5th Annual Transdermal & Intradermal Drug Delivery Systems 2018

Advanced Design, Development & Delivery of Skin-Mediated Therapies and Vaccines

September 6–7, 2018, Racquet Club of Philadelphia, PA

Featured Speakers Include:

PharmaEd Resources, Inc. • 2810 Robeson Park Drive • Champaign, IL 61822tel. 217.721.5774 • web. www.pharmaedresources.com

Bobby SinghCorium

Ajay BangaMercer University

Narasimha Murthy

University of Miss.

Conor O’MahoneyTyndall National

Institute

Audra Stinchcomb

University of Maryland

Lisa Dick3M

With Comprehensive Coverage On:• Product Development and Quality Control Expectations with

Respect to Transdermal and Topical Systems • MeetingUSP<661.2>SpecificationsforTransdermal

Packaging Systems--a Case Study• Dermal Penetration Enhancers – Key Formulation Considerations• ClinicalPKPDAspectsofTransdermalDelivery• Semisolids to Patches to Delivery Technologies: Unique IVPT

Challenges As We Adapt the Franz Cell

• SmartMicrosystemsforTransdermalDelivery&Diagnostics• Latest Advances in Microneedle Drug and Vaccine Delivery• MechanismsofDermalandTransdermalAbsorptionofDrugs• ResolvingRegulatoryComplianceIssuesforTDD&IDD

Systems• RegulatoryandExperimentalConsiderationsforExtractableandLeachableAnalysisofMicroneedlePatches:ACaseStudy

• And much more!

Thegrowinginterestinalternativeroutesofdrugadministrationhasexpertspredictingthatthemarketfortransdermalandintradermaldrugdeliverysystemswillexceed$30billionin2020.TheindustryisonthethresholdofbringingintocommercialproductionanewgenerationoftransformativeTDDandIDDtherapiesanddeliverysystems.Thatiswhyyoucannotaffordtomissthistwo-dayintensiveconference.PharmaEdbringstogetherleadingresearchersinthefieldtosharethemostrecentadvancesinthedesign,formulation,anddeliveryofskin-mediatedtherapiesandvaccines.

With Representation From:

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Transdermal & Intradermal Drug Delivery Systems 2018

Thursday,September6,2018

8:00 Complimentary Breakfast & Chairperson’s Welcome and Opening Remarks

Spotlight on IVPT—Key Challenges and Opportunities

8:30 Semisolids To Patches To Delivery Technologies: Unique IVPT Challenges as we Adapt the Franz CellDr. Ajay Banga, Chair & Professor of Pharmaceutical Sciences, Mercer University

Invitropermeationtesting(IVPT)inFranzdiffusioncellstypicallyinvolvesstudyofdrugtransportintoandacrossskinfromdermatologicalformulations.Experimentalde-signconsiderationsincludetypeofskin(ormembrane),spread ability of formulation, occlusion, and sink con-ditions in receptorchamber, toname justa few.Asweadapt the Franz cells for other uses, additional consid-erations and challenges need to be considered. For ex-ample,rubbingaformulationmaybedifficultandaspraydosage formmay be hard to apply.With a transdermalpatch,exposedvs.totalsurfaceareaneedstobeconsid-eredandthepatchmaynotremoveeasilyfromepidermisforassayofskin.Deliverytechnologiesorinvitromicro-dialyis bring additional unique challenges. When using microneedles, it may be advisable to use dermatomedskin rather than epidermis. Iontophoresis may need a largerinfinitevolumeplacedindonorchamberinsomecases. These and other challenges will be discussed.

9:10 Microstructural Characterization and In Vitro PermeationTestingofTopicalProductsS. Narasimha Murthy Ph.D., Professor of Pharmaceutics and Drug Delivery, University of Mississippi; Scientific Advisor, Topical Products Testing LLC

The topical products that are compositionally similar coulddifferintermsofarrangementofmatterdependingon the process variables. The generic products are gen-erallyrequiredtomatchthereferenceproduct(RLD)withrespect to all the quality attributes to be able to match the performance attributes of the RLD. In Vitro Perme-ation Studies (IVPT) is a great tool for testing the bio-availability/bioequivalence of topical products. In thispresentation, some of the microstructural characteris-tics, casestudiesanddevelopmentofan IVPTprotocolfortestingtopicalproductswillbediscussed.

9:50 MaximizingYourChancesofSuccess in Topical Product DevelopmentDr. Jon Lenn Ph.D., Senior Vice President for US Operations, MedPharm

Topical product development presents a suite of chal-lenges. This presentation will highlight key consider-ations in:

• API design and selection• Importanceofpreformulationandbaseline

understanding• Formulationselection;thedrug,thepatient,thedisease,

& the market• Performancetestingmodelsforformulation

optimization and selection• In vivo models – how relevant are they?

10:30 Networking Coffee Break

10:55 Dermal Penetration Enhancers – Key Formulation ConsiderationsJasmine Musakhanian, Scientific & Marketing Director, Gattefossé USA

The growing interest in percutaneous absorption is a reflection of a growing need for alternative routes ofadministrationtofacilitatedeliveryofchallengingmole-culesthatsufferfrompoororalbioavailability.Assistingthepassageofamoleculetooracrosstheskinhowev-er comeswith its own unique set of challenges, espe-ciallyiftheobjectiveistodeliverthedruginasafeandnon-invasive manner. This presentation explores the role of penetration and permeation enhancing excipients inmodulating thedeliveryofdifferent typesofmolecules.Providing examples and case studies, the presentationhighlights thekey issues; implicationsofdrugsolubili-zationvs.dispersioninthevehicle;selectionofvehicletype(s); and possible synergies between select combina-tions of excipients to drive molecules’ diffusion, parti-tioning,penetration,andpermeation.

Regulatory Spotlight—Meeting USP Guidelines for Transdermal Packaging

11:35 MeetingUSP<661.2>SpecificationsforTransdermal Packaging Systems—a Case StudyDr. Michael Ruberto, Material Needs Consulting; Lars Christensen, Technical Director, Danapak Flexibles A/S

Abstract Coming Soon

12:15 Complimentary Networking Lunch

Spotlight on Microneedle Delivery Systems—The Current State of Clinical Trials

1:25 ClinicalPKPDAspectsofTransdermalDeliveryDr. Bobby Singh, Ph.D., Chief Technology Officer, Corium International

Abstract Coming Soon

2:05 Recent Advancements in Intradermal DeliveryofBiopharmaceuticalsLisa Dick, Ph.D., Lab Manager & Technology Leader, 3M Drug Delivery Systems

Abstract Coming Soon

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Transdermal & Intradermal Drug Delivery Systems 2018

Research Spotlight—Dissolving Microneedles

2:45 DissolvingMicroneedlesfor Pharmaceutical Drug DeliveryDr. Hyungil Jung, Professor, Yonsei University; CEO, Juvic Inc., South Korea

Dissolving microneedles are referred to micro-scaleneedles that are capable of delivering pharmaceuticalcompounds, proteins andother largebiomolecules intothe skin in a minimally invasive manner. These micronee-dles depending on their matrix backbone structure may takefromsecondstohourstodissolve,providingfastorsustained release functionalities. Based on recent re-searches,achievementofahighlyefficientdeliveryhasbecome possible via dissolving microneedles and it is expected that microneedles would replace the widely used hypodermic needles in the near future. Also dis-solving microneedles have various potentials, the ac-tivity of encapsulated compounds can be significantlyreducedduringfabricationprocess.Therefore,wehaveevaluated and optimized dissolving microneedle fabri-cation factors by which activity of encapsulated com-poundsincludinglysozyme,exendin-4,etc.canbehighlymaintainedthroughoutthefabricationprocess.Wehavealsodevelopeddissolvingmicroneedlescapableofde-livering valproic acid that showed a higher efficiencycompared with topical application. Overall, our focusis on developing new methods to overcome the limita-tions of traditional microneedle systems through noveltechnologies.

3:25 Afternoon Networking & Coffee Break

3:50 Skin Vaccination against Ebola Virus Using Microneedle PatchesDr. Yasmine Gomaa, Research Scientist, School of Chemical & Biomolecular Engineering, Georgia Tech

There is arguably no single preventive health interven-tionmore cost-effective than immunization. It currentlyprevents between 2–3 million deaths every year. An ad-ditional1.5milliondeathscouldbeavoided,however,ifglobal preventative vaccination coverage is improved. Of equal importance are outbreaks that require quickandmassivevaccination topreventspreadofdiseases.Recently, an Ebola virus (EBOV) outbreak in Congo hasrequired mass vaccination to contain the disease using a yet-to-be-licensed Ebola vaccine that is given by in-jection like most other recommended vaccinations. This vaccination method is a major setback especially in pan-demic scenarios or in developing countries lacking the requiredinfrastructureandresources,asinCongo.Thisurgestheneedforadvancedtechnologiesthatcaneaselogistics, reduce the cost of vaccinations and improvecoverage.

Microneedle (MN) patches are a novel skin delivery technology forvaccines thathasbeendeveloped in re-centyears.Whenappliedtoskin,theMNspenetratetheskin layers and the vaccine is delivered. This technology offersnumerousadvantagesover the traditionalneedleand syringe used to administer vaccines. Being a small single unit dose that can be administered easily with minimal training can significantly help in controllingoutbreaks. With the proper vaccine formulation in thepatch,theneedforacoldchainofstorageandtranspor-tation can be alleviated which constitute a large sector in the vaccination campaigns costs helping in delivering patches to remote areas.

Georgia Tech, in collaboration with Emory University,hasrecentlyshowedsuccessfulcoatingofEBOVglyco-protein (GP)nanoparticlevaccinesorpurifiedGP (sGP)onto solid metal MN patches that resulted in stronger and longer lasting antibody responses compared to IM injectioninmice.Further,immunogenicityofbothEBOVGPvaccinesonMNpatcheswereeffectivelyaugmentedbyformulatingwiththeMatrix-Madjuvantandresultedin complete protection against lethal EBOV challenge in mice.Withthesefindingsandtheaforementionedadvan-tagesofMNs,MNpatchescouldplayanimportantrolein controlling pandemic Ebola outbreaks.

4:30 End of Day One

Friday,September7,2018

8:00 Complimentary Breakfast

Research Spotlight—Immunotherapies & Smart Microsystems

8:30 Cutaneous Peanut Allergen Immunotherapy using Coated MicroneedlesDr. Harvinder Gill, Associate Prof., Texas Tech University

Peanutallergyisalife-threateningcondition.About1%of theUSpopulation (~3millionpeople) haspeanut al-lergies, and there is no FDA-approved treatment. Strictavoidance, and a peanut-free diet is the only optionavailable to manage peanut allergies. We have recently hypothesized that microneedles (MNs) can be used to de-liverpeanutallergenintotheskinforcutaneouspeanutimmunotherapy.Inthispresentation,invivoefficacydatafrom the use ofMNs coatedwith peanut allergen in amousemodelofpeanutsensitizationwillbeshared.Bal-b/cmicewere first sensitized to peanut allergen. Theywere then treatedwithmultiple doses of peanut aller-gen delivered into their skin using coated MNs. Peanut IgG(totalIgG,IgG1,andIgG2a)andIgElevelsweremea-sured.Efficacyoftreatmentwasevaluatedbychalleng-ing the mice orally with peanut proteins. Anaphylactic score, serummast cell protease 1 (MCPT-1) and serumhistamine levels were quantified after oral challenge.

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Transdermal & Intradermal Drug Delivery Systems 2018

10:55 InVitro-InVivoCorrelation(IVIVC)ofTransdermalNicotine,Fentanyl,Lidocaine,andDiclofenacinHealthyHumanVolunteersAudra Stinchcomb, Ph.D., Chief Scientific Officer and Founder of F6 Pharma Inc.; Professor, University of Maryland

We have determined drug concentrations in healthy human volunteers by pharmacokinetic and skin (tape) strippinganalyses.Thisdatawasthencomparedfor itscorrelationwithcarefully harmonized in vitro skinper-meation tests. The effect of transient heat applicationon the absorption rates in vitro and in humans was also evaluated.TheIVIVCfromthislargeharmonizeddatasetwill be discussed.

11:35 Dermaject® Intradermal Injection Device Enables Reproducible And Standardized Intradermal Injections In Ex Vivo SkinMarkus Clemenz, Managing Director, Verapido

Dermaject® intradermal injection device is a novel, CEmarkedandconvenientdeviceforintradermalinjectionsinto thetoplayerof theskin (intradermal / intracutane-ous route). This best in class device features a newlydeveloped and patented cannula insertion mechanism,mimickingtheMantouxinjectionmethod,combinedwithmicroneedle technology. A special mechanism was de-veloped to protect against needlestick injuries. The de-sign iscompactand intended forsingleuse inhumans.Intradermal injections with dermaject® in ex vivo human skinwerelocatedsuperficiallyandshowedalowvari-anceofthedistancetotheskinsurface,thusdemonstrat-ing reproducibility and standardization for intradermalinjectiondepth.Thereforedermaject®isahighlyrelevantsolutionforallparenteralsubstancesinjectedviathein-tradermal route.

12:15 Complimentary Networking Lunch

Extractables & Leachables Testing for TDDS—What You Need to Know

1:15 ExtractableandLeachableTestingforTransdermal Drug Delivery Systems: HowtoResolveFDADeficiency Situations Related to Those IssuesGyorgy Vas, Ph.D., Trace Organic Analytical Group, Intertek Pharmaceutical Services (Contributing Authors: Louis Fleck, Howard Carpenter.)

Transdermal drug delivery systems are relatively com-plexpharmaceuticalproducts.Theformulationcontainsmultiple excipients and in addition a dermal contact ad-hesive.Theperformanceofthedeliverysystemsdependsonthequalityofthedermaladhesiveandtheformulation,which delivers the drug on a pre-determined rate.

The dermal delivery route is getting more and more popu-lar,sincetheeffectofthedelivereddrugcanbelocalized,

IgE levelswere alsomonitored. Itwas found thatMNstreatment induced significantly higher IgG antibodieswithout any significant increase in IgE levels as com-paredtountreatedmice(naïvemice).Significantlylow-eranaphylactic score,MCPT-1, andhistamine levels inserumwereobservedinMN-treatedmiceafterthemicewere orally challenged with peanut proteins, as com-pared to untreated mice (sensitized but untreated). The data of this study shows thatMN-based cutaneous al-lergenimmunotherapyisabletoofferprotectionagainstoralpeanutchallenge,andoverallitisanexcitingnewtechnologythathaspotentialtotreatfoodallergies.

9:10 SmartMicrosystemsforTransdermal Delivery & DiagnosticsConor O’Mahony, Senior Scientist, Tyndall National Institute

It is striking that expensive and frequently prescribeddrugs are still provided in rather basic delivery devices (i.e. conventional syringes or pen injectors) that incorpo-rate no diagnostic capability and that provide little or no feedbackregardingpatientcompliance.

In response to these limitations,MicroTransdermal In-terface Platforms (MicroTIPs) will merge microneedletechnologieswithwearableand flexibleelectronics toform intelligent, patch-like systems, capable of inde-pendently diagnosing physiological conditions and au-tonomouslydeliveringrelevanttherapeuticdoses,whilesimultaneously relaying information toclinicalsupervi-sors using wireless protocols. As well as microneedle arrays for transdermaldelivery, biopotentialmonitoringand interstitial diagnostics, other ancillary subsystemsfor ultraprecise fluidic control, data analysis, powermanagement,systemvalidation,andwirelessradioman-agementarerequired.Allofthesemustbeintegratedandpackagedinaflexibleandunobtrusiveformfactor.

Thispresentationidentifiesareaswherenewandemerg-ing microneedle technologies and electronics could be used in such platforms, and summarizes recent prog-ress at Tyndall towards various aspects of MicroTIPstechnology.

9:50 Networking Coffee Break

10:15 UpdateonaLong-TermSafety Trial Using a Microneedle SystemPeter Schmidt, Senior Director, Medical Affairs, Zosano Pharma

Zosano Pharma has been conducting a long-term (12 month)safety trialof itsADAMzolmitriptanmicroneedlesystem.Theprimarypurposeofthetrialistoquantifytheskin safety/tolerability of the ADAM system in subjectstreatingat least2migrainespermonth.AsofSeptember2018,wewill have treated over 250 subjects in this tri-al.Wewillpresentanoverviewofskin tolerabilityseento date.

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Transdermal & Intradermal Drug Delivery Systems 2018

and96hours,sampleandcontrolextractswereanalyzedvia LC/MS and GC/MS. Additional nitric acid digestions were analyzed via ICP/MS. Finally, SEM imaging wasperformedonthesamples.

2:25 Afternoon Networking Break

Critical Issues—Latest Advances in Semisolid Topical Formulations

2:40 OldandNewExcipientsforDermalandTransdermal Drug DeliveryNancy S. Marchant Ph.D., Global Technology Manager, Lubrizol LifeSciences

DeliveryofactivestoandthroughtheskinforcosmeticandtherapeuticapplicationshasbeenafocusofLubrizolCorp. forover50years.Carbopol®Polymersareused toformulateawidevarietyofsemisolidapplicationstoin-creasemucosalretention(buccal,vaginal,andophthal-mic),stabilizesuspensionsandemulsions,and improvethesensoryof topicalsemisolid formulations.Recently,LubrizolhasfocusedonourThermoplasticPolyurethane(TPU)polymersthatareusedforbreathablewoundcareand implantablemedicaldeviceapplications foruse intransdermal drug delivery. We have demonstrated the advantagesofTPUvia invitro testing forrapiddeliveryhydrogel filmsaswellascontrolledreleasemixedma-trixdruginadhesivepatches.Examplesofourpolymersanddemonstrationofefficacyindermalandtransdermalformulationwillbepresented.

3:20 Topical Dermatological Generic Drug Products: Advances demonstrating In Vitro Bioequivalence (Beyond the in vivo Clinical Endpoint Bioequivalence Study)Theo Kapanadze D.Sc., Ph.D., Chief Scientific officer, NDI ADRL Inc. dba Diteba

Bioequivalenceassessmentoflocallyactingtopicaldos-ageformsischallenging.Historically, therewerelimit-edoptionsforalternateapproachestoclinicalendpointBE studies. Regulatory agencies recognized the need to findmore sensitive and efficient surrogate approachesto demonstrate BE for topical dermatological products.US FDA Develops science-based regulatory standards that address product complexities and manufacturingissues,reducingthebarrierfornewgenericdrugdevel-opment and provides new valid and reproducible In Vitro approaches for topical generic product equivalence. Inorder tomeet new regulatory requirements, an In VitroRelease Testing (IVRT) methodology as well as Percuta-neousAbsorption,usinghumanskinInVitropermeation(IVPT) model should be appropriately developed and val-idated.HavinganappropriatevalidatedIVRT/IVPTmeth-ods ismandatory for topical products development andFDAapproval.Thispresentation isoutlinesspecificsofdeveloping and validating such In Vitro methodologies.

4:00 Close of Program

which may reduce the systemic side effects. Howeversince the formulation has extended contact time, be-sidesthedugisbeingdeliveredexcipients,degradationproducts and packaging related components can also be “delivered”withthesamerouteofadministration.

The extractable testing of transdermal systems arestraightforward,doesnotrequires“outofbox”thinking.The leachables testing requires more complex approach-es, as the regulatory expectation is to test the finishedproducts with biologically relevant extraction media. Thepresentationwillfocusondifferenttestapproaches,topresentoptionsforleachabletesting,howtoevaluatethe actual leachables and validate analytical methods what are requires non-routine extraction methods and as well detection capability down to ppb level.

The complex formulation combined with the low lev-el testing requirement are very challenging analytical task. Component identification, analytical method de-velopment and validation are not as simple as for thecomponents present at a ppm level or above. The presen-tationwillalsopresentingcasestudiesandsolutionsfornon-conformancesituationsrelatedtoTDSsystems.

1:50 Regulatory and Experimental Considerations forExtractableandLeachableAnalysisofMicroneedle Patches: A Case StudyDr. Xiao Jia, Analyst, EKG Labs

In recentmonths,microneedlepatcheshavebeenmak-ingheadlinesfortheirpotentialfutureasadrugdeliveryplatform.Microneedlepatchescurrently find theirwid-est application as cosmetic delivery devices, and theirdevelopers are not required to seek approval from theFDA.Duetothelackofregulatoryrequirements,thereislittleinformationabouttheextractableprofilesofthesedevices. Assuming these patches gain traction as a drug deliveryplatform, theFDAwillundoubtedly requireex-tractableevaluationofthesedevices.

Extractablesaresubstances inadeviceorproduct,po-tentially impacting its safety or efficacy,which can beforcedoutusingcertainsolventsorstressedconditions.Regulatory bodies often require in-depth analytical in-vestigations into the extractable profile of devices andproductsinordertogetafullprofileofthepotentialhaz-ards associated with a medical product and to ensure patientandconsumersafety.

EKG Labs performed an extractable evaluation on twobrands of commercially available microneedle patchcosmeticdevices.Rodan+Fields’s“RedefineAcuteCareSkincareforExpressionLines”claimstoholdthemselvesto FDA standards while ARTPE’s “Renutrive 3D Microsome Eyepatch” is not sold in the United States but is avail-able to purchase through online retailers. Testing was performed under the general guidance of ISO 10993-12. Patcheswereextractedat37°Cinbothhexane(anonpo-lar solvent) and ethanol (a polar solvent) alongside meth-odcontrols.Afterextractiontimesof24hours,48hours,

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Transdermal & Intradermal Drug Delivery Systems 2018

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Dates: September6–7,2018Venue: TheRacquetClubofPhiladelphiaVenue Address: 215 South 16th Street Philadelphia,PA19102Venue Phone: (215)735-1525

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