Shared Responsibility: A Millennial's Outsourcing Strategy

By Louis Garguilo, Chief Editor, Outsourced Pharma

“We were preparing to start our first clinical study,” recalls Sara McCutchan, co-founder and Senior Regulatory Affairs Manager, Aristea Therapeutics.

“We chose to take that study into a country particularly stringent on stability, so having solid data was on our critical path.”

“The day came to get the results, but instead we get an email that was not what we expected to see. An impurity had grown way outside of its allowable limit. We were shocked. We thought we understood the ebb and flow of the product’s stability, and were anticipating a relatively uneventful outcome.”

Here’s how McCutchan and team handled the situation with the CMO … and other actionable advice for all development and manufacturing outsourcers.

Taking Co-Responsibility

We featured McCutchan in this earlier editorial, A Path To Biotech For Young Women. She’s a millennial making an impact, one who has rapidly gathered her share of biotech industry and drug development outsourcing experiences.

She continues from above:

“After a few moments of chaos, you might say, we got on the phone with the CMO and our consultants. We carefully talked through the situation to address these key questions:

What exactly transpired there?

Was there anything wrong with the equipment?

Was there anything that could have gone wrong in the sample handling process?

“Subsequent to speaking with the project manager and members of the project team, the technician who had run the sample got on the phone. This product was a liquid formulation that had to be kept frozen until use. At first, we were told the sample was removed from the freezer, thawed, tested, and then when it failed, the same sample was re-tested. It yielded similar results

“We prompted for more detail. For example, were there any temperature excursions in the stability chambers, had the equipment been tested, system suitability passed? Still no clarity.

“After several days and exhausting all plausible explanations for why the stability test failed, we got back on the phone with the technician. We asked him walk us through every detail – from the moment the sample was taken out of the freezer until the failed test.

This time, we learned, for a number of reasons – equipment and scheduling conflicts – the sample sat on a bench top for a matter of days. It was finally obvious what had gone wrong.”

Despite all that, says McCutchan, all that had gone wrong was not at the CMO.

“The protocol used by the CMO to prepare the sample prior to a stability run did not adequately specify exactly how the sample was to be handled. It didn’t emphasize – nearly enough – that the frozen sample, once thawed, must be used within a specific time frame” she explains. “That was our oversight.”

And she says, that is also a first lesson of outsourcing: Ensure those operators actually responsible for handling your product have the right information in full – not just the project manager you deal with at the CDMO.

“It’s important to identify potential areas of risk based on known characteristics of the product, limitations of stability, etc., and preemptively act to ensure those potential risks are specifically covered in the CDMO’s protocols, methods, procedures,” McCutchan explains.

“All of us internally knew what the stability limitations would be for our product, but that information wasn’t accurately disseminated to our CDMO.”

McCutchan and team went back over their stability protocol to understand where more detail should have been added to better ensure everyone – “from management to project manager, to the technicians running the samples” – was clear on what exactly needed to be done.

“Once we understood what had happened, we got all the documentation in place, re-ran the sample, and got the exact results we were expecting, and hoping for.”

For the re-running of the sample, McCutchan was able to be on site at the CDMO, speak with the technicians, and observe the process. As we’ll learn below, travel can be a burden on start-up biotechs, but in this case, it was worth the price of presence.

“I undertook this travel and time,” she says, “so I could understand more about the process as well.”

“On site, I kept asking myself: ‘Is there anything else that we're missing here? Is there another piece to the puzzle the CMO doesn't have that might help them – and help us both share in a successful program?’”

That led to more improvements, and this conclusion: “I believe that’s the correct way to think about situations like this, and about CMO relationships overall. It is a collaboration, and we both share in the successes, and the challenges.”

A Crew Of Consultants

McCutchan next turns to a theme we’ve heard repeatedly over the past eighteen months or so:

There’s a discernable elevation in volume, value, and voracity associated with CMC consultants.

Various Big Pharma all the way to very virtual drug development companies say so.

McCutchan agrees. A key for her organization, she says, is to have “a crew of consultants specialized in each of the different disciplines, to advise us on how to approach certain steps, challenges and opportunities.”

Note that’s not a consultant here or there, but a “crew.”

And a first step in hiring those consultants is self-awareness.

“For example, my drug development expertise only goes so far when it comes to manufacturing,” explains McCutchan. “It's critical we employ consultants who can come in, understand the chemistry alongside corporate priorities, liaise directly with our CDMOs (in a language that can sometimes be quite foreign to a non-CMC person), and advise on steps forward. Adding this dedicated, expert oversight to the program has been invaluable to the success of our entire company.”

She continues: “Currently we have two individuals dedicated to CMC – one specializes primarily in formulation and drug product manufacture, and the other in API drug substance. Not only do they provide specific expertise in the aforementioned areas, but they’re also able to work together to advise on CMC regulatory strategy – navigating immediate needs while also planning for long-term success. We really see our consultants as extensions of our internal team.”

Moreover, she says, consultants are also important in helping biotechs come up with the right choice of service partner to begin with.

“It comes down to picking a CMO that's fit for our purpose,” concludes McCutchan.

“Good consultants have specific insights that can help identify those companies. If you need to run a quick proof-of-concept study with a formulation that's not your long-term formulation, you might lean toward one CMO over others. If you're looking for a manufacturer to carry you through to marketing approval, your factors are weighed differently. So the ‘fit-for-purpose’ evaluation is important in development. Consultants can help make those discernments.”