TRANSDERMAL DELIVERY: INTERVIEW: DESIGNING AN A NEW SOURCE FOR PATRICK ALEXANDRE, CEO, ULTRASOUND-ENABLED P04 BIOPHARMA INNOVATION P18 CROSSJECT P22 INSULIN PATCH TRANSDERMAL DELIVERY, MICRONEEDLES & NEEDLE-FREE INJECTION 49 O TM ISSUE N • 2014 2014 TH MAY 16 MAY Contents ONdrugDelivery Issue No 49, May 16th, 2014 Transdermal Delivery, Microneedles CONTENTS & Needle-Free Injection This edition is one in the ONdrugDelivery series of publications from Frederick Furness Publishing. Each Introduction: Skin in the Game: issue focuses on a specific topic within the field of Transdermal Delivery as a New Source for drug delivery, and is supported by industry leaders BioPharma Innovation in that field. 04 - 06 Dr Kevin Pang, Research Director EDITORIAL CALENDAR 2014/15 Lux Research May: Pulmonary & Nasal Drug Delivery Overview: Transdermal Delivery Device Design May/June: Injectable Drug Delivery: Devices Focus Bruce K Redding, Jr, President & CEO June: Injectable Drug Delivery: 08 - 09 Transdermal Specialties, Inc Pharmaceutics Focus July: Novel Oral Delivery Systems Your Solution for Successful Sep: Drug Formulation & Delivery Solutions Intradermal Delivery & Services Dr Paul Vescovo, Project Manager, Oct: Prefilled Syringes 10 - 14 and Dr Laurent-Dominique Piveteau, Nov: Pulmonary & Nasal Drug Delivery Chief Operating Officer Dec: Delivering Biotherapeutics Debiotech SA Jan: Ophthalmic Drug Delivery Feb: Prefilled Syringes Dermal Delivery of Biologics Dr Richard Toon, SUBSCRIPTIONS: 16 - 17 Technical and Business Development Manager To arrange your FREE subscription (pdf or print) Nemaura Pharma Limited to ONdrugDelivery Magazine: E: [email protected] 18 - 19 Interview: Patrick Alexandre, Crossject SA SPONSORSHIP/ADVERTISING: Contact: Guy Furness, Proprietor & Publisher T: +44 (0) 1273 78 24 24 21 Company Profile: Crossject SA E: [email protected] Designing an Ultrasound-Enabled Patch MAILING ADDRESS: for Insulin Frederick Furness Publishing Ltd 22 - 26 Bruce K Redding, Jr, President & CEO The Candlemakers, West Street, Lewes, Transdermal Specialties, Inc East Sussex, BN7 2NZ, United Kingdom Novel Transdermal Delivery Systems ONdrugDelivery Magazine is published by for Treatment of Diabetes Frederick Furness Publishing Ltd. Registered Office: The Candlemakers, West Street, Lewes, 28 - 30 Dr Alan Smith, Vice-President, East Sussex, BN7 2NZ, United Kingdom. Clinical, Regulatory & Operations Registered in England: No 8348388. 4P Therapeutics VAT Registration No: GB 153 0432 49. ISSN 2049-145X print ISSN 2049-1468 pdf Copyright © 2014 Frederick Furness Publishing Ltd All rights reserved The views and opinions expressed in this issue are those of the authors. Due care has been used in producing this publication, but the publisher makes no claim that it is free of error. Nor does the publisher accept liability for the consequences of any decision or action taken (or not taken) as a result of any information contained in this publication. 2 www.ondrugdelivery.com Copyright © 2014 Frederick Furness Publishing Ltd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ntroduction INTRODUCTION SKIN IN THE GAME: TRANSDERMAL DELIVERY AS A NEW SOURCE FOR BIOPHARMA INNOVATION By Kevin Pang, PhD, MBA Transdermal delivery technologies, despite a new fifth generation of devices and a new great promise, have thus far failed to live source of delivery innovation for biopharma up to their potential as powerful delivery companies and patients (Figure 1). devices for the sustained and controllable Current or fourth-generation platform delivery of active pharmaceutical ingredi- technologies use active or electronic deliv- ents (APIs). Although an almost-30-year-old ery, e.g. Nupathe’s (now Teva) iontopho- platform technology, today only about 16 retic sumatriptan patch. The combination of drugs are actively on market for delivery via active delivery with advanced formulation for enhanced skin penetration constitutes our definition of a fifth-generation platform. “If we assume that only The unique strength of 20% are US FDA- and/or EU EMA- transdermal patch delivery is approved over the next the ability to deliver constant regulated levels of API for the 2-3 years, then we can expect treatment of chronic condi- to see at least 16 new transdermal tions. Treatment of neurologi- patch products come to market” cal diseases and conditions like Parkinson’s disease, depression and pain are extremely well suited to this unique strength, transdermal patches. Hurdles to adoption avoiding the typical peak and trough phe- range from cultural and consumer prefer- nomena experienced with oral solids (Figure ences, to drug abuse problems, to limited 2) as well as first-pass clearance for greater API application due to solubility and pen- sustained bioavailability. An example of this etration issues. is Nupathe’s 2013 US FDA-approved ion- However, we believe that this is about tophoretic sumatriptan delivery patch for to change in a big way. The convergence of migraine, prompting Teva Pharmaceuticals advanced formulation technologies, com- to quickly purchase the company for its bat- bined with printed electronics, will transform tery powered transdermal patch franchise the adhesive transdermal patch platform into and technology platform. Dr Kevin Pang Research Director Poultices Reservoir driven Matrix Active delivery Active Lux Research and plasters patches embedded APIs + Formulation Contact: Carole Jacques Gen 1 Gen 2 Gen 3 Gen 4 Gen 5 Director of Marketing & Client Services T: +1 617 502 5314 E: [email protected] Lux Research, Inc Ciondine, Estradiol,1986Fentanyl, 1986Nicotine, 1990 1991 234 Congress St., 5th Floor Rotigotine, 2007 Scopolamine, 1979 Rivastigmine, 2007Sumatriptan, 2013 Boston, MA 02110 Nitroglycerine, 1981 Methylphenidate, 2006 United States Figure 1: A brief and compressed history of transdermal delivery. www.luxresearchinc.com 4 www.ondrugdelivery.com Copyright © 2014 Frederick Furness Publishing Ltd Introduction Yesterday Today Tomorrow Peak-Through Dosing Zero order Programmable, Electronics enables much more con- constant delivery adaptive delivery stant and dose effective delivery today. Increasing sophistication and application Figure 2: Transitioning into increasingly sophisticated delivery paradigms. of software, algorithms, sensor incorpora- tion, web and analytics, along with increas- than half for nervous disorders, pain man- We predict that combining active electronic ingly effective at-will skin penetration and agement, and behaviour modification such delivery with advanced formulation will pro- delivery, will drive personalised and adap- as drug and smoking cessation (see Figure 3). vide unprecedented innovation by expanding tive drug delivery. One of the major barriers to skin-based the size range of deliverable APIs, and efficacy The promise of thin, flexible, printed delivery is the low permeability of skin of delivery of APIs, greater bioavailability, and circuits and batteries layered on top of that makes it difficult to deliver molecules controlled release that is not just chemical and the transdermal platform is the increasing potential capability to titrate and customise drug delivery, in effect, personalising drug delivery tied to an individual’s metabolism “We predict that combining active electronic and disease state. Further convergence and delivery with advanced formulation will provide application of advanced microfluidics, sen- unprecedented innovation by expanding the size range sors, and web-based analytics will enable the eventual build of powerful biofeedback of deliverable APIs, and effi cacy of delivery of APIs, loops for even more exquisite near real-time greater bioavailability, and controlled release that is modulation. At the same time, innovators not just chemical and thermodynamically derived, but in the sector will push the miniaturisation frontier, resulting in increasing ergonomics electronically enhanced and programmed per individual” and comfort, and lower the development and production cost curves. As a result, we believe transdermal drug greater than 500 Da in size. Figure 4 details thermodynamically derived, but electronically delivery is in the midst of experiencing a a few examples of companies that are work- enhanced and programmed per individual. renaissance in development and application ing on advanced formulation to enhance Fifth-generation transdermal delivery should as part of the armamentarium of intelligently delivery, not just of small molecules, but not only open up more effective and effica- and co-ordinately dealing with multiple med- even biologics of 106 Da or greater in size, cious ways to deliver drugs to patients, but ication management. Advances in micro- and as either biological drugs or vaccines. Many also provide new forms of intellectual property nano-needle technology (e.g. Micropoint); are working on enhanced large molecule extension for biopharma companies. the use of ultrasound (e.g., Transdermal delivery, including biomolecules such as To provide an example of how big Specialties),