The Drug Development FDA’s Perspective January 2012 Volume 36 PLUS: and Analytical Toolbox on Starting Materials Number 1 The Authority on Drug Development & Manufacturing PharmTech.com Antibody–Drug Conjugates Looking ahead to an emerging class of biotherapeutic PEER-REVIEWED Assessing Tablet-Sticking Propensity Contract Services in 2012 Jim Miller’s Outsourcing Outlook: Choose Choice. Sustained-Release Immediate-Release Taste Masking Lyophilization Aseptic Filling Multi-Therapy Solubilization No other partner gives you more formulation options – royalty free. Get access to the industry’s widest range of complex formulation technologies for small molecules and biologics, and benefit from expertise forged over thousands of projects. At Patheon, we’re not tied to any technology. That means science alone drives the development of an optimal formulation, and you’ll never pay us a royalty. Our commitment is to your success. Choose choice – choose Patheon. Call +1 866-PATHEON (+1 866-728-4366) or email [email protected] US Headquarters European Headquarters Patheon Inc. Patheon UK Ltd. 4721 Emperor Blvd, Suite 200 Kingfisher Drive Durham, NC 27703-8580 Covingham, Swindon USA Wiltshire SN3 5BZ P: +1 919 226 3200 UK F: +1 919 474 2269 P: +44 1793 524411 www.patheon.com F: +44 1793 487053 www.patheon.com Published 9/11 PATH0214R0 Editorial Director Angie Drakulich [email protected] Executive Editor Patricia Van Arnum [email protected] LAB BLENDERS Managing Editor Susan Haigney [email protected] Editor (Europe) Rich Whitworth [email protected]; Scientific Editor Amy Ritter [email protected]; MAXIBLEND® LAB BLENDER Associate Editors Erik Greb [email protected], Stephanie Sutton [email protected], and Christopher Allen [email protected] 0.5, 1, 2, 4, 8 and 16 qt. 316L SS Art Director Dan Ward Washington Editor Jill Wechsler [email protected] interchangeable V-Shells, Double- Contributing Editors Jim Miller [email protected]; Hallie Forcinio [email protected]; Cones & Bins. Large & Small Bottle Susan J. Schniepp [email protected]; Lynn D. Torbeck [email protected]; Blending attachments. High speed and Eric Langer [email protected] JOUFOTJëFS
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'&"563&4 Professor, Department of Senior Director, Gurvinder Singh Rekhi, PhD Pharmaceutics, Pharmaceutical Sciences, Director, 1, 2, 3, 5 and 10 cu. ft. 316L University of Maryland Pfizer Global R&D Research and Development, Elan Drug Delivery Inc. SS, interchangeable V-Shells David H. Bergstrom, PhD Mansoor A. Khan, PhD COO, NovaDel Pharma Inc. Director, FDA/CDER/DPQR Susan J. Schniepp or Bins. All stainless steel Pharmaceutical Consultant, Rory Budihandojo Russell E. Madsen construction. Pharmaceutical Schniepp & Associates, LLC Director, Quality Systems Audit, President, The Williamsburg finish. On-caster design. PLC Boehringer-Ingelheim Shanghai Group, LLC David R. Schoneker controls. Low maintenance. Pharmaceuticals Co. (China) Heidi M. Mansour, PhD DAfirfeacirtso,r C oofl oGrlcoobnal Regulatory Todd L. Cecil Assistant Professor, Vice-President College of Pharmacy, Eric B. Sheinin, PhD 015*0/"-
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• Equipment & Processing Report, send content and ideas to [email protected] • Send product releases to [email protected] 4 Pharmaceutical Technology JANUARY 2012 PharmTech.com For more than 30 years, VAI has pioneered the design and manufacture of hundreds of clean room solutions. • Cleanest wipe • Saturated wipes in the industry are made with WFI • Asepti-Fill® closed • Lot Specifi c fi lling system Documention • Laundered in Class 1 for all wipers • Laser cut sealed edges Quadruple Bagged using the ABCD Introduction System® No other company off ers this broad a range of wipers… STERI-PEROX® HYPO-CHLOR® DECON-Clean® ALCOH-Wipe® STEEL-BRIGHT® DAS-Wipe® WIPE Wipe Wipe Wipe Dry cleaning wipe 70% USP IPA Saturated Saturated Sodium Removes residue Saturated with Stainless Steel Stainless Steel in Water for Hydrogen Hypochlorite Wipe from disinfecting DECON-AHOL® Cleaning wipe cleaning and Injection Peroxide Wipe agents WFI 70% USP lubricant wipe saturated wipe Isopropyl Alcohol www.sterile.com 1-888-4-STERILE PureWeld®XL tubing The performance weldable SALES OFFICE fluid path that lowers your risk Publisher Michael Tracey [email protected] Director of Sales Paul Milazzo Engineered by the [email protected] Eastern Sales Manager Suzanne Fillweber world leader in [email protected] biopharm peristaltic Mid-West Sales Manager Irene Onesto pumps, this weldable [email protected] Display, Web, Classified, and Recruitment Representative Tod McCloskey tubing eliminates [email protected], connectors, pumps Executive Assistant Barbara Sefchick longer than other [email protected] TPE tubing without 485 Route One South, Building F, First Floor, Iselin, NJ 08830, USA Tel. 732.596.0276, Fax 732.647.1235, PharmTech.com shedding and has the Sr. Production Manager Karen Lenzen, International Licensing Maureen ADCF purity to deliver Cannon [email protected], tel. 440.891.2742 or toll-free 800.225.4569 total process security. ext 2742, fax. 440-891-2650, Circulation Manager Anne Brugman Contact us for a free sample BioPharmaceutical Division wmtubing.com President, CEO Joseph Loggia, Executive Vice-President, Finance & CFO Ted Alpert, PureWeld Pumpsil Bioprene 800-282-8823 Executive Vice-President of Corporate Development Eric I. 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Outside the U.S. call 218.740.6477. 6 Pharmaceutical Technology JANUARY 2012 PharmTech.com Parenteral Drug Association Training and Research Institute (PDA TRI) Upcoming Laboratory and Classroom Training for Pharmaceutical and Biopharmaceutical Professionals March 2012 Lyophilization Week April 12-15, 2012 | Bethesda, Maryland | www.pda.org/lyoweek • Fundamentals of Lyophilization | March 12-13 • Validation of Lyophilization | March 14-15 April 2012 An Introduction to Visual Inspection – Session 2 April 3-4, 2012 | Bethesda, Maryland | www.pda.org/visualsession2 The 2012 PDA Annual Meeting Course Series April 19-20, 2012 | Phoenix, Arizona | www.pdaannualmeeting.org/courses • Reprocessing of Biopharmaceutical Products – New Course | April 19 • Recommended Practices for Manual Aseptic Processes – New Course | April 19 • Biotechnology: Overview of Principles, Tools, Processes and Products | April 19-20 • Sterile Pharmaceutical Dosage Forms | April 19-20 • Implementation of Quality Risk Management for Commercial Pharmaceutical and Biotech Manufacturing Operations – New Course | April 19-20 • Process Validation and Verifi cation: A Lifecycle Approach – New Course | April 19-20 • Process Simulation Testing for Aseptically Filled Products – New Course | April 20 • Investigating Microbial Data Deviations – New Course | April 20 May 2012 Environmental Mycology Identifi cation Workshop May 2-4, 2012 | Bethesda, Maryland | www.pda.org/mycology2012 2012 Aseptic Processing Training Program Bethesda, Maryland | www.pda.org/2012aseptic • Session 1: January 9-13 and February 6-10, 2012 – SOLD OUT • Session 2: March 5-9 and March 26-30, 2012 – SOLD OUT • Session 3: May 14-18 and June 4-8, 2012 • Session 4: August 20-24 and September 10-14, 2012 • Session 5: October 15-19 and November 5-9, 2012 Laboratory Courses The PDA Training and Research Institute is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. For more information on these and other upcoming PDA TRI courses please visit www.pda.org/courses January 2012 Volume 36 Number 1 ➲ On PharmTech.com Issue extras ➲ Find additional interviews from this month’s technical forum on multilayer tablet technology Pharmaceutical Technology is the authoritative source of peer-reviewed research and on PharmTech.com/multilayer. expert analyses for scientists, engineers, and managers engaged in process devel- Reader comment opment, manufacturing, formulation and drug delivery, API synthesis, analytical “Scientific facts should play a leading technology and testing, packaging, IT, outsourcing, and regulatory compliance in the role, but not an exclusive role, in de- pharmaceutical and biotechnology industries. termining what drugs are available to whom,” in response to a blog post on Cover Story: “Is HHS Using Scientific Standards?” Read more conversations on our blog Antibody–Drug Conjugates r at blog.PharmTech.com e 42 Looking Ahead to v Free eNewsletters o an Emerging Class of c Visit PharmTech.com/enews for: Biotherapeutic • ePT : Weekly eNewsletter keeps e by Amy Ritter you current with industry news h t A successful antibody–drug conjugate requires and business notes. n careful selection of the drug, antibody, and linker. • Sourcing and Management: O Compositing by Dan Ward. A monthly eNewsletter to help Images: Nick Koudis/Ingram Publishing/Getty Images you maintain a healthy supply chain. The January issue pro- Features vides an API market outlook. • Equipment & Processing Technical Forum Fda PersPecTives Report: Monthly reports on 48 Multilayer- 63 Designation of cutting-edge techniques and technologies. The January edi- Tablet Technology Regulatory Starting tion focuses on isolated robots. Materials in the Manufacturing Most popular articles Moderated by Rich Whitworth and Stephanie Sutton of Drug Substances: • FDA–EMA Joint Manufacturing Industry experts discuss formulation Impact on ANDA Review Time Inspections to Begin in 2012 and technical challenges in multilayer • FDA Warns Novartis of Violations Barbara Scott, FDA tablet manufacture. at Three Plants The author describes how provid- • Views from Pharma Leaders: ing appropriate information about A Year in Review and a Look Forward Pharma ingredienTs the API in the Common Technical 52 Document can aid FDA’s review of an Broadening the abbreviated new drug application. Drug Development and Departments/Products Analytical Toolbox Peer-reviewed research 18 In the Field Patricia Van Arnum 26 In the Spotlight A look at recent advances in FormulaTion develoPmenT accelerating reaction discovery, 57 Assessing Tablet- 81 Pharma Capsules inducing chirality and stereochemical 71 analysis, and nanotech applications Sticking Propensity Company Product for protein elucidation. Matthew P. Mullarney, and Service Profiles Plus: Formulation Development Forum. Bruce C. MacDonald, and Allan Hutchins 82 Industry Pipeline The authors designed an upper 86 Showcase/Markeplace punch with a removable punch tip to determine a tablet formulation’s pro- 90 Ad Index pensity to stick by weighing the mass of powder adhered to the punch tip. Continued on page 10 pharmtech.com Full Service Contract Manufacturing …Multiple Dosage Forms jublHS.com 800.655.5329 …Clinical to Commercial …Regulatory Excellence h s i n i F / l l i F e l b a t c e Bologna in his hair nj I e is hilarious to Beck. Nearly il r e as funny as when his dad St chases him around the • s house or his sister tickles c i t O his tummy. & s c Beck can laugh at bologna i m in his hair and silly times al h with his family because his ht p pediatrician gave him an O e injection that cleared up that il r e nasty virus. t S • Beck doesn’t think about s d i that medicine or how it u q i helped him get back to being L & happy and healthy, but we do. s l a c i Beck is the son of a JHS employee p o T e l i r e t Scan the barcode or visit jublHS.com to S review a video about our organization n- o N • e g a s o D d i l Helping people is what you do best. Let Jubilant HollisterStier take care of the details getting there. o S Spokane, WA, USA • Montreal, Quebec, Canada • Roorkee, Uttarakhand, India • Salisbury, Maryland, USA Continued from page 8 Columns From The ediTor washingTon rePorT inside usP 12 28 67 Here’s to a Budget Crunch, Politics global Harmonization year of Compromise Shape Policy Agenda opportunities and Challenges Angie Drakulich Jill Wechsler Anthony DeStefano and Kevin Moore The benefits of harmonization Pressure to approve new user fees To keep moving forward, the may be on the industry’s wish list, but opens the door to action on drug Pharmacopoeial Discussion Group buying into change is another story. shortages, prices, and regulation. needs industry participation. ouTsourcing ouTlook PharmTech Talk bio Forum 68 14 36 Contract Services for 2012 Cutting Prices Venture-Capital to Save Sales Funding Falls Jim Miller Erik greb Tracey T. Lefteroff Recent private-equity buyouts Challenges remain, particularly for of CROs show the up- and Copay coupons may help patients early-stage biopharm companies. down-side for investors. and drugmakers, but who ends up holding the bag? viewPoinT Packaging Forum 88 agenT-in-Place 38 Innovations for 2012 Innovator Liability Still Not 16 Viable after Pliva v. Mensing All Systems Slow Hallie Forcinio Control, a Senior Compliance officer Packaging innovations boost Zach Hughes productivity, meet regulatory Technology may expedite requirements, and protect products. Recent legal decisions have operations, but the absence of the further divided generic and human element could cost dearly. brand manufacturer cases. 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