CDMOs Pelted By Slings And Arrows

By Louis Garguilo, Chief Editor, Outsourced Pharma

I thought I was precipitating a frontal assault by canvassing the Outsourced Pharma Editorial Advisory Board with questions such as:

When outsourcing development and manufacturing, what are the challenges, and where are your pain points?

But before anyone claims “one-sided,” please read on. (Also see this earlier board assessment defending CDMOs from certain criticisms.)

Challenging Checklist

Here’s a “nice” list of overall not-so-good experiences to get us going.

Doug Bakan, recent EVP, Tech Ops and QA at Ventyx Biosciences, says despite what we sometimes hear to the contrary, small molecules also face these challenges. (Also see an earlier editorial he and I did on a related subject.)

1. Limited Capacity for advanced sciences/technologies (e.g. antisense oligonucleotides (ASO) manufacturing)
   1. Lack of Availability For Specialty Manufacturing procedures (e.g., spray drying, lyophilization
2. Long Commitment Lead Times to manufacuture coupled with Large Down Payments (e.g. 50% of entire run) at that early commitment
3. Increased Costs Of Deliverables/Services
4. Understaffed Analytical and QA teams (more below)
5. Technical Errors
   1. Chemical-reactor-train mishaps and product loss; equipment cleaning deficiencies; misplacing stability samples; calculation errors in analytical or manufacturing activities, etc., are often due to “overworked teams but can also occur in fully staffed CDMOs.”

A somber list for sure, but I suppose that's what I asked for – pain points. Hopefully, CDMOs view this as a list of  areas they might focus on improving.

We can all agree with how Bakan puts it:  

“Certainly, there is a solid business opportunity for CDMOs that can eliminate or at least minimize these frustrations.”

Gripe More (Positively)

While board member Jana Spes, VP and Principal Consultant, IQS Consulting, has experienced her share of challenges over the years, she's growing more sanguine.

“I am starting to see some CDMOs increase capacity, for example prefilled syringes, perhaps pushed by the GLP-1 craze,” she says. “And I'm generally hopeful we will see increased onshoring of various capacity in the U.S. specifically.”

To the delight of Bakan above, “In small molecules,” Spes adds, “I see CDMOs investing more into sterile manufacturing capacities – again, GLP-1 manufacturer may be a catalyst – and CDMOs do want and need high-speed, lean and continuous improvement programs. Importantly for sponsors, service providers desire to be innovation focused.”

Regarding innovation, CDMOs say they relish opportunities to have input into the design of Phase 1 products, as Spes puts it, “with commercial formulation/processes in mind.”

However, a problem is that “sponsors today still do not adequetely share information and objectives.”

Jana references an earlier editorial  on OutsourcedPharma.com that made the case for open-source information, a concept she finds makes a lot of sense.

Still, she says, “my experience to date working at several biotech startups has been this openness is difficult to turn into a reality.”

So there’s a takeaway for all you sponors out there.

Constructive Concerns

Let’s end with two points universally suggested by drug sponsors who, shall we say, outsource for a living.

1. QC/QA Capacity Caper

When will CDMOs finally staff up to meet customer needs? 

CDMOs have certainly heard enough related complaints from customers. CDMOs seemingly all struggle with turnaround times that adequately satisfy sponsors.

Board member Shawn Eisenberg, VP Technical Operations, ACELYRIN, Inc., has an interesting take on this, based on experiences accumulated at several biotech’s in relationships with CDMO’s and contract testing laboratories.

“I look at this by taking into consideration the analytical or other test with the longest duration to completion, and add one day for the return of results,” he explains his approach. “That would be the ideal, highly functioning QC/QA target for a CDMO.”

“I’m not suggesting this is attainable 100% of the time, but the discussion of timelines should start there.”

The reality, though, can unfold quite differently.

Sponsors might hear CDMOs mention 45-60 days for QC results, where, clarifies Eisenberg, “their longest test for drug substance is typically bioburden, at about 8 days, and for drug product, sterility at 21 days.” (These durations can be modality specific, but the concept of the longest test as a baseline remains relevant in any setting.)

Eisenberg then echoes outsourcing sponsors I’ve spoken with over the years.

“You would objectively think CDMOs would value the cash-flow advantages of releasing material and batches soon after production finishes, but the QC and subsequent QA turnaround time suggests otherwise.”

And back to cause and effect: The obvious reason for delays is understaffing.

Are CDMOs simply in the operational habit of trying to push too much work through too few resources?

If they are, at what point are they harming their own business by doing this?

“Perhaps CDMOs believe they’ve dialed in a good balance, and they have to be the judge of that for their business," says Eisenberg.

“However, as a customer, long turnaround times are problematic, and certainly wasteful in the clinical and then commercial space.”

Eisenberg shares a final thought.

“There seems to be an overreliance on turnaround times codified in quality agreements. These contractual commitments necessarily drive safely achievable estimates.

“But if the quality-agreement target can be accepted as a conservative threshold, the CDMO and sponsor can strive for more aspirational targets. There needs to be a shared understanding that 100% success is not expected nor achievable, but trending against a KPI target can be helpful. In the end, both parties benefit from faster turnaround times.”

2. Project Management

Project management at CDMOs continues to be, as another OutsourcedPharma.com board member put it, “hit-and-miss.” Other professionals, though, have reported overall improvements in this area.

The dividing line again appears to be proper staffing, and PM workload, more than any other factor.

What should be obvious to CDMOs – it is to their customers – is that unproductive PMs are clear indicators of an overall weakness of the CDMO’s ability for service and deliverables. 

This, frankly, became obvious to me when I worked in business development at an international CDMO years ago. For example, we were able to attract, maintain, and productively serve numerous (very finicky) Japanese drug sponsors precisely because of the time-devotion and leadership of our PMs.

Let’s be clear; this is not a suggestion for “dedicated” PMs for every project. But as Eisenberg hints at above, CDMOs should take another look at just how adequetly they have “dialed in” their PMs.

Too many customers feel they are getting the wrong number.