Make it warp

Before Operation Warp Speed, there had to be a Project Runway. Yes, the applicability of a reality TV show about high-end fashion design to the US’s Covid-19 response might not be immediately apparent, but, then again, The Apprentice (which launched in the same year) did help the country choose its 45th president.

Project Runway had a subtler influence; it gave Operation Warp Speed a mantra. Co-host and breakout star Tim Gunn (no relation), who used his expertise as a teacher and long-time fashion consultant to advise and mentor contestants on the programme, would never think to jab his finger at one with a phrase like, ‘You’re fired’. Instead, he crossed one arm over his chest, lifted the opposite hand to his chin and told his charges to “make it work”.

There are now hundreds of millions of voices chorusing those three little words to the pharmaceutical industry, though their accompanying arms are more likely to be pleadingly upraised than anything else. Even in countries that have managed to mitigate the outbreak’s impact, scalable, effective vaccines are needed as much for the health of the state as some vulnerable subset of its citizens. The time frames for developing, trialling, manufacturing and supplying candidates are, compared with last year, unimaginably short. But, while everything about their working environment might have changed, it’s still the same people tasked with making each of those stages possible. Every vaccine candidate might make a difference; this is not a crisis that can be solved by firing people.

Still, some were more prepared than others. For Peter Krulevitch, senior engineering director and lead of the primary container and device group at Janssen R&D, “Make it work” – a phrase he might use even more than its populariser – has summed up his role for almost a decade. Since 2012, R&D for Janssen’s devices and primary containers has followed something close to an open innovation model, emphasising outsourcing and end-to-end collaboration over in-house expertise. Given the subsequent increase in the importance of digital technology and the range of drug mechanism challenges that delivery devices need to overcome, Krulevitch is relieved that Janssen’s integrated structure was put in place when it was.

“It started because we’re a small team and a collaborative approach was the best way for us to make it work,” he explains, “but things have become so much more complex. Everything now moves in so many different directions, it would be very challenging to really think that you could have one organisation that develops all these things internally without having really strong partnerships to get it done.”

Indeed, as agreements between equals like the one forged between Pfizer and Sanofi attest, there’s a growing sense that the zero-sum vision of competition espoused by The Apprentice is out of date. Why waste time challenging someone else’s expertise when you can both gain from combining it with your own?

Open season

Asked about the philosophy behind his catchphrase, Gunn told Variety, “Life’s a big collaboration. We rarely do anything alone and you need to rally support. Roll up your sleeves and just do it. That’s ‘Make it work’.”

It’s not an attitude that allows colleagues to be opaque with each other – intentionally or otherwise. For Krulevitch, it’s a way to prevent siloing – meaning device development can actually support drug discovery. “We get involved from the very beginning, all the way through to commercialisation,” he explains. “Maybe our scientists in discovery are running across some challenges with a promising molecule, so we try to work with them to see if some technology on the device side can impact that and make it work.”

By integrating themselves with their colleagues in Janssen’s drug discovery arm, Krulevitch’s engineers are able to draw up specific needs statements and begin thinking through possible solutions with new or existing partners early enough to actually implement them. Particularly in cases where a new piece of technology is required, he contrasts the head start afforded by that approach with the desperate struggle to catch up if the physical aspects of device R&D were ignored until the discovery team was finished.

“Once you get the molecule declared, it’s a sprint,” he says. “We can’t slow it down. We need that early start so we can not only identify the technologies, but [also] start to invest in them and get them to the point where they’re ready to pair with the drugs.”

In such cases, it’s hard to see how even the richest and best-equipped insourcing strategy could compete with a flexible approach to forming partnerships with outside specialists. Device development still comes down to thoroughgoing trial and error, and the most valuable resource for finding out what works is time. Partnering with an organisation that has already had success with the approach or technology that best meets a need effectively gives a manufacturer access to hours it didn’t have time to put in. To use the phrase du jour, it’s like entering warp speed.

“People have been doing open innovation for a long time,” admits Krulevitch, “and it’s just one approach; it’s one way to do it. But it’s sort of naive and maybe self-centred to think that you have all the best ideas: that your team can do it the best and forget everybody else. It’s just not a healthy way to approach a problem. There are a lot of extremely smart, dedicated people out there with really good ideas that have really brought things along, and we want to go and find the best ones.”

There’s a self-assuredness to that approach, too. “It’s not just taking what they have,” stresses Krulevitch, “it’s making it better.” In particular, he points to the stringent programme of usability and performance tests that Janssen employs to identify the best solution and refine it. “If we’re going to do a new programme, we’ll identify three or four options that might meet the need, bring them in and test the heck out of them. We really determine which is the best option and then work with them to address any issues.”

Through the whole development process, then, Krulevitch’s job is to match engineering rigour with interpersonal tact. The advantages might be plain to see, but still, if delivery R&D presses too insistently back towards the structure of the molecule, it could stir up a feeling of resentment among the scientists in discovery, who have their own set of interests and goals.

The same is true of device and technology companies on the other side of Krulevitch’s team. Overall, there’s a real risk of collaboration creating as many complications as anything else – particularly when companies don’t just test different options, but develop multiple delivery devices in parallel before making a decision on what will become the final product. Krulevitch sums up the issue of how social sciences can impinge on the physical ones very aptly. “Two-body problems are already hard,” he sighs. “But when you start talking about three-body problems, the difficulty really grows exponentially.”

On the same hymn sheet

Unlike some other pharmaceutical companies, Janssen only rarely engages with multiple vendors in parallel, but the crux of the issue is always how to align the various stakeholders’ and contributors’ incentives. “In my experience,” Krulevitch continues, “the most important thing is to really think about what your partner needs to be successful. You’ve really got to set agreements up in a way that everybody’s pulling for the same thing and, if the project’s successful, then everybody wins.”

The pay-offs for doing so can be felicitous. Recently, BD approached Krulevitch’s team to ask for some guidance about how to improve its UltraSafe injection device platform, which is used by companies across the pharmaceutical sector. At that time, Janssen was having issues with the pharmacokinetic (PK) comparability of some of its novel drugs when they transitioned from being administered with hypodermic needles to auto-injectors, and was concerned about clinical trial subjects struggling to self-administer with syringes.

“Some drugs can be very sensitive to how they’re injected,” Krulevitch explains. “To the depth of the needle, for example. We had that problem on one of our programmes, and it caused a real issue where we didn’t achieve PK comparability between the syringe and the device, which resulted in a delay.”

BD’s suggestion that Janssen could help improve its UltraSafe platform, which it was comfortable making because of the good relationship fostered through previous incentive-aligning partnerships, collided with Janssen’s own comparability issue and actually sparked ideas for how to solve it collaboratively, resulting in a grip that allows for self-administering one-handed.

“The new device allows us to have a very similar injection method in the early part [of clinical trials] where you’re just using the syringe, and when you transition to your self-administration device, your auto injector or your self-dose device later on,” says Krulevitch. “The needle depth is the same, the angle it’s held against the skin is the same – you’ve eliminated all those potential variables, and that makes it much more likely that you’ll achieve PK comparability when you make the switch.”

That was one serendipitous instance, but it flowed into a cascade of benefits already established through Janssen’s partnership strategy. As BD was already providing his company with syringes and UltraSafe devices, Krulevitch could trust that the new grip would be designed from the start to work with the other components as a system, making it unlikely that incompatibility or tolerance issues would spring up later on – as often happens when a system is imposed on parts provided by different manufacturers.

Krulevitch works hard to ensure that the advantages go both ways, aligning incentives by allowing partners to implement innovations they make with Janssen in any non-competitive space. “They want great device offerings for their other partners as well, and that’s fine with us if it helps them,” he explains. “The device is getting tested more and potential issues are uncovered so that we can address them. They’re scaled for manufacturing so the costs are cheaper, too.”

Among other projects, Krulevitch’s R&D team is working on delivering Janssen’s Covid-19 vaccine candidate – which, appropriately enough, is one of the finalists receiving federal funding and support as part of Operation Warp Speed. The companies selected are almost exclusively the pharma giants large enough to develop and authorise a vaccine without any outside help, but, as he’s aware, that can be a weakness as much as a strength. Just as drugs can be sensitive to the way they’re administered, now more than ever, people care about how their pharmaceuticals are made and approved. If nothing else, a collaboration between different bodies and experts for the public good is a far easier sell than a race between competitors at the behest of a poll-watching politician. And, as Krulevitch points out, once you’re managing the relationships, the hardest part is identifying unmet needs. Covid-19 has made that part easy – the rest is just making it work.