Anatomical Therapeutic Chemical Classification System
The Anatomical Therapeutic Chemical (ATC) Classification System is a hierarchical method for organizing drugs based on their anatomical site of action, therapeutic use, and chemical structure, serving as the international standard for drug utilization research and statistics.[1] Developed by the World Health Organization (WHO) and its Collaborating Centre for Drug Statistics Methodology in Oslo, Norway, the system classifies active substances using International Nonproprietary Names (INNs) and assigns unique seven-character codes to facilitate the comparison of drug consumption data across countries.[2] The ATC structure consists of five levels: the first level divides drugs into 14 main anatomical or pharmacological groups (e.g., A for alimentary tract and metabolism, N for nervous system); the second and third levels specify therapeutic, pharmacological, or chemical subgroups; the fourth level denotes chemical, pharmacological, or therapeutic subgroups; and the fifth level identifies the specific chemical substance.[3] This classification emphasizes the primary therapeutic or pharmacological action of the drug, with separate codes often assigned for different routes of administration or combination products to reflect distinct uses.[2] Established in its current form since 1975 for statistical purposes and first published as guidelines in 1990, the system is updated annually by the WHO International Working Group for Drug Statistics Methodology, which meets biannually to review and assign new codes based on requests from regulators, manufacturers, and researchers, ensuring stability for longitudinal trend analysis.[3] Complementing the ATC is the Defined Daily Dose (DDD), a fixed unit representing the assumed average maintenance dose per day for a drug's main indication in adults, which enables standardized measurement of drug consumption volume rather than cost or value.[1] While primarily a research tool to improve the quality of drug use and support pharmacoepidemiological studies, the ATC/DDD system is not intended for decisions on reimbursement, pricing, or therapeutic substitution, as it does not reflect clinical efficacy or safety profiles.[3] Adopted globally by organizations such as the European Medicines Agency (EMA) and national health authorities, it underpins initiatives like the WHO's drug consumption monitoring and has been integral to international pharmacovigilance since its globalization in 1996.[4]Overview
Purpose and Scope
The Anatomical Therapeutic Chemical (ATC) Classification System is a hierarchical framework for organizing the active ingredients of medicines based on their primary anatomical site of action, therapeutic indications, pharmacological properties, and chemical characteristics.[5] This structure enables standardized categorization that supports consistent identification and analysis of pharmaceuticals across diverse contexts.[3] The primary purposes of the ATC system include serving as an essential tool for drug utilization research to enhance the quality of drug prescribing and consumption, advancing pharmacoepidemiological studies, informing reimbursement policies in healthcare systems, and enabling international comparisons of drug consumption patterns.[3][6] By providing a uniform method to quantify and compare drug use, it helps identify trends in drug use, evaluate utilization patterns, and promote rational drug use globally.[2] In terms of scope, the ATC system primarily encompasses human medicines, assigning approximately 6,900 unique codes to active substances as of 2025, while excluding medical devices, veterinary products, and classifications based on brand names or proprietary formulations.[5][7] It focuses exclusively on the therapeutic roles of active ingredients, ensuring applicability to a wide array of pharmaceuticals without regard to dosage forms or commercial identifiers.[3] Key applications of the ATC system extend to its adoption by the World Health Organization (WHO) for compiling global drug consumption statistics, by national health agencies for constructing essential medicines formularies and regulatory monitoring, and by researchers for analyzing drug utilization patterns to inform public health policies.[6][3] This broad utility underscores its role in fostering evidence-based improvements in healthcare delivery worldwide.[2]Development and Maintenance
The Anatomical Therapeutic Chemical (ATC) Classification System, developed in Norway, was established as an international standard by the World Health Organization (WHO) for drug utilization research and has overseen its evolution since its initial publication in 1976.[8] The system was developed in Norway during the early 1970s, building on earlier classification efforts like the European Pharmaceutical Market Research Association (EphMRA) system, to address the growing need for standardized drug monitoring following increased attention to drug utilization research in the 1960s.[9] WHO's endorsement in 1981 by its Regional Office for Europe marked formal recognition for international use, with global standardization recommended in 1996.[8] Primary maintenance of the ATC system is handled by the WHO Collaborating Centre for Drug Statistics Methodology, established in 1982 at the Norwegian Institute of Public Health in Oslo, Norway.[9] This centre coordinates ongoing development, including the classification of new active substances, assignment of Defined Daily Doses (DDDs), and revisions to existing codes to reflect advances in pharmacology and therapeutic practices.[10] Maintenance processes feature annual reviews, typically through expert meetings held in spring and autumn, where proposed changes are evaluated and implemented to ensure the system's relevance and accuracy.[11] Collaboration with international experts is facilitated via the WHO International Working Group for Drug Statistics Methodology, comprising 12 members selected from WHO's Expert Advisory Panels on Drug Evaluation and on Drug Policies and Management (including aspects related to the International Pharmacopoeia and Pharmaceutical Preparations).[12] This group provides technical advice on classifications, approves new ATC codes, and promotes the system's application in drug utilization studies worldwide.[10] The centre also responds to inquiries from national drug regulatory authorities and researchers to maintain consistency across global datasets.[13] Funding for the Collaborating Centre's operations is provided by the WHO and the Norwegian government, enabling its role as a non-profit entity dedicated to public health.[11] The ATC index, guidelines, and related resources are freely accessible through an online database hosted by the centre, supporting open use for research, policy-making, and pharmacovigilance without licensing fees.[11]History
Origins and Early Development
The conceptual roots of the Anatomical Therapeutic Chemical (ATC) classification system lie in mid-20th-century European efforts to standardize drug categorization for market research and statistical purposes. In the 1950s, organizations like the European Pharmaceutical Market Research Association (EPhMRA), founded in 1953, developed the Anatomical Classification of Pharmaceutical Products, which grouped drugs primarily by their therapeutic indications and anatomical targets to support sales data analysis across Europe.[14] This system emphasized a hierarchical structure based on organ systems and uses, influencing later therapeutic classifications.[15] Scandinavian models contributed significantly to the ATC's evolution, particularly through Norwegian initiatives in the 1960s and early 1970s. Amid rising interest in drug utilization research (DUR), Norway's Norwegian Medical Depot (NMD) adapted and expanded the EPhMRA framework into the ATC system around 1970–1972, adding therapeutic, pharmacological, and chemical subgroups for more precise statistical tracking.[16] This development was spurred by a 1969 WHO symposium in Oslo, which identified the need for an international standard to compare drug consumption patterns amid growing concerns over rational drug use.[8] The World Health Organization (WHO) initiated formal involvement in 1970 to address the demand for standardized drug statistics, leading to the establishment of the Drug Utilization Research Group (DURG) and the creation of an initial ATC prototype that integrated anatomical, therapeutic, and chemical elements.[8] This prototype built directly on the Norwegian modifications to EPhMRA, aiming to enable comparable international data for public health policy.[17] The first complete ATC index was published in 1975 by the newly formed Nordic Council on Medicines (NLN), providing a comprehensive list of substances classified under the system for use in Nordic drug consumption statistics.[10] This publication represented the culmination of early prototyping efforts and marked the system's readiness for broader application in utilization studies.[16]Adoption and Evolution
The Anatomical Therapeutic Chemical (ATC) classification system, initially developed in Norway in the mid-1970s based on earlier pharmaceutical industry systems, was first utilized for Nordic drug statistics around 1975–1976.[10] In 1981, the World Health Organization (WHO) Regional Office for Europe formally recognized the combined ATC/Defined Daily Dose (DDD) system for drug utilization studies and recommended its application across European countries to enable comparable consumption statistics.[8] This marked the initial endorsement for international use in monitoring drug consumption patterns. By 1982, the system was integrated into a formalized framework through the establishment of the WHO Collaborating Centre for Drug Statistics Methodology in Oslo, which coordinated its further refinement and application for global drug utilization research.[8] Key evolutionary milestones shaped the system's robustness and applicability. During the 1980s, the ATC structure expanded with additional subgroups to accommodate emerging pharmaceuticals, increasing the total number of classified substances from around 1,000 in the early years to over 3,000 by the decade's end, reflecting growing pharmaceutical diversity. The first formal ATC/DDD guidelines were published in 1990, standardizing the methodology for international use.[10] In 1996, WHO elevated the ATC/DDD methodology to an international standard, prompting the launch of digital tools and databases that facilitated easier access and data sharing for utilization studies worldwide.[8] The 2000s saw further adaptations to include biologics and vaccines, with dedicated subgroups such as J07 for vaccines and expansions in L (antineoplastic and immunomodulating agents) for biologics like monoclonal antibodies, ensuring the system addressed advances in biotechnology.[18] By 2025, the ATC system had achieved widespread global adoption, utilized in drug utilization and pharmacovigilance efforts across more than 100 countries, enabling standardized comparisons of medicine consumption at national and international levels.[6] In the European Union, it is mandated under regulations for pharmacovigilance reporting, with the European Medicines Agency assigning ATC codes to all authorized medicines to track adverse events and market trends.[4] In the United States, adaptations of the ATC have been incorporated into Medicare analyses for evaluating drug utilization patterns, complementing national coding systems like the National Drug Code.[19] Evolutionary challenges, such as harmonizing ATC with the International Classification of Diseases (ICD), have been addressed through mapping initiatives that link drug classes to disease codes, supporting integrated epidemiological research.[20]Classification Structure
First Level: Anatomical Main Groups
The first level of the Anatomical Therapeutic Chemical (ATC) Classification System provides a broad categorization of medicinal substances into 14 main groups, designated by the letters A through N, with an additional group V. This level organizes drugs primarily according to the anatomical region or organ system on which they primarily act, offering an initial therapeutic-independent grouping that facilitates international drug utilization studies and pharmacoepidemiological research.[2] By focusing on anatomical main groups, the ATC system enables a standardized framework for classifying active ingredients based on their site of action, such as the digestive tract or cardiovascular system, without delving into specific pharmacological mechanisms or chemical properties at this stage. This approach supports the comparison of drug consumption patterns across populations and healthcare systems globally.[5] The 14 main groups are as follows:| Code | Main Group | Brief Description |
|---|---|---|
| A | Alimentary Tract and Metabolism | Drugs primarily affecting the digestive system and metabolic processes. |
| B | Blood and Blood Forming Organs | Agents targeting blood components and hematopoiesis. |
| C | Cardiovascular System | Medications acting on the heart and vascular system. |
| D | Dermatologicals | Preparations for skin conditions and topical applications. |
| G | Genito Urinary System and Sex Hormones | Substances influencing the urinary tract, reproductive organs, and related hormones. |
| H | Systemic Hormonal Preparations, excl. Sex Hormones and Insulins | Systemic hormones excluding those for reproduction or diabetes management. |
| J | Antiinfectives for Systemic Use | Systemic agents combating infections. |
| L | Antineoplastic and Immunomodulating Agents | Drugs for cancer treatment and immune system modulation. |
| M | Musculo-skeletal System | Treatments for muscles, bones, and joints. |
| N | Nervous System | Agents affecting the central and peripheral nervous systems, including analgesics and psychotropics. |
| P | Antiparasitic Products, Insecticides and Repellents | Products against parasites and for pest control. |
| R | Respiratory System | Medications for the airways and lungs. |
| S | Sensory Organs | Preparations for eyes, ears, and other sensory structures. |
| V | Various | Miscellaneous substances not fitting other anatomical groups, such as diagnostic agents and allergens. |