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WHO Drug Information Vol WHO Drug Information Vol. 31, No. 2, 2017 WHO Drug Information Contents Medicines regulation Regulatory news 153 Regulating medicine manufacturers: 177 Pre-market assessment is an on-site inspection the only Assessment of generics in China; New fast- option? track pathway in India ; Australian orphan drug programme; EU Priority medicines 158 Placebo and drug kits in clinical trial scheme; EU medical devices regulation design 179 Adverse events reporting Pharmacovigilance in Europe; Adverse events of illicit drugs in UK Quality monitoring 180 Supply 162 Survey of the quality of selected GMP for compounded medicines; Reporting antiretroviral medicines circulating in of shortages in Canada; Dispensing five African countries categories in Switzerland 180 Antimicrobial resistance India national action plan; New investments in Safety news Canada; Tripartite alignment on requirements 166 Safety warnings for antibacterials Dulaglutide; Darbepoetin alfa ; Caspofungin 181 Collaboration ; Pneumococcal vaccine ; Pembrolizumab EU and African regulators meet; Report on ; Vemurafenib ; Denosumab; Gadolinium EMA–FDA assessment pilot; Swiss–Austrian contrast agents agreement; MedDRA expands global 168 Restrictions reach; EMA and academia Codeine, tramadol 183 Transparency and databases 168 To be removed from the market Publication of clinical study reports; India Oxymorphone injection builds centralized regulatory 169 New guidelines portal; Ingredients catalogue in Australia Vancomycin ; Opioids 184 Under discussion 170 Known risks Eluxadoline ; Canagliflozin ; Certain hepatitis Approved C medicines ; Bosutinib Severe skin reactions 186 Naldemedine ; Cerliponase alfa ; Nonacog ; Ponatinib; Idelalisib ; Hypnotics and beta pegol ; Dupilumab ; Abaloparatide anxiolytics ; Anaesthetics and sedatives in ; Inotuzumab ozogamicin ; Durvalumab young children; Iodinated contrast media ; Midostaurin ; Ribociclib ; Brigatinib 172 Unchanged recommendations ; Niraparib ; Ocrelizumab ; Sarilumab Selexipag ; Factor VIII-containing medicines ; Avelumab ; Autologous chondrocyte ; Mefloquine ; Docetaxel suspension ; Edaravone ; Valbenazine 173 Reviews started ; Deutetrabenazine ; Triple combination for Direct-acting antivirals; Daclizumab; Fingolim COPD; Cenegermin od ; Valproate 190 Biosimilars 174 Non-compliance with good practices Insulin lispro; Rituximab; Etanercept; Micro Therapeutic Research Labs ; Mylan Infliximab Laboratories; Qinhuangdao Zizhu; FDA 191 Extensions of indications warning letters; TGA reminder on good data Maraviroc ; Sofosbuvir, ledipasvir and management requirements sofosbuvir ; Pembrolizumab ; Regorafenib ; 176 Falsified product alerts Tocilizumab ; Ivacaftor Meningococcal ACWY vaccine in West 192 Early access Africa; Hepatitis C medicine in Germany Glecaprevir/pibrentasvir 192 EU ruling Paracetamol/ibuprofen fixed-dose combination Continued 151 WHO Drug Information Vol. 31, No. 2, 2017 Continued Publications and events Consultation documents 193 Access to medical products 202 The International Pharmacopoeia Fair Pricing Forum; Information guide on 202 Mebendazole tablets biosimilars; WHO to pilot prequalification of 206 Capreomycin sulfate biosimilars; Updated Essential Medicines 210 Capreomycin for injection List ; MPP licence for investigational 214 Transition from microbiological to hepatitis C medicine; Regulatory reforms physicochemical assays in monographs in Mexico; Access to Vaccines Index on capreomycin active pharmaceutical 2017; Reporting of clinical trial results ingredients and products 196 Safety evaluation and monitoring 220 Atenolol Confirmatory clinical studies 224 Capillary electrophoresis lacking; Importance of monitoring new drugs 235 WHO Medicines quality guidelines 196 Medicines supply and use ▪ Good practices for desk assessment New industry alliance to curb antimicrobial ▪ Considerations for requesting analysis of resistance; Antibiotics consumption in eastern medicines samples Europe and central Asia; Off-label use of ▪ Model certificate of analysis medicines in Europe; Combating medication ▪ “SRA” collaborative procedure errors; Toolkit to protect supply chains ▪ Good herbal processing practices 198 Disease updates Poliomyelitis ; Depression ; Neglected tropical diseases ; Malaria ; Hepatitis ; Ebola ATC/DDD classification 200 Upcoming events 236 ATC/DDD classification (temporary) Ireland to host 18th ICDRA; Joint 238 ATC/DDD classification (final) manufacturers meeting WHO news International Nonproprietary 201 Seventieth World Health Assembly; New Names (INN) WHO Director-General elected; Medicines prequalification updates 241 Proposed INN: List 117 Abbreviations and websites CHMP Committee for Medicinal Products for Human Use (EMA) EMA European Medicines Agency (www.ema.europa.eu) EU European Union FDA U.S. Food and Drug Administration (www.fda.gov) Health Canada Federal department responsible for health product regulation in Canada (www.hc-sc.gc.ca) IGDRP International Generic Drug Regulators Programme (https://www.igdrp.com) MHLW Ministry of Health, Labour and Welfare, Japan MHRA Medicines and Healthcare Products Regulatory Agency, United Kingdom (www.mhra.gov.uk) Medsafe New Zealand Medicines and Medical Devices Safety Authority (www.medsafe.govt.nz) PRAC Pharmacovigilance Risk Assessment Committee (EMA) PMDA Pharmaceuticals and Medical Devices Agency, Japan (www.pmda.go.jp/english/index.htm) Swissmedic Swiss Agency for Therapeutic Products (www.swissmedic.ch) TGA Therapeutic Goods Administration, Australia (www.tga.gov.au) U.S. United States of America WHO World Health Organization (www.who.int) WHO EMP WHO Essential medicines and health products (www.who.int/medicines/en/) WHO PQT WHO Prequalification team (https://extranet.who.int/prequal/) Note: The online version of this issue (freely available at www.who.int/medicines/publications/druginformation) has direct clickable hyperlinks to the documents and websites referenced. 152 WHO Drug Information Vol. 31, No. 2, 2017 Medicines regulation Regulating medicine manufacturers: is an on-site inspection the only option? The Australian approach to meeting inspection demands On-site inspections of manufacturing and testing sites for medicines are resource-intensive for both regulators and manufacturers, especially as an increasing number of sites are located outside regulatory authorities’ territories. To maximize the impact of limited resources, it is therefore good regulatory practice to leverage available evidence from other agencies as part of a risk-based inspection planning process. The Australian Department of Health’s Therapeutic Goods Administration (TGA) has been using a risk- and reliance-based approach in inspection planning for some time. This article describes the TGA’s pathways for granting good manufacturing practice (GMP) clearance. Background Pharmaceuticals Inspection Cooperation A cornerstone of effective medicine Scheme (PIC/S).(4) regulation is ensuring that the medicines Where the manufacturer has been available within a market meet appropriate previously inspected and approved by quality standards. To this end, a national the NRA, an onsite assessment may be regulatory authority (NRA) will assess avoided if the manufacturing steps are the product quality data during pre-market same. If the product is approved for supply, assessment. Generally, this involves the NRA monitors the manufacturer’s assessment of quality data provided as compliance with applicable GMP standards part of the application dossier (1) by the via regular inspections, either announced or applicant, and an onsite inspection of the unannounced. product manufacturer against compliance A key objective of a GMP inspections with the applicable Good Manufacturing programme is to provide the NRA with a Practice (GMP) standards, such as those proactive mechanism for identifying and developed by WHO and used in its preventing quality related medicine safety Prequalification Programme (2,3) or those of risks. Once a manufacturer is approved the Pharmaceutical Inspection Convention/ for supplying medicines to the market, re-inspections are usually conducted Authors: Hongxia Jin, Nicola Carr, Harry Rothenfluh Manufacturing Quality Branch, Therapeutic Goods Administration, Australian Department of Health 153 Medicines regulation WHO Drug Information Vol. 31, No. 2, 2017 Australian approach to meeting inspection demands within a risk framework that takes into Challenges associated with inspecting account product and process risks and international manufacturers include manufacturer compliance history.(e.g. 5,6) travel costs and logistics, visa and other The objective should be to conduct more entry requirements, language barriers and frequent inspections of manufacturers with inspector health and security risks. a higher risk profile. In contrast, where a manufacturer has demonstrated a high Demand for inspections outstrips capacity level of voluntary compliance with GMP As the pharmaceutical supply chain standards over time, re-inspections could be becomes more complicated, the demand conducted on a less frequent basis. for GMP inspections can exceed the capacity of an NRA to meet that demand. In particular, with the emergence of contract Challenges in meeting demand for manufacturing, multiple manufacturing sites GMP inspections may be associated with a single product. This Maintaining an effective GMP inspections can be mitigated to some extent by relying programme can be challenging for many on the supplier qualification processes of the reasons, including the following:
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