WHO Drug Information Vol. 25, No. 2, 2011 World Health Organization WHO Drug Information Contents WHO Prequalification of Abiraterone acetate approved for Medicines Programme late-stage prostate cancer 122 Rituximab approved for Wegener Facts and figures for 2010 101 granulomatosis and microscopic polyangiitis 122 Safety and Efficacy Issues Human normal immuno-globulin: lifting Safety trials for long acting beta-agonists104 of suspension 123 Rotavirus vaccination: risk of intus- Everolimus approved for pancreatic susception 104 cancer 123 Tumour necrosis factor blockers: hepato- Boceprevir approved for hepatitis C 124 splenic T-cell lymphoma 106 Linagliptin approved for type 2 diabetes 124 Dipeptidyl peptidase-4 inhibitors: Naproxcinod: withdrawal of marketing possible glycaemic complications 106 authorization application 124 Lenalidomide: risk of new malignancies 106 Lumiracoxib: withdrawal of marketing Pneumovax 23®: injection site reactions 107 authorization application 125 Dabigatran etexilate mesylate capsules: Erythropoietin: withdrawal of marketing storage and handling 107 authorization application 125 Proton pump inhibitors: low magnesium levels 108 ATC/DDD Classification Seasonal influenza vaccines 108 ATC/DDD Classification (temporary) 126 Ipilimumab: severe immune-mediated ATC/DDD Classification (final) 128 reactions 108 Fluticasone propionate: risk of osteonecrosis 109 Recent Publications, Varenicline: hyperglycaemia in patients Information and Events with diabetes 109 Selection and use of medicines 131 Quinine sulfate: serious adverse Policy guidelines on controlled reactions 110 substances 132 Risk of oral clefts in children born to List of medicines to save mothers and mothers taking topiramate 110 children 133 WHO training course on pharmaco- World medicines situation 133 vigilance 111 Artesunate instead of quinine saves lives134 Quality Assurance Issues Consultation Documents WHO Certification Scheme: questions The International Pharmacopoeia and answers 113 Revision of monograph on capsules 135 Revision of monograph on tablets 139 Regulatory Action and News Paediatric retinol oral solution 147 Buflomedil: marketing authorization suspended 122 Proposed International Dolasetron mesylate intravenous injection: withdrawal 122 Nonproprietary Names List 105 151 99 World Health Organization WHO Drug Information Vol. 25, No. 2, 2011 WHO Drug Information Digital Library, e-mail table of contents and subscriptions available at: http://www.who.int/druginformation 100 WHO Drug Information Vol. 25, No. 2, 2011 WHO Prequalification of Medicines Programme Facts and figures for 2010 ment guidelines. Additionally, the first invitation to manufacturers of active Evaluation of medicines by the WHO pharmaceutical ingredients (APIs) was Prequalification of Medicines Programme issued in October 2010, marking the (PQP) includes assessment of data and launch of WHO prequalification of APIs. information on safety, efficacy and quality. (A second, expanded invitation to API Inspections are performed to assess manufacturers to submit an EOI was compliance with good manufacturing issued in March 2011.) It is expected that practices (GMP) and include manufactur- time taken to reach prequalification will be ers of selected active pharmaceutical shorter for finished pharmaceutical ingredients (API) and clinical sites. products (FPPs) that are manufactured Clinical sites, including contract research using WHO-prequalified APIs, than for organizations (CROs), are also inspected FPPs that are manufactured using APIs to verify bio-equivalence with good that have not previously been evaluated laboratory practices and good clinical by WHO PQP. practices. Assessment activities Thirty-six products were prequalified in In 2010, 51 dossiers were submitted and 2010, of which 30 were generics. At the 53 dossiers (two of which were received end of 2010, the WHO list of prequalified in late 2009) were accepted for evalua- medicines totalled 252 products manufac- tion. Nearly 1000 assessment reports tured in 20 countries. WHO prequalifica- were produced. PQP also assessed tion “firsts” included artesunate powder nearly 600 variations submitted by for injection (which was the first prequali- manufacturers of prequalified products. fied sterile product made in China); the first combination tenofovir disoproxil The assessment sessions held in Copen- fumarate/lamivudine and the first generic hagen, Denmark, include a training emtricitabine. component which is enabling a growing number of developing country assessors Six medicines quality control laboratories to acquire stringent regulatory expertise. (QCLs) were also prequalified: one in The Copenhagen sessions also incorpo- Bolivia, one in Canada, one in Peru, two rate technical consultations so that in Ukraine and one in Uruguay. At the end applicants can discuss technical issues of 2010, a total of 17 QCLs had been relating to their dossiers with assessors. prequalified and a further 30 were work- The consultations benefit from the pres- ing towards becoming prequalified. ence of a range of assessors with consid- Invitations to manufacturers to submit an erable assessment experience. expression of interest (EOI) for product evaluation were issued for anti-TB medi- A new collaborative procedure for facilitat- cines, HIV/AIDS-related care and treat- ing registration of prequalified medicines ment products, and reproductive health in the East African Community (EAC) was products. The new invitations incorporate piloted. The overall aim was to identify a additional products and/or take into framework, for WHO-EAC, for joint account revisions made to WHO treat- evaluation and approval of dossiers and 101 WHO Prequalification of Medicines Programme WHO Drug Information Vol. 25, No. 2, 2011 inspections of medicine manufacturing plans, arranging of joint inspections, and sites, and to ensure that these assess- sharing of information and inspection ments are integrated into national regula- reports, with recognition by participating tory decision-making. Two assessors EAC parties and PQP. This will be further each from three EAC countries (Kenya, explored and possibly expanded. Joint Tanzania and Uganda) and six WHO inspections are planned for 2011 in an assessors jointly assessed two product attempt to prevent duplication of inspec- dossiers submitted by a single manufac- tions. Inspection reports will be shared by turer. The dossiers were submitted in the parties following the inspection. It is parallel, and with identical content, to hoped that the outcome of the inspection each participating EAC country and to will be accepted by all participating PQP. The products were both prequali- inspectorates. PQP continues to invite fied: HA488 (abacavir, dispersible tablets local medicines regulatory authority staff 60 mg) in August 2010 and TB217 or observers to participate in inspections. (amikacin, injection 500 mg/2 ml) in January 2011. For the manufacturer, the The risk assessment procedure for principal benefit of this joint assessment identifying which API manufacturing sites was that once the products had been should be inspected has been completed jointly assessed and approved by WHO- for substances used to manufacture EAC, they were granted immediate products for the treatment of malaria and access to the markets of each of the TB. It is planned to expand this risk countries that had participated in the joint assessment to APIs used in products for assessment. For the regulators involved, the treatment of HIV/AIDS. such joint assessment contributes to harmonization of regulatory requirements Advice and assistance at regional level. PQP is hoping to use PQP continues to respond to manufactur- the same model for assessing selected, ers’ request for assistance concerning technically complex, high-priority prod- issues relating to, for example, bioequiva- ucts. Several partners and stakeholders lence study protocols and choice of see joint assessment as an effective comparator products. means of speeding up access to much needed products. PQP continues to provide technical assistance to manufacturers and national Inspections QCLs that aims at resolving specific PQP inspectors carried out 59 inspec- practical problems related to GMP, good tions in 18 countries: 38 of finished practices for QCLs and/or meeting pharmaceutical product manufacturing medicines regulatory requirements. sites; five of API manufacturing sites; Assistance is given in the form of an seven of CROs and nine of pharmaceuti- audit, advice on development of an cal QCLs. (Inspections were carried out improvement plan, and training in techni- mostly in India and in China, but also in cal or regulatory areas. Follow-up mis- Algeria, Belgium, Bolivia, Egypt, France, sions are also organized to support Iran, Kenya, Morocco, the Netherlands, implementation of improvement plans. In Peru, Russia, South Africa, Tanzania, 2010, PQP organized 22 technical assist- Uganda, Uruguay, the United States and ance missions to pharmaceutical manu- Zimbabwe.) facturers in four countries (Argentina, China, India and Indonesia) and 10 A new collaborative procedure for joint technical assistance missions to national inspections was initiated at the beginning QCLs (in Argentina, Brazil, Burkina Faso, of 2010. A secure web site has been China, Egypt, Jamaica, Panama, Peru established for the sharing of inspection and Yemen). 102 WHO Drug Information Vol. 25, No. 2, 2011 WHO Prequalification of Medicines Programme Training and hands-on practice remain antituberculosis