HFC - 227 pharma and HFC-134 a pharma Supply of HFA 227 and HFA 134a in MDIs - Past -...

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 RocheInc., 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)


CFC Essential Use Exemptions Approved and Actually Used (in metric tons) from 1997 to 1999 under the Montreal Protocol

EU: USA:Source: April 2000 TE DAP Report

CFC´s approved

CFC´s actually used or acquired6000

4000

2000

0 1997 1997 1998 1999 1998 1999

6636

6592 5463

4660 44294168

4656

2255

4363

2426

3665

2644


Use of HFA 227 and HFA 134a in MDIs - 134a Present -

Active Product Company

Beclometasone QVAR ® (USA: 09/00), UK: 09/98) 3M

BECLOJET ® (F: 05/00) Chiesi

BECLAZONE ® (F, J: 06/2000) Norton

Salbutamol AIROMIR ® (1995;Japan 02/97) 3M

VENTOLIN EVOHALER ® Glaxo(D: SULTANOL N ® : 1997, UK: 01/98)

Salmeterol SEREVENT ®, ARIAL® Glaxo

Fluticasone FLIXOTIDE ® (D: FLUTIDE N®: 06/97) Glaxo

Salmeterol SERETIDE EVOHALER ® (UK: 07/00) Glaxo

+ Fluticasone


Active Company

Disodium Cromoglycate INTAL Aerosol A®

(J: 07/00) Aventis Pharma Ltd (Eu 12/98)

(RoW 7/99)

Nedocromil TILADE® (Eu 1999, RoW 2000) Aventis Pharma Ltd

Disodium AARANE® N (Ge 7/99) Aventis Pharma Ltd Cromoglycate + Reproperol Allergospasmin® N(Ge 10/99) Asta Medica AG

Product

Use of HFA 227 and HFA 134a in MDIs - 227 Present -

HFA 227 products now launched in >15 countries


Propellant chosen by history rather than optimisation historical experiences and choices made by companies In mid 1990s

price differential and availability of supplyinitial performance of delivery systems/valvesIP web preventing free access to early formulations

Product optimisation now available as properties and understanding has increased

partnerships available for “proven” technologies and capabilities

Use of HFA 227 and HFA 134a in MDIs - Current -


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 formulaMajor patent/IP “web” developed by most companies

Major process and equipment developmentsignificant capital and human resource investmentcritical skills in developing and industrialising productscompetitive barrier to many competitors and high entry price

Expanding use to partnerships with other companiesaccess to know how, capability, IP and development-supply


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 %


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)






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)


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




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.



MobileAdditionVessel

AqueousClean InPlace

HFA supply

In vesselHomogeniser and Agitator

Recirculateto FillingMachine

PowderEductor

Process optimised for each product eg INTAL high dose hygroscopic drug Fully enclosed process to give product/operator protection Much reduced emissions and cleaning with aqueous system to improve environmental impact 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 DeyDirector, Respiratory Technology, Aventis PharmaLondon Road, Holmes Chapel, Cheshire CW4 8BE Tel +(44) 1477 538113 email [email protected]

HFC - 227 pharma and HFC-134 a pharma Supply of HFA 227 and HFA 134a in MDIs - Past -...

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