When it reaches criticality – like the potential delivery delay of clinical material at your CDMO – it’s Hypercare time.
That’s the word Irfan Ali Mohammed, Director CMC Team Lead, says his company, Alexion Pharmaceuticals, Inc., has coined for an intensified coordination and managing of activities at CDMOs in crucial moments.
Alexion is a rare-disease biotech that has already commercialized a number of drugs. But when Mohammed joined as CMC team leader in December of 2020, the COVID-19 omicron variant was presenting challenges.
“Like with other drug companies, operations at our CDMO were impacted,” he says to start the second half of our recent conversation. (part one is here)
The impacts included schedule delays of some months. “Thankfully,” he says, “it did not ultimately impact maintaining investigational-product (IP) supply continuity”
That’s due to the implementation of certain “failproof methods,” and keeping top-of-mind that disruptions could reoccur. This required a proactive and collective brainstorming to assess any potential bottlenecks, supply-chain delays, or other possibilities across the CMC/development operations.
“Our foremost priority is to ensure subjects enrolled in the study receive their supplies on time. It was critical to understand how our CDMO network could be impacted, their adaptability and flexibility to mitigate delays and meet demands.”
Some of those challenges at the CDMOs were caused by employees contracting the virus, and in general, a difficult recruiting environment, as well as those supply-chain delays.
Companies will be impacted by hiring delays going forward, if they are without mitigating and critical managing strategies, Mohammed says. “A three-month delay to clinical supplies could be detrimental, or at the least, signify you are not capable of reliably supplying patients with your IP.”
At such critical moments, special actions are needed.
More Than Productivity
The aim of Hypercare is aligning the goals and understanding their significance at both the sponsor and CDMO. This starts via clear, concise, and more regular communication, and requires the CDMO is willing to participate. Key is coordinating efforts to attain mutual assistance in overcoming possible gaps or bottlenecks and agreeing on turnaround times.
Hypercare, Mohammed tells me, is a term Alexion created internally. “We wanted to come up with a positive term that signifies the urgency of escalation,” he explains. “Certainly not something that sounded like ‘micromanage.’”
“Hypercare relays the sense we are not trying to micromanage every single aspect of what is transpiring. Instead, we are staying involved and looking for ways to be helpful where we can, more agile, efficient and staying quality driven.”
He gives the example of a packaging project, where it is the sponsor who can “help track each contributing item that needs to fit into a schedule until the supplies are ready to go out the door.”
This heightened status is actually a breakdown of the activities associated with a project, both at the CDMO and sponsor, “with the intention to project supply-readiness and a base-case involving standard timelines versus the new hypercare model."
The sponsor clearly lays out the impact of further delays, helps the teams at the CDMO and internally to focus on assistance, and understand expectations.
For example, Mohammed insists his team has “full clarity on an up-to-date basis during projects on when batch records will be available, and how quickly QA on both sides can turn them around.”
“It requires a lot of care on our part as the sponsor to help everyone understand where we are and where we need to be. That’s the hypercare model we typically employ at critical times.
“Our service-provider network has been a true partner to our programs. We are fortunate to work with them. They appreciate the hypercare model is not something we employ on a regular basis, but only when the situation warrants. It has further strengthened the relationship.”
The Emergency Room
The indication of a near-term risk often sets off the immediate need to create a hypercare plan.
This can start out by something as simple as increasing “agenda-driven sponsor-CDMO meetings to twice a week.”
But this suggests at least two questions:
Doesn’t this increased meeting time actually inhibit productivity and lessen the ability to overcome a crisis?
Are CDMOs open to this constant dialing into the drug sponsor at such a time?
Regarding the latter question, Mohammed insists CDMOs appreciate more communication at critical times – if it’s a two-way event where they learn from the sponsor as circumstances evolve, can report openly on their end, and when challenges are fully identified, there’s problem-solving instead of recriminations.
Regarding the first question above, allow me an editorial interjection:
The argument can be made that development and manufacturing outsourcing professionals do not focus enough on productivity – or at least not enough directly, and by name. It’s talked around, and embed in capacity considerations and at times non-constructive timelines.
We have, for example, introduced much more automation to our labs facilities, as well as some artificial intelligence (AI) and machine learning (ML).
Of course, outsourcing is often in-and-of-itself a decision based on allowing a sponsor to focus on its most productive attributes and its “core.”
However, Mohammed admits, “productivity ends up meaning existing teams, both internally and at CDMOs, put a little more on their plates.”
As unfortunate as that is, he says there is an opportunity through those increased meetings we questioned above to enhance productivity.
“First, we don't ask the whole team to come, just the project manager. And these are quick updates, sometimes just 15- or 30-minute calls,” he explains. “As the sponsor, based on what we track internally, we should have a focused agenda, and that should be shared with the CDMO in advance.”
These hypercare meetings ensure both sides understand what to measure and track – areas where misunderstanding is a productivity killer. When delays are forecasted, communicating the precise impacts they can or will have on Alexion and patients can sharpen everyone’s resolve.
Focus brings clarity, and clarity introduces opportunity for both sponsor and service provider to find ways to improve a situation.
“We feel more prepared to take action and find opportunities to mitigate,” says Mohammed, “And so do they.”