Paragon Solutions recently announced regulatory affairs and operations expert Brooke Casselberry will lead its Life Sciences R&D Regulatory Domain.

In her role, Casselberry will be assuming leadership responsibilities for Paragon’s Regulatory Optimization Practice, to expand the company’s capabilities in providing solutions that assist regulatory organizations with defining process optimization and implementing the latest industry standards and technologies to realize business outcomes. 

With more than 15 years of experience in regulatory affairs and operations, she has led projects and initiatives involving more than 50 biopharmaceutical companies globally, contributing submissions, intelligence, management expertise and thought leadership. 

What are Casselberry's views on emerging trends and opportunities in regulatory optimization? Let's find out!

Brooke, one of your primary goals over the next 12 months is to expand Paragon’s capabilities in providing solutions that enable regulatory organizations to define process optimization and implement the latest industry standards and technologies to realize business outcomes. What will be your greatest areas of focus in the next year?

Brooke-1Brooke CasselberryUltimately what our clients want to achieve is reduced time to market for their products while maintaining compliance at a lower cost. Process optimization and standardization provides a pathway for these goals, however what really needs to be achieved is improved interoperability across systems to harness big data as it is created.

The problem is data is being moved and manipulated too many times. In some cases it is duplicated in systems or not in systems at all, there is lack of accessibility across partners, and data is not standardized, which makes it less consumable. Our industry is in a perfect position for the next disruptive technology. 

The International Conference of Harmonizaton (ICH) and Heath Level Seven (HL7) are developing and pushing forward the disruptive trends, which are changing the regulatory landscape, however the technology and business development is struggling to keep up.

This challenge is not just occurring within the industry, agencies are facing the same dilemmas. How to get legacy data across disparate systems into consumable, traceable, and reportable formats.

The goal that needs to be achieved for our clients is business process optimization outside of the technical requirements to improve business work streams from content development, Regulatory Affairs and Strategy through to Regulatory Operations and product maintenance. The advantage at Paragon Solutions is we are a product agnostic company, this allows us the ability to be non-biased and to openly evaluate what is best for the client from business capabilities to technical support.

Brooke, what do you mean when you say 'business process optimization outside of the technical requirements to improve work streams' ...can you elaborate on this and how it achieves business goals?

regulatory.affairsBrooke CasselberryThe term Regulatory is quite broad. At a high level it encompasses the full product lifecycle from development through to post market approval and tracking.

There is an upstream flow of information as data changes, business strategy changes, product development changes; it affects all areas of the regulatory spectrum. 

For example, imagine a product in Phase III clinical trials, and the NDA is in development for marketing approval in the United States with an expectation to file shortly after in the European Union under a Mutual Recognition filing.

At this stage the Authors, whether in house or via a CRO has authored most of their content, and are likely finalizing the pivotal study reports. The Regulatory Affairs leads are managing the expectations for the product approval, gathering the remaining administrative documents and signatures, and defining the future markets for registration. The regulatory operations group is working, likely overtime, to keep the submission timeline on target for receipt to the FDA without delay. 

Now imagine that filing strategy changes to add an indication for approval to this application. In doing so, a two-month extension to the filing date is granted. This new strategy has a complete trickle down affect.  The medical writers must update or include new clinical study reports, CMC, and summary information for the additional indication; the Regulatory Affairs leads must re-evaluate the filing strategy, administrative requirements, and confirm expectations with the executive team; the labeling team must develop the updated labels for the new indication for all applicable markets and in compliance with language laws. And finally, the Regulatory Operations team must include the new and updated content in the submission while maintaining a short turnaround time.

Now imagine if the Authors are creating their documents in legacy CSR paper format without utilizing eCTD compliant templates. The documents do not include cross references, bookmarks, ICH E3 granularity, or any document properties for content control.

When the Regulatory Affairs groups receive these study reports, they do not have an automated way to extract information for study type, control types, indications, etc. This information is manually extracted and then input into a Regulatory owned system; this could be as simple as excel sheets. Then once the Regulatory Operations group receives these reports, the STF required metadata for that report must be manually extracted again and placed in the XML backbone for eCTD compliance. For the CSR’s that were updated, likely the bookmark and cross-references need to be re-created and thus, making it very difficult to maintain time lines. 

While this is a very simplistic overview of one part of the regulatory product process, it demonstrates a real world scenario, in the worst case where the vulnerability for error is very large. Through business process optimization and standardization along with interoperability, organizations are more agile for these types of adjustments and through metrics can demonstrate improved compliance and quicker turnaround times.

You have more than 15 years of experience in regulatory affairs and operations.  What have been some of the most significant paradigm shifts to occur in the regulatory arena – and what is your forecast as time marches forward?

Brooke Casselberry: The biggest shift has been the transition from paper to electronic and creation of the Electronic Common Technical Document (eCTD) by the ICH. The purpose of the eCTD was to create a harmonized submission format for global applications.

Brooke.Casselbery.2The eCTD was adopted by the US-FDA, EMA, and JP-PMDA as early as 2008 and companies began adopting the eCTD structure and process for content authoring and delivery of their submissions. It has reduced time to market, created ease in document re-use, and while there are still application differences across regions, the content reuse has increased greatly across New Drug Applications (NDAs) and Marketing Authorisation Applications (MAAs) in EU Regions. 

As an extension, additional technological advancements were developed and adopted within the FDA including Structure Product Labeling (SPL), Study Tagging Files (STF), CDISC Standards, and overall better use of Metadata. 

In our current state, the FDA has released the Final Guidance “Providing Regulatory Submissions in Electronic Format – Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications, May 2015.” This means that as of May 2017, all CDER and CBER submissions will be required in electronic format in compliance with the guidance, with some exceptions.  

To expand on the development of the eCTD application, the FDA began accepting applications using the updated Module 1 specifications (v 2.3), which includes submission of Advertising and Promotional information in eCTD format.

With regards to what is coming next, it is an ongoing transition to data access and management.

Identification of Medicinal Products (IDMP) is scheduled for release June 2016.  This initiative drives standardization across product lifecycles.  Data typically exists in disparate systems, including Pharmacovigilance databases, Regulatory databases, Clinical, Labeling, and other databases containing drug substance and drug product information.

This initiative along with the need to access data faster has created a need for Master Data Management (MDM).  The next few years is going to be the definition of MDM and Regulatory Information Management (RIM), where they converge and how to standardize, collect, and process this data without duplication and undue burden on both the agency and industry regulators. 

Brooke, you have led projects and initiatives involving more than 50 biopharmaceutical companies globally, contributing submissions, intelligence, management expertise and thought leadership. You have considerable product management experience as well. What do you view as driving requirements in your industry today?

brooke.casselberry.regulatoryBrooke Casselberry: Industries everywhere are looking at ways to do more with less, while improving quality and quantity. This is a challenge. Safety issues and patient endangerment are very serious concerns.  In fact, a proven gross negligence of patient safety can lead to not only a loss of employment, licenses, and money, but it can result in imprisonment. Organizations are always looking for ways to optimize their resources, while maintaining compliance and improving their return on investment. 

The regulatory agencies have a similar goal, as a government body they are required to operate under a budget cap with high expectations from the general public to push forward innovation while maintaining high levels of safety and trust. It is ebb and flow of public meets private with watchdog oversight.

In order for success, the FDA and industry work together to define what each other needs to improve success.  Through open commenting periods, industry conferences, emails, and direct contact. This partnership has allowed for a push in modernizing the agency and industry, which creates more time and money for research and development.These modernization changes are driving requirements in our industry and are rapidly changing the way regulatory professionals operate.  

Earlier this year, DIA has released its third annual “What Lies Ahead?” report, providing expert insights into the year ahead for pharmaceuticals, biotechnology, medical devices, and diagnostics. What in the DIA forecast was most significant to you as you look toward 2016 trends?

regulatory.affairs.2Brooke Casselberry: This report covers a lot of areas in Regulatory, however the point that I feel is the most significant and creates the most change is the reauthorization of the Prescription Drug User Fee Act (PDUFA V) in 2017. 

The User Fee Acts within PDUFA authorize increased funds for the FDA and divisions within the FDA to make improvements in structure, technology, and over all improvements in innovation and reducing review timelines. 

As PDUFA V falls right around the time the eCTD v.4 (Regulatory Product Submissions) is due to be draft, I hope to see a shift in the Center for Radiological Heath (CDRH) under the Medical Device User Fee Amendments (MDUFA) for less paper and an adoption of RPS structure in the medical device submission process. 

With all the progress made across the other divisions in the FDA (CBER and CDER) CDRH is still operating in a full paper review cycle. This leaves a lot of opportunity for improvements with the field of Medical Devices regarding review times, patient safety and recall, and of course globalization to other markets.

What area of business do you view as a challenge for organizations to address?

Brooke Casselberry: Regulatory Intelligence. Regulatory Intelligence is the gathering and dissemination of relative information to the organization and the product line. It can include, but is not limited to, scientific data for product components, relative regulations in regions where information is not easily accessible, statistics and competitive intelligence gathering.

Larger organizations can afford to establish teams dedicated to Regulatory Intelligence, however in mid- and smaller-sized companies, regulatory intelligence is an additional job description that is tacked on to the already existing roles of regulatory affairs. Intelligence is lost or duplicated, or the resources are not available to find the relative information needed to make strategic decisions, so a lot of time is exhausted on research.    

regulatory.intelligence.1Brooke, what is your vision for the regulatory landscape in 2020?

Brooke Casselberry: 2020 is really just around the corner. Along with some of the timelines I stated earlier - IDMP Requirement for implementation in 2018 in the United States (2016 in EU), RPS eCTD V. 4.0 expected in 2017 - I expect that 2020 will be a continuation on these initiatives. I expect that social media will become much more involved in the direct-to-consumer advertising. 

Communication and partnership between agencies such as Health Canada and the United States FDA will continue to improve so there is more transparency and ease to product approval, manufacturing, and distribution across borders. Overall, these initiatives and itemization of content as metadata and standards leads to the increased use and development of artificial intelligence within our industry. 

Recently, I read an article on, “How Artificial Intelligence is now Telling Doctors How to Treat You.” The article referenced an app called Modernizing Medicine, where doctors can plug in the symptoms and other relative information and then the app will return results of approved medicines for treatments. While this AI technology is used in so many areas, it is under-utilized in regulatory development by both business and agency. I expect in 2020 and the years thereafter, we will continue to see a shift in this direction - which is likely going to be that disruptive technology finally adapted.  

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