From The Editor | December 11, 2017

The Future Of CMC Leadership At Radius Health

Louis Garguilo

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

The Future Of CMC Leadership At Radius Health

Michael Markey and I worked together years ago when he was the lead process chemist on customer projects I brought to our CDMO. I recall his ability to deliver on the science, but as importantly, a low-key personality that lent itself to superior customer service. He listened intently to what the customer – and his colleagues in other functional groups – had to say. Then he’d outline clearly how he and his team could assist. It was a formula our customers and we colleagues appreciated.

I hadn’t kept up with Markey until I recently heard he’d become CMC director of pharmaceutical sciences at Radius Health, Inc. Radius is a virtual biopharma with a commercial product – TYMLOS (abaloparatide) injection was FDA approved for the treatment of postmenopausal women with osteoporosis at high risk for fracture – and a full pipeline of candidates also in the pursuit of oncology and endocrine diseases.

Besides a group of professionals devoted to the commercial product, and one small lab for some preclinical in vitro testing, the company maintains the “virtual” label by way of utilizing outsourcing for all of its drug development and manufacturing activities. 

I caught up with Markey at Radius headquarters, in Waltham, Mass. After some small talk of the “glory days,” I ask him about two topics specifically. The first is one we cover in depth at Outsourced Pharma – the role of the CMC leader in today’s outsourced model. And as we enter a new calendar year, the timing is fortuitous: How is CMC management practiced by a new leader as we enter 2018? As you’ll see, Markey serves up a well-defined assessment.

The second topic is actually his reversal of one we’ve also talked quite a bit about – the migration to CDMOs of biopharma professionals. I wonder what skills and experiences Markey brings to Radius after a career spent at two CDMOs. This, too, has good timing: We’ve made it ritual to investigate employment trends and challenges in our outsourcing arena as we end and enter each new year.

Emulating the Markey trait for careful listening, we’ll set out our discussion in two articles, with this first focused on the current role of the CMC leader.   

Objective 1A And 1B

To start, let’s find out what Markey needs to concentrate on most, and how he relates that to his day-to-day activities at Radius.

“I think of this as having priorities 1A and 1B,” he replies. “If I had to put one above the other – which I try not to – I would say safety and quality is always top priority. Then nearly equally as important in my role is maintaining supply continuity. It’s tough to run trials if you are short or limited in your drug supply.”

These two priorities – quality/safety and supply continuity – are both tactical and strategic. “They have to be managed within the timeframe of months and quarters, as well as to meet long-term goals. Decisions come in gates and waves, propelled by things such as regulatory reviews and approvals. Throughout the process, we keep the regulatory bodies apprised of what we're doing, and ensure we're commensurate with our phase of development.”

Markey says CMC professionals must keep an eye on the ultimate goal: commercial success. “We’re mindful of understanding the process so we’ll be in position later in development to justify the attributes of our drug, and to ensure a safe medicine for patients.”

He adds: “And you do need to think about process optimization to make the drug as cost effective as possible.”

The Team

Accomplishing 1A and 1B starts with a team from multiple functional groups supporting the CMC effort.

Markey mentions the importance of the “formulation aspect,” and working with colleagues focused on the manufacture and optimization of the drug product and drug substance. “Quality and analytical representation spans both ends of that focus,” he says. “And I work closely with our clinical operations team. They help us understand enrollment strategy and study design, which lends to our supply continuity plans. I’ve learned to consider them as the end user at the clinical phase.”

All functions help address both those short- and long-term goals. “For example,” Markey says, “maybe a re-test date is coming. We have to evaluate stability data in hand and make some projections to understand if we can extend the date. Since the product will have limited stability data in early development, this requires collaboration with the analytical team, the quality function, and usually subject matter experts.” Markey always seeks regulatory input to “align with guidance, and understand how any decisions may be perceived.”

“However,” he says, “what’s most important to remember about a virtual company like Radius, is all of those functions work at a desk. None of us actually have hands on; we rely on our CMO partners to get the work done. There's strong external collaboration that goes into planning and updating. That’s where the innovation and execution takes place; CMOs are guidance on what is realistic and can be delivered. For me, the external project managers are an integral part of my day-to-day work.”

Project Managers: Common Goals, Different Priorities

Markey says he has learned this: “There are common goals between sponsors and CMOs, and there are different priorities. The more you understand and identify both, the better you can drive programs forward in an outsourced model. These goals and priorities will always be there; you can’t find a situation where neither is present.”

“Given that, and our virtual aspect,” he continues, “we rely on those PMs [project managers] at the provider.” Their input, he stresses, aids the sponsor’s ability “to navigate both sides of the collaboration.”

To CMOs he offers this: “Don’t undervalue the benefit of good project managers to your customers. Particularly, your CMC counterparts at the sponsor have a lot on their plates. I never realized how much.”

And project managers at CMOs are best at getting answers to questions such as:

  • Are our timelines realistic?
  • Can we expect complete supply continuity?
  • What realistically can we do within our clinical trials regarding material?
  • What should we be budgeting now and longer term?
  • What shelf life can we really expect?
  • What sort of timeline can we meet for an NDA submission?

Role Models       

I ask Markey if he witnessed good examples of CMC leaders at drug sponsors he worked with when on the CDMO side.

“Absolutely, and that was inspiring,” he says. “They give me models to reflect back on, particularly on how they approached and managed certain situations … I can also think back on the ones that did not work as well.”

The difference?

“The simpler and clearer the message from the CMC sponsor, the better the results delivered from the CMO. That’s always the case. The clearer the expectations, the more you get out of the relationship. The challenge is trying to ‘deconvolute’ drug development, which has constantly changing priorities, into simple objectives. If you ask me how I got this role at Radius – and how I’ve been able to manage the role – it starts with understanding the CDMO’s needs as well as the sponsor’s, where the common goals are, and how both sides can come out with wins. Challenges will always be there – and affect both partners – but working them out together leads to successful and future collaborations.”

He pauses, then adds: “But sure, I had some trepidations when stepping into this new role, having never been on the sponsor side. I wasn’t sure about approach, and what sort of style I needed.”

For some of us, it was evident even years ago that Markey had the CMC “style” needed for leaders in the outsourcing model.