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Shifting to a digital regulatory environment is forcing pharmaceutical companies to confront knowledge gaps across key research and development (R&D) functions. As health authorities streamline information exchange through data standardization, the separation between regulatory operations and other functions within the pharmaceutical industry begins to blur. By advancing implementation of ISO identification of medicinal product (IDMP) standards, companies are improving interoperability and information sharing among key clinical, pharmacovigilance, quality, manufacturing, and supply-chain–logistics teams. However, a company’s important regulatory and strategic planning information often is found in paper documents, bogging down the organization’s data value chain.

The need to prepare for new digital regulatory-submission requirements can present obstacles for companies. European Medicines Agency (EMA) requirements include adherence to the InterSystems IRIS platform for reporting marketing status and the Clinical Trials Information System (CTIS) to support the new Clinical Trials Regulation; and using substances, products, organizations, and referentials (SPOR) data management services for centralized management of master data (1). The Digital Application Dataset Integration (DADI) portal went into effect in the northern hemisphere in October 2022, heavily affecting the process of submitting regulatory variations, which is one of the main activities performed by regulatory departments. The annual throughput in Europe alone reaches hundreds of thousands of submissions (2). The examples mentioned above are specific to the EU jurisdiction, but similar developments are advancing in other regions. For example, the Draft Pharmaceutical Quality/Chemistry Manufacturing and Controls (PQ/CMC) Data Exchange document, issued by the US Food and Drug Administration (FDA), introduced new data standards for electronic common technical document (eCTD) Module 3 (3). Therefore, to sell their products worldwide, companies must prepare to address the different technological and digital requirements of multiple international health authorities. The responsibility is on regulatory and other organizational teams to understand those requirements and develop informatics expertise in addition to their other work. For most regulatory professionals, that is an unrealistic expectation.

Instead of placing additional burden on regulatory workers, organizations can implement an R&D informatics function to navigate the different entities that bring processes, technologies, and systems together within a product’s life cycle. Such a function can provide an architectural foundation that supports and enable harmonized decision-making across all groups involved in a product life cycle. Intelligent automation technologies such as robotic process automation (RPA) and natural language processing (NLP) can underpin the expertise and support provided by an R&D informatics team.

Breaking Down Barriers
To generate the most revenue from marketing authorization (MA) and mature product portfolio assets, companies need regional growth in appropriate market access and MA programs. However, it’s important to harmonize data collection, given that an MA application gathers data from multiple sources, largely held in documents that are maintained in discrete systems. Harmonization can be simplified by using intelligent automation technologies that find and extract data, then structure them in a way that is valuable for multiple purposes. For example, companies can use those data to build predictive models and respond to health authority questions quickly and accurately.

Predictive models also are hugely beneficial for the strategic planning of product development and market oversight. They provide companies with revenue data for marketed products and help to define the cost of establishing and authorizing new products for different regions and countries. Lacking accurate data about where their products are sold, many companies can’t easily compare the regulatory costs associated with those products to the income earned from sales. Finding registration information also can be difficult. Most companies can’t easily access information documenting changes to registrations, including what those changes might have cost.

To address those problems, companies began adopting regulatory information management (RIM) solutions to improve their data oversight. Even so, challenges remain. In Europe, factual information about a product is held in a document called a summary of product characteristics (SmPC). That has led to a growing interest in structured content writing, whereby documents are generated automatically from raw data. In this way, documents that are sent to health authorities during the submission process can be traced back to their associated data. Real headway will require regulators to move away from documents and toward structured data, and to that end there has been progress. For example, the EMA has taken steps to merge information on clinical trials and postauthorization into its SPOR platform, which is a single master-data approach.

Managing Information Continuity
Many manual steps remain in creating and maintaining MA dossiers. Such processes inevitably result in human error, often with disastrous results. Furthermore, even single-source data remain isolated without the process management needed to ensure that they reach other areas within an organization where changes are made. Technological innovations depend on people within an organization adopting an integrated mindset. Doing so can be difficult for departments that don’t understand the broader business impact of those digital capabilities.

Defining an R&D informatics function is important because it addresses those potential setbacks. Such a group can understand the processes and problems that an R&D organization encounters, identify technology solutions, and align those solutions with the organization’s existing information technology (IT). The informatics department should be staffed by experts who can navigate disciplines across the R&D value chain and translate information processing requirements for the rest of the organization.

Although an R&D informatics function would provide leadership and advice to guide broader operations, its staff would not make final decisions. Instead, they would support colleagues in other operating groups by recommending innovative solutions to support those departments and the broader corporate informatics strategy.

R&D informatics would help to ensure that technologies adopted by one department can interface with solutions in other departments to support process and information management. Staff from R&D informatics can help map an integrated and harmonized data model with standardized terminologies. Doing so ensures that when, for example, the pharmacovigilance team talks about a product, it does so using the same language as regulatory affairs, clinical, manufacturing, and other functions use. Ensuring consistency of technology and data enables each department to process and use information coherently. Of course, R&D informatics must ensure that every technology, data-management approach, and process complies with regulatory and legal requirements.

Where Can Companies Begin with an R&D Informatics Approach?
Pharmaceutical companies can struggle to adopt change, so it’s best to start with an integrative approach, such as looking for synergies and similarities among departments. By monitoring and understanding different functions, an informatics team can identify seemingly independent changes, then find overlaps and synergies to improve efficiency.

Needs can become evident when you analyze how different departments discuss and understand seemingly simple terms. For example, regulatory teams use the word product as a synonym for an MA or registration — even though that is technically incorrect. For manufacturing and supply-chain teams, a product typically is a manufactured item that a company delivers to different markets under different MAs. Meanwhile, groups that process adverse events as part of pharmacovigilance typically focus on an active substance, because that plays the main role in a medical assessment. Although different uses for the word product are understandable, they reference different aspects. For that reason, even such a simple word can cause confusion. ISO IDMP standards that refer to regulated pharmaceutical product information (ISO 11616) and regulated medicinal product information (ISO 11615) provide clear definitions of many terms in the pharmaceutical domain. R&D informatics therefore can leverage those standards to support a synergistic approach within an organization.

Changes in one department can have a knock-on effect for other functions, so it’s important for an informatics team to understand that interplay. For example, if the pharmacovigilance unit changes its systems or methods of information processing, that inevitably will affect how regulatory affairs leverages data for submissions. The R&D informatics team, therefore, needs to understand how data are used in support of different functions and how a change in one function might affect seemingly unrelated processes in other departments.

Finding synergies and bridging gaps will become increasingly important during interactions with regulatory authorities. For them, one department’s particular source of data is irrelevant because all departments are referring to the same product. Companies therefore need to adopt process and informatics harmonization terminology established by an R&D informatics function that understands regulations and how changing requirements from health authorities will affect decisions about solutions and processes.

Can the Industry Respond to a Digital Regulatory Future?
The transition to digital technology for regulatory submissions presents new ways of working for both industry professionals and health authorities. Workers need to develop new skills, including a better understanding of digital workflows and the consequences of data input. Digitization requires a structured way of thinking through the processes of information collection and database entry, including knowledge of disruptive software solutions that can support a more crossfunctional and harmonized way of working.

While some companies are progressing, many others struggle with disconnected systems and processes. In turn, they experience interfunctional gaps that can slow the MA process and harm their efforts toward efficient life-cycle management. Even when companies consider initiatives meant to improve digitization and data harmonization, their approach often is IT-driven with little consideration for business processes. Therefore, although management may discuss data governance and traceability mechanisms, projects may struggle to bridge interfunctional gaps without the connection provided by a discrete R&D informatics function.

Those gaps will be obvious when variations are submitted to the Product Management Services (PMS) unit of SPOR. In the future, only product variations that are input correctly and completely in the SPOR database will meet the requirements. Such an approach brings many benefits because companies applying for an authorization change will need to identify only the affected product(s) in the SPOR database rather than fill out entirely new product-description forms. The new process should make regulatory responsibilities easier, while accelerating the review process and improving safety oversight for patients. For companies that continually struggle to meet global compliance requirements, a harmonized crossfunctional approach that is supported skillfully by an R&D informatics team can help reduce the risk of noncompliance and improve business efficiency.

References
1 SPOR Data Management Services. European Medicines Agency: Amsterdam, The Netherlands, 2023; https://spor.ema.europa.eu/sporwi.

2 Digital Application Dataset Integration (DADI) and Product Management Service (PMS) Webinar. Variations Form for Human Medicinal Products: What Will Happen at Go-Live. European Medicines Agency: Amsterdam, The Netherlands, July 2022; https://www.ema.europa.eu/en/documents/other/questions-answers-digital-application-dataset-integration-dadi-product-management-service-pms_en.pdf.

3 Draft Standardization of Pharmaceutical Quality/Chemistry Manufacturing and Control Data Elements and Terminologies; Request for Comments. US Food and Drug Administration: Silver Spring, MD, July 2017; https://www.regulations.gov/document/FDA-2017-N-2166-0001.

Corresponding author Karl-Heinz Loebel is director and principal consultant, regulatory operations, at PharmaLex Rennbahnstraße 72-74, 60528 Frankfurt am Main, Germany; [email protected]; 49-0-617-27-64-64-0. Jim Nichols is chief product officer at Phlexglobal (now part of PharmaLex).