Raymond Skwierczynski places value on the journey as much as the outcome.
By Mark Crawford
Raymond Skwierczynski, Ph.D., former vice president of pharmaceutical operations for CoLucid Pharmaceuticals in Cambridge, Massachusetts, is currently a consultant to the pharmaceutical industry. He also chairs the AAPS Manufacturing Science and Engineering (MSE) community and is an expert committee member for the United States Pharmacopeial Convention.
Skwierczynski served as a department head within pharmaceutical sciences for Takeda (formerly Millennium Pharmaceuticals) from 2003 to 2015, where he led scientists and engineers responsible for small-molecule preformulation, formulation, and analytical development for oral and IV routes of delivery. He also directed the late-stage development of NINLARO (ixazomib) and developed process maps for all stages of pharmaceutical development, ranging from initial studies through regulatory approval.
Some of the inventions he has patented over the years include pharmaceutical compositions of several oncology and immune-response-modifying drugs, polymorphic crystal forms, and pharmaceutical salts.
One of the greatest achievements in his career is NINLARO, a multiple myeloma drug approved by the Food and Drug Administration (FDA) in November 2015. Skwierczynski helped develop the formulation and manufacturing process that allowed development of the intrinsically unstable drug ixazomib. “When we received FDA approval, I took some time to reflect on the significance of our accomplishment, as well as my own personal journey that brought me to that moment in time,” he says. “The first patient was dosed in 2008, the year in which my two brothers died of cancer. Seven years later, after FDA approval, myeloma patients had more hope because of the groundbreaking work our team accomplished.”
The breakthrough that led to the successful development of a solid oral dosage form of NINLARO was when a colleague crystallized ixazomib citrate, which is a prodrug of ixazomib. Until that time, the proteasome inhibitors being developed were all injectables; ixazomib was the first oral proteasome inhibitor. For Skwierczynski, the highlight of this project was working with such a high-performing chemistry, manufacturing, and controls (CMC) team. Its outstanding inter -department collaboration solved many challenging technical problems. “I know this team will be one of the highest performing teams I will ever work with,” he adds.
Shortly after NINLARO was approved, Skwierczynski left Takeda, a multinational company with about 30,000 employees, and joined CoLucid Pharmaceuticals, a seven-employee, phase-3 clinical-stage biopharmaceutical company, as head of pharmaceutical operations in November 2015. The company had only one molecule—lasmiditan, for the acute treatment of migraines.
Skwierczynski adapted well to the small-company environment presented by CoLucid Pharmaceuticals.
“It allowed me to set the development strategy and execute the plan,” he says. “I greatly enjoyed the focus and quick decision making, as well as seeing how each of us contributed toward the corporate goals through innovation and teamwork.”
Although he was officially head of pharmaceutical operations for CoLucid Pharmaceuticals, Skwierczynski was essentially a one-man CMC department that closed a significant gap between clinical and CMC development. This was a critical accomplishment, which included the start of registration stability studies for drug substance and drug product, drug substance scale-up to commercial scale and Stage-1 validation, drug product scale-up, and development of new analytical methods. CoLucid Pharmaceuticals was acquired by Eli Lilly and Company in 2017 for about $1 billion, and the new drug application submission for lasmiditan is planned for 2018. After he completed his obligation with Lilly in December 2017, Skwierczynski formed his own consulting firm that works with biotech startups.
When CoLucid participated in a NASDAQ stock market bell ceremony,
Skwierczynski was featured in New York's Times Square.
COLLABORATIVE LEADERSHIP AND MSE
Skwierczynski served as MSE section vice-chair in 2016, chair-elect in 2017, and section chair in 2018. The MSE section was formed as a result of a re-organization of sections that occurred more than a decade ago, with little change in approach or direction since then. As chair, Skwierczynski seeks to modernize the section by bringing together all members who share an interest in process development and manufacturing.
This, however, is just the first step.
“It became clear to me that we could not exist solely by bringing members together,” he says. “We have to re-invent ourselves.”
MSE’s leadership team made two strategic decisions at the 2017 annual meeting. First, the team decided to convert the section to a community. Second, the new community would not compete with former focus groups. “With the move to communities, the focus groups and the sections will be on the same rung of the AAPS organizational chart,” says Skwierczynski. “The hierarchy and the administration function are gone.”
The team solicited input from members on how to implement these decisions. MSE focus groups wanted their community type to be science; MSE leaders suggested pharmaceutical innovation and management as its community type. “We will still be scientific but will look at these other areas that are bigger and more complex than what a focus-group-derived community would tackle,” adds Skwierczynski.
The team also plans to create a new vision and mission for MSE. “We are searching for new opportunities that will unify and engage our community,” he continues. “We have reached out for input within our community, as well as AAPS.”
MSE will also not “recycle” its goals from the previous years. The leadership team drafted goals that are consistent with the new community status, as well as AAPS goals. For example, one new goal is to partner with other organizations to sponsor workshops and to identify and influence key scientific policy and regulatory issues. Another goal is to create opportunities to collaborate with former focus groups because there will be some overlap (and interest) with missions and goals.
Are these changes necessary?
“Absolutely!” says Skwierczynski, who points out that FDA has had a Pharmaceutical Quality for the 21st Century initiative in place for more than a decade. Although progress has been made, the pharmaceutical industry is far from fulfilling the initiative’s vision of “a maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drugs without extensive regulatory oversight.” Skwierczynski says, “The pharmaceutical sector is currently operating at two to three sigma; the number of product recalls is still large, and there are drug shortages. There is opportunity for the MSE community to contribute toward the initiative’s vision as we contribute toward our own.”
Skwierczynski has enjoyed many opportunities to build or re-invent capabilities and functions within pharma during his career. Examples include establishing a discovery-development interaction at 3M Pharmaceuticals, leading a high-performing NINLARO CMC team to the new drug application approval of the first solid oral dosage form at Takeda Boston, and improving the state of CMC development at CoLucid using only external resources. “In each case, the journey was as important as the outcome,” he says. “We had to change the status quo, get buy-in from and influence stakeholders, take risks, set the direction or vision, and lead people to create value for the organization and achieve the desired result.”
Each journey creates experience and an awareness that adds value to the next journey. For Skwierczynski, this could be pursuing his strong desire to be a management team member of a start-up pharmaceutical company from Day 1. Building the next successful journey often depends on maintaining or expanding professional relationships along the way. These provide industry knowledge and potential fruitful partnerships. There is no better resource for networking, building professional relationships, and taking advantage of leadership opportunities than AAPS.
Skwierczynski found AAPS workshops especially beneficial. “I attended two impactful workshops early in my career that helped me with understanding the scientific and regulatory aspects of formulation development—the Arden House on Pharmaceutical Powders: Properties, Processing, and Regulatory Issues and the AAPS/FDA Workshop on Bioequivalence of Topical Dermatological Dosage Forms,” he says. Later in his career, he became involved with focus groups, section leadership, and developing the annual meeting agenda.
“Being an active AAPS member is the best way to stay in touch with pharmaceutical scientists and key leaders,” states Skwierczynski. “It is the perfect place to network, exchange ideas, and find people who share the same visions and goals, and can help make your next journey a success.”
Mark Crawford is a science and technology freelance writer based in Madison, Wis.