1. Metered Dose Inhalers (MDIs)
INDIAN INDUSTRY PERSPECTIVE ON ALTERNATIVES TO HYDROFLUOROCARBONS (HFCs)
FOR
Metered Dose Inhalers (MDIs)
Presentation by
MDI manufacturers in India
INDO-US WORKSHOP
18th February 2011
NEW DELHI

2. CFC MDI’s Tiotropium+ Formoterol Salmeterol + Fluticasone
Tiotropium Bromide
Salbutamol + Ipratropium
Beclomethasone + Formoterol
Fluticasone Propionate
Salmeterol Xinafoate
Levalbuterol + Ipratropium
Levalbuterol
Beclomethasone + Salbutamol
Ipratropium Bromide
Sodium Chromoglycate
Budesonide
Isoprenaline
Beclomethasone
Salbutamol
YEARS
1975
1976
1983
1990
1991
1993
1993
1995
1998
2000
2000
2003
2004
2004
2006
2007

3. HFC MDI’s Beclomethasone + Salbutamol Levalbuterol Autohaler
Ciclesonide+Formoterol
Salbutamol + Ipratropium
Ipratropium Bromide
Salmeterol + Fluticasone Autohaler
Formoterol Fumarate
Levalbuterol + Beclomethasone
Salmeterol Xinafoate
Budesonide + Formoterol
Salmeterol + Fluticasone
Ciclesonide
Formoterol + Fluticasone
Fluticasone Propionate
Tiotropium + Formoterol +
Ciclesonide
Salbutamol Sulphate
Beclomethasone
Troventol
Budesonide
YEARS
1999
1999
1999
2002
2002
2003
2003
2003
2004
2005
2005
2005
2007
2007
2008
2008
2008
2008
2010

5. Achievements in Phase out of CFC
India has transformed majority of CFC MDI’s to HFC in domestic as well as export market.
Also, In addition of transforming old CFC products to HFA, some of the new molecules / combinations / new Breathe Actuated Inhalers were developed & introduced using HFC .
India, being one of the large generic market, has introduced around 25+ products including various strengths in HFC formulations over the period of 15 years.

6. Current status of Alternatives to HFCs as Propellant
Globally HFCs are used as propellants for MDIs.
There are still some concerns in acceptance of HFC based MDIs in some parts of the world.
No technically proven alternatives to HFC for MDIs.
MDIs are used as life saving drugs hence due care has to be taken in selection of suitable HFC alternatives. 6

7. HFC alternatives - Concerns
Pharmacological concerns:
Safety: Toxicological screening: The most important property of a medical propellant is impeccable toxicology. Everything else is secondary.
Reasons :
Significant quantity of propellant gas is taken by the user on a daily basis for many years, often a lifetime.
Gas is taken into an organ which is already weakened by a disease.
An organ in which the gas inhaled is quickly available to the bloodstream.

8. Technical concerns: Compatibility
Compatibility of new alternative with active ingredients and different components of MDI’s.
Compatibility
Filling machines
(Seals ,Pumps)
Surfactant
API
(Timelines 1-3 years)
Device
Valve (Investments & Resources)
Can
Timelines
Investments
Resources
Rubber gasket
Plastic Components

9. Formulation Re-designing
Technical concerns (cond.):
Re-designing of formulation as per the physico-chemical properties of the new alternative.
Formulation Re-designing
Suspension stability
Optimization of devices
Particle Size Engineering
Choice of Surfactant

10. Regulatory concerns: Toxicology Safety & Efficacy
Regulatory approval timelines (3 – 8 years)
IP Strategy

11. Patient concerns: Cost is the key factor Patient – physician interface
Patient acceptability
Change in taste & odour
Cold freon effect
Lack of confidence in new product

12. Way Forward:
We had 5 decades of CFC’s for Medical Aerosols and over a decade of development replacing CFC’s to HFC’s. Therefore Changing to a new HFC alternative raises concerns as any change to the alternative propellants will have a significant impact on product development, timelines and cost.

13. Way Forward:
we therefore need to make a very informed judgment on the introduction of new HFA alternative for Medicinal Aerosols based on commercial viability, development & regulatory challenges expected ahead.
Inspite of that, Pharma industry is definitely open for a dialogue.

14. THANK YOU !