1. HFCs in Aerosols Workshop on HFC Management: Technical Issues Side Event Bangkok, 21 st April 2015

2. Dr Helen Tope Principal Consultant, Energy International Australia and Co-Chair Medical Technical Options Committee Disclaimer: The views presented here are those of the presenter alone and do not necessarily represent the views of TEAP or its TOCs.

3. Aerosol products and propellants Aerosols are used in a wide range of different applications. “Aerosol product” describes a product pressurized with a propellant that expels its contents from a canister through a nozzle. Propellants include: – Compressed gases – nitrogen, nitrous oxide, carbon dioxide – Liquefied gases – CFCs, HCFCs, HFCs (134a, 152a), HFO- 1234ze, hydrocarbons, dimethyl ether (DME) Some aerosols also contain solvents, including: – CFCs, HCFCs, HFCs (43-10mee, 365mfc, 245fa), hydrocarbons, hydrofluoroethers, esters, ethers, alcohols, ketones, low-GWP fluorinated compounds

4. “Not-in-kind” technologies There are competing products based on “not- in-kind” (NIK) technologies including trigger sprays, finger pumps, squeeze bottles, roll-on liquid products (e.g. for deodorants) and non- sprayed products (e.g. for polishes and lubricating oil). Aerosols are often preferred for ease of use.

5. Aerosols sector Aerosols can be divided into three main product categories: – Consumer aerosols including cleaning products, tyre inflators, personal care products, spray paints, novelty aerosols, food products, safety horns – Technical aerosols including lubricant sprays, dusters, contact cleaners, pesticides, degreasers, mold release agents – Medical aerosols including MDIs. There are also aerosols that deliver treatment for other medical purposes e.g., nasal and topical aerosol sprays. These “other medical aerosols” are used to deliver topical medication mostly onto the skin, but also to the nose, mouth, and other body cavities.

6. ODS use and phase-out Historically, aerosols sector was the major source of ODS emissions (75% of all emissions) – Completely emissive technology CFCs used in aerosols as propellants and solvents have been gradually phased out – mainly migrating to non-fluorocarbon alternatives. Small quantities of CFCs and HCFCs are reportedly still used – e.g. for medical aerosol products such as topical anaesthetic sprays and coolants to numb pain. HCFC use is estimated as about 100 ODP tonnes or less worldwide (HCFCs 22 and 141b) for medical aerosols, with the majority used in China. Possibly another 100 ODP tonnes (HCFCs 22, 141b, 225ca/cb) for consumer and technical aerosols?

7. Changes to propellants in aerosols Significant proportion propellants migrated to hydrocarbons and DME – Lower cost than HFCs – Dominate in the consumer aerosol market – Used in technical aerosols where flammable propellants are safe to use Smaller proportion migrated to HFC propellants where VOCs are of concern (HFCs 134a, 152a) or a non-flammable and/or safe to inhale propellant is necessary (HFC 134a). MDIs migrated to HFC propellants, with extensive R&D, toxicity and clinical testing.

8. Changes to solvents in aerosols CFC and HCFC solvents migrated to hydrocarbons, HFCs 43-10mee, 365mfc, 245fa, HFEs, HCs, chlorinated solvents, oxygenated organic compounds, NIK, low-GWP fluorinated compounds, e.g. -1233zd(E)

9. Global HFC consumption for aerosols In 2010, GWP-weighted HFC consumption for all aerosol products was ~54 million tonnes CO 2 -equivalent (~5% of GWP-weighted total for global HFC consumption). Medical aerosols, mainly MDIs, use ~10,000 metric tonnes, mainly HFCs 134a, and also 227ea (< 15 million tonnes CO 2 -equivalent). US aerosol industry considers HFC use in aerosols to be flat or declining.

10. HFC Aerosol Propellants PropellantGWPFlammabilityTypes of aerosol product HFC-134a1430Non-flammableTechnical and consumer aerosols MDIs and some other medical aerosols HFC-227ea3220Non-flammableMDIs HFC-152a124Moderately flammable Technical and consumer aerosols that can use a moderately flammable propellant

11. HFC Aerosol Propellants (2) HFC propellants are used in aerosols where emissions of VOCs are regulated, or a non-flammable or non-toxic propellant is required – HFC-134a fits all of these criteria, and is the dominant HFC propellant used in medical aerosols and probably also technical aerosols In non-medical applications, HFC-152a is used: – Lower GWP than HFC-134a – Lower flammability than HC or DME – Can be blended with HFC-134a, HCs or DME – Can be used where emissions of VOCs (HCs and DME) are regulated – Probably the dominant HFC propellant used in consumer aerosols – Not approved as safe for medical uses where inhalation possible A small proportion (5%) of MDIs use HFC-227ea. It is not used in non-medical applications due to cost and high GWP

12. Alternatives to HFC propellants Propellants and Alternatives GWPFlammabilityTypes of aerosols Hydrocarbon blends (propane, n-butane, iso- butane) 3HighAerosols that can use a highly flammable propellant Dimethyl ether (DME)1HighAerosols that can use a highly flammable propellant; convenient to use with water-based formulations HFO-1234ze7LowAerosols requiring a very low flammability propellant Compressed gases - CO 2 - N 2 - Air - N 2 O 1 0 298 Non-flammable } Some technical and consumer } aerosols } Some food products (e.g. cream) Not-in-kind -Pump sprays -Liquids -Roll-on liquids/sticks -Powders 0Non-flammable where liquid dispensed is non- flammable e.g. cleaners, nasal sprays e.g. lubricating oils e.g. deodorants e.g. dry powder inhalers

13. Safety, practicability, cost, and commercial availability Where flammability not a consideration, HCs and DME are used as low cost option. Where flammability of concern, non-flammable or very low flammability options are used. Other considerations that determine choice include pressure, ease of use, VOC controls, formulation characteristics. In many cases, HFC propellants can be substituted with non-HFC options. HCs and DME are lower cost propellants than HFCs. HFO-1234ze is more expensive than HFC-134a but often used in high value or discretionary products, where HFO may not add significantly to cost. All of the low GWP propellants are commercially and widely available. NIK alternatives are commercially available where suited for purpose.

14. Training for flammable propellants Training of factory personnel in the safe handling of flammable propellants or solvents is required for aerosol filling factories. Consumer information is needed to ensure safe use.

15. Medical aerosols (excluding MDIs) Medical aerosols (excluding MDIs) represent slightly more than 1% of all aerosol products, with approximately 250- 300 million cans per year. Medical aerosols (excluding MDIs) cover a wide range of uses from numbing of pain, nasal inhalation, to the dosage of corticosteroids for the treatment of colitis. Less than ~10% of medical aerosols (excluding MDIs) use HFC propellants (< 1,000 tonnes per year). Majority are used for nasal inhalation, throat topical medication, and nitroglycerin sublingual application. Suitable alternatives include N 2 or “not-in-kind” metered pump sprays. Registration of new HFC-free formulations would be costly and requires time.

16. HFCs in Aerosols: Metered dose Inhalers Workshop on HFC Management: Technical Issues Side Event Bangkok, 21 st April 2015

17. MDIs as medical aerosols Metered dose inhalers (MDIs) are medical aerosols of specific particle size, delivering drugs in a precise dose directly into the lungs during inhalation (for treating respiratory diseases such as asthma). – Other medical aerosols include nasal and topical aerosol sprays.

18. History of inhaler technology CFC-propelled MDIs were historically the inhaled delivery device of choice in the treatment of asthma and COPD. CFC MDIs have been replaced with HFC MDIs, dry powder inhalers (DPIs, with two main types, single-dose and multi-dose), nebulisers, aqueous mist inhalers, and possible emerging alternatives such as iso-butane propelled MDIs. HFC MDIs and DPIs are available for all key classes of drugs.

19. Global market for inhaled medicine, 2012

20. HFC consumption in MDIs, 2014 About 630 million HFC MDIs are manufactured worldwide, using approx. 9,400t HFCs. – 95% HFC-134a (8,900 tonnes) – 5% HFC-227ea (480 tonnes). – About 3% of global GWP-weighted emissions of HFCs used as ODS replacements – About 0.03% of annual global GHG emissions Major user of HFCs in medical aerosols sector.

21. Future HFC demand and impact Under a BAU model, for the period 2014-2025, the total cumulative HFC consumption in MDI manufacture is estimated as 124,500 tonnes – (119,000 t HFC-134a; 5,500 t HFC- 227ea) Corresponds to direct emissions with a climate impact of approximately 173 million tonnes CO 2 equivalent HFC MDIs have 10-fold less climate impact than CFC MDIs

22. Safety and efficacy of alternatives DPIs have been subjected to extensive regulatory assessments for safety, efficacy and quality. Clinical evidence indicates that HFC MDIs and DPIs are equally effective for the treatment of asthma and COPD, for patients who use both devices correctly.

23. Technical & economic feasibility DPIs are alternatives that could minimise the use of HFC MDIs. – New drugs are mainly being developed as DPIs. – In India, single-dose DPIs account for more than 50% of inhaled therapy. – In Sweden, multi-dose DPIs (90%) are used in preference to MDIs (10%). Nebulisers and emerging technologies may also be technically feasible alternatives for avoiding some use of HFC MDIs.

24. Limitations of alternatives Salbutamol HFC MDIs account for the majority of HFC use in inhalers. The availability of affordable alternatives to salbutamol HFC MDIs varies from country to country. Salbutamol HFC MDIs are significantly less expensive per dose than multi-dose salbutamol DPIs, making them an essential and affordable therapy. At present, it is not yet technically or economically feasible to avoid HFC MDIs completely because: – HFC MDIs are less expensive than multi-dose DPIs for salbutamol – a minority of patients (10-20 per cent or less) cannot use available alternatives to HFC MDIs – the role for traditional nebulisers in replacing MDI use is limited, mainly because of convenience and portability.

25. Limitations of alternatives There would be indirect costs and implications in switching patients to alternatives: – patient re-training, such as physician visits, – marketing by pharmaceutical companies, and – guidance provided by healthcare agencies and patient advocacy groups. Costs would be borne by patients, pharmaceutical companies, government and/or private health insurance. A range of options is important because some devices, or drug products, are more effective for some patients. Patient and physician preferences and resistance to switching medication is a potential barrier to change.

26. Future possibilities DPIs may play increasing role over next 10 yrs. By about 2025, the cost effectiveness of DPIs is likely to improve compared with HFC MDIs. More affordable DPIs are likely, due to: – expiry of patents, – more competition and more widespread DPI manufacture, such as in Article 5 Parties.