Operational vision: Adoption of in-line monitoring and real-time release

Historically, the biopharmaceutical industry has relied on traditional pharmaceutical manufacturing practices to make and release products. This publication examines the future of biopharmaceutical manufacturing by presenting the vision of fully implemented in-line monitoring (ILM) and real-time release (RTR) (as described in BioPhorum biomanufacturing technology roadmap first edition¹).

This aspirational vision includes full ILM, predictive analytics and advanced process controls (APC) enabling release of product in real time, with concomitant predictive and preventative alerts and resolution of process, equipment and other production issues.

A strategic high-level overview for engaging senior sponsors and stakeholders in achieving the vision of full adoption of ILM/RTR with process analytical technology (PAT) and embedded quality by design (QbD) is presented in this document. Achieving the vision will provide benefits in efficiency and yield, due to better process understanding allowing real-time adjustment of conditions and reducing time to market. RTR will reduce the time for existing products to get to patients and enable efficiencies in the supply chain.

To facilitate adoption and ensure global consistency, new regulatory guidelines and policies are needed to support the future state of ILM/RTR, as well as to facilitate submissions for new and existing products. Regulatory agencies need to be involved throughout the process to prevent bottlenecks resulting from missing or inconsistent guidelines.

This publication outlines a scaled approach to adoption, from stage one to five, to aid in establishing a baseline and setting a target. The operational vision paints a picture of the required ways of working to operate a factory with the technology of the future at adoption stage 05.

Each organization will start at a different stage and will define their own vision and targets. An organization may operate at a range of adoption stages, per product or per plant, depending on business requirements, capabilities and justification for investment.

To support the adoption of ILM/RTR, this publication includes case studies from member companies demonstrating different approaches to, and stages of, ILM/RTR and real-time release testing (RTRT). RTRT refers to the testing and process controls required to ensure the quality of raw materials, intermediates and product. RTRT is a subset of the overall vision for RTR.

BioPhorum is working with the industry, bringing together thought leaders and fostering rich and dynamic discussions that enable forward movement of the ILM/RTR vision. The groups are multi-disciplinary and provide a place to draw on one another’s experience, accelerating ILM/RTR as a whole in the industry. This is the first in a series of publications that will eventually form a playbook for adoption of
ILM/RTR covering stages one to five.