One conversation with Michael Blackton, VP QA CMC at Adaptimmune, proves why he is known for being a passionate, results-oriented leader focused on QA, analytical development, and more. Validate for yourself as Blackton answers my questions about process development and quality management. And, he provides a fresh outlook on recruiting senior-level executives.
Harris: What are the challenges unique to process development?
Blackton: From a quality perspective, the challenge is getting to a defined process that has enough documentation and rigor to allow you to move forward with your clinical trials.
For cell therapy, there’s not enough existing, historical data. Cell therapy is unlike monoclonal antibodies, which has years and years of process understanding as well as a whole class of drugs that are essentially the same process and a large pool of scientific knowledge within and across the industry to bring these drugs to market.
Many precedents exist for traditional biologics. But when it comes to cell therapy, these products are so new, and they’re so academic that there’s not a lot of life cycle understanding to bring these drugs to market.
The quality professional’s challenge is guiding a largely academic understanding into a commercializable process. That has many implications — it has implications in how you design your department and your quality organization. It has many implications on how you recruit; it has a lot of implications on how you position your coaching, if you will, with the scientists on how to bring these to market.
In terms of recruiting, because the products are so academic, the talent pool is largely from academia, which isn’t exposed to the regulatory requirements that we see in traditional drug products.
The quality organization must work with these groups in order to guide them through that, which requires you, when you recruit, to recruit people that have a solid basis in GMP and life cycle, but also have a defined streak of innovation so they can help guide academics through these waters.
Harris: What does this mean from a quality management system perspective?
Blackton: Let’s look at the design of a quality organization. Here’s how I design my quality organization; we know that the primary focus for early phase is life cycle. It’s all about achieving product understanding and process understanding.
Associated with that is quality risk management. The first subset of quality that comes to mind there is the validation piece, but it’s not just validation anymore. I have this group called quality life cycle management; their remit is to marry quality risk management with control strategy and life cycle documentation, including traditional validation.
This implementation group is the link to process development, manufacturing, and manufacturing science and technology. Their remit is to shepherd what we call the control strategy. The other function within quality that’s important as we started to grow is quality systems, which includes all the documentation around product. That’s married with computer validation, and the reason for that is because we’re such a young company; when I started, we didn’t have any quality systems, so we decided to start electronically. We do not have paper systems. The quality systems group manages document control, computer validation compliance, and GMP or GXP system administration.
They’re the superusers, if you will, for all our GMP-focused electronic systems, like LIMS, environmental monitoring software, document management software, electronic batch records, and so on.
The other groups are operational. We have quality control operations, which is designed to get product tested and out the door, and quality assurance operations, which is designed is to get lots released or documentation review for lot release. They’re also responsible for quality metrics, because there is one patient, one batch. The challenge is getting these products to patients as soon as possible.
We do not have the benefit of two or three years of supply in a warehouse. We have one patient. We know all the details about that patient. They’re going to get that product. If the product is late, we could lose that patient. They can come off the trial for various reasons, or they can progress their disease.
That quality operations group is the the front-facing groups that gets the product reviewed or gets the batch records reviewed and gets that product shipped to the patient as soon as possible while maintaining our patient safety.
I have other groups, analytical development, which is the development arm of QC operations, and then we have a quality organization in the UK, which is matrixed in with the rest of the quality organization. Their remit is research, quality, and European supply. Their job is to work with the QP to get European supply released, and they’re just matrixed in with the rest of the group.
The reason the organization is organized that way, and the reason we’re so focused on immediate need versus long-term need, is because quality in this space is like walking a tightrope. In traditional pharma, the tightrope is like a five-lane highway. You have a warehouse full of product. If you fail a batch, yes, it’s going to have an economic impact, but it’s not really going to have a patient safety impact, because you have three or four years of supply in a warehouse. That’s not the case in cell therapy. Any mistake with cell therapy, and you fall off that tightrope. We must be efficient early on.
Gaining understanding early is key, so that you can design your organization to address that challenge of supply. In terms of product understanding, these are very early products. Back in 1992, ‘93, when I started to work on my first monoclonal antibody, we thought, “Oh, these are uncharacterizable. Nobody knows anything about these products.” Then within three or four years, products were approved, companies like Genentech came along, and we learned that we can very easily characterize these products. Well, this is where cell therapy is today — where monoclonals were in 1993. We’re still learning about cell therapy products. As an industry, we’re learning the mechanism of action.
This translates to quality — into your product understanding and your product specification. That’s another challenge — part of that tightrope. My last company was a very large, 50,000 people pharma company. We had change controls and a change review board and everything, and things would just chug along. That will never work in cell therapy with a small company, because a small company depends on innovation and the ability to manage your process as rapidly as possible while maintaining the documentation and the product understanding such that you can preserve patient safety.
Harris: What specific qualities do you look for when recruiting talent for your team?
Blackton: When we recruit senior-level people, or relatively senior people, I look for that innovation piece. I’m not too concerned about whether people understand cell therapy. I am very concerned with whether the applicant has the capacity to learn quickly and think out of the box.
I’m not looking for that Ph.D. immunologist from an Ivy League university. I’m looking for that person who has a vision for what they want to do, but also has an open mind and is not be afraid to suggest something that could prove to be preposterous.
I want people to challenge the status quo, because that’s the only way we’re going to get these products to market. In my own career, I have often found that if I take on a role I’ve never done before, I’m more successful because I’m not bound by the paradigm of what has been done before. I think that’s important for talent — for quality professionals especially — as we consider senior people.
Further, quality must be at the table with your development people and your manufacturing people on equal terms. The head of manufacturing, the head of development, and I manage CMC. We literally sit together, we collaborate, and we entertain together. We make good decisions, and we’re brutally honest with each other always. I believe that’s another key to quality challenge — remove the silos. Make sure everybody has a voice, everyone is heard, and that there are no barriers between departments and functions.