RDD Europe 2009 Workshop

Transcription

1 RDD Europe 2009 Workshop 20 May 2009, Lisbon, Portugal This file is a redacted version of the presentation used during the Workshop and is suitable for electronic distribution.

2 An Introduction to Differentiating Characteristics Achieved Through the Use of Active Compared to Passive DPI Drug Delivery Technology This workshop will highlight the differentiating characteristics of active dry powder inhaler (DPI) devices versus traditional passive DPI devices. It will include discussion on the various device design elements of devices as well as the importance of the patient s perspective. The various design elements will be discussed by comparing and contrasting different design approaches as well as through visual methods (e.g. high speed video/research video). In addition, a new DPI device design will be discussed that incorporates several design characteristics we believe have been optimized. 2

3 An Introduction to Differentiating Characteristics Achieved Through the Use of Active Compared to Passive DPI Drug Delivery Technology Workshop Objective: To provide a deepened appreciation around active vs passive DPIs as well as the importance of the patient s perspective in device design. Presenters: Rich Sitz Steve Stein Georgina Fradley Mike Needham 3

4 Agenda DPIs: An Introduction Sub-Systems of a DPI Active vs Passive Patient Perspective Commercialization Support 3M s DPI Offerings 4

5 DPIs: The Beginning A Century and a Half of DPIs First patented DPI (patent granted in 1852) Designed to maximize lung deposition while minimizing deposition in mouth No evidence of commercial success First commercially successful DPI: Fisons Spinhaler Delivered sodium cromolyn Commercialized 1971 Individual doses in capsules 5

6 DPIs: A Variety of Approaches 6

7 What Must Every DPI Do? API Delivery Performance: Measure using industry recognized methods Requirements defined by product definition, clinical performance, regulatory requirements Performance repeatability to insure commercial viability Patient Interaction: Intended and unintended use Ideally intuitive to use Stability: Meet regulatory requirements to a defined specification to enable a commercially viable shelf life 7

8 Sub-Systems Systems of a DPI Formulation: Neat drug Drug/excipient (e.g. lactose) blend Engineering powder Dose Storage and Metering: Reservoir device drug stored in reservoir and metered at time of dosing Capsule device drug stored in capsules metered at factory Blister device drug stored in blisters metered at factory Aerosolization Engine : Passive DPI: Relies solely on the energy of the patient s inhalation to aerosolize the powder. Active DPI: An energy source in addition to that of the patient s inhalation is used to aerosolize the powder. 8

9 Active Methods of Aerosolization Active DPIs transfer stored energy to the formulation to aerosolize the powder Source of Stored Energy: Battery Compressed gas Loaded spring Energy Transfer to Powder: Vibration Impaction Gas discharge Impeller Energy may be stored for the duration of the device s life (e.g. a battery) needs to be stable over that entire duration Stored energy may be created by the patient at time of use by a patient priming step or by cover opening 9

10 Dura Spiros DPI - Active Aerosolization First active DPI device in late-stage development Developed in 1990s Source of energy: battery driven motor Method of energy transfer: impeller 10

11 3M Taper Multidose DPI Neat drug contained in microstructured carrier tape Breathe-triggered spring impacts tape to aerosolize powder Holds up to 120 doses Source of energy: spring compressed by patient opening of mouthpiece cover Method of energy transfer: impaction of tape by metal spring 11

12 High speed video not included. 3M Taper Multidose DPI - Active Aerosolization High speed video: triggering mechanism 12

13 3M Drug Delivery Systems High speed video not included. Replaced with still images. 3M Taper Multidose DPI - Active Aerosolization High speed video: powder aerosolization Transmission Optical Microscope Image of Microstructure Before and After Dosing. 13

14 Nektar Pulmonary Inhaler First commercialized active DPI device Commercialized with Exubera in 2006 Source of energy: compression of piston from separate patient step Method of energy transfer: compressed air 14

15 Exubera - Active Aerosolization Blister pierced prior to delivery Patient compresses air prior to dosing Powder entrained by airflow through blister 15

16 Exubera - Active Aerosolization High speed video: powder aerosolization High speed video not included. 16

17 Other Active DPI Technologies MicroDose DPI Source of energy: battery powered piezoelectric crystal Method of energy transfer: piezoelectric vibration Oriel Therapeutics DPI Source of energy: battery powered piezopolymer Method of energy transfer: piezoelectric vibration WO2004/ Source of energy: propellant-filled canister Method of energy transfer: compressed propellant 17

18 Active Methods of Aerosolization Propellant DPIs 3M Taper DPI Device Dura Spiros DPI Nektar Pulmonary Inhaler Vectura Aspirair MicroDose DPI Oriel Therapeutics DPI Battery Propellant canister Loaded spring via patient opening mouthpiece cover Battery Battery Source of Energy Compressed air via patient priming step Compressed air via patient priming step Method of Energy Transfer to Formulation Impaction via rotating impeller Air impingement Air impingement Air impingement Impaction of API loaded tape Piezoelectric vibration Piezoelectric vibration 18

19 Passive Methods of Aerosolization Methods of Powder Entrainment: Airflow through powder container Venturi airflow Centrifugal discharge of particles from rotating powder container Method of Powder Deagglomeration: Airflow shear (e.g. due to airflow turbulence) Particle-to-surface impaction Particle-to-particle impaction 19

20 Passive Methods of Aerosolization Ordered blend formulations typically used: Micronized in respirable size range (< 5 µm) Large lactose need to entrain powder in airflow Blend often contains fine lactose to improve fine particle fraction (e.g. Zeng et al., IJP, 1998) Challenge associated with deagglomeration: Detachment of micronized drug from carrier is key challenge limiting FPF Detachment has been studied extensively in literature Nichols and Wynn (RDD 2008) demonstrated that torque for detachment is much higher for impaction than for airflow manipulation 20

21 Passive Methods of Aerosolization DPI Device Spinhaler Turbuhaler Clickhaler Diskus/Accuhaler Multihaler Aerolizer Conix Primary Method of Powder Entrainment Centrifugal Airflow through Container Airflow through Container Airflow through Container Venturi Centrifugal Airflow through Container Primary Method of Powder Deagglomeration Shear + Surface Impaction Particle-to-Surface Impaction Shear Shear Shear Shear + Surface Impaction Particle-to-Particle and Particleto-Surface Impaction 21

22 Spinhaler DPI Capsule pierced prior to inhalation Centrifugal release of powder from capsule on rotating impeller Patient airflow drives impeller rotation 22

23 High speed video not included. Spinhaler DPI - Passive Aerosolization High speed video: powder aerosolization 23

24 3M Conix DPI Cyclone-shaped blister pierced prior to inhalation Powder entrained by airflow through cyclone Particle-to-particle and particleto-surface deagglomeration method Selective release of respirable particles 24

25 3M Conix DPI - Passive Aerosolization High speed video: powder aerosolization Reverse vortex laden with respirable drug particles High speed video not included. Replaced with cyclone graphic. Primary vortex with drug & lactose 25

26 The Role of the Patient Product Requirements are met by: Device Formulation Patient Patient The patient s interface with the device is crucial to its success. Device Developer Formulation 26

27 Understanding Customer Needs Wide variety of DPI designs and modes of use Patient research conducted in 2 stages: Had patients keep diary for a week and interviewed in home Tested device design options with patients in 1:1 interviews Research conducted in US, UK and Italy Included all FDA age groups Asthma and COPD patients Respiratory nurses interviewed: Specialists who work in primary care and train other respiratory nurses Pharmaceutical Developer needs identified 27

28 Stage 1: Observing Inhalers in Use Able to gain understanding into frustrations, fit to daily lifestyle and work-arounds Learn how inhalation devices ingrain themselves into the lives of users: Must be discrete Fit in the pocket Easy to use Natural/organic mouthpiece Legible dose counter Not look medical 28

29 Stage 2: Testing Designs with Patients Top need expressed by patients: Size Easy to conceal in hand Transportability Common themes: Feedback the dose has been taken (through audible or visual indication) Intuitive to use Shape/design : like familiar designs, don t want it to look medical Other important features: Discreet: shape and audio cues also important Comfortable ergonomically shaped mouthpiece 29

30 Respiratory Nurses Opinions Top needs: Cost is a top factor, but not the sole factor (esp. for nurses) Easily concealable (and doesn t look like a medical device) = compliance Feedback so the patient (or carer) knows the dose has been taken Other points: Nurses expect to select different devices for different types of patients Make devices intuitive to use Fewer steps can be helpful If designed correctly, capsule devices can be intuitive as well 30

31 Pharmaceutical Developer Perspective Top needs: Efficacy fine particle fraction Consistent dosing Compatibility with range of formulations Important features: Simple to use (number of steps, clarity of numerals ) Robustness Secondary features: Stylish and discrete design Operation independent of orientation 31

32 Commercialization Support Product Requirements: Device Formulation Commercialization Requirements: Analytical Capabilities Tox and Clinical Supply Scale-up Regulatory Expertise Commercial Supply 32

33 3M s s DPI Offerings 3M Conix DPI: Available in disposable, reloadable and multi-dose formats Utilizes reverse-cyclone technology to increase delivery effectiveness Flexibility for a variety of applications 3M Taper Multidose DPI: Simple open, inhale, close mechanism Delivers up to 120 doses in small, pocket sized device Utilizes active aerosolization of neat API 33

34 Thank You! For more information: US: UK: 44 (0) Japan: (81)

35 Image references Slide 5 Slide 6 Slide 10 Slide 14 Slide 17 Spinhaler Direct haler Dura Spiros Spinhaler Exubera Handihaler Clickhaler Novolizer Diskus Turbohaler Twisthaler Microdose Omnihaler Aerolizer Dura Spiros Exubera Microdose 35