Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Switch from CFC-containing to CFC-free metered dose inhalers - current status and regulatory aspects ***

Verena Stumpf (Abschlußjahr: 2004)

Chlorofluorocarbons (CFCs) have been broadly used as solvents, cooling agents in refrigerators, additives for the production of foam plastics and propellants for cosmetics as well as medicinal products. In the production of metered dose inhalers (MDIs) they have gained major importance as propellants. Because of their ozone depleting potential, CFCs became discredited, a fact which eventually found expression in the establishment of the Montreal Protocol in 1987. This document not only regulates the phase out schedules for ozone depleting substances (ODS), e.g. CFCs, but also defines the exemptions as the essential use of ODS which applies predominantly for medicinal products as MDIs.

Accordingly the parties to the Montreal Protocol had to develop a national or regional phase out strategy for the transition from CFC-containing MDIs to CFC-free alternatives by January 1999, ensuring an uninterrupted supply of medication for patients suffering from asthma and COPD. The EU, being a party to the Montreal Protocol, published a European Commission communication paper in 1998 dealing with the strategy for the phase out of CFCs in MDIs. According to this communication the phase out should be effected by a so called therapeutic class approach. This means that all active substances used for the inhalative treatment of asthma and COPD are grouped into different classes. For each class the phase out criteria are determined separately, for instance the number of CFC-free alternatives which have to be available in order to withdraw the CFC-containing products from the market.

The EC communication does not only lay down the phase out strategy but also provides important information concerning the dossier requirements for MDIs with new propellant systems. In addition to this communication paper there are several guidelines and notes for guidance to be considered with respect to the replacement of CFCs in medicinal products, e.g. the CPMP "Note for Guidance on requirements for pharmaceutical documentation for pressurised metered dose inhalation products" (October 2002).

Germany has implemented the European strategy in several BfArM notifications fixing time limits for the withdrawal of certain therapeutic classes. According to these notifications, MDIs containing short-acting beta agonist bronchodilators had to be withdrawn from the market by December 2000 and corticosteroids by the end of 2002. The total phase out of CFC-containing MDIs in Germany will probably achieved by the end of 2004.

In contrast to the EU, the US have chosen a different strategy to phase out CFC-containing MDIs: the moiety-by-moiety approach. This means that the phase out is done active substance by active substance, if two CFC-free alternatives are available on the market. The alternatives do not necessarily have to be MDIs but may also be DPIs. Due to the different approach there is no time limit for the total phase out of CFC-containing MDIs in the US.

In the meantime there are CFC-free MDIs available on the German market for the most important active substances, e.g. salbutamol, belometasone, and budesonide using norflurane, a hydrofluoroalkane (HFA), as new propellant system. Although the HFAs´ ozone depleting potential can be considered as negligible, they do have an adverse impact on the environment because they are acting as greenhouse gases, and as such contribute to changes in climate. This is the reason why pharmaceutical companies are encouraged to develop and promote formulations which take into account both the therapeutic needs of the patient and environmental considerations.

Pages: 42