The rapidly expanding field of cell and gene therapies (CGT) could revolutionize curative treatments. Regulatory guidance has been developed to address manufacturing guidelines and CMC specifications for CGT drug products, but occupational health and safety guidelines for manufacturing CGT products have been lacking. For example, there is no ‘universal’ toxicological or potent compound classification or risk assessment scheme for CGT manufacturing processes.
This is why BioPhorum’s CGT environmental health and safety (EHS) and biosafety team was created to bring together biopharmaceutical industry leaders. It aims to develop best practices for personal and environmental safety when conducting CGT research or clinical and commercial manufacturing.
One of the team’s outputs is an article called Environmental Health and Biosafety Risk Assessment Guidance for Commercial-Scale Cell and Gene Therapy Manufacturing, which was published in Applied Biosafety: Journal of ABSA International.
The article aims to identify best practices, improve risk controls, and help regulatory agencies develop guidance for environmental and biosafety risk assessment for commercial-scale CGT manufacturing. It includes a risk assessment template highlighting the complexity of commercial-scale manufacturing, the areas to assess, the potential questions to ask, and which other parties may input to the risk assessment.
We spoke to two subject matter experts about the article and risk template and how they have used them in their work.
Summarize the landscape of this area
“EHS is a pretty well established discipline in our industry,” said Simon Godwin, Head of Gene Therapy Technical Operations at Sanofi and one of the authors of the article. “But with these new cell and gene therapy modalities, there are unique challenges in establishing EHS systems that provide the appropriate level of control for the operator, facility, and environments. The challenge is associated with the use of human origin materials in manufacturing (e.g., cell lines) where the biosafety risk profile is case-by-case and is impacted by sourcing, testing, and control of manufacturing.”
He added, “There is also a very diverse portfolio of genetic medicines and delivery platforms all intended to provide persistent and enduring therapeutic benefit, to which the long-term safety is yet to be realized. To this end, the HSE challenges for such dynamic and diverse biological entities cannot be standardized and managed under a universal safety data sheet. As such, it requires a directed biosafety risk assessment tool that enables the site to establish its own safety practices commensurate to the risk profile of its products and processes.”
Godwin explained that, like many other organizations, Sanofi had been challenged to find a balance between the corporate need to move fast and be more flexible, against having more safety, control, containment, and established practices.
This is why working with BioPhorum has been useful as the article and template help us calibrate as an industry and work together to establish best practices based on our combined and shared experiences.Simon Godwin, Head of Gene Therapy Technical Operations at Sanofi
How did you use the BioPhorum article and template?
Ashley Holland, a safety specialist for Trinity Consultants supporting AstraZeneca Gaithersburg SHE, said its team used the template as a guide while designing its cell therapy lab. “We had a good idea of which projects would be assigned to the lab, and the template helped us ask questions about these projects and the hazards they presented. From there, we were able to update the lab’s design with additional control measures.”
She added that a concern during the design process was whether there were any ‘open’ steps. However, working with the scientists, the team identified the full process and where there was a potential for open steps. Section 4 ‘Process operations and control’ of the template fed into the questions asked by the team.
“At the time, the design phase was a fluid process,” Holland said. “So Section 6 ‘Facilities, equipment and utilities’ was a useful guide. When we met with the team, I asked similar questions about operating space, bearing in mind how materials would be transported. Section 10.0 ‘Storage, shipping and distribution’ was helpful in this step.”
Her team found Sections 6 through 12 ‘Emergency response’ were the most helpful in the design phase because they covered each aspect of the actual operation.
“While Sanofi already has an established EHS process,” said Godwin, “the BioPhorum template helped us ratify what we were doing. And because it was published in a reputable journal, it gave the whole thing more kudos.”
How did you apply the BioPhorum recommendations?
“During the design phase, we used the template as guidance and consulted with the site’s biosafety expert, Kimberly DiGiandomenico – Director SHE-Research & Animal Safety and an author of the Applied Biosafety article,” explained Holland. “At the time, we only used the template. After that, however, we adopted some BioPhorum recommendations, such as those on employee gowning and PPE, sanitization via vapor phase hydrogen peroxide (VHP), facility design with ballroom and ‘batch-dedicated’ rooms, and employee training.”
What lessons did you learn from going through this process?
“My overall takeaway from this process is that it is good to ask these questions during the design phase,” suggested Holland. “That’s when we have the most opportunity to make changes and plan ahead for topics such as those on training and admin controls. It’s also critical to consider future projects coming to the facility, not just what is scheduled. For us, projects in the pipeline have the opportunity to be moved to the facility, so asking whether the design is fit for future projects is important to keep in mind.”
Godwin said it was a little early for him to discuss lessons learned from using the template. “But I imagine that in a year or so, we’ll be able to compare how we applied the template in our businesses, how we interpreted the questions, whether we looked at things in the same way, etc. Reviewing our experiences might lead to greater harmonization.”
He added that documents like the template are always ‘translated’, so the correct use of language was crucial. “We might use British English or American English – it’s still English, but we interpret words differently. So how we use and translate the template might depend on how we understand and manage the risks. We’re still learning, so those future conversations will be really important.”
What are the benefits of being part of BioPhorum?
“For me, it’s taking a novel and complex situation and pulling together a diverse community of people with the same mindset and goal of establishing a common way of working,” said Godwin. “The template allows industry to have a great dialog, which might lead to new regulations, systems, or standards that could be applied more broadly across the industry rather than just in our own companies.”
He said that this community approach to improving our industry and the safety of our staff is what BioPhorum brings to the table. “It lets me go back to my company and look at our systems and say, ‘They’re not good enough’, or ‘Yes, we’re doing a good job’. Of course, we can’t prevent all accidents, but if one does happen, we know that we’ve done everything possible to make it the safest system available.
“As we adapt to these new modalities, these conversations help me ask, are we on the right path? Are we thinking about this the right way? So one of the main things to come out of the risk assessment is the team’s wider conversation. That’s where lessons are being learned, as it helps us ask where we’re aligned with each other and where we’re not. That’s the power of BioPhorum.”