Unlocking the Power of Data: How FHIR is Transforming Drug Approval and Safety at the FDA

The US FDA’s Embrace of HL7 FHIR: Revolutionizing Pharmaceutical Data Exchange with SPL-on-FHIR and PQ/CMC

The United States Food and Drug Administration (FDA) is at the forefront of a transformative shift in how pharmaceutical data is prepared, submitted, and analyzed. Central to this transformation is the adoption of the HL7 Fast Healthcare Interoperability Resources (FHIR) standard. While FHIR has gained significant traction in the clinical domain, the FDA’s initiatives are pushing the boundaries of FHIR into new data domains crucial for both the pharmaceutical industry and regulators. This article delves into two pivotal FDA initiatives leveraging FHIR: SPL-on-FHIR and PQ/CMC, highlighting their significance, objectives, and the critical need for software solutions to facilitate their successful implementation.

Expanding the FHIR Landscape Beyond Clinical Data

FHIR, with its modern, web-based approach to data exchange, has rapidly become the standard of choice for sharing electronic health information. Its modular, resource-based architecture, coupled with RESTful APIs, allows for flexible and efficient data exchange, making it ideal for a wide range of healthcare applications. However, the FDA’s vision extends beyond the traditional clinical use cases of FHIR, venturing into the realm of pharmaceutical product information and quality data.

With the release of FHIR R5, a new module called “Medication Definition” was introduced. This suite of resources provides a comprehensive framework for representing detailed information about medications, including their ingredients, composition, dosage forms, strengths, indications, contraindications, and other critical data. This expanded scope of FHIR has paved the way for the FDA to address long-standing challenges in the pharmaceutical regulatory landscape.

The Need for Modernization: Addressing the Limitations of Legacy Systems

The pharmaceutical industry and regulators rely heavily on the exchange of vast amounts of data to ensure drug safety, efficacy, and quality. Historically, this exchange has been hampered by the use of outdated and inefficient systems. For instance, the FDA’s current Structured Product Labeling (SPL) standard, based on HL7 version 3, has been in use since 2005. While it represented a step forward at the time, it suffers from several limitations:

• V3 Complexity: HL7 version 3 is a complex and cumbersome standard, making it difficult to implement and maintain.
• Limited Support: As an older standard, V3 has limited vendor support, creating challenges for software development and integration.
• Lack of Flexibility: The rigid structure of V3 makes it difficult to adapt to evolving regulatory requirements and data needs.
• Unstructured Data: Much of the information submitted to the FDA, particularly in the area of pharmaceutical quality, is in unstructured formats like PDF documents, hindering efficient analysis and data mining.

These limitations have created a pressing need for modernization, and the FDA has recognized FHIR as the key to unlocking a new era of pharmaceutical data exchange.

SPL-on-FHIR: Transforming Structured Product Labeling

Structured Product Labeling (SPL) is a critical component of the drug approval and post-market monitoring process. It encompasses the comprehensive information contained in a drug’s labeling, including indications, dosage and administration, warnings and precautions, adverse reactions, drug interactions, use in specific populations, and other essential details. This information is crucial for healthcare providers, patients, and regulators to make informed decisions about drug use and safety.

The FDA’s SPL-on-FHIR initiative aims to replace the existing V3-based SPL standard with a FHIR-based implementation guide (IG). This initiative, launched in 2019, has several key objectives:

1. Modernize the SPL Standard: Migrate from the outdated V3 standard to the modern, widely adopted FHIR standard.
2. Improve Data Exchange: Facilitate more efficient and seamless exchange of SPL information between the pharmaceutical industry and the FDA.
3. Enhance Data Quality: Improve the consistency, accuracy, and completeness of SPL data through the use of FHIR’s validation capabilities.
4. Support Regulatory Processes: Streamline the drug approval process and enhance post-market surveillance through improved access to structured SPL data.
5. Enable Innovation: Leverage FHIR’s capabilities to go beyond the limitations of the current SPL standard, potentially incorporating additional codable information and linking to other relevant data sources.

The SPL-on-FHIR Implementation Guide: A Blueprint for Modern Labeling

The SPL-on-FHIR IG provides a detailed specification for representing SPL content using FHIR resources. It leverages the Medication Definition resources introduced in FHIR R5, along with other relevant FHIR resources, to create a comprehensive and structured representation of drug labeling information.

The IG defines how various sections of a drug label, such as indications, contraindications, dosage forms, and ingredients, are mapped to specific FHIR resources and data elements. It also specifies the use of standard terminologies and code systems, such as SNOMED CT and RxNorm, to ensure consistency and interoperability.

Harmonization with International Efforts: The Epi Connection

Recognizing the global nature of the pharmaceutical industry, the FDA has been actively collaborating with international partners to ensure harmonization of standards. One notable collaboration is with the European Medicines Agency (EMA) and the Gravitate Health project, which are developing the electronic Product Information (ePI) standard, also based on FHIR.

The ePI initiative shares many of the same goals as SPL-on-FHIR, aiming to create a structured, interoperable format for drug product information across Europe. Through the Biomedical Research and Regulatory Work Group at HL7, the FDA and EMA have been working to align the SPL-on-FHIR and ePI IGs, ensuring that they use FHIR resources and data elements in a consistent manner. This harmonization effort will facilitate the exchange of drug product information across jurisdictions, reducing the burden on the pharmaceutical industry and promoting global regulatory convergence.

Pilot Implementation and Future Directions

The SPL-on-FHIR initiative is currently in a technical pilot phase, with participation from various pharmaceutical companies. This pilot aims to validate the IG and demonstrate the feasibility of submitting SPL data in FHIR format. The FDA is also developing internal systems to support parallel submission of both legacy SPL and SPL-on-FHIR, allowing for a gradual transition to the new standard.

The successful implementation of SPL-on-FHIR will pave the way for a more efficient and data-driven regulatory process. It will enable the FDA to better analyze drug labeling information, identify potential safety concerns, and make more informed regulatory decisions. Furthermore, it will facilitate the development of innovative tools and applications that leverage structured SPL data to improve patient safety and public health.

PQ/CMC: Revolutionizing Pharmaceutical Quality Data

Pharmaceutical Quality, Chemistry, Manufacturing, and Controls (PQ/CMC) data encompasses a vast amount of information about a drug product’s composition, manufacturing process, and quality control measures. This data is essential for ensuring that drug products are consistently produced to meet established quality standards and that they remain safe and effective throughout their lifecycle.

Currently, PQ/CMC information is submitted to the FDA primarily in unstructured PDF documents. This poses significant challenges for both the industry and the FDA:

• Manual Review: The FDA must manually review these lengthy and complex documents, which are time-consuming and resource-intensive.
• Data Extraction Challenges: Extracting specific data points from unstructured documents is difficult and error-prone.
• Limited Analysis Capabilities: The lack of structured data hinders the FDA’s ability to perform comprehensive analyses and identify trends or patterns that could indicate quality issues.
• Inefficient Communication: The unstructured format makes it difficult for the FDA to communicate effectively with sponsors about potential quality concerns.

The PQ/CMC Initiative: A FHIR-Based Solution

The FDA’s PQ/CMC initiative aims to address these challenges by standardizing the submission of PQ/CMC data using FHIR. This initiative will migrate the submission process away from unstructured PDF documents to a structured, FHIR-based format, enabling more efficient data exchange, analysis, and communication.

The PQ/CMC IG, currently under development, will leverage the Medication Definition resources in FHIR R5, along with other relevant resources, to represent the detailed information contained in PQ/CMC submissions. This will include:

• Drug Substance Information: Detailed information about the active pharmaceutical ingredients (APIs) used in a drug product, including their chemical structure, properties, and manufacturing process.
• Drug Product Composition: A comprehensive description of the drug product’s formulation, including all excipients (inactive ingredients) and their quantities.
• Manufacturing Process: A detailed description of the manufacturing process, including the equipment used, the steps involved, and the critical process parameters.
• Quality Control: Information about the quality control tests performed on the drug substance and drug product, including the specifications, methods, and results.
• Stability Data: Data demonstrating the stability of the drug product over time under various storage conditions.
• Packaging Information: Details about the packaging materials and configuration used for the drug product.
• Facility Information: Information about the manufacturing facilities involved in the production of the drug product, including their location, capabilities, and quality management systems.

Staged Development and Implementation

The development of the PQ/CMC IG is being carried out in stages, starting with solid oral dosage forms (e.g., tablets and capsules), which represent the majority of drug product submissions. Subsequent stages will address other dosage forms, such as liquids, injectables, and topical products.

Each stage involves the development of specific profiles and extensions to the core FHIR resources to accommodate the unique data requirements of each dosage form. The IG will also specify the use of standard terminologies and code systems to ensure consistency and interoperability.

The FDA is planning a series of connectathons and pilot implementations to validate the IG and demonstrate the feasibility of submitting PQ/CMC data in FHIR format. A reference implementation is also under development to provide a working example of how the IG can be implemented in software.

The Critical Role of Software Solutions

The successful implementation of both the SPL-on-FHIR and PQ/CMC initiatives hinges on the availability of software solutions capable of creating, validating, and consuming FHIR messages that conform to the respective IGs. These software solutions will play a critical role in bridging the gap between the pharmaceutical industry and the FDA, enabling the seamless exchange of structured data.

For the industry, software will be needed to:

• Author FHIR Messages: Create FHIR messages that accurately represent SPL and PQ/CMC information according to the IGs.
• Validate FHIR Messages: Ensure that the created FHIR messages conform to the IGs and are free of errors.
• Transform Legacy Data: Convert existing SPL and PQ/CMC data from legacy formats (e.g., V3, PDF) to FHIR.
• Manage FHIR Data: Store, manage, and retrieve FHIR messages efficiently.
• Integrate with Internal Systems: Integrate FHIR capabilities with existing internal systems, such as regulatory information management systems (RIMS) and laboratory information management systems (LIMS).

For the FDA, software will be needed to:

• Receive and Process FHIR Messages: Receive, validate, and process FHIR messages submitted by the industry.
• Store and Manage FHIR Data: Store and manage the large volumes of FHIR data received from the industry.
• Analyze FHIR Data: Perform comprehensive analyses of FHIR data to identify trends, patterns, and potential safety or quality concerns.
• Communicate with Sponsors: Communicate effectively with sponsors about potential issues identified through the analysis of FHIR data.
• Integrate with Internal Systems: Integrate FHIR capabilities with existing internal systems, such as review tools and databases.

Reference Implementations and Community Engagement

To facilitate the development of these software solutions, the FDA is developing reference implementations for both SPL-on-FHIR and PQ/CMC. These reference implementations will provide working examples of how the IGs can be implemented in software and will serve as valuable resources for developers.

The FDA is also actively engaging with the FHIR community to raise awareness of these initiatives and solicit feedback on the IGs. This engagement includes participation in connectathons, presentations at conferences, and collaboration with industry stakeholders and software vendors.

Conclusion: A Call to Action for the FHIR Community

The FDA’s SPL-on-FHIR and PQ/CMC initiatives represent a significant step forward in the modernization of pharmaceutical data exchange. By embracing the HL7 FHIR standard, the FDA is paving the way for a more efficient, data-driven, and collaborative regulatory process.

The successful implementation of these initiatives will have far-reaching benefits for the pharmaceutical industry, regulators, healthcare providers, and patients. It will improve the quality and consistency of drug information, streamline the drug approval process, enhance post-market surveillance, and ultimately contribute to improved patient safety and public health.

However, the realization of these benefits depends on the active participation of the FHIR community, particularly software developers. The development of robust and interoperable software solutions capable of creating, validating, and consuming FHIR messages that conform to the SPL-on-FHIR and PQ/CMC IGs is essential.

This is a call to action for the FHIR community to engage with these initiatives, contribute to the development of the IGs, and develop the software solutions that will enable the successful implementation of these transformative efforts. By working together, we can revolutionize pharmaceutical data exchange and usher in a new era of data-driven regulation that benefits all stakeholders. The time to act is now. The future of pharmaceutical data exchange depends on it.