WHO Drug Information Vol. 28 No. 1, 2014 WHO Drug Information Contents Regulatory harmonization Strontium ranelate: further restrictions The International Generic Drug due to cardiovascular risks 25 Regulators Pilot 3 Methysergide-containing medicines: new WHO support for medicines regulatory restrictions 25 harmonization in Africa: focus on East African Community 11 Regulatory action and news Regulatory options in the fight against Technologies, standards and norms antimicrobial resistance 26 Standards for biological products 16 EMA and FDA collaborate on bioequivalence inspections 26 Safety and efficacy issues Tafenoquine receives FDA Breakthrough Combined hormonal contraceptives and Therapy designation 27 venous thromboembolism 21 Regulatory action against Ranbaxy’s Clobazam: serious skin reactions 21 Toansa facility 27 Amiodarone: pulmonary toxicity 21 WHO response to FDA findings at Methylphenidate: rare risk of long-lasting Ranbaxy’s Toansa site 27 erections in males 22 New partnership to strengthen regulatory Glibenclamide: risk of hypoglycaemia in systems 27 elderly and renal-impaired patients 22 Canada-US Common Electronic Subcutaneous epoetin alfa: Submissions Gateway 28 contraindicated in Singapore in chronic Updated guidance for annual strain kidney disease patients 22 change of seasonal influenza vaccines 28 Acipimox: only to be used as additional or EMA and FDA strengthen collaboration on alternative treatment 22 pharmacovigilance 28 Estradiol-containing creams: new European Medicines Agency publishes restrictions 23 first summary of a risk-management Clopidogrel: rare reports of acquired plan for a medicine 29 haemophilia 23 EMA and FDA extend parallel assessment Sodium phosphate products in high pilot 29 doses: severe dehydration 23 Australia and New Zealand harmonization Emergency contraceptives – high activities 29 bodyweight may reduce effectiveness 24 ► Approvals Testosterone: possible risk of stroke and First adjuvanted vaccine for H5N1 avian heart attack 24 influenza approved 29 Lithium: hypercalcaemia and Umeclidinium and vilanterol approved for hyperparathyroidism 24 chronic obstructive pulmonary disease 30 Saxagliptin: possible risk of heart failure 25 Dapaglifozin approved for type 2 diabetes 30 Continued 1 WHO Drug Information Vol. 28 No. 1, 2014 Continued Trametinib and dabrafenib approved in Atazanavir capsules 38 combination for advanced melanoma 30 Implementation of the revised general Droxidopa approved for neurogenic monograph on parenteral preparations orthostatic hypotension 31 in The International Pharmacopoeia: Bedaquiline recommended for approval to Limits for the test for bacterial treat multidrug-resistant tuberculosis 31 endotoxins (3.4) 41 Metreleptin approved to treat rare Revision of general monograph: metabolic disease 31 Suppositories 45 Revision of method of analysis: Recent publications, information 5.3 Disintegration test for tablets and and events capsules 50 World malaria report: financing needed to Revision of method of analysis: sustain major progress 32 5.4 Disintegration test for suppositories WHO Prequalification: A quiet revolution and rectal capsules 54 in global public health 32 RADIOPHARMACEUTICALS: 56 AIDS drugs for all: how global advocacy Sodium iodide (131I) solution 56 transformed pharmaceutical markets 33 Technetium (99mTc) exametazime complex Who are the originators of innovative injection 59 medicines in the EU? 33 Thallous (201Tl) chloride injection 63 Medicines Patent Pool and Bristol-Myers Squibb sign agreement 33 ATC/DDD Classification Report calls for cooperation to strengthen ATC/DDD Classification (Temporary) 66 post-market surveillance systems 34 ATC/DDD Classification (Final) 69 ► Events Annual ATC/DDD Methodology course 34 International Nonproprietary Names Recommended List No. 71 71 Consultation documents ► The International Pharmacopoeia Atazanavir sulfate 35 WHO Drug Information is available electronically at http://www.who.int/medicines/publications/druginformation/en/ International Conference of Drug Regulatory Authorities (ICDRA) The 16th ICDRA will be hosted by the Brazilian National Health surveillance Agency (ANVISA) Rio de Janeiro, Brazil 24 - 29 August 2014 http://www.icdra.com.br/ 2 WHO Drug Information Vol. 28 No. 1, 2014 Regulatory harmonization The International Generic Drug Regulators Pilot The pre-market review of generic medicines puts mounting pressures on health regulatory authorities around the world due to increasing workloads and risks associated with complex global supply chains. This has led a group of regulators to launch the International Generic Drug Regulators Pilot (IGDRP), aimed at regulatory convergence and cooperation. The three-year pilot entails a series of concrete measures to facilitate the timely authorization and availability of safe, effective and quality generic medicines. Results of the pilot will inform decisions on establishing a more permanent information and work-sharing arrangement as part of broader international efforts related to regulation of medicines. The success of the initiative will require the support of industry as well as other stakeholders interested in promoting access to affordable, quality generic medicines. Introduction regions become aligned over time as the The availability of quality generic drugs, same harmonized technical guidance also known as multi-source medicines or documents, standards and scientific pharmaceuticals, plays an increasingly principles are adopted and similar important role in helping to address rising regulatory practices and procedures are health care costs and in promoting access introduced. Regulatory convergence in turn to essential medicines worldwide. This, makes possible additional, enhanced forms however, has led to significant pressures of cooperation and collaboration between on medicines regulatory authorities (RAs) regulatory authorities. charged with the review and approval of these products. In addition to an increased Exploratory meeting workload associated with the growing In an effort to address the challenges number of generic drug applications, associated with the increasingly RAs must now also contend with more demanding review of generic drug sophisticated generic drug products and applications, regulatory authorities from complex global production and distribution Australia, Brazil, Canada, the European chains. Union, the Republic of Korea, Singapore, Given these challenges, the need for Switzerland and the United States as well regulatory cooperation and convergence as the World Health Organization (WHO) has long been recognized. “Regulatory met in Ottawa in October 2011 to explore convergence” represents a process opportunities for collaboration. A number whereby the regulatory requirements of positive developments and precedents and approaches across countries and were identified that favour a collaborative drug review model, including: Article by Mike Ward, Manager, International • a common set of quality requirements Programs, Therapeutic Products Directorate, and application format provided by ICH Health Products and Food Branch, Health Canada. 3 Regulatory harmonization WHO Drug Information Vol. 28 No. 1, 2014 Quality guidelines (1) and the Common Findings from the surveys and views Technical Document (CTD); expressed in the exploratory meeting • the increasing number of multi-national confirmed strong support in principle for generic companies, including the regulatory collaboration in the pre-market generic arm of innovator companies, review of generic drugs, although the with a potential for common products, degree of support was conditional for some ingredients and manufacturing sites RAs on the scope and form of collaborative across markets; model chosen. In general, there was • the success of existing collaborative also agreement on the main advantages, models, including the WHO’s challenges and enablers to international Prequalification Programme as well as collaboration (Table 1). Although important the EU’s Centralised and Decentralised challenges were identified, they were not Procedures (and the EU’s Mutual felt to be insurmountable. Recognition Procedure, wherein a marketing authorization has already The path forward been granted by an EU Member State); Recommendations from the exploratory and meeting helped to shape the path • the restricted set of scientific disciplines forward. Key among these was the need involved in generic drug reviews, to be pragmatic and to adopt a step-wise compared with reviews of first market approach, starting with selected areas entry drugs (“new drugs”). of collaboration, a mapping of regulatory programmes and information-sharing Preliminary surveys between authorities. The meeting in Ottawa was preceded It was also recognized that many of the by surveys, commissioned by Health prerequisites for collaborative generic Canada, with a number of multi-national drug review – such as secure electronic generic drug manufacturers and with the platforms for sharing of documents, participating RAs. Regulatory frameworks, and mechanisms to treat and exchange data exclusivity, patent rules, submission confidential business information – management and other pertinent issues also apply to other areas of potential were also compared to help inform cooperation. Finding solutions to these discussions. issues, together with the building of greater RAs were asked about the potential knowledge and trust between regulatory advantages and disadvantages of a authorities, will facilitate additional areas of