Guidelines For ATC Classification - WHOCC
Guidelines forATC classificationand DDD assignment2021
ISSN 1726-4898ISBN 978-82-8406-165-8Suggested citation: WHO Collaborating Centre for Drug Statistics Methodology,Guidelines for ATC classification and DDD assignment 2021. Oslo, Norway, 20 CopyrightWHO Collaborating Centre for Drug Statistics Methodology, Oslo, Norway.Use of all or parts of the material requires reference to the WHO CollaboratingCentre for Drug Statistics Methodology. Copying and distribution for commercialpurposes is not allowed. Changing or manipulating the material is not allowed.
Guidelines forATC classificationand DDD assignment24rd editionWHO Collaborating Centre for Drug Statistics MethodologyNorwegian Institute of Public HealthP.O.Box 222 SkøyenN-0213 OsloNorwayTelephone: (47) 21078160E-mail: whocc@fhi.noWebsite: www.whocc.no
Previous editions:1990: Guidelines for ATC classification1)1991: Guidelines for DDD1)1993: Guidelines for ATC classification1993: Guidelines for DDD1996: Guidelines for ATC classification and DDD assignment1998: Guidelines for ATC classification and DDD assignment2000: Guidelines for ATC classification and DDD assignment2001: Guidelines for ATC classification and DDD assignment2002: Guidelines for ATC classification and DDD assignment2003: Guidelines for ATC classification and DDD assignment2004: Guidelines for ATC classification and DDD assignment2005: Guidelines for ATC classification and DDD assignment2006: Guidelines for ATC classification and DDD assignment2007: Guidelines for ATC classification and DDD assignment2008: Guidelines for ATC classification and DDD assignment2009: Guidelines for ATC classification and DDD assignment2010: Guidelines for ATC classification and DDD assignment2011: Guidelines for ATC classification and DDD assignment2012: Guidelines for ATC classification and DDD assignment2013: Guidelines for ATC classification and DDD assignment2014: Guidelines for ATC classification and DDD assignment2015: Guidelines for ATC classification and DDD assignment2016: Guidelines for ATC classification and DDD assignment2017: Guidelines for ATC classification and DDD assignment2018: Guidelines for ATC classification and DDD assignment2019: Guidelines for ATC classification and DDD assignment2020: Guidelines for ATC classification and DDD assignment1)A co-publication between the WHO Collaborating Centre for Drug Statistics Methodology and the NordicCouncil on Medicines
PREFACEThe Anatomical Therapeutic Chemical (ATC) classification system and the DefinedDaily Dose (DDD) as a measuring unit are recommended by the WHO for drugutilization monitoring and research. The system is widely used internationally andthe number of users is increasing. The purpose of preparing guidelines is to makeinformation about the ATC/DDD system available to the users.The members of the WHO International Working Group for Drug StatisticsMethodology have given expert advice and comments on the work with theseguidelines.This edition of the Guidelines for ATC classification and DDD assignment is basedon the ATC classification index with DDDs valid from January 2021.The guidelines consist of a general part including information about the proceduresand data requirements for ATC/DDD assignment and alterations. The second part ofthe publication, the interpretative guidelines, describes the different ATC levelsdown to the 4th level. These guidelines should be consulted whenever the ATC/DDDsystem is used for drug utilization monitoring and research. They describe particularissues, which have been discussed and resolved by consensus of the Working Group.The Guidelines and the ATC index with DDDs are updated annually. Bothpublications can be ordered as electronic or paper copies (English or Spanishversions) from the Centre (order form, see website www.whocc.no). A pdfdocument of the Guidelines and a searchable version of the ATC/DDD index linked tothe text from the Guidelines are available on the website (ATC/DDD index).We hope this book will prove helpful to the users of the ATC/DDD system.Suggested improvements can be addressed to the WHO Centre in Oslo.Oslo, December 2020WHO Collaborating Centre for Drug Statistics MethodologyNorwegian Institute of Public Health
Staff of the CentreChristian Lie Berg, MScPharm/MPHHege Salvesen Blix, MScPharm/PhDLive Storehagen Dansie, MScPharm/MPhil Int Comm HealthIrene Litleskare, MScPharmMohammad Nouri Sharikabad, MScPharm, PhDKristine Olsen, MScPharmHilchen Thode Sommerschild, MD, PhDTove Granum, secretary
TABLE OF CONTENTSI.Introduction . 10A.History of the ATC/DDD system . 10B.Present Organizational responsibility for the ATC/DDD system .101. WHO Collaborating Centre for Drug Statistics Methodology .102. WHO International Working Group for Drug StatisticsMethodology. 11C.II.The purpose of the ATC/DDD system . 14The anatomical therapeutic chemical (ATC) classification system . 14A.Structure and nomenclature . 14B.Inclusion and exclusion criteria . 15C.Principles for classification . 161. Therapeutic use or pharmacological class . 162. Only one ATC code for each route of administration .173. More than one ATC code for a medicinal substance .174. New ATC groups and “other” groups (X groups) .185. Other general principles . 18III.D.Classification of combination products . 19E.Principles for changing ATC codes . 21F.The EphMRA classification system . 22DDD (Defined Daily Dose) . 23A.Definition and general considerations. 23B.Principles for DDD assignment . 241. General principles . 242. Combination products . 263. Other factors . 27a) Fixed doses. 27b) Depot formulations . 27c) Intermittent dosing . 27d) Duration of treatment . 284. Selection of units . 287
IV.C.Pediatric DDD . 29D.Principles for reviewing and changing DDD . 30E.Description of other drug utilization metrics . 31Uses of the ATC/DDD methodology . 33AImplementation and maintenance of the ATC/DDD methodology 33B.Drug utilization. 341. Data sources . 352. DDD indicators and interpretations . 36V.C.Drug Safety Assessment . 37D.Drug information. 38E.Drug costs, pricing, reimbursement and cost-containment.38F.Pharmaceutical marketing purposes . 39Procedures and data requirements for ATC/DDD assignment andalterations . 40A.Requests for ATC classification . 401. Procedures and timing . 402. Data requirements for submission. 42B.Requests for ATC changes . 431. Procedures and timing . 432. Data requirements for submission. 44C.Requests for DDD assignment . 441. Procedures and timing . 442. Data requirements for submission. 46D.Requests for DDD changes . 461. Procedures and timing . 462. Data requirements for submission. 46VI.Description of ATC index with DDDs . 47VII.Other ATC classification systems . 48VIII.8A.ATCvet classification. 48B.ATC herbal classification . 48ATC/DDD Interpretative guidelines . 49
ATC system main groups . 50AAlimentary tract and metabolism. 51BBlood and blood forming organs . 82CCardiovascular system . 92DDermatologicals . 115GGenito urinary system and sex hormones . 130HSystemic hormonal preparations, excl. sex hormones and insulins . 143JAntiinfectives for systemic use. 150LAntineoplastic and immunomodulating agents. 167MMusculo-skeletal system . 176NNervous system . 185PAntiparasitic products, insecticides and repellents . 205RRespiratory system . 212SSensory organs . 225VVarious . 234List of terms. 2479
I.INTRODUCTIONA.History of the ATC/DDD systemThe field of Drug Utilization Research (DUR) began attracting attention in the1960’s. This followed the publication of a breakthrough study on drugconsumption from 1966-1967 (pioneered by the WHO Regional Office for Europe)which further exemplified the importance and applicability of DUR (ref: Engel A,Siderius P. The consumption of drugs. Report on a study, 1966-1967. WHORegional Office for Europe, Copenhagen 1968 (EURO 3101). In addition, the WHOsymposium in 1969 highlighted the need for an internationally acceptedclassification system for drug utilization studies. As a result the Drug UtilizationResearch Group (DURG) was established and entrusted with the development ofinternationally applicable methods for DUR. Inspired by this interest, theAnatomical Therapeutic Chemical (ATC) classification was developed in Norway asa modification and extension of the European Pharmaceutical Market ResearchAssociation (EphMRA) classification system.In order to measure drug use, it is important to have both a classification systemand a unit of measurement. To deal with the objections against traditional unitsof measurement, a technical unit of measurement called the Defined Daily Dose(DDD) was developed for use in drug utilization studies.Several decades of experience using ATC/DDD methodology has demonstrated itssuitability in drug utilization monitoring and research. The increase in number ofusers indicates the usefulness of the system.B.Present Organizational responsibility for the ATC/DDD system1.WHO Collaborating Centre for Drug Statistics MethodologyIn 1981, the ATC/DDD system was recommended by WHO as the internationalstandard for drug utilization studies, and in 1982 the WHO Collaborating Centrefor Drug Statistics Methodology was established and given the responsibility forcoordinating the development and use of the ATC/DDD system. In 1996, theCentre was recognized as a global centre. This was seen as important to allowclose integration of international drug utilization studies and WHO’s initiatives toachieve universal access to needed drugs and rational use of drugs particularly indeveloping countries. Access to standardised and validated information on druguse is essential to allow audit of patterns of drug utilization, identification of10
problems, educational or other interventions and monitoring of the outcomes ofthe interventions.The Centre is located at the Norwegian Institute of Public Health and funded bythe Norwegian Government. The first agreement was drawn up by WHOHeadquarters with the Government of Norway in 1996. The latest redesignationof the Department of Drug Statistics, Norwegian Institute of Public Health asWHO Collaborating Centre for Drug Statistics Methodology, was in 2020. Allactivities related to ATC/DDD classification are conducted in accordance with thepolicies determined by WHO.The Terms of References (TOR) and activites are described in details in theredesignation documents of the WHO Collaborating Centre for Drug StatisticsMetholology. According to the TORs, the Centre has under guidance of WHO thefollowing activities:- Assignment of new ATC codes and DDDs based on requests from users indifferent countries- Review and revise existing ATC codes and DDDs based on proposals from usersof the ATC/DDD system- Handle requests and guide users regarding the use and misuse of the ATC/DDDsystem- To provide specialized training on the use of the ATC/DDD methodology toprovide technical support to countries in setting up their national medicinesclassification2.WHO International Working Group for Drug Statistics MethodologyIn 1996, when the decision on globalizing the ATC/DDD system was taken, theWHO Division of Drug Management and Policies established the WHOInternational Working Group for Drug Statistics Methodology. The InternationalWorking Group includes 12 expert members selected by WHO Headquarters torepresent a wide range of geographical and professional backgrounds, includingclinical pharmacology, clinical medicine, international public health, drugutilization and drug regulation. All six WHO regions are represented in the group.The WHO Collaborating Centre for Drug Statistics Methodology receives expertadvice from the Working Group. The tasks of the Working Group are:- To continue the scientific development of the ATC/DDD system.11
- To discuss and approve all new ATC codes, DDD assignments and alterations toexisting ATC codes and DDDs.- To develop further the use of the ATC/DDD system as an international standardfor drug utilization studies.- To revise as necessary the guidelines for assignment and change of ATC codesand DDDs.- To revise as necessary the procedures for applications for assignment of andchanges to ATC codes and DDDs to ensure they are consistent and transparent.- To assess the sources and availability of statistics on drug use internationally,and to encourage the systematic collection of comprehensive drug usestatistics in all countries and regions using the ATC/DDD system as theinternational standard.- To develop methods, manuals and guidelines for the practical application andappropriate use of the ATC/DDD system in drug utilization studies in a varietyof settings, particularly those applicable to developing countries.- To work with groups involved in rational drug use initiatives to integratemethods for measurement of drug use in assessing needs and outcomes ofinterventions with the aim of improving drug use.The International Working Group meets twice annually. A teleconference mayreplace one of the two annual meetings. Members are required to complete aWHO declaration of interest form before the meeting. Observers from the WHOCollaborating Centre for International Drug Monitoring and the InternationalFederation of Pharmaceutical Manufacturers Association are invited to attend themeetings of the International Working Group. An open session is arranged priorto one of the annual meetings to which any interested party can register (seefurther information below).Decisions on ATC classification or DDD assignment from the meetings arepublished on the website of the WHO Collaborating Centre for Drug StatisticsMethodology and in the publication WHO Drug Information. Any decision on anew or revised ATC classification or DDD assignment is first published astemporary. Any interested party wishing to dispute this decision is invited tocomment within a specified deadline after its publication. If there are noobjections to a temporary decision, it will be published as a final decision and12
implemented in the next issue of the ATC classification index with DDDs. In caseof any objection, the decision will be reconsidered at the next meeting of theInternational Working Group. If a new decision is made at the second meeting,this decision will be published as temporary and will be open to comments similarto the first decision. WHO has the final responsibility for the decisions and anydispute arising in the course of this work must be referred to WHO for finalresolution.Open SessionAn open session is arranged once a year in connection with the meeting of theWHO International Working Group for Drug Statistics Methodology. It isorganised in the interest of transparency and consists of a 90 minutes sessionprior to the closed decision-making session of the meeting of the Working Group.Anyone with a legitimate interest in the Anatomical Therapeutic Chemical (ATC)classification system and Defined Daily Dose (DDD) assignment can attend theopen session. This includes regulatory authorities, the pharmaceutical industry,academia and non-governmental organisations, and it provides an opportunity topresent additional information to the experts to assist them in their decisionmaking. It is also an opportunity for the international experts of the WorkingGroup to exchange ideas and opinions with interested parties.The open session is not intended to be used as a mechanism to challenge thedecision of the Working Group. The procedures for applying for and commentingon an ATC classification or a DDD assignment are outlined in these Guidelines (seesection V).Interested parties are requested to register for the open session to the WHOHeadquarter at least 14 days in advance of the meeting and are requested toprovide a relevant reason for attending. WHO Headquarter will restrict the timeallowed for each presentation in order to keep the duration of the open sessionwithin 90 minutes. Information on these meetings are made available on theWHO website at www.who.int/medicines.13
C.The purpose of the ATC/DDD systemThe purpose of the ATC/DDD system is to serve as a tool for drug utilizationmonitoring and research in order to improve quality of drug use. One componentof this is the presentation and comparison of drug consumption statistics atinternational and other levels.A major aim of the Centre and Working Group is to maintain stable ATC codesand DDDs over time to allow trends in drug consumption to be studied withoutthe complication of frequent changes to the system. There is a strong reluctanceto make changes to classifications or DDDs where such changes are requested forreasons not directly related to drug consumption studies. For this reason theATC/DDD system by itself is not suitable for guiding decisions aboutreimbursement, pricing and therapeutic substitution.It is essential that a tool for drug utilization monitoring and research is able tocover most medicines available on the market. An important aim of drugutilization is to monitor rational as well as irrational drug use as an important stepin improving the quality of drug use. The classification of a substance in theATC/DDD system is therefore not a recommendation for use and it does notimply any judgements about efficacy or relative efficacy of drugs and groups ofdrugs.II.THE ANATOMICAL THERAPEUTIC CHEMICAL (ATC)CLASSIFICATION SYSTEMA.Structure and nomenclatureStructureIn the ATC classification system, the active substances are classified in a hierarchywith five different levels. The system has fourteen mainanatomical/pharmacological groups or 1st levels. Each ATC main group is dividedinto 2nd levels which could be either pharmacological or therapeutic groups. The3rd and 4th levels are chemical, pharmacological or therapeutic subgroups andthe 5th level is the chemical substance. The 2nd, 3rd and 4th levels are oftenused to identify pharmacological subgroups when that is considered moreappropriate than therapeutic or chemical subgroups.14
The complete classification of metformin illustrates the structure of the code:AAlimentary tract and metabolism(1st level, anatomical main group)A10Drugs used in diabetes(2nd level, therapeutic subgroup)A10BBlood glucose lowering drugs, excl. insulins(3rd level, pharmacological subgroup)A10BABiguanides(4th level, chemical subgroup)A10BA02metformin(5th level, chemical substance)Thus, in the ATC system all plain metformin preparations are given the codeA10BA02.Nomenclature- International nonproprietary names (INN) are preferred. If INN names are notassigned, USAN (United States Adopted Name) or BAN (British Approved Name)names are usually chosen. For herbal medicinal products, Latin names are used.B.Inclusion and exclusion criteriaThe WHO Collaborating Centre in Oslo establishes new entries in the ATCclassification on requests from the users of the system. These includemanufacturers, regulatory agencies and researchers. The coverage of the systemis not comprehensive. A major reason why a substance is not included is that norequest has been received.Substances which fulfil one of the following criteria will normally be included inthe ATC system:- new chemical entities or biologicals proposed for licensing. A new chemicalentity is normally not included in the ATC system before an application formarketing authorisation is ready for submission in at least one country.- existing well defined chemical entities with an approved marketing15
authorization in one or more countries. An INN should preferably beestablished for the substance. Alternatively other official names, e.g. USAN orBAN names should be available.- herbal medicinal products assessed and approved by regulatory authoritiesbased on dossiers including efficacy, safety, and quality data (e.g. the wellestablished use procedure in EU).- cell/gene therapy products with an INN, USAN, BAN or another official namewhich have obtained a positive opinion (EU) or marketing authorization in oneor more countries.Other medicinal products are considered on a case by case basis.Complementary, homeopathic and herbal traditional medicinal products are ingeneral not included in the ATC system.C.Principles for classification1.Therapeutic use or pharmacological classMedicinal products are classified according to the main therapeutic use of themain active ingredient. The ATC system is, however, not strictly a therapeuticclassification system. In many ATC main groups, pharmacological groups havebeen assigned on the 2nd, 3rd and 4th levels allowing drugs with severaltherapeutic uses to be included without specifying the main indication. Forexample, calcium channel blockers are classified in the pharmacological groupC08 Calcium channel blockers, which avoids specifying whether the mainindication is coronary heart disease or hypertension. Subdivision on themechanism of action will, however, often be rather broad (e.g. antidepressants),since a too detailed classification according to mode of action often will result inhaving one substance per subgroup which as far as possible is avoided. Some ATCgroups are subdivided in both chemical and pharmacological groups (e.g. ATCgroup J05A - Direct acting antivirals). Preference will be given to establishing anew pharmacological 4th level rather than a chemical subgroup.Many medicines are used and approved for two or more indications, whilenormally only one ATC code will be assigned. Besides, ATC codes are oftenassigned according to the mechanism of action rather than therapy. An ATC groupmay therefore include medicines with many different indications, and drugs withsimilar therapeutic use may be classified in different groups.16
2.Only one ATC code for each route of administrationMedicinal substances are classified according to the main therapeutic use orpharmacological class on the basic principle of only one ATC code for each routeof administration (e.g. oral formulations with similar ingredients and strength willhave the same ATC code). This is an important principle for ATC classification as itallows aggregation of data in drug utilization monitoring and research withoutcounting a pharmaceutical product more than once. This principle is strictlyhandled by the WHO Centre so that users in different countries shall be able toclassify a pharmaceutical product (defined by active ingredient/s, route ofadministration and strength) in the same way.A pharmaceutical product may be approved for two or more equally importantindications, and the main therapeutic use may differ from one country toanother. This will often give several classification alternatives. Such drugs areonly given one code, the main indication being decided on the basis of theavailable information. Problems are discussed in the WHO International WorkingGroup for Drug Statistics Methodology where the final classification is decided.Cross-references will be given in the guidelines to indicate the various uses ofsuch drugs.3.More than one ATC code for a medicinal substanceA medicinal substance can be given more than one ATC code if it is available intwo or more strengths or routes of administration with clearly differenttherapeutic uses.Example of different strengths:- Finasteride is available in two different strengths. A low strength tablet for thetreatment of male pattern baldness is classified under D11AX - Otherdermatologicals. A high strength tablet used in the treatment of benignprostatic hypertrophy (BPH) is classified under G04C - Drugs used in BPH.17
Example of different administration forms:- Prednisolone in single ingredient products is given several ATC codes due todifferent therapeutic use and different 1BA04S02BA034.Intestinal antiinflammatory agentsAntihemorrhoidals for topical useDermatological preparationsCorticosteroids for systemic useNasal decongestantsOphthalmologicalsOtologicals(mainly enemas and foams)(suppositories)(creams, ointments and lotions)(tablets, injections)(nasal sprays/drops)(eye drops)(ear drops)New ATC groups and “other” groups (X groups)A new medicinal substance not clearly belonging to any existing ATC 4th level willas a main rule be placed in an X group ("other" group) in the relevant 3rd level.To avoid a situation of several 4th levels with only one single substance in each,new specific 4th levels are as a general rule only established when at least twosubstances with marketing authorisations fit in the group. In addition, a new 4thlevel should be regarded a benefit for drug utilization research. New andinnovative pharmaceutical products will therefore often be classified in an Xgroup and such groups could be established for only one single substance.5.Other general principlesImmediate and slow release tablets will normally have the same ATC code.Different stereoisomeric forms will normally have separate ATC codes.Exceptions will be described in the guidelines for the respective ATC groupsProdrugs are usually assigned separate ATC codes if the dosages used aredifferent and/or the nonproprietary name (INN) of the prodrug and the activedrugs are different.18
Example:J01CA08 pivmecillinamJ01CA11 mecillinamObsolete drugs or drugs withdrawn from the market are kept in the ATC system,since exclusion of substances from the ATC system may create difficulties for theusers of the system when considering historical data.D.Classification of combination productsPharmaceutical products containing two or more active ingredients are regardedas combinations (incl. combination packages) and given different ATC codes fromplain products containing one active ingredient. Stereoisomeric mixtures areregarded as plain products. Medicinal products which in addition to one activeingredient contain auxiliary substances intended to increase the stability of theproduct (e.g. vaccines containing small amounts of antibacterials), increase theduration (e.g. depot formulations) and/or increase the absorption (e.g. differentsolvents in various dermatologicals) are considered as plain products.The clas
1. WHO Collaborating Centre for Drug Statistics Methodology . In 1981, the ATC/DDD system was recommended by WHO as the international standard for drug utilization studies, and in 1982 the WHO Collaborating Centre for Drug Statistics Met
0403 Oslo Norway Visiting address: Marcus Thranes gate 6, 0473 Oslo, Norway Tel: 47 21 07 81 60 Fax: 47 21 07 81 46 E-mail: whocc@fhi.no ATC classifi cation. Guidelines for ATC classification and DDD assignment 2011. ISSN 1726-4898 ISBN 978-82-8082-438-7
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3.5 ATC Criteria CR-0061; Overhead Transmission Line Ampacity Ratings 3.6 ATC Criteria CR-0062; Underground Transmission Line Ampacity Ratings 3.7 ATC Design Criteria DS-0000; Substation 3.8 ATC Design Guide ECS-GD-0130, Equipment Connection Diagram Requirements 3.9 ATC Design Guide GD-3100; Bus 3.10 ATC Guide GD-0480; Document Control
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