needle-free devices latest developments - who.int · needle-free devices – latest developments...
TRANSCRIPT
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
1/14/2013 Page 2
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.
1/14/2013 Page 4
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.
Page 5
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
Slide 6
http://clinicaltrials.gov/ct2/show?term=stratis+influenza&rank=2
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.
Page 8
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.
Slide 12
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
Slide 13
The Future for ID Injections
The New
ID PEN™
It is a re-usable Needle-free ID PEN™ !!!! “Investigational use only”
Slide 14
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
Slide 16
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
Slide 18
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
Slide 20
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
Slide 21
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
Slide 22
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
Slide 24
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.
Slide 26
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
Slide 28
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
Slide 29
Darin Zehrung, MBA Portfolio Leader, Vaccine Delivery Technologies PATH [email protected] Vaccine Technologies Group [email protected]
Thank you!
Slide 30