Industry continues to feel the pressure of significant workloads and the need to juggle priorities. Sharing experiences about how to improve routine development activities is seen as one way to drive industry-wide benefits.
Spurred on by lessons learned from the Covid-19 pandemic, BioPhorum has been working hard in this area. The Development Group’s Speed to First-In-Human Workstream is a great example of how BioPhorum recognizes industry’s ever-pressing need to streamline development and get much-needed medicines into clinics faster.
One such piece of work is a major benchmarking survey looking at the technical practices of key process/product development activities when manufacturing therapeutic proteins. It also considered the impact of Covid-19 accelerated work programs, whether any changes could be retained as part of sustainable long-term business practices, and the impact of any accelerative actions on the wider development process.
The findings and analysis have been documented in Accelerated CMC workflows to enable speed to clinic in the Covid‐19 era: A multi‐company view from the biopharmaceutical industry, which has been published in Biotechnology Progress.
“The paper discusses acceleration levers for the future and shows there are many opportunities to get faster to clinic,” said Klaus Kaiser, Head of Downstream Development at Bayer. “It will also help us challenge our conservative development procedures and show how we can take some managed risks. I think it will help regulatory authorities understand our risk-based approach, hopefully leading to more standardization and industry acceptance.”
Some of the key findings from the survey include:
Investigational new drug timelines
Most Covid‐19-specific development programs took 6–9 months, while most non‐Covid-19 development programs took 13–18 months. The ‘slowest’ Covid‐19 program took broadly the same time as the ‘fastest’ non‐Covid program (10–12 months).
Some companies modified their workflows for candidate screening for Covid programs, e.g., 1 in 3 of Covid accelerated programs bypassed transient screening of candidate molecules, compared to roughly 1 in 25 non‐Covid programs.
Cell line selection
Developing a product during a pandemic requires consideration of different factors; this saw the number of respondents rating product quality as ‘highly important’ change from ~93% to 60% for non‐Covid and Covid accelerated programs, respectively.
Toxicology to clinical process
Several companies took a risk‐based approach to drug product stability to accelerate clinical timelines. For example, the availability of clinical material for first-in-human studies was expedited by providing fewer non‐GMP drug product stability time points in regulatory filings before administering the first human dose.
Minimizing early phase development time means candidate treatments can be clinically evaluated as early as possible in support of this goal – but if not managed properly, a failed regulatory submission is possible.
Learning from Covid
When asked what acceleration actions taken during Covid programs would become part of their non‐Covid programs, there was a fairly strong overlap between certain areas focused on to reduce early phase CMC development timelines, i.e., platform development and cell line development.
“I think the value of this paper is that it provides insight into the approaches taken across industry (e.g., pharma companies, CDMOs, and suppliers) to accelerate development activities to meet the urgent need brought on by the pandemic,” said Frank Ritacco, Senior Director, Cell Culture Development at Regeneron. “It’s really interesting to see what approaches were commonly used, which were not used as much, and which proved successful enough that they may become standard approaches for development moving forward. The paper provides the kind of cross-industry benchmarking trends and insights that only a consortium such as BioPhorum can facilitate.”
The paper also contains a table on technical development suggestions for how to optimize the speed-to-clinical evaluation.
“The main value of this paper is that it generates awareness of how we can accelerate towards the clinic when developing innovative medicines, and thus bring potentially life-saving therapies to patients earlier,” said Ingo Gorr, Head of Therapeutic Virus Development at Boehringer Ingelheim. “Having options collected by an industry consortium creates a common understanding and makes it easier for companies to follow the accelerated route. It also provides a foundation for regulatory authorities to accept new ways to do this.”
The Covid‐19 pandemic has created unique challenges for biopharmaceutical companies to formulate and manufacture effective medicinal solutions. Given the urgency for such treatments, expediting the speed to initial clinical evaluation requires accelerated development. The paper emphasizes that it is possible to make safe and efficacious products quicker than what is currently accepted. This learning will benefit everyone, including patients, industry, and all associated stakeholders.
“I hope companies share their experience of accelerating development,” added Kaiser. “For example, was there more risk created when they shortened their stability program or when they only had a limited number of drug product formulations? This just leads to further learning for everyone.”
Want to read more? Download a copy of the benchmarking survey here and the analysis article.