WHO Drug Information Vol. 23, No. 4, 2009 World Health Organization WHO Drug Information Contents International Nonproprietary Prequalification of Medicines Names Programme INN identifiers for biological products 273 Prequalification of quality control laboratories 300 Safety and Efficacy Issues Rituximab: multifocal leuko- Pharmacovigilance Focus encephalopathy 282 A/H1N1 vaccination safety: PaniFlow® Darbepoetin alfa: risk of stroke 282 surveillance tool 305 Vigabatrin and movement disorders 283 Alendronate: risk of low-energy femoral Regulatory Action and News shaft fracture 283 Influenza vaccines for 2010 southern Ceftriaxone and calcium containing hemisphere winter 306 solutions 284 Romidepsin: approved for cutaneous Etravirine: severe skin and hyper- T-cell lymphoma 306 sensitivity reactions 285 Orciprenaline sulphate: withdrawal 306 Oseltamivir phosphate: dosing risk 285 Artemisinin antimalarials: not for Safety signal: hyponatraemia 286 use as monotherapy 307 Clopidogrel and omeprazole: reduced Vitespen: withdrawal of marketing effectiveness 286 authorization application 307 Bisphosphonates: osteonecrosis of Aripiprazole: withdrawal of application the jaw 287 for extension of indication 307 Intravenous promethazine: serious Substandard and counterfeit medicines: tissue injuries 287 USAID–USP Agreement 308 Cyproterone: risk of meningiomas 288 Vandetinib: withdrawal of marketing Gadolinium-containing contrast agents 289 authorization application 308 Cesium chloride: cardiac risks 290 Washout or taper when switching antidepressants 290 Consultation Document Zanamivir inhalation powder must International Pharmacopoeia not be nebulized 291 Artesunate 309 Pandemrix®: risk of fever 291 Artesunate tablets 313 Weekly pandemic pharmacovigilance updates 292 Recent Publications, Information and Events Biomedicines and Vaccines Illegal weight-loss medicines and International biological standards: dietary supplements 318 2009 update 292 Southern Med Review 318 International Harmonization Proposed International ICH Implementation: Quality Working Nonproprietary Names Groups 295 List 102 319 ICH Pharmacopoeial Discussion Group 296 271 World Health Organization WHO Drug Information Vol. 23, No. 4, 2009 Announcement The 14th International Conference of Drug Regulatory Authorities (ICDRA) will be hosted by the Health Sciences Authority, Singapore, in collaboration with the World Health Organization The ICDRA will take place in Singapore from 30 November to 3 December 2010 Updated information is available at: http://www.icdra2010.sg http://www.who.int/medicines/icdra 272 WHO Drug Information Vol. 23, No. 4, 2009 International Nonproprietary Names INN identifiers for cal substances of well-defined structure although other groups of non-homo- biological products genous established products, including from natural sources, were also consid- The International Nonproprietary Names ered. When substances which had (INN) Programme was created by WHO already been named by the INN Pro- in the 1950s with the intention of provid- gramme became available through new ing convenient common names for biotechnological processes, earlier pharmaceutical substances. At the time of decisions on naming non-homogenous its origin, as well as during its later products had an influence on defining development, the INN Programme was and naming novel products. Practices inherently linked to progress in drug recognized in naming and defining two research and its success was reliant on specific product groups: low molecular the ability to deal appropriately with each weight heparins and insulins strongly new group of medicinal products that influenced this approach. (A discussion entered into therapeutic use. In the of these practices is found on page 274 1980s, the development of biotechnology and 275.) products based on recombinant tech- niques led to highly novel therapeutic Specific approaches are needed when agents, thus creating a new need for formulating definitions and, in particular, adaptation of the INN system. The for creating suitable INN for biotechno- present article describes the ways that logical products. These approaches have the INN Programme has responded to the been under active consideration by the challenges that arose in connection with INN Programme since the 1980s and this evolution. were finally formulated in a 1994 INN guideline (1). Until now, 45 INN with Basic rules for the INN system set the Greek letter identifiers have been se- limits within which all INN can be con- lected for glycosylated biological prod- structed. They include the need to prop- ucts. erly define the substance or product that is named, to indicate in the name the Application of the guidelines in naming of pharmacological or therapeutic class to individual groups of biological products which the substance or product belongs containing carbohydrate residues in their by use of the INN stem system and, structure is described on pages 275–277. finally, to shape the name in a manner Difficulties that relate to the use of Greek which facilitates its use by prescribers. letter identifiers in naming of interferons (These issues are summarized on page are presented on page 279. The naming 274.) of monoclonal antibodies (mAbs), an important group of glycoproteins obtained In its initial phase, the INN Programme by biotechnology, is not considered in this was designed to cover only single chemi- document as issues related to mAb names have been discussed separately * Professor Witold Wieniawski,Counsellor, at recent INN meetings and are also Polish Pharmaceutical Society, Poland and reviewed in two issues of WHO Drug Member, WHO INN Expert Group. Information (2). Related documents of 273 International Nonproprietary Names WHO Drug Information Vol. 23, No. 4, 2009 interest are also available on the INN is selected for an active moiety, while a website including a document on INN for salt or an ester are employed in practice, biological and biotechnology substances an INNM system is used to create suit- (3), documents relating to biologicals and able two-word names. mAbs (4) and an INN document on biosimilars (5). However, creating INN for products obtained by biotechnology is a more com- Creating INN plex process. While the selection of basic stems (-ase, -mab, -micin, -mycin, In the selection of INN, two separate -poetin, etc.) can be carried out according issues are considered which influence the to the normal INN system, the naming of final shape of the name: (i) the way in individual components of each series which the substance is identified, and (ii) requires specific decisions on the extent the structure of the name. of supplementary information to be included in the name. Those issues may In the case of individual chemical sub- vary for individual groups, but the follow- stances, the identification process is ing remarks apply to all situations. based on chemical names established by the International Union of Pure and General rules for the construction of INN Applied Chemistry (IUPAC). The chemical offer only a few options for introducing designation is further supported by a elements of additional information. In graphic formula. one-word names this can be done by insertion of specific infixes (or prefixes). In the case of products obtained by bio- Otherwise, inclusion of a second or even technology, the identification process is third word is necessary as in the case of more complicated because such products INNM names. This approach is also used usually form a mixture (the word “com- when describing complexes with metals plex” is sometimes used) of several (or or radioactive elements. The second- more) individual substances of similar word approach is used frequently for structure and activity. The use of these biological products when the second word products occurs without separation into consists of a spelled out Greek letter. individual active components. Definition of such products is complicated and is Other identifiers widely used in scientific made individually for each product group. texts like numerals (Arabic or Roman), Formulation of definitions has progressed single letters (Latin alphabet), or single in line with analytical methods that Greek letters in the original script, are increasingly allow a highly precise de- precluded in INN. The reason for this rule scription of the structure of individual is that such elements of names could components. Examples of such changes lead to confusion and mistakes when occurring for individual groups are pre- used on a medical prescription, as sented later. numerals are used also to describe the dose (or concentration) or the number of Creation of INN for single chemical dosage units. Single letters may also be substances involves selection of an confused, especially in handwriting. appropriate stem indicating the expected activity (or the decision to select an INN The rules indicated above are also outside the stem system) followed by applied when selecting names for biologi- additional elements (usually the prefix) to cal products with a glycoprotein structure. create a distinctive name. When an INN This can sometimes create additional difficulties, and is described later. 274 WHO Drug Information Vol. 23, No. 4, 2009 International Nonproprietary Names Selecting INN for natural and followed (or preceded) by another word semisynthetic products (or words) which is indicative of changes in the structure of the parent compound. INN for LMW heparins Low molecular weight (LMW) heparins Insulin as such was never