Process Development: The Rodney Dangerfield Of Outsourcing?

By Louis Garguilo, Chief Editor, Outsourced Pharma

Rodney Dangerfield was the comedian/actor whose schtick revolved around his saying, “I don’t get no respect.”

In the biopharma industry, process development (PD) may be our Dangerfield.

Sponsors want to jump-start to that first cGMP batch and coveted clinical-material delivery. Time and money, they say, is of the essence.

However, giving short shrift to the art, science – and need – of PD can end up leading you down a primrose path.

This was agreed by three experienced professionals during a recent webinar on the subject. With all due respect presented, they then went into detail on how to select the right CDMO to provide those services.

Best Place To Outsource

Scott Zook, SVP, Global Manufacturing, Primmune Therapeutics, has been involved in process development from academic training through nearly three decades in the biopharma industry.

“I’ve had fortunate experiences, and some challenges,” he said.

“Key when selecting a CDMO for process-development services, is location, location, location. Are there nearby restaurants? Particularly good hair salons? … No, I’m joking,” said the longer-haired Zook, adding a bit of Dangerfield-like humor.

“It has little to do with location, and everything to do with technology!”

He provided a fundamental example: Even if a CDMO is your preferred provider for some of your programs, if you are looking for clinical material that requires oral-solid dose experience, and they are predominately a sterile-fill shop, you are not going to go there for that need.

“Technology has to be the starting point,” said Zook.

Questions he considers that might not come first-to-mind when searching for PD services at CDMOs:

• Is the technology a fit for your specific goal in further development?
• Does the technology you bring to a CDMO allow them to use their quality systems in an effective and familiar manner?

Regarding that second consideration, Zook says you must determine beforehand if a CDMO has the appropriate quality systems in place. Once that's confirmed, he says, “You have to allow their system to govern.”

“I've actually been through this,” he adds. “If you try and impose your SOPs or procedures, what happens is you inevitably push them into a corner where they are violating their own procedures to suit your specific, idiosyncratic need.” 

“So picking the right vendor considering program alignment is important … along with, of course, the location.”

But hold on. All joking aside, said another of our speakers, Knut Niss, Chief Technology Officer, Mustang Bio:

“I'm in the cell and gene space. Especially for the autologous-therapy assets we handle, location is actually critical. We make one batch of product that has to go back to the same patient the starting material came from – one batch for one patient. That can be a logistical nightmare. Location matters.”

As well as technology, and of course, quality.

Let’s Ask Quality

On cue, we heard from our third interlocutor, Kim Burson, Head of Quality Assurance/Quality Control, Denali Therapeutics.

“In terms of working with process development, my big ‘watch out’ and advice is to get quality on the project team from the get-go,” she said.

She works closely with her technical process-development teams to ensure any potential CDMO fills out a specific questionnaire including quality-related content.

“If they're progressing work into the GMP manufacturing– such as Phase I clinical trials – you want to consider including such items as health-authority inspection history at the CDMO,” said Burson.

“Talk to CDMOs about audits. What are their expectations? If you can get that in the RFP, all the better. You can negotiate before they're selected.”

Her other suggestions:

• Ensure the CDMO shares raw data; be specific about what you want
• Find out the ratio of QA and QC personnel to development or manufacturing personnel
• Ask about QC analytical capabilities
• Acquire an equipment list
• Ask what they outsource, such as QC testing

When Is It Enough?

Process development considerations can range from, “Now how do we actually make this material?” to “How will we know when we’re finished and ready for manufacturing?”

The second question may be the harder to answer.

“That is the rub,” says Zook. “In a larger organization, the goal tends towards ‘chronically improve” – sort of a perpetual state of improvement.”

“It can become a financial runway issue,” he adds.

On the other hand, in an organization with limited funds and more targeted outcomes, needed is a recognition of what is “appropriate and adequate, versus the potential ambitions and interest of the development scientists.”

Says Zook:

“If the ultimate goal is defining a brand-new method to produce a material because the current is in the way of commercialization, then that’s what you have to do. It comes down to what enablement is necessary for success.

“You always define your own success, and it changes over time. For me, ‘Good enough means I'm fully enabled’ is one consideration. Another: ‘Is there no specific challenge we are facing’ – for example, if we were to transport this elsewhere?’

How involved should the CDMO be in making the determination you’ve met your goals, and it’s time to move on?

“To be honest, the CDMO may be pushing for ‘perpetual success.’ It fits their business model. I'm not chastising anybody for that,” said Zook. “But, yes, decisions should be collaborative.”

“We should always go back to the rule of thumb: It’s always the sponsor's responsibility to ensure the process is appropriate and adequate, and meets quality expectations. Within that, I've always been able to work collaboratively with vendors.”