Technical operations personnel at biopharma companies – “Tech Ops” –can feel as if they are running in circles as much as advancing programs forward.
That’s because too often they need to circle back to earlier supply decisions regarding materials and timelines that are subsequently uncovered as inadequate or miscalculated. Or less negatively, because test results, trial outcomes, or even regulatory environments, can be unpredictable.
To straighten out those loops, Arena Pharmaceuticals relies on Doug Bakan, Executive Vice President, Technical Operations. Bakan oversees operations in four critical areas: drug substance, drug product, analytical, and supply chain.
Complicating matters, today at Arena all activities for those areas are outsourced.
A Brief History of Arena
With 500 employees at its peak, Arena brought to market Belvique, for weight loss management, as well as multiple programs in various stages of clinical development.
Soon after that success, though, the company reversed strategy.
In less than a year it reduced to about 20 employees to initiate a rebuilding process. Now Arena’s bounced back to about 200, but, says Bakan, “We do everything through contract service providers.”
“It’s been a successful change in philosophy,” he continues. “We’ve had good clinical results on three different [small-molecule] programs in the last 18 months. We’ve raised over $600 million in the open market, and lucratively licensed out a lead product. It’s been an exciting time, with over $1 billion in cash to invest in all our programs.”
Here’s how Bakan and his Tech Ops team keeps things moving forward.
Bakan starts with people. His Tech Ops employees in the drug substance group are experienced synthetic-organic chemists or process and scale-up chemists by training. Heading up drug substance is a 19-year veteran of Merck.
These “classically trained chemists” do everything from developing initial routes of synthesis, to troubleshooting all issues that come with scale up … and are responsible for managing relationships with CDMOs.
“When I first joined Arena [two years ago], we had just switched over to the new CMO business model,” explains Bakan. “Tech Ops had to search out and identify all the partners we were going to use to manufacture drug substance. That was an important responsibility. We have an extremely rigorous CMO selection process. It’s objective with a bit of subjectivity, for example when we do site visits.”
He adds: “Key in the selection process is to feel confident that not only can the CDMO do the work at the scale we need today, but also at potential commercial scale. We don’t want to do tech transfers all the time.”
Tech Ops oversees drug product development, formulation, and manufacturing. Currently, Arena’s products are all solid oral dosage forms, but candidates in the pipeline may soon change that.
Four of the 20 employees under Bakan are dedicated here. The group is led by “a world-class expert in drug product pre-formulation characterization and formulation development.” The team consists of degreed scientists trained in pharmaceutical sciences, formulation development, manufacturing, and competent in understanding how to perform appropriate scale-up and process validation. Like with drug substance, this group takes on the responsibility of identifying, selecting, and engaging CDMO partners.
Bakan interjects that for both drug substance and drug product, he’s been faced with a growing and “particular challenge” for Arena.
“The 60 medicinal chemists we had developing our compounds early on at Arena were so good that almost all our compounds are highly potent. The number of CDMOs who can handle both substance and product is limited.”
We’ll look further at this in a separate editorial that will also include analytical challenges, which we outline next.
Analytical includes a team of five, supporting drug substance and product activities. The group is led by a professional with over 30 years industry experience.
“You name an analytical technique. At least one or more of the people in the group could be called a subject matter expert on it,” boasts Bakan.
Bakan says every member has a minimum of 15 years experience doing analytical method development and validation, and troubleshooting. This group is responsible for defining the specifications for starting materials, intermediates, the drug substance itself, and for developing the methodology and specs for drug product. Another component is stability testing, including designing and managing studies.
“We fully support our colleagues in the non-clinical group in different ways,” says Bakan. “If I go back to the drug substance side, if they need radio-labeled material for a human mass-balance study, bio-distribution study or synthesis guide, we’ll arrange that. Then as we make that material and get it ready to use, the analytical group is responsible for all the release testing that goes with those samples.”
Confirming what we’ve reported at Outsourced Pharma and discussed at our conferences, Bakan told me:
“The feedback you’ve received regarding the criticality and shortage of analytical services at CDMOs is an accurate assessment of what we experience. I will tell you with every project we’ve done since I’ve been at Arena, a limiting factor has been analytical, or at least that’s always the pinch point.”
Arena is currently focused on clinical supplies, but the supply-chain group in Tech Ops is led by a professional with extensive commercial and clinical supply experience, and “well versed in U.S. and foreign distribution.” There are five individuals in this group.
“Because several of our programs are late stage, including Phase 3,” says Bakan, “they tend to be extremely complex. Some include upwards of 50 countries and hundreds of clinical sites. You can imagine the expertise you need to work within clinical packaging, labeling, and distribution at that scale. It has to be both broad and incredibly attentive to detail. You have to be creative and flexible in planning to ensure whatever clinical sites are activated first, we have clinical trial material ready for them.”
“I’m proud that in the two-plus years I’ve been here, we’ve never missed a deadline on delivering clinical-trial material. I credit that entirely to the team. They’re experienced supply-chain professionals, but we also have some younger people we’re bringing up to speed.”
But again Bakan identifies a challenge area. This time it is “tapped out bandwidth at service providers for clinical packaging, labeling, and distribution.” Today if a biopharma client – especially those with high potent compounds – misses a starting date on packaging or labeling activities, “it can be months before they can get back into the queue.”
Tech Ops has taken all these challenges head on, and moving Arena in that desired straighter line forward; no circular motions needed to date.
The recent addition of an experienced CMC operations and project manager with a strong technical background has helped ensure that. “Having someone who has worked on both sides of the CDMO business has provided us with insight into how we can get the most out of our partners, while being a collaborative client that’s enjoyable to work with.”
“It’s a testament to the 20 individuals on our team,” sums up Bakan. “Delivering drug substance, making drug product, getting it tested, packaged, labeled, released and sent to the clinical sites on time, is an expensive pathway I think people don’t fully appreciate. Those who do this day in and day out are unsung heroes in our industry.”