Toward Global Identification of Medicinal Products (IDMP) Implementation: A Focus on Biologics

This webinar, presented by FDA subject matter experts and an industry leader from Bayer, provides a detailed overview of the ongoing global efforts toward implementing the ISO Identification of Medicinal Products (IDMP) standards, with a particular focus on the complexities introduced by biologics. The core purpose of IDMP, a collection of five ISO standards (11615, 11616, 11238, 11239, 11240), is to define the data elements and structure necessary to uniquely and unambiguously identify medicinal products, substances, and packaging globally. Key benefits include improved data quality, enhanced interoperability for cross-jurisdictional information sharing, faster pharmacovigilance response times, and easier identification of alternative products during shortages.

The presentation highlights significant challenges hindering global IDMP implementation, primarily the lack of cross-region agreement on common substance identifiers and standardized dose forms. The speakers detailed how different regional granularities in dose form terminology (e.g., "capsule" vs. "soft capsule") prevent the generation of identical Level 4 Pharmaceutical Product IDs (PhPIDs) for the same product across regions. To address this, the Global IDMP Working Group (GITWIG), chartered by EMA, FDA, and WHO Uppsala Monitoring Centre (UMC), has been established. This group is focused on five key pilot projects for 2022-2023, including mapping regional substance IDs to a proposed global identifier, investigating the use of EDQM dose form characteristics as an alternative to generate global PhPIDs, and developing an operating model for WHO UMC to serve as the International Maintenance Organization (IMO) for global substance and PhPIDs.

A significant portion of the discussion is dedicated to the unique complexities of identifying biologics versus small molecules. The industry speaker emphasized that unlike small molecules, which are defined by a predictable molecular structure, biologics are large, complex, heterogeneous, and critically defined by their manufacturing process. Changes in manufacturing equipment or facilities can alter the biological product, requiring comparability protocols and potentially new clinical studies. The ISO 11238 standard groups substances into five categories (chemicals, proteins, nucleic acids, polymers, and structurally diverse substances like vaccines), each requiring different defining elements. Examples using COVID-19 mRNA vaccines illustrated that even within the same technology, different manufacturing processes (e.g., Moderna vs. Pfizer) result in distinct active substances with different Unique Ingredient Identifiers (UNIs), underscoring the need for scientific identification beyond traditional nomenclature like INN (International Nonproprietary Name), which often lacks the necessary granularity for IDMP.

The speakers concluded by stressing that global PhPID generation is impossible without first achieving unique identification of substances on an international scale, maintained by a recognized IMO. The collaboration framework between FDA and EMA, and the formation of GITWIG, represent a concerted effort to resolve these foundational data challenges through structured pilot projects and international consensus building, paving the way for eventual global use of IDMP standards in regulatory, clinical, and healthcare domains.

Detailed Key Takeaways

• IDMP is Foundational for Global Public Health: The ISO IDMP standards are critical for improving data quality, enhancing interoperability, speeding up global pharmacovigilance (identifying adverse events across regions), and efficiently managing product shortages by enabling easy comparison and identification of alternative products globally.
• Substance Identification is the Primary Roadblock: The core challenge to generating a global Pharmaceutical Product ID (PhPID) is the lack of a globally agreed-upon common substance identifier and a global consensus on dose form terminology. Without these, PhPIDs cannot be generated consistently across jurisdictions.
• WHO UMC Proposed as IDMP Maintenance Organization: The Global IDMP Working Group (GITWIG) has recommended that the WHO Uppsala Monitoring Centre (UMC) be established and recognized as the International Maintenance Organization (IMO) responsible for generating and maintaining both global substance IDs and global PhPIDs. This requires defining a sustainable process and conducting pilots to validate the operational model.
• Biologics Require Process-Based Identification: Biologics are fundamentally defined by their manufacturing process, unlike small molecules defined by molecular structure. Unique identification of biologics must account for factors like expression systems, cell banks, purification methods, and stability, which are critical defining elements under ISO 11238.
• Dose Form Characteristics as a Solution: To overcome regional differences in dose form granularity (e.g., US "capsule" vs. EU "soft capsule"), the GITWIG is piloting the use of EDQM dose form characteristics as an alternative method to generate global PhPIDs, aiming for a consistent mapping approach across regions.
• Five Critical Pilot Projects Underway: The GITWIG has chartered five key pilots for 2022-2023: 1) Mapping regional substance IDs (UNI, EU TCT) to a global identifier, 2) Investigating dose form characteristics mapping, 3) Clarifying strength presentation and concentration rules, 4) Developing HL7 FHIR messages for IDMP data exchange, and 5) Designing the operational model for WHO UMC as the PhPID IMO.
• Nomenclature (INN/USAN) is Insufficient for IDMP: Traditional naming conventions like INN and USAN often lack the necessary granularity (e.g., failing to distinguish between trihydrate and anhydrous forms, or different manufacturing processes for biologics) required for the scientific, unique identification mandated by IDMP standards.
• HL7 FHIR is the Future Exchange Standard: Collaboration is underway to develop, verify, and ballot HL7 FHIR resources related to IDMP, which will be the mechanism for successfully exchanging medicinal product and substance information between systems like EU SRS, FDA GSRS, and WHO UMC SRS.
• IDMP Implementation is Not Immediate Regulatory Change: IDMP implementation is not intended to impose new Module 3 regulatory requirements but rather to standardize how existing required information is represented to support unique global identification. Companies must focus on structuring and managing substance data internally according to ISO standards (like 11238).
• Agile Approach to Pilot Projects: The GITWIG is utilizing an agile approach for its pilot projects, setting three, six, and nine-month milestones to ensure continuous progress and reporting, with results planned to be posted publicly on a WHO-hosted webpage.
• Strength Expression Harmonization is Needed: Regional differences in expressing strength (e.g., percentage, International Units, milligram per milliliter) and the associated units require harmonization and documented business rules, including conversion factors, to ensure accurate PhPID generation.

Key Concepts

• IDMP (Identification of Medicinal Products): A collection of five ISO standards (11615, 11616, 11238, 11239, 11240) defining the data elements and structure for the unique and unambiguous identification of medicinal products globally.
• PhPID (Pharmaceutical Product Identification): An identifier generated based on the combination of substance, strength, and dose form (ISO 11616). Level 4 PhPID is the most precise level.
• GSRS (Global Substance Registration System): The system used by the FDA and being leveraged globally to capture and manage substance data in compliance with ISO 11238, including defining elements for complex substances like biologics.
• IMO (International Maintenance Organization): The proposed organization (WHO UMC) responsible for the ongoing generation and maintenance of global substance IDs and PhPIDs to ensure consistency and sustainability.

Tools/Resources Mentioned

• ISO IDMP Standards (specifically 11238, 11615, 11616): The foundational regulatory data standards.
• FDA's Substance Registration System (SRS) / Global Substance Registration System (GSRS): Open-source resource for tracking and managing substance identification criteria, particularly for complex biologics.
• HL7 FHIR (Fast Healthcare Interoperability Resources): The messaging standard being developed for the exchange of IDMP information between regulatory authorities.
• EDQM (European Directorate for the Quality of Medicines & HealthCare): Their dose form characteristics are being piloted as an alternative solution for global PhPID generation.
• UNICOM: An EU-commissioned initiative focused on IDMP implementation beyond the regulatory domain into clinical and healthcare domains.

Examples/Case Studies

• Ibuprofen Example: Used to illustrate how different regional dose form expressions ("capsule" vs. "soft capsule") prevent the generation of identical Level 4 PhPIDs, hindering global pharmacovigilance and product comparison.
• COVID-19 mRNA Vaccines: Used to demonstrate that even within the same technology (mRNA), the Moderna and Pfizer vaccines are identified as having different active substances (different UNIs) due to differences in their manufacturing and formulation processes, highlighting the complexity of biologics identification.
• AstraZeneca Vaccine Strength: Used to highlight regional differences in strength expression (e.g., infectious unit vs. viral particle) and unit of measure, which complicates global PhPID generation.