Transcript HFA Market - Fluorocarbons

HFC - 227 pharma
and HFC-134 a pharma
Supply of HFA 227 and HFA 134a in MDIs
- Past 1980`s Synthesis of HFA 134a and HFA 227
(134a: DuPont (1993), ICI (1991), Aussimont (1994), Atofina (1993/5), Solvay (formerly Hoechst) 1994
(227ea: Solvay (formerly Hoechst): 1996, pilot plant since 1987, Great Lakes (1993)
1990`s Toxicological Testing of HFAs for MDIs
(IPACT-I for 134a: ADIR (Institut de Recherches Internationales Servier), Aeropharm Technology, Inc.,
ASTA Medica AG, AstraZeneca plc, Aventis Pharma Ltd., Boehringer Ingelheim GmbH, Hoffmann-La Roche
Inc., 3M, Norton Healthcare Ltd, Novartis Pharma, Inc., and TAP Holdings Inc.)
(IPACT-II for 227: ASTA Medica AG, AstraZeneca plc, Aventis Pharma, Ltd., Boehringer Ingelheim GmbH,
Glaxo Wellcome R&D, Hoffmann-La Roche Inc., 3M, Norton Healthcare Ltd., and Schering-Plough Corp.)
1994/5 Safety Assessment of HFAs for Use in MDIs by CPMP
(134a: July 1994 for IPACT-I; Sept 1994 for Glaxo Inhalation Grade)
(227ea: Sept 1995 for IPACT-II)
HFC - 227 pharma
and HFC-134 a pharma
CFC Essential Use Exemptions Approved and
Actually Used (in metric tons) from 1997 to 1999
under the Montreal Protocol
CFC´s approved
6636
CFC´s actually used
or acquired
6000
6592
5463
4660
4000
4429
4168
4363
3665
2255
2000
0
4656
1997
1998
EU:
1999
1997
Source: April 2000 TE DAP Report
2426
1998
USA:
2644
1999
HFC - 227 pharma
and HFC-134 a pharma
Use of HFA 227 and HFA 134a in MDIs
- 134a Present Active
Product
Company
Beclometasone
QVAR ® (USA: 09/00), UK: 09/98)
BECLOJET ® (F: 05/00)
BECLAZONE ® (F, J: 06/2000)
3M
Chiesi
Norton
Salbutamol
AIROMIR ® (1995;Japan 02/97)
3M
VENTOLIN EVOHALER
®
Glaxo
(D: SULTANOL N ® : 1997, UK: 01/98)
Salmeterol
SEREVENT ®, ARIAL®
Fluticasone
FLIXOTIDE ® (D: FLUTIDE
N®: 06/97)
Salmeterol
+ Fluticasone
SERETIDE EVOHALER
®
Glaxo
(UK: 07/00)
Glaxo
Glaxo
HFC - 227 pharma
and HFC-134 a pharma
Use of HFA 227 and HFA 134a in MDIs
- 227 Present Active
Disodium
Cromoglycate
Product
INTAL Aerosol A®
Company
(J: 07/00)
Aventis Pharma Ltd
(Eu 12/98)
(RoW 7/99)
Nedocromil
TILADE®
Disodium
Cromoglycate
+ Reproperol
AARANE® N (Ge 7/99)
Aventis Pharma Ltd
Allergospasmin® N(Ge 10/99)
Asta Medica AG
(Eu 1999, RoW 2000)
Aventis Pharma Ltd
HFA 227 products now launched in >15 countries
HFC - 227 pharma
and HFC-134 a pharma
Use of HFA 227 and HFA 134a in MDIs
- Current 
Propellant chosen by history rather than optimisation
historical experiences and choices made by companies In mid 1990s
price differential and availability of supply
initial performance of delivery systems/valves
IP web preventing free access to early formulations

Product optimisation now available as properties and
understanding has increased
partnerships available for “proven” technologies and capabilities
HFC - 227 pharma
and HFC-134 a pharma
Use of HFA 227 and HFA 134a in MDIs
From Past and Present- into the future
Major technical challenge for entire industry

Redevelopment of valves, mouthpieces and devices
> 10 yrs investment for most companies to reach new formula
Major patent/IP “web” developed by most companies

Major process and equipment development
significant capital and human resource investment
critical skills in developing and industrialising products
competitive barrier to many competitors and high entry price

Expanding use to partnerships with other companies
access to know how, capability, IP and development-supply
HFC - 227 pharma
and HFC-134 a pharma
Use of HFA 227 and HFA 134a in MDIs
- Future Are HFAs going to be phased-out in MDIs ?
 Phase - out of CFCs in MDIs still Priority
Complete replacement by HFA in MDIs/ DPIs, corresponds to
a reduction in greenhouse gas emissions of approx. 75 %;
IPAC data: 73 %
HFC - 227 pharma
and HFC-134 a pharma
Use of HFA 227 and HFA 134a in MDIs
- Future Are HFAs going to be phased-out in MDIs ?
 Phase - out of HFAs in MDIs would result in

Almost no reduction of emissions
(0.05% worldwide/ 0,13 %EU)

Highest cost per t CO2 saved
>100 € to > 500 €/ tonne CO2 equiv., with an average of 7 €/ tonne CO2 equiv.
for 42 Mtonnes of CO2, better 1 - 2 €/ tonne CO2 equiv.; recommendation not
to implement measures > 30 €/ tonne CO2

Longest duration for alternative developments
(8 - 12 years; for new technology: 10 - 20 years)
HFC - 227 pharma
and HFC-134 a pharma
Use of HFA 227 and HFA 134a in MDIs
- Future Are HFAs going to be phased-out in MDIs ?
 MDIs are reliable, cheap, convenient
(EU wide patients primarily rely on MDIs: 85%, DPIs: 15%)
 Certain patient groups depend on MDIs
 Supply issue rather than legislation
(year 2000: CFC MDIs in US: 100%, EU: 75%, HFA pharma grade
supply ensured over long-term period (DuPont, ICI, Solvay)
HFC - 227 pharma
and HFC-134 a pharma
Use of HFA 227 and HFA 134a in MDIs
- Future Are HFAs going to be phased-out in MDIs ?
European Federation of Asthma & Allergy Associations:
„EFA urges the national governments,
while developing policies to meet the Kyoto protocol
obligations not to take measures against medical
uses of HFC MDIs“,
EFA Position Paper on the need for Metered Dose Inhalers (MDIs)
September 17, 2000
HFC - 227 pharma
and HFC-134 a pharma
Use of HFA 227 and HFA 134a in MDIs
- Future -
Use of pMDI/ DPI Technology for the Treatment of:
 Diabetes (e.g. insulin Pfizer/Aventis/ Inhale; EliLilly/ Generex)
 Influenza (e.g. neuraminidase inhibitor, zanamivir, Relenza®; Glaxo)
 Osteoporosis
 Cancers
 Septic Shock
 Viral Diseases etc.
HFC - 227 pharma
and HFC-134 a pharma
HFA supply
Aqueous
Clean In
Place
Mobile
Addition
Vessel
Powder
Eductor
Process optimised for each product
eg INTAL high dose hygroscopic drug
Recirculate
to Filling
Machine
 Fully enclosed process to give
product/operator protection
 Much reduced emissions and cleaning with
aqueous system to improve environmental
impact
In vessel
Homogeniser and Agitator  Lab (1-10kg) – pilot (100kg)-production
scale(1000kg) for solution and suspension
aerosol using “identical” equipment
 Aventis patented formulations and exclusive
Optimised valve for HFA 227
For further details contact Dr Mike Dey
Director, Respiratory Technology, Aventis Pharma
London Road, Holmes Chapel, Cheshire CW4 8BE
Tel +(44) 1477 538113 email [email protected]