How will FDA introduce IDMP?
FDA proposes structured data for the CMC Module 3 of the eCTD standard
(Blog content by our partner Dieter Schlaps)
A few days ago, FDA has circulated a remarkable document for commenting, entitled “Pharmaceutical Quality/Chemistry Manufacturing and Controls (PQ/CMC) Data Elements and Terminologies”[1]. The document is the result of a study, in which FDA exploits the extensive use of structured data to describe the chemical, manufacturing and quality aspects of a drug product/ drug substance as it is described (currently only in text) in the Quality module 3 of the Common Technical Document (CTD).
The FDA project team identified and prioritized pharmaceutical quality/chemistry, manufacturing and controls (PQ/CMC) information that would benefit from a structured submission approach. This information would be submitted in the Common Technical Document as defined by the International Council for Harmonisation’s (ICH) Common Technical Document (CTD)[6].
The goals of this project were:
- identifying pieces of PQ/CMC information that are already available in product applications, that are important for the evaluation of an application, and are “common denominators” across the various application types,
- recommending standardized categories and data types necessary for application review. In this, the substance and product identifiers as described by the International Organization of Standardization for the Identification of Medicinal Products (ISO IDMP) standards are key.
- The project team consisted of Subject Matter Experts (SMEs) from the Center for Drug Evaluation and Research (CDER), the Center for Veterinary Medicine (CVM), and the Center for Biologics Evaluation and Research (CBER).
The circulated draft document provides a first set of key data elements and terminologies associated with PQ/CMC subject areas and scoped to some of what is currently submitted in Module 3 of the electronic Common Technical Document (eCTD)2 submission. The set is not comprehensive and does therefore not cover all eCTD product quality information, as there are currently only limited existing data standards and terminologies for PQ/CMC data.
Benefits for the Submission Review
It is expected that with the submission of structured data in a standardized format, the efficiency of FDA’s review of PQ/CMC data contained in the Module 3 of eCTD submissions shall be increased significantly.
Not only the New Drug Application (NDA) would be impacted, but also:
- Investigational New Drug Application (IND),
- Biologics License Application (BLA),
- Abbreviated New Drug Application (ANDA),
- New Animal Drug Application (NADA),
- Abbreviated New Animal Drug Application (ANADA),
- Investigational New Animal Drug (INAD),
- Generic Investigational New Animal Drugs (JINADs),
- and Master File (MF).
Proposal of a structured representation of the CMC Quality eCTD Module 3
The draft document is structured in three sections:
- Section 1 introduces the PQ/CMC information elements to be included as structured data.
The information elements are arranged in CMC domains as “Specification”, “Quality Control”, “Batch Information” etc. - Section 2 described which controlled terminology is to be used for the information elements from section 1.
- Section 3 contains a glossary of the terms used.
Whereas some information elements are to be represented as text fields still, others are drawn from established sources like the NCI Thesaurus (Field “Container Type”), CAS[1] or INN[2], and some already make use of identifiers in the same way as IDMP does, e.g.
- Substances – to be coded according to the Unique Ingredient Identifier (UNII), currently used in the FDA’s Substance Registration System (SRS) which is going to be replaced by IDMP-compliant Global Substance Registration System (G-SRS),
- Manufacturer and testing sites – to be coded according to the Data Universal Numbering System (DUNS), which is said to be the primary system for Marketing Authorisation Holders and Drug Manufacturers Identifiers for the US implementation of IDMP,
- Units and measures – to be coded based on the SPL Units of Measure (UoM) list, which is a subset of the Unified Code for Units of Measure (UCUM) values
- Other data fields are to be coded based on HL7 SPL controlled vocabularies, e.g. for “Closure Type”, “Container Type”, and “Dosage Form”. As HL7/SPL has been used in the ISO IDMP implementation guidelines it is very likely that these will also be the controlled vocabularies for the US implementation of IDMP.
Conclusion and Outlook
Both EMA as well as FDA obviously have chosen a pragmatic approach to introduce the IDMP concepts and identifiers – either already existing or being introduced identifiers – into (upcoming) electronic submission standards:
- In Europe, where EMA has just rolled out the Organisations and Referentials Management Systems (OMS resp. RMS) of SPOR[3][3], the organisation identifiers and some of the controlled vocabularies are already integrated into a next version of the Electronic Application Form (eAF), replacing some of the text fields by codes from OMS and RMS.
- In the US, where G-SRS will be released with a new version this fall potentially serving as the basis for the first New and Specified Substance Submissions by Industry, more and more sections of the submission dossier will be augmented by structured data.
In the long run, this will lead to a situation, where dossier documents will be increasingly replaced by structured information, and where “dossier submissions/ variations” will be replaced by much more efficient and painless online database updates.
References:
[1] Pharmaceutical Quality/ Chemistry Manufacturing and Controls (PQ/CMC) Data Elements and Terminologies, círculated by the FDA in August 2017 for annotation and review [2] Dieter Schlaps: Identification of Medicinal Products (IDMP) Standards Part 1: Impact on the Regulatory World, Regulatory Affairs Professional Society, December 21, 2016 [3] Dieter Schlaps: Identification of Medicinal Products (IDMP) Standards Part 2: The Implementation Roadmap, Regulatory Affairs Professional Society, February 28, 2017 [4] Dieter Schlaps: Identification of Medicinal Products (IDMP) Standards Part 3: Steps to Prepare for IDMP implementation, Regulatory Affairs Professional Society, April 26, 2017 [5] Dieter Schlaps: Identification of Medicinal Products (IDMP) Standards Part 4: Technical Approaches to IDMP, Regulatory Affairs Professional Society, June 10, 2017 [6] International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH):The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Quality – M4Q(R1). Quality Overall Summary of Module 2. Module 3 : Quality, September 12, 2002
[1] Chemical Abstracts Service
[2] International Non-Proprietary Name
[3][3] SPOR: Substances, Products, Organisations and Referentials, the four pillars of the European IDMP implementation