Optimism Is Not A Strategy For Outsourcing

By Louis Garguilo, Chief Editor, Outsourced Pharma

When you embark upon your drug development program, and connect that to patients who need that drug, you have to be optimistic.

Optimism, so to speak, is a biopharma’s opening gambit.

“This is going to work, and we are going to make a difference” is an attitude imbedded in your culture. That positivism goes on to help you and your team navigate inevitable setbacks along the development, clinical trial, and manufacturing continuums.

Danger lurks, though, when optimism gets codified in unrealistic, aspirational planning and timelines. If you then further certify those goals– i.e., internally to your board or externally to potential investors – those plans become strict operating dogma, and difficult to alter.

Because of that early enthusiasm, emerging biopharma is prone to inculcate a culture where it’s always easier to keep optimism flowing than pull up at critical points, and say: “Actually, let's take a pause on this. I don't think it’s going to work out exactly as planned. We need to reassess.”

This all plays out in concert with your CDMOs, where initially, you need to portray enthusiasm and confidence in your program:

“We're in phase one already; we've got an incredible development pathway. We need capacity in 6 months for our phase-two manufacturing.”

Particularly in today’s outsourcing environment, development time and/or manufacturing capacity needs to be booked well in advance (and includes a financial down payment for that commitment); that does not start with negative vibes.

But again, at some point down the road, you may end up asking your CDMO to push that reserved slot back, say three or six months. You were (among other vagaries of our difficult drug-finding activities), overconfident.

The CDMO, whose role we will consider further in a moment, is not overly surprised. As we’ve stipulated above, this scenario seems nearly preordained. The CDMO politely answers, “We understand, but we have other (optimistic) customers in line for that timeframe.”

A solid relationship with the CDMO – informed by but forged beyond the contract – allows for some compromise and the sorting out of schedules to a degree (and a change fee). Looking back, you see optimism got you going, but it became over-institutionalized, impacting your CDMO (among many others).

Instead, if you had recognized the challenges all development/manufacturing programs face, you could have created space to operate, more time to assess data before crucial next steps, and inserted buffers to rework resultant changes throughout implementation.

 Less Sentiment, More Science

Did I just drive the optimism right out of your sunny day?

Hopefully not, but the intent was to put optimism in its proper place. It belongs in your culture, and yes, to a degree, must be accepted by your CDMO.

But it needs to be driven out of your actual development or manufacturing plans.

Don’t take all this on my authority. I set down the above narrative based on a discussion with Jason Cameron, who after 18 years at Genzyme (Sanofi) and six at Amicus Therapeutics, became Chief Operating Officer at Orphan Drug Consulting last summer. 

Unchained optimism can run wild on the development or manufacturing path when organizations don’t “fully understanding technical hurdles and risks that may – or will – be encountered,” says Cameron.

This is compounded when you're working with CDMOs and – to save money, time, or because the hurdles/risks are not understood – you underweight the importance of process and technical development.

Champions of drug programs tend to get comfortable during preclinical or phase one progress: “Hey, I can produce a biologic, and lyophilize it. Fantastic.”

But Captain Fantastic can’t be shielded from scaling up at a hundred times – because that's what he’ll need to be commercially viable.

What are those technical challenges of going from a 100-liter to a 4,000-liter vessel? Will the cells still grow? How are you going to do the fermentation? Is it going to be perfusion or fed batch?

There should, says Cameron, be a complexity of thinking about what you need to do so you can  arrive at your end game. The right development pathway must be created, allowing the ability to make even minor changes in a regulatory environment.

And if you move too rosily along without considering potential larger changes, it can spin you back to earlier work – or require additional clinical trials.

Of course, we all know this instinctively, but even experienced professionals may start talking way too early about their “billion-dollar drug,” or “novel cure.”

Cameron says that talk actually sets biopharma up for “a much less valuable drug, perhaps from a cost of goods perspective.”

The risk to the drug in development, then, “is science, manufacturing and commercial teams not taking the initiative to work out what success looks like at each step forward.”

And not bringing that open discussion to your CDMO – or in fact assessing the added risk inherent in outsourcing itself.

Enter CDMO

As mentioned above, you want an enthusiastic CDMO.

However, the valuable countervailing role your CDMO can play is to curb your enthusiasm.

“We've heard this story before,” a good partner may say to a new-drug sponsor. “It’s never that easy.”

When your CDMO pulls you aside to say, “We believe your development and analytical plans, and timelines, are unrealistic,” take that invitation to listen. Carefully.

Don’t reply: “OK. Well warned. Now get on with it.”

If you have chosen correctly, the CDMO should be your trusted partners who can provide you that thoughtful discussion – based less on enthusiasm and more on real-world experience.

That experience may play out as advice that it could take at least six months to produce a certain analytical method, without which you cannot perform required process testing for phase three.

This advice, though, may come up against your internal (optimistic) expert who tells you, “No, it can be done in three at most.” Others in your company then pick up on the three-month timeframe.

How do you manage that?

Send yourself right back to the cautionary tale we’ve woven above.

Optimism is a biotech’s beginning reality, but more reality later on brings a brighter future.