International Electronic Standards
Identification of Medicinal Products (IDMP)
Validation and verification of product information across regulatory submissions, especially in adverse event (AE) reports, product labeling, manufacturing facility registration and lot distribution reports, has been a major challenge for the Agency and internationally, which limits its ability to reconcile and link information across a product's lifecycle (pre-market to post-market). The development of a global standard for the Identification of Medicinal Products (IDMP) serves as a foundational step to enable the Agency and other global partners to achieve this goal.
A suite of standards were developed within the International Organization for Standardization (ISO) for the IDMP which provide an internationally-accepted framework for consistent documentation, coding and exchange of product information between global regulators, manufacturers, suppliers and distributors. The tremendous benefit to healthcare providers and to the Agency is the ability to harness the power of information technology by using these standards to support automated validation of content, eliminate manual data entry and coding errors, reduce redundant submission of the same information, and facilitate the creation and use of global drug dictionaries and product dossiers. The suite of ISO IDMP standards provides a mechanism for globally unique identification of medicinal products on an international level by developing a method and process for generating global product identifiers that can be used for international product reconciliation and linking across the entire product supply-chain.
The suite of IDMP standards include: substances/specified substances, dosage forms, routes of administration, units of measurement, pharmaceutical product identification, and medicinal product identification. These international standards will provide a globally-accepted coding terminology and exchange method which can be used to support a variety of product-related activities and events: manufacturing, distribution and use throughout the global healthcare marketplace, validate and monitor correct product usage (based upon a product's labeling information) and AE surveillance. These standards will be used to assist in the creation of an international drug dictionary, which can be used to populate and validate product information in electronic health records, pharmacy information and prescribing systems, product registries, pharmacovigilance systems and adverse event reports. The IDMP standards are consistent with other HHS initiatives for Health Information Technology (HIT) adoption under Meaningful Use (MU) for electronic prescribing.
CBER provided critical leadership and technical expertise to the development of these standards and currently continues leading international efforts to delineate a common approach for their implementation and to consider their future application.
Individual Case Safety Report (ICSR)
CBER has provided leadership and technical support for the development of an internationally- accepted standard and Step 4 ICH Implementation Guide for electronic exchange of adverse event and medication error reporting between ICH global regulators (US, EU, Japan and Observers), pharmaceutical/biopharmaceutical manufacturers and the World Health Organization – the Individual Case Safety Report (ICSR). Finalized in the fall of 2012, this work culminated eight years of international collaboration with several standards development organizations, regulated industry, global regulators, healthcare providers and vendors to establish standards that will improve and transform global pharmacovigilance activity. The ICSR is a global, multi-part ISO standard that supports all FDA regulated products, and various releases of this specification have been adopted by three FDA Centers - two of which have been done under the International Conference on Harmonisation (ICH E2B), and the Veterinary Conference on Harmonisation (VICH GL42), which FDA's Center for Veterinary Medicine implemented in 2010. Reaching Step 4 status in ICH, E2B was considered a major milestone because it aligned FDA’s human drug and biologics AE reporting format with standards used in the healthcare sector.
The agency can leverage the ISO ICSR specification to create additional regional reporting guides without compromising the overall reporting format or processing requirements for non-ICH/VICH reporting (e.g., dietary supplements, food, tobacco, medical devices). It supports IT infrastructure reuse for both the agency and global manufacturers that produce a variety of medical/health products that are subject to FDA reporting. CBER completed Phase I vaccine pilot testing in 2012, which included the creation of a new electronic submissions template (eSubmitter - which is based upon the updated ICH Step 4 guideline) to create and send reports through FDA's Electronic Submissions Gateway. Ongoing CBER activities include collaboration with the European Medicines Agency to expand use of CBER’s template for international pilot testing for drugs, biologics and vaccines.
Electronic Common Technical Document (eCTD)
The electronic Common Technical Document (eCTD) is a harmonized electronic interface for the transfer of regulatory information from regulated industry to regulatory authorities that was originally developed by an expert group in the International Conference on Harmonisation (ICH). The specification for the ICH eCTD is based upon content defined in the original paper-based CTD also developed by experts within ICH. CBER and CDER have been accepting eCTD submissions since 2003 and published guidance in May 2015 requiring pre-market submissions in the eCTD format starting in May 2017.
Overall, the eCTD has been very successful and has facilitated the ability to submit global submissions to the FDA and other counterpart, foreign regulatory authorities. However, there have been a number of change requests since the original implementation of the eCTD (current version is v3.2.2), reflecting a need to introduce enhancements to the original construct. Additionally, workstreams in other standard development organizations, notably Health Level Seven International (HL7), required a different approach and a dovetailing of effort for the next version of the eCTD. In response, ICH formed the M8 Expert Working Group to specifically focus on the development and implementation of an upgraded eCTD (v4.0), leveraging the HL7 Regulated Product Submission (RPS) normative standard (Release 2). The goal of upgrading to eCTD v4.0 is to facilitate the processing and review of electronic regulatory submissions by incorporating new functionality (e.g., two-way communication) and by providing flexibility to meet future requirements.
CBER has been an active participant in the development and implementation of both the HL7 RPS standard and the implementation of the eCTD as a global standard for human biologic and pharmaceutical products. We will continue to participate and to provide expertise in these international efforts to ensure that shared solutions can be leveraged globally.