In-house regulatory database development: Solution for a competitive oncology landscape

The unprecedented number of new investigational agents in clinical development in the competitive oncology space presents a significant challenge for regulatory intelligence professionals. Strategic decisions are complicated by the overwhelming amount of regulatory information scattered across numerous repositories. The development of an in-house database may facilitate success for businesses in the prevailing information-centric world. Effective implementation of an in-house database addresses a clear need for resources dedicated to cancer drug development. This article provides an overview of in-house regulatory database development and explores its potential within the evolving oncology treatment landscape. Keywords – database, oncology, regulatory intelligence, regulatory strategy
 

Introduction

Cancer care has evolved significantly in recent decades, with advancements reflecting an increased focus globally on cancer research and oncology by researchers and healthcare providers, patients and the public, and lawmakers. The COVID-19 pandemic has done little to stymie advancement within the oncology therapeutic area, as demonstrated by continuously rising clinical trial activity and an expanding pipeline of new treatments. In 2020, a record 1,600 clinical trials were initiated. That same year, the total number of new molecules in development reached almost 3,500, an increase of 75% from 2015. The US Food and Drug Administration’s (FDA’s) Center for Drug Evaluation and Research approved 50 novel therapeutics in 2021. Cancer medicines accounted for 30% of those new approvals, higher than the 5-year average of 28%.¹ This extent of growth was not limited to the US. China approved 37 new oncology therapies over the last 5 years, and France, Germany, Italy, Spain, and the UK together have approved 53 therapies since 2016.¹ This substantial research focus by biopharmaceutical companies on oncology highlights the progress in understanding cancer as a disease and the need to support a vulnerable patient population.
 
As the healthcare industry and regulators continue to better understand the biology of cancer, sponsors must remain current on their competitors’ strategies and the precedents generated by past approvals. For example, understanding the shifting definition of clinical benefit for cancer therapies and the role of surrogate endpoints has proved advantageous for emerging drug development programs. Regulators rely on clinical trials and the use of relevant clinical endpoints to accurately assess the safety and efficacy of new cancer therapies. Overall survival has previously dominated as the gold standard. However, the endpoint’s utility is inhibited by its time-consuming nature. This has led to a recent push to explore surrogate clinical endpoints as a measure of clinical outcomes. Between 2010 and 2012, the FDA approved 45% of new drugs based on a surrogate endpoint.² Understanding the fluid scope and lens of regulators can provide clear approval advantages over competitors.
 

Opening new pathways

In parallel with a knowledge leap in cancer as a disease, health authorities have seen increasingly unique submissions for oncology therapies globally. With the introduction of new regulatory initiatives and guidelines, the standard pathway from development to market has become ambiguous. Health authorities are taking initiative to open new pathways for applicants to bring cancer therapies to market. Recent pilot programs from the FDA’s Oncology Center of Excellence’s (OCE’s) serve as prime examples.
 
The introduction of Project Orbis provided an international framework for concurrent submission and review of oncology products. Collaboration among global regulators allows patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions, regardless of whether the product has received FDA approval.³ In addition, pivotal clinical trials in oncology are commonly conducted internationally and these global trials are increasingly important for investigating the safety and effectiveness of cancer drugs for approval in the United States.
 
In 2018, the FDA also developed the assessment aid to facilitate the agency’s evaluation of new drug applications, biologics license applications, and supplemental applications. The assessment aid allows applicants to voluntarily submit summaries of their own, taking on a significant portion of the agency’s workload and expediting the review process.⁴ The assessment aid may be combined with other pilot programs from OCE, such as real-time oncology review. Biopharmaceutical companies are leveraging these new regulatory pathways dedicated to oncology therapies to bring innovative medicines to market at an unprecedented rate. As the oncology space is rapidly progressing, both the regulators and industry need to be agile and flexible to accommodate these novel programs.
 

Regulatory strategy in the oncology landscape

Identification of impactful regulations drives a competent organization’s actions, decisions, and results. Understanding the nuances of regulatory pathways within target markets offers an immense competitive lead. At the same time, failing to effectively evaluate and use regulatory resources can completely extinguish the commercial potential of any molecule. Creating a successful regulatory strategy tailored to an oncology drug development program demands knowledge of a complex regulatory landscape. Before approaching health authorities, companies should have a clear regulatory plan aligned with the characteristics of the molecule, including, but not limited to, the target indication, dosing regimen, clinical development plan, subject selection strategy, and applicable biomarkers and diagnostics.
 
The dynamic oncology environment thrusts regulatory intelligence into a prominent role within the biopharmaceutical industry. A regulatory intelligence team monitors, gathers, and analyzes publicly available and experience-based regulatory information necessary to develop a compliant and timely strategy. Regulatory intelligence is not limited to information and knowledge collection alone, however. The profession meets the demands of functional areas across the drug development spectrum through the interpretation of specific considerations for product development and marketing submissions. Regulatory intelligence adds value to the knowledge and sets the tone for programs to create a competitive advantage.
 
However, there is a rapidly expanding volume of information released by global health authorities, contributing to a growing burden on regulatory intelligence professionals to capture, filter, analyze, and disseminate sophisticated data crucial to business strategy. Publicly available resources, such as government sites, can hold substantial details about a cancer drug’s development and lifecycle, including registrational studies, the drug’s labeling history, safety profile, regulatory review, and the company’s previous agency interactions. Furthermore, the information is typically dispersed across multiple repositories, demanding substantial time for collection. Data will have to be assessed for general compatibility with the company’s product development plan. This poses a difficult challenge to regulatory intelligence professionals. The advancements in the regulatory field have outpaced the ability to manually collect and disseminate to the company information vital to the success of the business. Modernized approaches to comparing regulatory data through emerging technology will be vital to support regulatory intelligence professionals’ drug development programs by efficiently navigating the modern world complexities of healthcare and regulatory environments. 
 

Novel technologies and regulatory strategy

Regulatory intelligence professionals often use technological innovations to build a foundation for successful regulatory strategy. Third-party organizations propose an enticing solution to the rising demand for access to different kinds of information. Expansive, fee-based regulatory intelligence databases serve as a central hub containing comprehensive, global information related to all functions across the research and development lifecycle. Their products often mitigate the manual labor associated with data collection and allow users to focus on critical decisions.
 
However, this sleek platform is not without its limitations. As an external business serving numerous clients, there is always a potential for a disconnect with each individual consumer. Streamlined into a single source, an external database is plagued with irrelevant material covering a vast spectrum and rendering the final product inflexible to specific requisites. The responsibility falls on the users to further filter the data into actionable intelligence pertinent to their development programs. Management of the database depends on the third-party organization, reducing quality control and putting regulatory professionals at risk of missing potentially impactful material. Furthermore, external databases are rarely extensible, and customized data fields or alterations of interface attributes cannot be generated on demand.
 
Moreover, the depth of an external database is unlikely to scale alongside a specific organization. As the number of users increases, the architecture of the product may not be capable of seamlessly integrating a growth in demand or have the precision to cater to more specific product development needs. The size of third-party databases is independent of the consumer’s userbase. Extensibility is limited to the third-party organization and the sum of its clientele. There are costs to using third-party products. Depending on buy-in or perceived need for regulatory intelligence from leadership, these databases may appear unfavorable. These contracts should be taken into consideration and may prove costly for those with less individual demand for regulatory intelligence. The overwhelming amount of regulatory information available within third-party products still places the onus on regulatory professionals to efficiently generate actionable intelligence for the needs of the organization.
 

In-house database: Personalized tools for a targeted purpose

Modern tools for monitoring impactful regulations must be personalized to address the unique challenges encountered by each user. Massive projects like regulatory intelligence databases will succeed when they have the capabilities to cater to the needs of a company’s users.
 
An in-house regulatory database avoids the potential pitfalls of external solutions while generating immense benefits for companies operating within the oncology space. It offers a collection of directed information so that a particular group of people can find what they want by searching an internal database in the organization rather than being restricted to commercial or external options. The databases can be personalized to cover any discipline in any depth and breadth or in any format at the local, national, or international level. It can also provide access to a subject for which no database or organized retrieval system yet exists. In-house development removes the pressures to predict user preferences in advance, unlike external solutions. It allows the extensibility for the solutions to those needs to be built after the initial launch. The database does not have to be large to be useful. It can be designed to cover certain fields, and the coverage can be general or limited to some specific and definable traits. With in-house development, the breadth and granularity of captured regulatory data will be driven directly by target stakeholders.
 
Features of the user interface and presented content can be precisely adapted to specific drug development demands over time:
 

• Flexibility to customize the database allows greater ease in incorporating specific features within the interface that cater to users while integrating cohesively within the existing infrastructure. An internal interface with users and stakeholders forms a natural feedback loop with owners to improve the system.
   
• Scalability is the ability of an application to handle a growing number of users. The concept is directly related to the ability of a developer to maintain the system and data consistency. Internal development ensures that the intelligence database will be capable of efficiently scaling alongside the unique growth of a company’s user base, unlike in external products where there are multiple consumers under consideration.
   
• Saturation points for positive user experience are under the jurisdiction of the organization. Collaborative effort to produce an in-house database further solidifies connections between different stakeholders, often siloed by their departments, who may use content to accomplish common program objectives.

 
A variety of functional areas may provide input into the direction of the data presented and reap the benefits of actionable intelligence. As the database continues to incorporate global considerations, greater accessibility may also produce alignment across international regions.
 
In-house databases do have limitations that must be taken into consideration by companies.
 

• Development requires considerable manpower and time investment from an organization that has no previous system foundation.
• Regulatory intelligence professionals, stakeholders, and users must be trained on the user interface to ensure full reaping of the database’s potential.
• The regulatory intelligence content must be regularly verified through quality control measures as accurate and up to date if it is to be used as a basis for action.
• In-house database maintenance and launch greatly depend on the expertise of individuals familiar with the software.
• Turnover of any personnel involved with the program, in turn, strains the maintenance, capability, and development of the database.
• Leadership and organization buy-in is crucial because palpable benefits are rarely seen immediately after the launch database.
• Smaller organizations may find decreased benefits without sufficient resourcing. Improvements from feedback stem from the initiative and communication from the userbase. Nonetheless, there are significant returns for invested companies in the long-term investment of in-house database development.