Data Elements and Standards for Drug Dictionaries
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACETUICALS FOR HUMAN USE
Draft Guideline
DATA ELEMENTS AND STANDARDS FOR DRUG DICTIONARIES
M5
Released for Consultation on 10 May 2005,
at Step 2 of the ICH Process
Revision 5.1, 23 February 2007
This guideline has been developed by the appropriate ICH Expert Working Group and is subject to consultation in accordance with the ICH process.
Topic Reference:Data Elements and Standards for Drug Dictionaries
Version: 4..0
Dated: 2 February 2007
Comments to be sent to the Rapporteur:
Name:Dr. Sabine Brosch
Address:European Medicines Agency (EMEA)
7 Westferry Circus, Canary Wharf
London E14 4HB UK
E-mail address:
Fax+ 44 (0) 207 418 8668
Circulation list:
ICH Coordinators
ICH Secretariat
EU Regulatory (EMEA)Dr. Sabine Brosch / Rapporteur / M5 EWG
Mr. Fabrizio Abbinante / Deputy Topic Leader / M5 EWG
Dr. Manfred Haase / Expert / M5 EWG
Dr. Bob Alkin / Expert / M5 EWG
Dr. Barbara Steinhoff / Interested Party
Mr. Hans-Georg Wagner / Expert / M2 EWG
Ms. Ilaria Del Seppia / Expert
Mr Franck Diafouka / Expert
Ms. Agnieszka Szmigiel / Expert
EU Industry (EFPIA)
Dr. Gaby Danan, / Expert / E2B M
Mr. Barry Hammond / Topic Leader
Mr. Hans-Peter Kraemer / Expert
Dr. Gerhard Schlueter / Deputy Topic Leader
JPRegulatory (MHLW)
Mr. Masahiko Yokota / Topic Leader
Dr. Tetsuya Kusakabe / Deputy Topic Leader
Ms. Kaori Nomura / Deputy Topic Leader
Ms. Aya Fukuda / Expert
Mr. Daisuke Koide / Expert
JPIndustry (JPMA)
Mr. Manabu Inoue / Topic Leader / M2
Mr. Jiro Shimada / Deputy Topic Leader
Dr. Tetsuo Kawahara / Expert
Mr. Keiji Sawamukai / Expert / M2
Mr. Sen Shinohara / Expert
US Regulatory (FDA)
Dr. Randy Levin / Topic Leader
Dr. Ann Schwartz / Topic Leader
Dr. Roger Goetsch / Expert / E2BM
Mr. William A Hess / Expert
Ms. Lise Stevens / Expert
US Industry (PhRMA)
Mr. Kostas Kidos / Co-Rapporteur, Topic Leader / E2B
Dr. William Gregory / Expert
Mr. Kris Spahr / Expert
CA Regulatory (Health Canada)
Ms. Jennifer Lo / Observer
Mr. Bill Willson / Observer
WHO
Dr. Marie Lindquist / Observer
Table of Content
1.INTRODUCTION
1.1Objectives of the Guideline
1.2Background
1.3Scope of the Guideline
2.GUIDELINE
2.1Medicinal Product and Term Identifiers
2.1.1Medicinal Product Identifier (MPID)
2.1.2Pharmaceutical Product Identifier (PhPID)
2.1.3Controlled Vocabulary Term Identifier (TermID)
2.2Controlled Vocabulary
2.2.1Background
2.2.2Drug Substances Controlled Vocabulary
2.2.3Pharmaceutical Dose Form Controlled Vocabulary
2.2.4Routes of Administration Controlled Vocabulary
2.2.5Unit and Measurements Controlled Vocabulary
2.3Data Elements for the Controlled Vocabularies
2.3.1Data Elements for the Drug Substance Controlled Vocabulary
2.4Data Elements for Medicinal Products
2.4.1Medicinal Product Identifier Section
2.4.2Medicinal Product Naming Section
2.4.3Marketing Authorization Holder Section
2.4.4Marketing Authorization Section
2.4.5Pharmaceutical Product Section
2.4.6Ingredient Section
2.4.7Pharmaceutical Dose Form Section
2.4.8Route of Administration Section
2.4.9Maintenance Section
3.GLOSSARY
4.REFERENCES......
5.Annexes
5.1Parts of Plants Annex
5.2Production Processes and General Treatments for Herbal Preparations Annex
5.3Solvents for Herbal, Animal and Mineral Preparations Annex
5.4Physical Form for Crude Drug Substances Annex
5.5Parts of the Animal Annex
5.6Class of Infectious Agent Annex
5.7Antigen State Annex
5.8Inactivation Method Annex
5.9Inactivation Agent Annex
5.10Name of Protein Annex
5.11Conjugation Method (Coupling) and Procedure Annex
5.12Antigen Characterisation Annex
5.13Antigen Identification Annex
5.14Production System Annex
5.15Adjuvants Annex
5.16Type of Imunoglobulins Annex
5.17Intended Use Annex
5.18Immunoglobulin Origin Annex
5.19Primary Biological Source Annex
5.20Expression System Annex
5.21Antigen Specificity Annex
5.22Immunoglobulin Class Annex
5.23Immunoglobulin Sub-Class Annex
5.24Method of Preparation Annex
5.25Fractionation Annex
5.26Purification Annex
5.27Viral inactivation/Removal Annex
6Examples
6.1Examples for the Chemicals and Radioactive Compounds Controlled Vocabulary
6.1.1Examples for the Chemicals Controlled Vocabulary
6.1.2Examples for the Radioactive Compounds Controlled Vocabulary
6.2Examples for the Plant/Animal Names Controlled Vocabulary
6.2.1Examples for the Plant Names Controlled Vocabulary
6.2.2Examples for the Animal Names Controlled Vocabulary
6.3Examples for the Crude Drug Substance Preparation Controlled Vocabulary
6.3.1Examples for the Herbal Substance Preparation Controlled Vocabulary
6.3.2Examples for the Animal Substance Preparation Controlled Vocabulary
6.3.3Examples for the Complex Compound Substance Preparation Controlled Vocabulary
6.4Examples for the Vaccine Drug Substance Controlled Vocabulary
6.4.1Example for the Viral Antigen Vaccine Drug Substance Controlled Vocabulary
6.4.2Example for the Bacterial Antigen Vaccine Drug Substance Controlled Vocabulary
6.5Examples for the Immunoglobulins Controlled Vocabulary
6.6Examples for the Routes of Administration Controlled Vocabulary
6.7Examples for the Pharmaceutical Dose Forms Controlled Vocabulary
6.8Examples for the Units and Measurements Controlled Vocabulary
6.9Examples for the PhPID Controlled Vocabulary
6.10Conventions for the ICH M5 Strength Section
6.10.1Example of different use of the Strength Section:
6.10.2Conventions on the use of the Strength Section accordingly with the type of medicinal product:
Data Elements and Standards for Drug Dictionaries
1.INTRODUCTION
1.1Objectives of the Guideline
Regulators and pharmaceutical industry engage in an intensive information exchange during drug development, drug evaluation and approval phase and the post-authorization phase. The standardization of medicinal product information is regarded as one of the key elements of this information flow.
However, regulators in the ICH regions and observer countries have established their own procedures and applications with standards that differ in data format, content, language and applied terminology (e.g. terminology used for drug substances, routes of administration, pharmaceutical dose forms).
Due to the lack of a common and harmonized approach, both regulators and pharmaceutical industry are confronted with the following issues:
-No possibility to exchange medicinal product information between regulators and industry in a structured and efficient way;
-Difficulties in ensuring data consistency and in evaluating and comparing medicinal product -related information across the ICH regions due to the lack of harmonized definitions of terminologies and data sets. This currently impairs pharmacovigilance activities in particular;
-For the pharmaceutical industry, major administrative burdens and duplication of efforts requiring substantial human and financial resources to comply with and handle different regional requirements;
-Lack of consistency in the use of terminology in the health care community.
The objectives of this guideline are to address the issues outlined above by developing harmonized standards that build on the regulatory and technical processes currently established in the three ICH regions and observer countries and to support the population and maintenance of existing systems/applications with fully reliable regulatory medicinal product information. More specifically, the objectives focus on the development of:
-‘Unique identifiers’ at the level of
- Medicinal products: Medicinal Product Medicinal product Identifiers (MPID)
- Pharmaceutical products: Pharmaceutical Product Identifiers (PhPIDs)
- The controlled vocabulary: Terminology Identifiers (TermIDs)
-‘Controlled vocabulary’ based on defined data elements as a standard for the electronic transmission of core sets of medicinal product information related to the following terminologies:
- Drug substances
- Pharmaceutical dose forms
- Routes of administration
- Units and measurements
- Units of presentation
- Pharmaceutical products
-‘Data elements’ for the electronic transmission of core sets of medicinal product information based on the following data set:
- Proprietary medicinal product[1] name
- Drug Substance(s)
- Pharmaceutical dose form(s)
- Strength of the drug substance(s)
- Route(s) of administration
- Marketing authorization holder
- Marketing authorization number
- Country of authorization
The ‘Data elements’ have been developed for the electronic transmission of MPIDs and the related core medicinal product information as well as for the electronic transmission of the ‘Controlled vocabulary’ and the ‘Unique Identifiers’.
This guideline does not cover the establishment and maintenance of a drug dictionary.
1.2Background
The lack of internationally harmonized standards related to core sets of medicinal product information and medicinal product terminology is hindering the scientific evaluation and comparison of product data as well as healthcare. This applies in particular to the area of pharmacovigilance, where the exchange and management of medicinal product information in expedited and periodic adverse reaction reports at the international level is a key aspect of ensuring drug safety.
This document provides guidance on the harmonized standards that are being proposed by the ICH M5 EWG to facilitate the exchange and practical use of medicinal product data by regulators and pharmaceutical industry.
1.3Scope of the Guideline
This guideline refers to authorized/approved medicinal products. Homeopathic medicinal products and investigational medicinal products are currently excluded from this guideline. Those category of medicinal products including new therapies being developed and not covered by this guideline will be addressed at a later time.
For the purpose of this guideline the term ‘medicinal product’ should be considered synonymous with the term ‘drug product’ in line with the Common Technical Document (CTD), the internationally agreed format for the presentation for applications to be submitted to regulatory authorities in the ICH regions. The same principle applies to the term ‘active ingredient’, which should be considered synonymous with the term ‘drug substance’. The ICH M5 data elements and standards referred to in chapter 1.1 and presented in this guideline, have been developed based on the available regulatory data exchange standards for the handling of medicinal product information established in the ICH regions.
The guideline and the described standards serve the following purpose:
-The collection of a core set of medicinal product information based on regional processes and standards, which are fully compatible with the ICH M5 data elements and standards;
-The electronic exchange and maintenance of the core set of medicinal product information based on the ICH M5 data elements and standards between the ICH regulators including observer countries;
-The publication of core set of medicinal product information based on the ICH M5 data elements and standards by the regulators in the ICH regions and observer countries, to allow for the widespread and free use of the information by pharmaceuticals companies, in the healthcare sector or by any other interested stakeholders;
-Based on defined data elements, the structured and standardized characterization of ‘drug substance(s)’, pharmaceutical products, pharmaceutical dose forms, routes of administrations and units and measurements in the frame of a Controlled Vocabulary which is related to the medicinal products;
-The publication of the ‘Unique Identifiers’ and ‘Controlled Vocabularies’ by ICH, to allow for the widespread and free use of the information by pharmaceuticals companies, in the healthcare sector or by any other interested stakeholders;
-The maintenance of the ‘Unique Identifiers’ and ‘Controlled Vocabularies’ based on the ‘Standard Operating Procedures for Maintenance of ICH Terminology Lists’ conducted by the ICH Implementation Working Group (IWG) for Maintenance of ICH Terminology Lists.
With regard to the ICH M5 electronic data exchange standards on the ‘Data Elements for Medicinal Product and Term Identifiers’ and the ‘Controlled Vocabulary’ refer to the companion technical document (to be developed by the SDO).
With regard to the maintenance process of the ICH M5 ‘Controlled Vocabulary’, refer to the ‘Standard Operating Procedures for Maintenance of ICH Terminology Lists’.
Japanese translations to all terms and guidelines in respect of M5 are to be provided as deliverables in ICH official language.
2.GUIDELINE
2.1Medicinal Product and Term Identifiers
2.1.1Medicinal Product Identifier (MPID)
Definition:An identifier assigned to a medicinal product by the regulator of the country/territory of authorization.
General Conventions:
The regulators in the regions and observer countries have various processes established to identify individual medicinal products. Because medicinal product information is exchanged internationally, worldwide unique medicinal product identifiers (MPIDs) are desirable.
Regulators assign MPIDs as follows:
- At the ‘medicinal product level’, which means that a specific medicinal product has only one identifier for different pack sizes.
or
- At ‘medicinal product package level’, which means that for each package presentation of the medicinal product a different MPID is assigned.
Methodology:
The world-wide unique MPID is constructed as follows:
-Prefix of the country code of that region followed by
-The regionally-assigned identifier followed by
-An error detection code[2]
The regionally-assigned identifier refers to the medicinal product level or to the medicinal product package level. As a general rule, the MPID should always accompany the exchange of the medicinal product information.
Examples:
EU-XXXXXX-7B5AD9BD
EU-YYYYYYY-E2538807
US-ZZZZ-YYY-WW-XX-841B8ADD
US-XXXX-HHH-MM-LL-A72BEAAB
JP-SSSS-TTT-B95D1FF3
JP-BBBB-KKK-73B44E83
CA-DDDDDDD- B9F451FF
CA-EEEEEEEE- FE95AFF
2.1.2Pharmaceutical Product Identifier (PhPID)
Definition:An identifier assigned at the level of the pharmaceutical product based on the drug substance(s), the strength(s) of the drug substance(s) and the pharmaceutical dose form.
Methodology:
PhPIDs represent the pharmaceutical product at four levels as defined as follows:
-PhPID4 = Drug substance(s) - Strength(s) - Strength unit(s) - Pharmaceutical Dose Form
-PhPID3 = Drug substance(s) - Pharmaceutical Dose Form
-PhPID2 = Drug substance(s) - Strength(s) - Strength unit(s)
-PhPID1 = Drug substance(s)
-Each PhPID is a unique, non-semantic, alphanumeric code and is derived from the ICH M5 data elements, but is not part of these data elements.
Examples: / -Medicinal products with the same drug substance(s), strength(s) and pharmaceutical dose form share common PhPID4, PhPID3, PhPID2 and PhPID1 .
-Medicinal products with the same drug substance and pharmaceutical dose form share common PhPID3 and PhPID1.
-Medicinal products with the same drug substance and strengths share common PhPID2 and PhPID1.
-Medicinal products with the same drug substance share a common PhPID1.
PhPID Level 1: / ABACAVIR SULFATE + LAMIVUDINE
PhPID Level 2: / ABACAVIR SULFATE 600 MG + LAMIVUDINE 300 MG
PhPID Level 3: / ABACARIR SULFATE + LAMIVUDINE, TABLET
PhPID Level 4: / ABACAVIR SULFATE 600 MG + LAMIVUDINE 300 MG, TABLET
2.1.3Controlled Vocabulary Term Identifier (TermID)
Definition:An identifier assigned at the level of each term of the controlled vocabulary (drug substances, pharmaceutical dose forms, routes of administrations and units and measurements).
Methodology:
The TermID is a unique, non-semantic, alphanumeric code assigned for each term of the controlled vocabulary.
2.2Controlled Vocabulary
2.2.1Background
Different regulatory standard terminologies are in place in the ICH regions and observer countries, which makes it difficult to exchange this information at international level. These terminology differences complicate specifically activities in the area of pharmacovigilance and healthcare and the management of medicinal product information.
To address the identified terminology differences, the ICH M5 EWG is developing controlled vocabularies for:
-Drug Substance(s): Drug Substance Controlled Vocabulary
-Pharmaceutical Dose Form(s): Pharmaceutical Dose Forms Controlled Vocabulary
-Route(s) of Administration:Routes of Administration Controlled Vocabulary
-Unit(s) and Measurement(s): Units and Measurements Controlled Vocabulary
-Unit(s) of Presentation(s):Units of Presentation Controlled Vocabulary
-Pharmaceutical Product(s): PhPIDs Controlled Vocabulary
The following method has been applied to establish the concepts for the Controlled Vocabulary:
-Preparing an inventory of the different regulatory standard terminologies including those defined in the ICH E2B(M) guideline (version 4.4.1 includes the Post Step 4 corrections agreed by the Steering Committee on 5 February 2001);
-Analyzing definitions for the different regulatory standard terminologies where available;
-Developing a sample for the controlled vocabulary that supports good terminological practice;
-Developing data elements and outline the relationship of these data elements based on the example of conceptual models that accommodate the specific characteristics of drug substances;
Defining mapping procedures to determine unique terms and related synonym terms on the basis of the regional definitions in place;
-Mapping the individual terms;
-Assigning unique TermIDs.
The maintenance of the ICH M5 Controlled Vocabulary will be conducted by the ICH Implementation Working Group (IWG) for Maintenance of ICH Terminology Lists (see chapter 1.3) and the ICH M5 Controlled Vocabulary will be published on the ICH website.
2.2.2Drug Substances Controlled Vocabulary
Scope:The Drug Substances Controlled Vocabulary includes drug substance terms related to authorised/approved medicinal products. Excluded are active ingredients related to homeopathic medicinal products and investigational medicinal products (see chapter 1.3).
General Definitions:
A drug substance is defined as a substance that alone or in combination with one or more drug substances produces the intended activity of a medicinal product .
A substance is any matter and can be of human, animal, vegetable or chemical (natural, semi-synthetic or synthetic) origin.
An active moietyis the portion of the drug substance that is responsible for the effect.
General Methods:
For the creation of the ICH M5 Drug Substance Controlled Vocabulary, the first three main categories of substances have been classified as follows: Chemical Drug Substances, Crude Drug Substances and Biologic Drug Substances. Other classes of drug substances will be addressed at a second stage.
The categories addressed in this guideline are as follows:
-Chemical Drug Substances include chemicals and radioactive compounds (radiopharmaceuticals).
-Crude Drug Substances include herbals (i.e. plant names and herbal preparations), animals (i.e. animal names and animal preparations) and complex compounds (i.e. organic or inorganic compounds, which cannot be classified as Chemical Drug Substances).
-Biologic Drug Substances, which currently include vaccines, in particular vaccine antigens, and immunoglobulins.
For each category of drug substances, an inventory of drug substance terms has been established on the basis of the standard terminologies currently used by the EMEA and EU National Competent Authorities, FDA, MHLW and Health Canada. The collected drug substance terms are limited to the use of the English language, with the exception of Crude Drug Substances and certain categories of the Biologic Drug Substances (i.e. vaccines) for which the Latin language is also used. The indication of the provenance of the term (i.e. its reference source) is also included in each of the Controlled Vocabularies.
A Drug Substance TermID is to be assigned to each unique term by the IWG for Maintenance of ICH Terminology Lists, and where available, regional codes are also specified and mapped against the assigned TermID.