1
`
`3M COMPANY 2008
`Mylan Pharmaceuticals Inc. v. 3M Company
`IPR2015-02002
`
`

`
`Tim
`
`1
`
`f r Phase Out
`
`THE MONTREAL PROTOCOL
`
`The process was started by the Vienna Convention, a meeting organised by the UN which
`was held in Vienna in March 1985. At this convention it was recognized that ozone depletion was
`occurring and that CFCs were a major cause of this. The countries represented in Vienna agreed
`that it was necessary to do everything possible to protect the ozone layer.
`In 1987 46 countries
`signed the Montreal Protocol, an international treaty which undertook to reduce the production of
`ozone-depleting substances in developed countries by 50% by the year 2000. However, further
`research amassed evidence to show that the rate of depletion was greater than at first thought, and
`so subsequent meetings of the Parties to the Protocol advanced the phase-out schedule.
`In June
`1990, at a meeting in London, the Parties announced a complete ban, rather than a 50% reduction,
`by the year 20()0.
`In 1992 the phase-out date for developed countries was brought forward to 1st
`January 1996.
`In deciding to implement the Montreal Protocol, the EU member states undertook to
`accelerate their own phase-out schedule so that the EU ban on CFC production would become
`effective from 1 January 1995 for all but essential uses (Council Regulation [EEC], 1991, 1992).
`The Montreal Protocol has already been effective in reducing the amount of CFCs which are
`produced within the EU. The peak of CFC production in the EU occurred in 1987, 2 years after
`the Vienna Convention (European Chemical Industry Council, 1994). At that time about 300,000
`tonnes of CFC were produced in Europe for aerosols, foams, refrigeration, solvents and for other
`uses. As a result of the Montreal Protocol these industries have undertaken the necessary measures
`to reduce the amount of CFCs they use (Figure 1).
`A number of these industries are using hydrocarbons or hydrofluoroalkanes (HFAs) as
`substitutes for CFCs, and they are well on target for phasing out CFC use entirely in accordance
`with the Protocol and EU Regulations. The one major exception is the manufacture of MDIs.
`The complexities of reformulating MDIs with the new HFA propellants, and fulfilling the
`regulatory requirements for approvals of reformulated products mean that MDIs are unable to
`meet the phase-out dates.
`
`350
`
`LA) OO
`
`IN) U‘! C
`
`N) .0O
`
`‘:— Regulation EC 594/91 March 91
`----- -- Regulation EC 3952 December 92
`
`FOAM PLASTIC
`
`150 ODPtonnes
`(0005)
`
`
`
`'1I’ SOLVENT&OTHER
`
`I REFRIGERATION
`
`
`
`76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99
`Year
`
`FIGURE 1.
`
`CFC Usage in the EU (1976 — 1992) and‘Targets for Phase Out as a Result of Council Regulations.
`
`S-1 4
`
`2
`
`

`
`nil
`
`s ’Exem tion
`
`In order to qualify for exemption from the phase—out date it must be shown that MDIs are,
`in fact, an ‘essential use’ as defined by the Montreal Prptocol. There are four criteria agreed to by
`the Parties to the Protocol for defining what constitutes an essential use of CFCs (Decision IV/25,
`1992). An essential use must be critical for the health, safety and wellbeing of society; there must
`be no technically or economically feasible alternatives or substitutes; all economically feasible steps
`must be taken to minimize CFC emissions; and the use of stockpiled or recycled CFCs should not
`be viable options.
`Seventeen governments worldwide reviewed the case for MDIs and concluded that they
`clearly fulfil all of these criteria and do qualify as an ‘essential use’ of CFCs (Montreal Protocol,
`1994). These countries submitted nominations to the UN Environment Programme (UNEP),
`which administers the Montreal Protocol, making the case for the exemption of MDIs. MDIs fulfil
`the first criterion because asthma is such a common and serious disease, and MDIs are the
`mainstay of treatment for this condition. MDIs are thus necessary for the health and safety of
`society. Secondly, although other forms of inhaled treatment do exist for asthma, such as powder
`inhalers and nebulizers, these alternatives cannot substitute for the use of MDIs in all cases. MDls
`are used by approximately 80% of asthma patients, and they have an important place in asthma
`management. The second criterion is therefore fulfilled. Thirdly, manufacturers have made
`strenuous efforts to reduce CFC emissions during the production of MDIs and they have also
`introduced systems for recovery or destruction of CFCs from waste materials, thus fulfilling the
`third criterion. Finally, it is impossible to use recycled CFCs, eg from an air conditioner or
`refrigerator, in MDIs because of the possible contaminants and toxic impurities there might be in
`such recycled material. Thus all four criteria were fulfilled.
`The essential use nominations were reviewed by committees set up by the UNEP (Montreal
`Protocol, 1994). The most detailed examinations were undertaken by the Technical Options
`Committee which is responsible for nominations of aerosols as an application. This Committee
`consists of experts from relevant disciplines eg respiratory disease specialists, aerosol technologists
`and pharmaceutical scientists. Their recommendation was reviewed initially, by the UNEP
`Technology and Economic Assessment Panel, subsequently, by representatives from the Parties to
`the Montreal Protocol, and finally, officials from the Parties. The final decision was taken by these
`senior officials.
`
`The outcome of this review process occurred in October 1994 at the Sixth Meeting of the
`Parties to the Protocol (Decision VI/9, 1994). The Parties granted an exemption for the production
`of specified quantities of CFCs for use in MDIs for the treatment of asthma and COPD during
`1996, and, for those countries which requested two year exemptions, 1997. The European
`Commission has also exempted MDIs from its accelerated phase out schedule during 1995
`(Commission Decision, 1994). These initial exemptions are extendable subject to further
`nominations from Parties fulfilling the criteria for essentiality in future years. In summary, patients
`and physicians can have a high degree of confidence that MDIs will continue to be available for the
`treatment of asthma and COPD for the foreseeable future.
`
`Environme ta
`
`act
`
`The environmental impact of the Montreal Protocol ‘essential use’ exemption is summarized
`in Figure 2. Industrial uses, such as aerosols, refrigeration, and foam blowing, account for the major
`proportion of CFCs produced (Grant Thornton, 1993). In 1987, the peak year of production, over a
`million metric tonnes of CFC were produced worldwide for these industrial uses and MDls
`accounted for a very small proportion of the total, only 0.8%. Since the introduction of the Montreal
`Protocol the total production of CFCs has declined quite dramatically, having been halved to about
`500,000 tonnes by 1992. MDIs accounted for around 7000 tonnes or 1.41% of the total production in
`1992 (Dunn Group, 1992). By 1996 production of CFCs for industrial use in developed countries
`should be virtually nil because of the Montreal Protocol deadline. The residual production of about
`10,000 tonnes, which has been exempted, will be predominantly for MDIs. Thus CFC production in
`1996 and beyond will be minimal compared to the quantities produced in the past.
`
`S-15
`
`3
`
`

`
`
`
`I CFC in MDI
`
`D Total CFC
`
`1200
`
`1 000
`
`800
`
`600
`
`400
`
`200
`
`
`
`
`
`Metrictonnes(0005)
`
`1987
`
`1992
`
`(Peack CFC production)
`
`FIGURE 2.
`Effect of the Montreal Protocol on CFC Production
`
`(Data from European Chemical Industry Council).
`
`The impact of this small exempted quantity has been assessed using a model (Pyle, 1993)
`which takes into account the fact that, in the 60 years since CFCs first came into widespread
`industrial use, over 19 million tonnes have been produced and used worldwide (Grant Thornton,
`1993). These CFCs have an atmospheric residence time of 70 years or more, thus there is already a
`very large environmental burden in the upper atmosphere. The model assumes that 15,000 tonnes of
`CFCs will be used in MDIs each year for the next 4 years. This figure is an overestimate for the
`purposes of this model since the currently forecast requirement is less than 10,000 tonnes per annum.
`In the context of the existing burden, the environmental impact of exemptions for MDIs will
`be extremely small (Pyle, 1993). On the basis of the model, the exemption of 15,000 tonnes of
`CFCs for the next 4 years has no significant impact on the peak value of the chlorine concentrations
`which will be achieved in the upper atmosphere. It also does not significantly affect the timing at
`which that peak will be attained, nor does it affect the rate at which chlorine will be cleared from
`the upper atmosphere to reach pre-ozone hole levels.
`
`CONCLUSION
`
`In conclusion, both Governments and the pharmaceutical industry worldwide are committed
`to phasing out the production and use of ozone-depleting CFCs as quickly as possible. They also
`recognize the medical need for the continued availability of CFCs for use in MDIs until suitable
`reformulated products, using alternative non-CFC propellants, are available. The ‘essential use’
`exemptions granted thus far last until 1996/7 but they may be extended, depending on the rate at
`which MDI products can be reformulated and approved for marketing by regulatory authorities.
`The small quantity of CFCs which has been exempted for use in MDIs will add very little to the
`existing environmental burden in the atmosphere.
`
`S-16
`
`4
`
`

`
`REFERENCES
`
`COMMISSION DECISION. (1994). Commission Decision of 27 July 1994 on the quantities of
`controlled substances allowed for essential uses in the Community pursuant to Council
`Regulation (EEC) No. 549/91 on substances that deplete the ozone layer.
`
`COUNCIL REGULATION (EEC). (1991, 1992). Council Regulation (EEC) No. 594/91 of 4 March
`1991 and amended by Council Regulation (EEC) No. 3952/92 of 30 December 1992, on
`substances that deplete the ozone layer.
`
`DECISION IV/25. (1992). Decision IV/25 of the Fourth Meeting of the Parties to the Montreal
`Protocol. November 1992.
`
`DECISION VI/9. (1994). Decision VI/9 of the Sixth Meeting of the Parties to the Montreal
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`
`DUNN GROUP. (1992). Dunn Group; An analysis of Present and Future Worldwide Usage of
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`
`EUROPEAN CHEMICAL INDUSTRY COUNCIL. (1994). The Changing Pattern of Use of
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`
`GRANT THORNTON. (1993). Production, Sales and Atmospheric Release of Fluorocarbons
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`
`MONTREAL PROTOCOL. (1987). Montreal Protocol on Substances that Deplete the Ozone
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`
`MONTREAL PROTOCOL. (1994). Report of the Technology and Economic Assessment Panel
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`
`PYLE, J. A. (1993). Report on chlorine loading calculations — CFCs in Metered Dose Inhalers.
`In: Metered Dose Inhalers: A Special Case.
`International Pharmaceutical Aerosol
`Consortium. May 1993.
`
`Address reprint requests to:
`Dr Sheila D’Souza
`
`Propellant Strategy Manager
`Glaxo Research & Development Ltd
`Stockley Park West
`Uxbridge
`Middlesex
`UB11 1BT
`UK
`
`S-1 7
`
`5
`
`

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