From The Editor | March 28, 2016

Genentech Speaks The Language Of CMOs

Source: Outsourced Pharma
Louis Garguilo

By Louis Garguilo, Chief Editor, Outsourced Pharma
Follow Me On Twitter @Louis_Garguilo

Genentech Speaks The Language Of CMOs

Todd Mabe, head of External Quality, Biologics Drug Substance for Genentech, knows that nowadays his company has an inherent advantage when contracting for biologics production capacity. “It’s fair to say we’re a popular customer target,” he explains. “Most CMOs want to find out details about our business and get involved with our supply chain.”

That doesn’t make the selection process a walk in the park. Genentech has exacting criteria for choosing CMOs; the need’s often for large-scale capacity for commercial operations, and requires specific capabilities, including for monoclonal antibodies (MABs).

Whether you’re a biotech or pharma on the CMO “preferred list,” or less well-known, Mabe’s discussion of Genentech’s selection criteria, and how the company overcomes outsourcing challenges, can provide some actionable insights.

Outsourcing MABs

Mabe is responsible for overseeing a supply-chain network for six of the seven drug substances related to Genentech’s monoclonal antibodies manufacturing. Each of the six MABs is manufactured at a separate CMO, although Mabe says, “We’re not opposed to having more than one MAB at a CMO. Selection comes down to capacity, quality mindset, and process fit.”

Genentech has different approaches to these manufacturing relationships. Some rise to the level of strategic partnering, while others are particular to “the right fit as in size, run-rates, and availability at the CMO.” Fundamental to the selection process, and any relationship that develops, is whether a CMO has all the technology to manufacture a specific MAB, and what other specific or unique technologies a CMO may bring to the table.

Mabe says some CMO relationships have started with cold calls from service providers they hadn’t worked with in the past, but the contracting process is more typically driven internally by specific demand. “We identify needs for a new molecule that we decide will include outsourcing,” says Mabe. This starts Genentech’s RFP process, leading to due diligence with a diverse team of experts. The evaluation includes quality management systems, skillsets and expertise, technology fit, and safety assessments. “We also perform financial audits,” adds Mabe. “There’s a large volume of work around ensuring the CMO is a fully viable entity for us before we move forward.”

The science and technology itself adds to the complexity of the selection process. MABs have been around for a number of years, but Mabe says there remain challenges that only specific expertise can overcome.

“The complexity of a biologic manufacturing process can be quite challenging; you change just a bit of a parameter and it could have a huge impact on the molecule,” Mabe says. “That, by the way, is really the rub of outsourcing to different countries as they start to develop infrastructure to support monoclonal antibody production. It really is still a young industry for almost all countries outside of parts of Europe and the U.S. I view that as an elevated risk.”

But Mabe says even with the most experienced CMOs, clear communication is essential to an overall successful relationship, particularly when it comes to determining and communicating the criticality of the processes, deviations, and those parameter changes he mentions.

Speak The Same Language

“CMOs today know their business. They know what they’re doing,” says Mabe. “Still, it can feel like we’re talking in two different languages at times. CMOs have certain expectations. What they might consider a minor event could actually be a major concern, simply because we have a history with our drugs and running these processes.”

Mabe, whose international career includes positions at Boehringer Ingelheim, Allergan, and 12 years at Genentech, says all communication has to run on a two-way street. He acknowledges the challenges contract manufacturers have simply due to the nature of their business. “A CMO has to deal with a variety of companies. Many of those customers sound like they are speaking different languages as well. They provide varying oversight to the CMO, and every client has their own set of expectations.”

Because of this, Mabe recognizes that if Genentech determines a process needs to be run a certain way – or an activity considered critical and “regulatory driving” – it not only impacts his business, “but we need to follow the potential impact to the CMO.”

He adds: “CMOs have regulatory obligations that can have a knock-on effect. If they implement something on our behalf, it potentially implicates other molecules they manufacture. It’s a fine line to straddle: Do what’s right from a compliance perspective, but also take into account the impact to the CMO. They have a business to maintain. The only way to truly work together is with strong communication, learn to speak the same language, if you will, and a spirit of understanding on both sides.”  

This communication and understanding can benefit from the parties being close by. As we’ll explain next, at Genentech, proximity can be a prerequisite to partnership.

We’re Right Next Door

Mabe employs site managers who “represent the relationship with the CMO.” In many cases, these individuals are actually embedded at the CMO, or at the least, located nearby  in centralized Genentech offices established close to manufacturing partners. Mabe says, for example, his Genentech office in Boston was established to support East Coast operations.

Decisions around change controls, quality management, and deviation investigations are first dealt with through the interactions of the site managers. “We tend to put our stake in the ground to establish more oversight of our CMOs than others. We’ve been told that,” Mabe says. “What’s the right number of resources for oversight of each CMO? It’s determined with each situation. The cost of these resources is not the limiting factor, although taken into consideration. Ensuring the supply of drug substance to our patients is at the heart of our decision making.”

Mabe says site managers certainly aren’t on their own when working with CMOs. They actually work within “a defined group both internally and externally, and are a part of joint management teams that facilitate communication.” These teams have “escalation paths” to joint steering committees, or to an executive steering committee level when necessary. Internal and external communications are the key here.

Mabe himself says he likes to stay close to other biotech managers and executives to discuss subjects such as pipelines, and outsourcing trends. In April, he’ll join a panel discussion at Outsourced Pharma Boston entitled, Quality Conflicts: War stories from the quality side.

“I’m excited about this conference in particular,” he says. “There’s a good amount of senior executives I can interact with, and benchmark where other companies are going. I’ll learn about their challenges, and how they’re planning to bridge any roadblocks. Are there any changes in the outsourcing arena? Are there risks associated with the changes? It really helps to understand what the roadmap is for outsourcing, and some of the risks that you can proactively mitigate moving forward.”

Perhaps above all, Mabe is one to help ensure the industry is speaking in a common and perceptible language.