Needle-Free Devices – Latest Developments 11th WHO/UNICEF Consultation with OPV/IPV Manufacturers and National Regulatory Authorities WHO Geneva, Switzerland – October 25, 2012

Darin Zehrung, MBA

Senior Technical Officer Portfolio Leader, Delivery Technologies Vaccine Technologies Group

© PATH/Amynah Janmohamed

Presentation Outline

• FDA Disposable Syringe Jet Injector (DSJI) Update

• FDA Communication on Jet Injectors

• Requirements for Jet Injectors and Vaccine Labeling

• PharmaJet (Stratis) Influenza Vaccine Study

• WHO DSJI Prequalification Update

• Device Developer Updates

• Bioject (ID Pen Injector, Zetajet)

• PharmaJet (Tropis)

• Planned Intradermal DSJI Research

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FDA DSJI Update

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FDA Communication – Jet Injectors

• Requirement for relabeling for “jet injection” - influenza vaccines and other medications / vaccines.

• FDA / DSJI Manufacturers Meeting held January 2012.

• Studies now being pursued to include jet injection in labeling.

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FDA Process – Jet Injectors and Vaccine Labeling • The FDA Center for Biologics Evaluation and Research (CBER) now

requires non-inferiority-based clinical studies to relabel vaccines for DSJI delivery.

• The vaccine manufacturer must submit a Biologics License Application (BLA) amendment to the FDA in order to change the label.

• DSJI devices will continue to be cleared by the Center for Devices and Radiological Health (CDRH) through the 510(k) process.

• The vaccine label may indicate delivery by jet injection as a class of devices, enabling any 510(k)-cleared DSJI to be used, or can identify a specific jet injector.

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PharmaJet Stratis Influenza Vaccine Study

• A Phase 4 randomized controlled clinical trial assessing the immunologic response to an FDA-approved influenza vaccine delivered using an FDA-cleared jet injection vaccine delivery device versus a needle and syringe.

• The study is currently ongoing in Colorado, USA. A total of 1,400 patients will be enrolled.

• Vaccine: AFLURIA

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http://clinicaltrials.gov/ct2/show?term=stratis+influenza&rank=2

WHO DSJI Prequalification Update

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WHO DSJI Prequalification

• Prequalification requirements based upon ISO standard for jet injectors (ISO+).

• Requires device clearance through global recognized NRA.

• PharmaJet Stratis technology first DSJI to complete process.

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Device Developer Updates

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Bioject

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Injection placement & dispersion

Slide 11

12

Bioject Robust Design Paradigm

The Bioject design paradigm is to use robust materials in all critical areas of the device.

The housings of these devices are of metal alloy construction. The disposables are Polycarbonate, a plastic capable of withstanding high injection pressures.

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Biojector® 2000 - Gas Powered Device Bioject® ZetaJet™ - Spring Power

Gas-powered FDA cleared for ID, SC and IM

Used in many human studies in all age groups for ID over last 10 years

Spring-powered FDA

cleared for SC and IM

Currently being used in several human clinical studies for ID application

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The Future for ID Injections

The New

ID PEN™

It is a re-usable Needle-free ID PEN™ !!!! “Investigational use only”

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Bioject Zetajet Device Data

Three treatment, single blind, Phase I study comparing ID (0.1 ml), SC (0.5 ml) and IM (0.5 ml) saline injections using the Zetajet in 60 adults. ID injections formed wheals 100% of the time. A drop of visible moisture without flow was seen at 23% of the ID injection sites. 47% felt no pain when given the ID injection, compared with 34% with the SC and 22% with the IM injection.

Slide 15

Bioject ID Pen Device Data

0.1 ml and 0.05 ml saline injections given intradermally in opposite deltoids of 30 adults. Wetness and wheal size measured quantitatively.

Average wetness:

0.1 ml: 0.010 ml 0.05 ml: 0.007 ml

Average wheal diameter: 0.1 ml: 9.9 mm 0.05 ml: 7.8 mm

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PharmaJet

Slide 17

Click to edit Master title style

Optimizing delivery to the skin: The development

of Tropis ®, a needle-free intradermal delivery

solution

Mantoux (needle and syringe)

PharmaJet

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Confidential

Stage of Device

Development FDA 510k

filing

Preclinical Testing

Adult Evaluations

(USA)

Pediatric Optimization

(India) Clinical Trials

Commercial Transition

2012 2013

Tropis® - Stage of Device Development

Slide 19

Confidential

Pediatric Optimization Study, Pune India

Design:

• Age de-escalation

• 6 age-grouped cohorts

• 30/cohort

• Age range 2-36 months

• 2 injections normal

saline/child in R/L deltoid

(D), or if ≤ 1 y-o, R thigh

(T), L deltoid

Goal: to assess injection

quality, as indicated by:

1) Bleb diameter

2) Residual surface moisture

2-3 year-old subjects D/D

18-24 month-old subjects D/D

12-17 month old subjects D/D

6-11 month old subjects D/T

4-5 month-old subjects D/T

2-3 month-old subjects D/T

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Confidential

Bleb sizes by cohort (age), 60 injections/cohort

ISO standard for expelled volume accuracy (volume ejected from syringe) of doses ≤100µl is +/- 10%.

In this study, Tropis achieved DELIVERED volume accuracy of >90%, 95% of the time.

Published data on Mantoux success rates are 75-85%.

1.2% 1.5% 1.8% 4.7%

90.9%

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

>40% 20% - 39% 10% -19.9%

5% - 9.9% 0% - 4.9%

Cu

mu

lati

ve P

erc

en

t

% Moisture Category

Residual Moisture Data

≥ 90% of vaccine delivered to patient when data falls to the right of the dotted line

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Confidential

Tropis demonstrated large improvement in pediatric

injection performance when compared to v1.0 device

0

2

4

6

8

10

12

14

25-36 18-24 12-17 6-11 4-5 2-3

Ble

b D

iam

ete

r (m

m)

Cohort (months of age)

Comparative device performance across cohorts Means (95% CI for means)

v1.0

Tr

op

is

25 children/cohort x 2

injections/child = 50

injections/cohort and a device

total of 300 injections

30 children/cohort x 2

injections/child = 60

injections/cohort and a device

total of 360 injections

Device

performance

objective: to

create ID

blebs ≥ 5 mm

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Confidential

Step 4: Inject

Step 2: Charge

Step 3: Load

- ID Workflow

Step 1. Fill

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Confidential

Very Efficient Vaccine Usage:

• Tropis has a retained dead space volume of 3µl, a

reduction of 28x over a conventional 3cc syringe and

needle.

BD's Low Waste Space white paper # 0554

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Confidential

Creating Pre-filled Capacity

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Confidential

Planned Clinical Trials - Tropis

Rabies

Domestic: US, ID Rabies Completes rabies efficacy data for PJ technology

International:

1) Leiden University, Netherlands Commercial use in travel clinic

2) IIL/PATH Hyderabad On Label?

Polio

Cuba, WHO, Q4 2012 To support use within global polio eradication program.

China, BMGF, Kunming (KIMB) Q2 2013 Sabin ID IPV, first in preclinical models, followed by clinical trial(s).

BCG

EU-member country, Q4 2012 1,000 infant safety study.

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Planned Intradermal DSJI Research

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Overview of planned intradermal DSJI studies

Vaccine Location When Partners Device(s)

Rabies India 2013 PATH, IPM, IIL ID adapter, PharmaJet Tropis

BCG South Africa Q4 2012

PATH, SATVI, University of Cape Town, GPEI

Bioject ID Pen

IPV Cuba Q1 2013 GPEI PharmaJet Tropis, Bioject ID Pen, Bioject B2000

sIPV China 2013 Kunming, BMGF

TBD

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IPV Cuba Study

• 5 arm comparison study of immune response of full and fractional dose of inactivated poliovirus vaccine (IPV) administered intramuscularly and intradermally using different techniques.

• IM needle and syringe (0.5ml)

• ID needle and syringe (0.1ml)

• Device A: Bioject B2000 (ID, 0.1ml)

• Device B: Bioject ID Pen Injector (ID, 0.1ml)

• Device C: PharmaJet Tropis (ID, 0.1ml)

• Purpose: To demonstrate the non-inferiority of a fractional dose of IPV administered intradermally with needle free devices compared with full doses of IPV.

• The data generated by this clinical trial are intended to facilitate the regulatory approval for use of fractional doses of IPV.

Device A

Device B

Device C

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Darin Zehrung, MBA Portfolio Leader, Vaccine Delivery Technologies PATH dzehrung@path.org Vaccine Technologies Group vaccinetech@path.org

Thank you!

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