By Louis Garguilo, Chief Editor, Outsourced Pharma
“My opinion is not theoretical. It reflects having seen it in action at Amgen, from 1986 to 1995, with the launching of Epogen & Neupogen.
At that time, many of the problems of biopharmaceutical development and manufacturing had not yet been solved, but we still moved at warp speed. Today, there are a variety of 21st century technologies and tools available.
However, the industry continues to use 20th century thinking.”
-- Thus Spoke Mark Witcher --
Like biopharma’s Nietzsche, Witcher wants us to rethink and slay outdated beliefs – “tech transfer” being a prime target.
We pick up this discussion with Witcher (part one is here), particularly regarding:
Why aren’t there “early Amgens” in the industry today, building out capabilities to nurture new drug programs?
And why, with the industry so reliant on CDMOs, does he feel these external partners are letting us down?
Back To Basics
As documented previously, “early Amgen” represents an integrated and non-siloed organization internally capable of “evolving” a drug R&D program from start through commercialization.
No tech transfers needed.
But I remind Witcher nary a biopharma employs that model. And that’s why the CDMO industry flourishes. To do as he suggests seems, well, improbable.
He remains immovable: “Nobody does it that way because they're using 20th century methods. There's no reason it can't be done other than everybody is essentially stuck in 1990s thinking.”
I ask: Isn’t the “virtual” model based on attracting creative 21st century financing that today feeds a rapacious biopharma industry?
“That's not the issue,” he retorts. “There’re gobs of money floating all over the place.”
“It's the ability to fully understand what needs to be done, and how to do it most efficiently. There are basic principles which can facilitate the construction of the procedures necessary to put together the processes, facilities, and quality management systems necessary to advance drug programs [see: A Straightforward, Risk-Based Approach to Better Quality Management System Design].
“It's not that expensive an approach. I just think the industry today has no idea of how to do it anymore. They try to design everything to be compliant – by studying what has become a complex and sometimes conflicting set of regulations and guidelines – in an effort to figure out what the regulatory agencies want. This instead of focusing on sound engineering and scientific principles to produce high-quality processes and products resulting in compliant systems.
“You need to concentrate on the product and its process rather than trying to focus on giving the regulatory agencies what you think they might want. That’s a very difficult game to play.”
Money Talks; Talk Back
I’m not so sure about the gobs of money. There’s certainily evidence biopharma funding is booming. Readers, of course, will know best.
Nor am I sold on an assumed lack of vision on the part of biopharma executives or investors (see: Today’s Biotech Start-Up: Experienced Leaders, Wise Investors).
But following Witcher’s case for (non-siloed) internal capabilities, I ask what might rearrange the mindset of biopharma entreprenuers to establish a different strategy?
“It starts with not assuming from the outset the only model is to tech transfer your research at some point in the development stage. That’s the first assumption they need to let go,” he begins.
“Then, if you're not going to tech transfer, how are you going to do it? There's no reason today’s biopharma can’t build a flexible facility to bring products through more quickly and supply a normally expanding market.
“They do this by learning how to prevent silos between research, development, clinical and commercial, rather than transferring their technology to a CDMO – with its own internal silos.
“You can take products out of a university, start carefully by building labs and facilities to do the development and scale up, with a defined but flexible plan for how you'll move ahead at each step in the lifecycle. I’ve written a lot on this (for example: Developing And Manufacturing Cell & Gene Therapies: Do Biopharma Methods Apply?).”
The basic Witcher principle here seems unassailable:
If you start with a business plan to do tech transfer to CDMOs at some point in development or scale up, then that’s what you focus on and work towards.
“If biopharma doesn't start with that plan,” explains Witcher, “they instead work towards building out an efficient infrastructure – and that means creating the necessary manufacturing facility as they successfully evolve the product.”
The elephant in Witcher’s room, of course, is what happens when products fail?
That, he and I agree, is a complex topic – both business- and science-wise – we’ll have to cover in detail another time. I will interject, though, Witcher is not a proponent of the “fail fast” strategy.
“Focusing on the product’s weaknesses to make it fail has significant implications,” he says.
I am, though, still pressing him on the finance side:
If you're starting a biopharma today, your investors may very well indicate they don't want you building out infrastructure. That’s what CROs and CDMOs are for – our enabling 21st century strategy. The money won’t be there for that “early Amgen” model.
Witcher isn’t convinced.
“Perhaps its that people don’t understand the full product-development pipeline, and the risk-benefit tradeoffs, well enough to build a plan that accomplishes what I’m suggesting.
“Yes, it does take a lot of puzzle pieces; that's pretty much how things work in most industries It’s a high-reward game, requiring the acceptance of smart risks.
“Unfortunately, the pharmaceutical industry is a locked in bunch. I can understand why the finance folks would be against doing anything different.”
No Go At The CDMO?
Finally, we return to why Witcher is critical of today’s CDMOs.
“They have mostly failed to be anything different from siloed pharmaceutical companies. It's this same issue of tech transfers,” he explains.
“The only advantage the CDMO has is it’s better at managing its own resource risks,” he continues. “In theory, its product portfolio is larger with a wider variety of products. It can better manage facility utilization.
“Internally, though, they are doing all kinds of facility-limited tech transfers, and have all kinds of silos.”
Witcher believes still today CDMO facilities are designed with inflexible layouts, lacking a required agility to “evolve your product” over its lifecycle.
And that brings him to the MPF (Multi-Purpose Facility) concept: A design based on “an adaptable matrix of non-dedicated clean rooms,” which we cannot go into detail on here (but see: Are Good Manufacturing Practices No Longer Good Enough?).
Instead, Witcher ends by providing Outsourced Pharma readers who will continue to outsource, with three basic questions to ask CDMOs before you commit:
- How will my product be nurtured through each step of the development and manufacturing process?
- What individuals will be responsible for evolving my product? Will they stay with the product throughout?
- Will each scale change, or process improvement, also require a move to a new part of a facility, a new facility altogether, a whole new location?
In other words, if you can’t beat tech transfers altogether, work with the people and facilities that can minimize those risks and costs.
Mark F. Witcher will be a speaker at our next OP-Virtual discussion: “What COVID-19 Vaccines Teach Us About All Tech Transfers,” on Wednesday, November 4th. Register here (for free) to join us.
This completes my four-part series on the current physical and mental state of tech transfer in drug development and manufacturing. Here are our earlier segments:
A Real Dissertation On Tech Transfer
Tech Transfer, Self-Esteem, And A Fitting Facility
The Witcher Way: Can We “Eliminate” Tech Transfer?