Considerations when designing a scale up strategy; Tools for scale up calculation and facility fit assessment; Case studies.

This presentation will cover the strategy for clone and process platform selection for a therapeutic fusion protein. The selection process involves generating clonal cell lines, assessing the cell culture process performance, and evaluating product quality attributes in automated microbioreactors. Perspectives from product development, analytical product quality comparability, cost of good reduction, and strategies for further process development will be discussed.

The focus on accelerated development of new modalities for advanced therapies and challenges with complex drug candidates has driven adoption of novel concepts and technologies in biopharmaceutical development and manufacturing. The active drug substances have become more structurally complex and R&D timelines continue to be compressed, the technologies necessary to provide safe, robust and economical access to these molecules needs to keep pace. Emerging technologies such as continuous processing, automation, high throughput experimentation, predictive modeling in an integrated fashion can expedite process development and commercial manufacturing while ensuring efficiency and delivering quality products. All these aspects help to minimize the time and cost associated with development and manufacture of drugs and bring medicines to patients more effectively. This presentation will share AbbVie’s strategy and experiences in integrating such end-to-end technologies into process development and manufacturing facilities and discuss the challenges and opportunities associated with our approaches.

Given the complexity of biological products, effective control strategy and life cycle management are critical to delivering quality products with intended efficacy. This presentation will focus on an overview and guidelines to develop and implements analytical control strategy approach to streamline and harmonize quality control testing and method life cycle.

Antibody drug conjugate therapeutics are an increasingly common modality due to their targeted ability to deliver various cytotoxic or immune-modulating payloads to specific cell types or tissues. This presentation covers a case study navigating the added complexity of selecting an appropriate mAb binder, payload, conjugation method, and drug-antibody ratio with emphasis on opportunities and challenges to accelerate pre-clinical development and IND filing.

• An update on NIIMBL’s activities working towards key fundamentals
  • Security of supply chains
  • Flexibility of facilities to match varied and changing demand across portfolios of products
  • Faster development with supply chains that can match this
  • Sustainability for raw materials, components, and energy

Disposable technology is being used more each year in the biotechnology industry. Disposable bioreactors allow the user to avoid expenses associated with cleaning, assembly and operations, as well as equipment validation. Disposable bioreactors have played a key role to meet the increasing run rate of the Cell Culture Pilot Plant while maintaining a high success rate, reducing labor costs, increasing efficiency, and lowering the risk of contamination. Recent effort to evaluate the next generation 10:1 turndown single use bioreactor with different cell retention devices to challenges oxygen mass transfer, carbon-dioxide stripping while assessing foaming, and vent filter sizing. This presentation will focus primarily on the advantage of the next generation high turndown single use bioreactor that comes with different sparger options (enhanced DHS and mircrosparger), and tubing for different cell retention device connection. Additionally, the high turndown provided a wide range of working volume allowing us to truly test the true scale down of the cell retention device for its maximum flux and filter throughput. The evaluation provided important system performance, operation experience, and cell culture performance data when comparing the next generation high turndown disposable system with respect to the legacy 2:1 and 5:1 turndown single use bioreactors, and conventional stainless-steel bioreactor system.

• Can scale down models help with implementation?

Next generation manufacturing through implementation of advanced technologies is one of the current focus areas to enable agile, reliable, cost-effective, and timely production of biopharmaceuticals at highest quality standards. New modalities beyond standard mAB characteristics and complex supply chain logistics in a VUCA environment are factors to consider when designing the plant of the future and will impact the competitive advantage through application of advanced technology concepts. The talk will provide examples of deployment in context with business needs and added value.

Shifting from batch to continuous manufacturing is a promising way of lowering manufacturing costs of by allowing operations to run simultaneously with reduced downtime, higher productivity, and at several-fold smaller scale. This is particularly promising for gene therapy products using recombinant adeno-associated viral vectors (AAV), as treatments currently cost up to USD 3.5 million per patient and have high cost-of-goods ranging up to USD 1 million per dose. In this talk, we present approaches for intensification of downstream AAV manufacturing processes using principles of continuous processing.