No Facility? No Problem! Redefining "Controlling Your Destiny" In C&G Manufacturing

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

There’s a lot of conventional wisdom and best practices to share about outsourcing your manufacturing, regardless of your therapy. In many cases, your success hinges on your ability to do this one critical (but vague) term: communicate. Generally speaking, being transparent and communicative with your outsourcing partners is crucial for finding the right partner and moving your product — whatever it may be — swiftly through development.  

However, I’d argue that “communication” within the C&G industry is even more essential today for one reason that is very rarely articulated. Being a gold-medal communicator with your outsourcing partners can also set your company up to “control its own destiny” without owning your own facility.  

Now, far be it from me to disagree with the many well-known benefits, opportunities, and liberties owning a facility can provide to C&G companies. But in the reality of the market today, owning a facility is not the current or near-future reality for a majority of companies. So, for those of you that are working with one or juggling multiple outsourcing partners, I’d like to offer a different perspective. Yes, owning a facility fosters valuable hands-on experience and ensures that a company can directly “control its own manufacturing destiny.” But given what I regularly hear/read about the challenges of outsourcing today, it seems that working with outsourcing partners provides just as large an opportunity of owning and fine-tuning your scientific/technological know-how and manufacturing destiny. In fact, I’d argue you will never realize just how much (or how little) you know about something until you find yourselves having to teach it to someone else. And there’s a heck of a lot of teaching going on these days in C&G therapy outsourcing relationships. 

My thoughts on the “buy-but-still-controlling-our-destiny” equation were reinforced after reading this article by my colleague Louis Garguilo of Outsourced Pharma. The article, entitled “The Right Words For Optimal Outsourcing,” emphasizes just how important it is to align on the terminology you use with your CDMO from the very beginning — especially in the C&G space. Making sure you’re speaking the same language will ensure you’re both envisioning the appropriate manufacturing paradigm and controls to meet regulators’ expectations for your therapy. As Erich Bozenhardt explained in the article: 

“A CDMO basically begins with, ‘You have a cell therapy? That's great. We can grow cells.’ But in fact what you really need to be focused on is handling a certain viral vector. Now you start to hear, ‘We're actually not set up to do that specifically. We didn't think you were talking about gene therapy.’” If you are dealing with a bigger CDMO, at the least you then get switched to – and start over with – a different facility and business unit. At the worst, you’ll need to move on altogether.  

As you’re all painfully aware, there is a smorgasbord of vocabulary, terminology, and acronym differences between global regulators. Aligning around the wrong or different terminology will likely result in a therapy’s CMC needs not matching up between the sponsor, CDMO, and regulator. “Picking the right terms can put you in the right slot for all expected CMC activities,” Bozenhardt clarified. In turn, this will also ensure your CDMO and their processes are equipped for future regulatory audits and inspections.  

There’s also quite a bit of due-diligence companies can prepare to carry out when evaluating potential partners. As Tony Khoury of Project Farma shared during a recent panel discussion at the Gene Therapy For Rare Disorders Summit, C&G sponsors (or any sponsors, really) can select a partner based on the wrong parameters: 

Sponsors often select a partner based on the name and reputation of the company. What ends up falling by the wayside are evaluations and assessments of the facilities, capabilities, technologies, and — just as important — the culture and how that will align with the particular project and team. 

One you’re beyond identifying potential or future partners, panel participant Palani Palaniappan, SVP and head of global technical operations for Aruvant encouraged other companies to take their time on establishing their outsourcing contracts. He shared:

I try to be as specific and clear as possible in the contract stage. Because of the newness of a lot of the work we’re doing, defining expectations for established processes [e.g., yields and failure rates] in the contract will set the tone for this relationship from the beginning. If you can agree on these parameters upfront with your CDMO(s), your life becomes easier. 

It goes without saying there are quite a few complexities in the outsourcing space today that make managing outsourced development programs far from cut-and-dry. As panelist Andrew Bellinger, CSO of Verve Therapeutics, pointed out, the novelty of these therapies and their development paradigms may require multiple vendors. “Trying to piece together your needs from a variety of different organizations and keep the process integrated and running smoothly is its own challenge,” he said. Similarly, there are inherently going to be risks in asking a CDMO partner to carry out a task that they perhaps have never done before.  

But herein lies the opportunity, dear readers. As Bellinger stated: 

This risk forces you to have the internal expertise to do a tech transfer, for example, in cases where your partners may lack the experience. They’re learning everything about the process from you.  

We often talk about the make vs. buy equation as a black-and-white equation. If you outsource, you will lack control over your product, process, and destiny. The only way to best understand and learn your process is to invest in your own capabilities. However, as the aforementioned examples will demonstrate, there’s still an awful lot of power a sponsor can and currently does have over their outsourced development — whether it be doing their due-diligence in selecting the right partner, aligning on terminology, clearly outlining their needs and expectations in the contract, and continuously reiterating those needs and educating their partners on their process. Owning a facility may be the best approach for your company now or in the future. But it seems there’s still a lot of room to flex (and tone) your scientific and technical muscles and control your manufacturing destiny within outsourcing relationships.