After two decades working at CDMOs, Matthew Johnson decided to give it a go directly pushing along NCEs at a biopharma.
Astex Pharmaceuticals (US), the company he selected for this new endeavor, has an interesting organizational matrix – components of an international, external-internal supply chain.
That setup, and Johnson’s new role as Executive Director, Process Development, provide him – and Outsourced Pharma readers – fertile ground for insights into outsourcing and internal partnerships, and in fact the overall state of drug development today.
We’ll cover this ground over three editorials, starting here with what I’d call organizational outsourcing.
How It Works
A quick history will explain that term for us.
In 2011,U.S.-based SuperGen, Inc. purchased U.K.-based Astex Therapeutics Ltd., and selected the new name Astex Pharmaceuticals, Inc.
Today, according to Johnson, the U.K. side focuses exclusively on drug discovery, the U.S. on “clinical development” – defined as everything from phase one through NDA and drug approval – and then other Otsuka-operating companies assume the responsibility for commercial manufacture, marketing, etc.
Astex U.S. receives some of its programs from Astex U.K., but there is no predetermined “pass through” policy.
Programs originating at Astex U.S. include those revolving around Decitabine and Cedazuridine, and lead compound ASTX727, which received an NDA in 2020 and goes by the tradename Inqovi. (The complete pipeline/product list is here.)
Whatever the program source, Astex U.S. outsources all its development and clinical manufacturing, and thus its external partnerships or as vital as its internal relations.
The “Supply Chain”
“My role is basically following all the API programs we have,” says Johnson. “I’m responsibe for the management of the API manufacturers, specifically for the API sections of the various regulatory documents.”
He says currently (and typically) there are half a dozen programs ongoing, and a little more than that number of CDMOs he’s working with in total to serve those programs.
Of course a number of those relationships were in place when Johnson joined Astex in March of 2020, but he’s needed to make adjustments, and find new partners as well.
“As a fairly small company on our own, we want a CDMO able to respond to our needs, which start with flexibility,” he explains of his selection thought-process.
“We set ourselves aggressive goals and timelines, but need to be able to pivot, and adjust to project needs. Two examples could include additional batch manufacturing at short notice to cover changing clinical supply needs or trouble-shooting during manufacturing campaigns, and adjusting overall strategy as required.”
Next, Johnson says, “it goes without saying it’s the quality of the CDMO we look at.”
He also desires CDMOs to possess “strong technical capabilities that are well defined, and well organized manufacturing operations.”
He explains that:
“A well-organized manufacturing operation to us means that all functions involved (R&D, manufacturing, engineering, analytical, quality, EH&S and regulatory) work well together to execute projects on time, and meet quality and cost targets.
“Therefore, quality and techincal capability would be our first criteria for selecting a CDMO, but flexibility and ability to meet our evolving manufacturing needs is something which makes certain CDMO's distinguish themselves from the crowd.”
The good and not-so-good news surrounding this criteria today, says Johnson, is there are quite a lot of those flexible, high quality, strong technical and competent manufacturing CDMOs out there to select from.
“It's actually difficult to distinguish among them,” he says. “Everybody has a lot of the same facilities, and they all talk the same game.”
What to do with an abundance of riches?
“We typically look to establish long-term relationships with our CDMO partners. We develop the working relationships, and if the CDMOs are appreciative of what we want to achieve – perhaps particularly that flexibility we sometimes need – that’s what distinguishes them.”
Word From Japan?
I have a background of working with Japanese companies. It prompts my next line of thought: How much does Otsuka participate in the CDMO-selection process at Astex U.S.?
It would make sense if they are involved. As mentioned above, if indeed the clinical development succeeds, Otsuka will take on the commercial-supply responsibilities. So do they want to be involved with Johnson’s supply-chain selection process?
His reply surprises me.
“No, not really.” In fact, he says, “We develop the supply chain ourselves for the commercial manufacturing, then Otsuka takes over the management of that. The relationship is more like the handing over of an intact supply chain to Otsuka. “
“Whether they subsequently develop alternative suppliers or other related decisions is then up to them. But our goal is to provide what I’d call a neat supply-chain package for them.”
“But this should not come across as “organizational silos,” says Johnson.
While Astex owns the supply-chain development and decision-making, Otsuka’s involvement naturally increases as NDA preparation approaches, and tech/knowledge transfer activities as part of the commercial manufacturing hand over commence.
“And conversely, commercial manufacturing activities may still involve Astex team members to varying degrees depending on the project, but overall responsibility belongs to Otsuka.”
Further clarifying the relationship, Johnson says Astex functions under an “SOP umbrella” that's aligned with Otsuka.
“There are due diligence items in terms of selecting the CDMOs. So within that infrastructure we have the freedom to select our development partners.
Johnson says the model is productive, and he feels comfortable operating within the organizational structure. After years of working within CDMOs, he’s getting his wish to perform development for an interesting sponsor.
Next up, Johnson reveals how Astex’s organizational outsourcing actually benefits from his past experiences working at those CDMOs.