Chapter mz | DRUG AND DISEASE CLASSIFICATION Objectives: ‘After completing this chapter, reader will be able to: * Describe the ATC classification of drugs. © Explain about the International classification of diseases. * Describe DDD. * Know the International Non Proprietary Names for drugs. From'the beginning of the era of Allopathy, various drugs are used to treat variety of diseases. Pharmacovigilance was initiated to prevent drug related problems and to promote rational use of drugs. Traditional system of disease classification and drug classification caused difficulty in measuring the drug use and morbidity and mortality reporting which further caused problem in monitoring the drug use and drug related problems. Hence, to ease the drug use measure and reporting of morbidity and mortality caused by diseases, drugs and diseases were classified by WHO as ATC classification (for drugs), ICD classification (for diseases). 4.1 ANATOMICAL, THERAPEUTIC AND CHEMICAL (ATC)/(DDD) _ DEFINED DAILY DOSES CLASSIFICATION OF DRUGS e quality of drug use WHO created drug classification system a tool for drug In order to improve th called as ATC/DDD system in 1976. WHO created this classification system as utilization monitoring and research. Organizational Responsibility for the ATC/DDD System: } 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 ru sei Methodology was established and given the responsibility for co-ordinat an 2 e development and use of the ATC/DDD system. In 1996, the Centre was recognize lobal centre. 2 atte of Public Healtn ana Tundeg , \ in Institu' e development and Mainten,! My of the Centre ar - at the tre is located 2 main activitl The Cen| nme ian Gover! m ing: Norwegian oe tem, including tothe ATC system: ihe ATC/DDD § jqned an ATC code. ofp classify drugs 20° ich have been assigne ificati m and DDDs, To establish ope cessary the ATC classification syste! To review and revise as Ne tical use of the ATC system by co-operating « nd influe i peat in the ATC/DDD methodology and to lecture & inin rs organized by others. / ; | support to countries in setting up their national medicin, ry in the use of medicines consumpy, To stimulate researchers in To organize tral courses and seminal i hnical Jo provide tec ; ; classification systems and build capacit information. WHO International Working Group for Drug Statistics Methodology: In 1996, when the decision on globalizing the ATC/DDD system was taken, the Wiy Division of Drug Management and Policies established the WHO International Workin, Group for Drug Statistics Methodology. The International Working Group includes 12 expe members selected by WHO headquarters to represent a wide range of geographical an; professional backgrounds, including clinical pharmacology, clinical medicine, internation; public health, drug utilization and drug regulation. All six WHO regions are represented i the group. The WHO Collaborating Centre for Drug Statistics Methodology receives expet advice from the Working Group. The main terms of reference of the Working Group are: * To continue the scientific development of the ATC/DDD system. . To discuss and approve all new ATC codes, DDD assignments and alterations t) existing ATC codes and DDDs. * To develop further the use of the ATC/DDD ii el system as i Grug utilization studies, ‘ me arent ‘ * To revise as necessary the DDDs. To revise as necessary, the procedures for applications for assignment of at changes to ATC codes and DI re that they are consistent and transpare! DDs to ensui y that consistent a encourage the systematic colune es Ea On tug ues internationally, and Countries and regions usi of comprehensive dr istics in 2! Teen gions using the ATC/DDD system as the inter io Geet , ee fethods, manuals and “adideine national standard. ie fe use of the ATC/DDD system in di S for the SF Particularly those applicable to develop opi guidelines for assignment and change of ATC codes ané te practical application and 9 utilization studies in a variety Ng countries, : 4.2pharmacovigilance Drug and Disease Classification * To work with groups involy, for measurement of dru ‘ed in rational drug, use initiatives, to integrate methods with the aim of improvin 9 used in assessing needs and outcomes of interventions 9 drug use. The International Worki ope bf the two aiincal et Group meets twice annually. A teleconference may replace interest ‘form before the me Members are required to complete a WHO declaration of International Drug Monitoring jobsene from the WHO Collaborating Centre for 7 and the Internati i i Manufacturers Association are invite ional Federation of Pharmaceutical 'd to attend the meetings of the In i i Group. An open session is arranged prior to one of the 2 REGIS ' annual meeti i interested party can register, ‘ings to which any Decisions on ATC classification or DDD assignment from the meetings are published on the website of the WHO. Collaborating Centre for Drug Statistics Methodology and in the WHO Drug Information Publication. Any decision on a new or revised ATC classification or DDD assignment is first published as temporary. Any interested party wishing to dispute this decision is invited to comment within a specified deadline after its publication. If there are no objections to a temporary decision, it will be published as a final decision and implemented in the next issue of the ATC classification index with DDDs. ATC Classification System: ATC drug classification system classifies the drugs’ active ingredients according to the organ on which they act and their therapeutic and chemical properties. In this system, the active ingredients are classified into five different levels. In this, drugs are coded according to the organ on which they act and their therapeutic and chemical properties. Different brands share same code if they have same active ingredients and indications. Five different levels in ATC classification system are: Level 1: Describes the organ system the drug treats or the anatomical site of drug action. Level 2: Describes the drug's therapeutic main group or the drug's therapeutic effect. Level 3: Describes the therapeutic subgroup or mechanism of action. Level 4: Describes the general chemical properties of the drug. Level 5: Describes the chemical'components of the drug or the name of the actual drug. All these 5 levels are represented as a code. This code contains 7 characters including numbers and alphabets. Level 1: This level indicates the anatomical group where the drug acts. The first letter of the ns code indicates level 1. There are 14 main groups in level 1. The code for different anatomic group is given in Table 4.1. eega: Code for Differen ede ‘Anatomical group | ct and metabolism Alimentary, tra Blood and blo Cardiovascular system od forming organs Dermatologicals Genito-urinary system an Systemic hormonal preparations, id sex hormones excluding sex hormones and insulin —| Antiinfectives for systemic use dulating agents ‘Antineoplastic and immunomo: Musculo-skeletal system Nervous system, ucts, insecticides and repellents ‘Antiparasitic prod Respiratory system Sensory organs <|4|~\v\2zle2[-|-|zlaloln|alsla 2 $ Various Level 2: The second level int representing therapeutic main group is highlighted in Tabl dicates the therapeutic subgroup. It consists of two digits. The je 4.2. Table 4.2: Example from: Alimentary Tract and Metabolism coe Code Drug’s therapeutic main group AOL Stomatological Preparations A02__| Drugs for Acid Related Disorders ‘A03_| Drugs for Functional Gastrointestinal Disorders A04_| Antiemetics and Antinauseants A05_| Bile and Liver Therapy A06_| Drugs for Constipation A07_| Antidiarrheals, Intestinal Antiinflammatory/Antiinfective Agents A08_| Antiobesity Preparations, Excl. Diet. Products A09_| Digestives, Incl. Enzymes A10_| Drugs used in Diabetes Al1_| Vitamins A12_| Mineral supplements A13_| Tonics Al14_| Anabolic Agents for Systemic Use A15_| Appetite Stimulants ALG Other Alimentary Tract and Metabolism Products 44jl Pharmacovigiiance Drug and Disease Classification Level 3: It indicates the therapeutic subgroup/pharmacological subgroup of the drug. It consists of one letter in the code. The code representing th r subgroup is highlighted in Table 4.3. g therapeutic subgroup/pharmacological Table 4.3: Example from: Alimentary Tract and Metabolism: Drugs for Functional Gastrointestinal Disorders Code Drug’s Pharmacological subgroup/Therapeutic subgroup ‘A03A_| Drugs for functional gastrointestinal disorders ‘A03B_ | Belladonna and derivatives, plain ‘A03C_| Antispasmodics in combination with psycholeptics ‘A03D | Antispasmodics in combination with analgesics ‘A03E_| Antispasmodics and anticholinergics in combination with other drugs | A03F_| Propulsives Level 4: It indicates the chemical properties/therapeutic/pharmacological subgroup of the drug. It consists of one letter in the code. The code representing chemical/ pharmacological subgroup is highlighted in Table 4.4. Table 4.4: Example from: Alimentary Tract and Metabolism: Drugs for Functional Gastrointestinal Disorders: Drugs for functional gastrointestinal disorders Chemical/Pharmacological Subgroup Code Drug’s Chemical/Pharmacological subgroup ‘AO3AA | Synthetic anticholinergics, esters with tertiary amino group [A03AB | Synthetic anticholinergics, quaternary ammonium compounds ‘AO3AC | Synthetic antispasmodics, amides with tertiary amines ‘A03AD | Papaverine and derivatives AO3AE | Serotonin receptor antagonists A03AX | Other drugs for functional gastrointestinal disorders Level 5: It indicates the chemical components in the drug. It consists of two digits in the code. Example for ATC Classification of Drugs: A10BA02: It is the ATC code for Metformin. A indicates the level 1 (Anatomical main group of the drug) Hence, the anatomical group of the drug is Alimentary Tract and Metabolism. A10 indicates level 2 (Therapeutic main group of the drug). Hence, the main therapeutic group of the drug is Drugs used in Diabetes. A10B indicates level 3 (Therapeutic/Pharmacological subgroup of the drug). 45Drug and Disease Classy Pharmacovigilance a ae te, | subgroup of the drur 00d Gluco, Hence, the therapeutic/pharmacological subg 5 Log. Agents excluding Insulins. Pri (A) * Some ATC groups are subdivided in b A1OBA indicates level 4 (Chemical subgroup a the drug). Hence, the chemical subgroup of the drug is Biguanides. "A10BA02 indicates level 5 (Chemical component) Hence, the chemical component is metformin, inciples for ATC Classification: , ; Drugs are classified based on their main therapeutic use or Pharmacological Use: * Medicinal products are classified according to the main therapeutic use of the me, active ingredient. But ATC system is not strictly a therapeutic classification SYste In many ATC main groups, pharmacological groups have been assigned on the 7: 3% and 4 levels allowing drugs with several therapeutic uses to be included Withos specifying the main indication, For example, calcium channel blockers are classified in the pharmacolo. C08 Calcium channel blockers, which avoid specifying whether the main coronary heart disease or hypertension. gical grow, indications oth chemical and pharmacological groups (eg ATC group JOSA - Direct acting antivirals). Preference will be given to establishing: new pharmacological 4" level rather than a chemical subgroup. Many medicines are used and approved for two or more indications, while normal) only one ATC code will be assigned. Besides, ATC codes are often assigned accordirs to the mechanism of action rather than therapy. An ATC group may therefore incl medicines with many different indications, and drugs with similar therapeutic us may be classified in different groups. (B) Only one ATC code for each route of administration: Medicinal substances are classified according to the main therapeutic use 0 Pharmacological class on the basi _ ic principle of only one ATC code for each route administration (e.g. oral formulations with similar ingredients and strength will havé the same ATC code), This is an important principle for ATC classifi drug utilization Monitoring and research wit More than once. This principle is stricth ication as it allows aggregation of data’ thout counting a pharmaceutical produ ly handled by the WHO Centre, so that, users in differet Countries shall be able to Classify a pharmaceutical Product (defined by activ? ingredient/s, route of administration and strength) in the s A Pharmaceutical Product may be approved for two indications, and the main therapeutic use may differ f This will often give several classification alternatives, 5 code, the main indication being decided on the basis o 46 ame way. or more equally importa" rom one country to anothe! uch drugs are only given of # the available information.Pharmacoviallance, Drug and Disease Classification (©) More than one ATC code for a medicinal substance: A medicinal substance can be given more than one ATC code if it is available in two or more strengths or routes of administration with clearly different therapeutic uses. Example of different strengths: Finasteride is available in two different strengths. A low strenath tablet for the treatment of male pattern baldness is classified under D11AX - Other dermatologicals. A high strength tablet used in the treatment of benign prostatic hypertrophy (BPH) is classified under GO4C - Drugs used in BPH Example of different administration forms: Prednisolone in single ingredient products is given several ATC codes due to different therapeutic use and different formulations. AQ7EAOI Intestinal anti-inflammatory agents (enemas and foams) COSAA04 Antihemorrhoidals for topical use (suppositories) D07AA03 Dermatological preparations (creams, ointments and lotions) H02AB06 Corticosteroids for systemic use (tablets, injections) ROLADO2 Nasal decongestants (nasal sprays/drops) S01BA04 Ophthalmologicals (eye drops) $02BA03 Otologicals (ear drops) D) New ATC groups and “other” groups (X groups): * In a new medicinal substance not clearly belonging to any existing ATC 4" level will be placed in an X group (“other" group) in the relevant 3 level. * To avoid a situation of several 4" levels with only one single substance in each, new specific 4" levels are as a general rule only established when at least two substances with marketing authorisations fit in the group. * Anew 4" level should be regarded as a benefit for drug utilization research. New and innovative pharmaceutical products will therefore often be classified in an X group and such groups could be established for only one single substance. (E) Other General Principles: * Immediate 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 groups. * Prodrugs are usually assigned separate ATC codes if the dosages used are different and/or the non-proprietary name (INN) of the prodrug and the active drugs are different. Example: JO1CA08 pivmecillinam J01CA11 mecillinam * Obsolete 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 the users of the system when considering historical data. a7prug and Disease Classifica, Pharmacovigilance Principles for Changing ATC Codes: As the selection of drugs and their uses are con revisions of the ATC system will always be necessary. 2 . i Changes in the ATC classification should be kept to a minimum. An important aim iss; keep a stable classification system over time with as few changes as possible and still ha classification where new therapy and new pharmacological principles find an appropi place. Before alterations are made, any potential difficulties for the use of the ATC system i, rug utilization monitoring and research are considered and related to the benefits the itinually changing and expanding, regu, could be achieved by the alteration. Alterations in ATC classification can be made when the main use of a drug has cleat eee eevee ioe to al new substances or to achiev tter ir 7 reasons for changes can be ni mechanism of action or the need for splitting large and complex cou ee eee When it is decided to make an alteration, the following Principles are used: * When new therapeutic or pharmacological ATC groups are asi ne i be considered if there are substances in other groups that honld be aes roe Should be included in th ¢ When changing ATC codes for plain products, it should ah necessary to change the ATC code for any combinatig NYS be considered if ti active ingredient. ” Products with the sam * When an ATC code is changed for a substance, the previ new substances. (OUS Code is nat raise &