The fast-evolving global regulatory landscape has led many companies to outsource regulatory affairs and regulatory intelligence operations, turning to biopharmaceutical services organizations for an expert, scalable workforce. To understand how this model helped Otsuka Pharmaceutical, Contract Pharma and Leslie DeVos, vice president of PAREXEL Consulting, and Judith Atkins, a principal consultant with PAREXEL, spoke with David Goldberger, vice president of global regulatory affairs Otsuka Pharmaceutical Development & Commercialization, Inc. Mr. Goldberger oversees all strategic regulatory affairs including the CNS, oncology, cardio/renal, and digital medicine therapeutic areas, CMC regulatory affairs, labeling and medical writing.

Contract Pharma: What drove Otsuka to outsource some of its regulatory affairs activities?

David Goldberger: The company decided to pursue outsourcing as a model for more efficient, flexible use of regulatory affairs resources about seven or eight years ago. Before 2009, there had been a number of regulatory staff in-house, but as attrition naturally occurred, we contracted with external resources for support.  We now keep a small team of employees to set our global regulatory strategies and we rely on contractor agencies, such as PAREXEL, to support the strategic work by assisting in getting regulatory filings and activities done on time. With this model, as our workload changes, we can quickly scale the team up or down. Luckily, we have steadily expanded over the years and have been mostly flexing up as our regulatory activities have grown.

Leslie DeVos: How has regulatory intelligence support outsourcing benefitted you?

Goldberger: Regulatory intelligence alerts and detailed extraction/summarization of regulatory background information, guidance documents and product information is key to devising and executing effective regulatory and product development strategies.A good example is a European filing we completed a few years ago. We were exploring a new, intramuscular route of administration for an extended-release formulation of an approved injectable drug to treat schizophrenia. We planned to incorporate modeling and simulation data in the clinical data dossier so we needed regulatory guidance in advance. We knew that advice would be most useful from EU member states that were thought leaders in this area. Otsuka, using PAREXEL regulatory Intelligence resources, researched which countries were open to such an approach and identified three. We then scheduled scientific advice sessions with those, gathering opinions and recommendations. With the targeted feedback in hand, we met with the EMA and submitted a well-vetted proposal that led to approval of the new route of administration.

Judith Atkins: How has the use of outsourced resources evolved as Otsuka has grown?

Goldberger: We grew our regulatory needs and our outsourcing capabilities in tandem. When we started out, there were only a few products. I knew then that we needed to build a strong foundation for our regulatory group to do all our submissions and approvals as we grew. As the number of products and new indications has expanded substantially, we’ve quadrupled our outsourced regulatory resources from about four to about a dozen. Our blended team of internal and external professionals has seen multiple new products and indications approved in the U.S., Canada, and the EU. And we’ve supported filings in Asia and elsewhere around the world. It has been a smooth journey with a talented collaborator who understands our goals and needs.

At this point in the relationship, a majority of our day-to-day regulatory work is outsourced, such as routine submissions, freeing our employees for strategic work. Our relatively lean internal team can cover multiple products and programs because the background research into product categories and specialized or shifting regulations is handled by expert consultants. Our people can read, think about and utilize that research without having to scramble to produce it.

For example, this dynamic was a critical factor in getting our new drug-device combination product, ABILIFY MYCITE, approved this past November. The product was the first-ever digital medicine system approved by the FDA so we were in uncharted regulatory waters during development. But whenever we had a meetingwith the agency, we received background information on all meeting participants ahead of time.  We were also briefed on anticipated issues the agency would want to discuss, so that we went into meetings prepared, knowing what we wanted to accomplish and what to expect.

Atkins: It seems that this timely regulatory intelligence is a big part of what you can accomplish through outsourcing more effectively than in-house.

Goldberger: Exactly. In the past when we mapped out the requirements for a global development program, we had to gather regulatory information country by country and region by region. We also had to perform a landscape assessment of competitor products, both marketed and investigative. Now, we can obtain that intelligence from providers such as PAREXEL so that we can focus on making informed, strategic decisions.

Recently we were considering the timing of an application for Breakthrough Therapy Designation (BTD) from the FDA for a new product indication in development. In this case we sought assistance from PAREXEL. After reviewing PAREXEL’s report about a competing company that opted to apply for BTD later in development (i.e., in Phase III versus in Phase I or II), we decided to delay the submission. By studying how a competitor did it, we realized it was possible to retain some important BTD benefits even with a later application, while simultaneously avoiding some complications associated with an earlier filing.

In another instance, we were analyzing the different requirements for establishing bioequivalence across three different regulatory jurisdictions—the U.S., Europe, and Japan. We wanted to find a way to conduct the studies that would produce the right evidence for all three regions. Again, our outsourcing model allowed us to obtain the relevant information and lay out the requirements of each country and region side by side. Analyzing that, we found a solution that worked for all three.

DeVos: How do you bridge any cultural differences between contractors and the in-house team?

Goldberger: At Otsuka, our strength is how we collaborate across functions and groups to make sure we deliver on time with high quality to health authorities, and patients. From the beginning, we treated our external regulatory contractors as a valued part of our team. That has been effective for us because everyone is invested in what we are doing.

The flexibility of an outsourced team is crucial though. When you have a culture as unique as ours, the hiring process takes a lot of time and energy because you need to be 100% certain a candidate will fit with the organization. When you establish a relationship with a contractor, you can have confidence that they have the resources you need. 

Also, we have a flexible approach to people working remotely on our regulatory team. The expertise we need is quite specific, and naturally, not everybody lives where the work is. We have team members in Canada, California, North Carolina and some in Europe. Being flexible about location helps us access the talent we need, especially when you tap into the resources of a solid, talented regulatory consulting services provider.
 
Atkins: Any final observations?

Goldberger: The tactical and operational resources of the PAREXEL personnel have enabled us to move our products through the development process, get products approved and do product maintenance activities. At Otsuka, our corporate culture is to move fast. We come to decisions fast and we like to execute on them quickly. PAREXEL has been able to support us in that successfully.