Reviewer No. 2 checklist for:

Request to add the dosage of 100μg for inhaled beclometasone in the WHO essential drug list of medicines 2009

The International Union against Tuberculosis and Lung disease (The Union) request to add in the WHO essential list the dosage of 100µg of inhaled beclometasone.

Asthma drugs are available as pressured meter‐dose inhalers propelled either by chlorofluorocarbons (CFCs) or hydrofluoroalkanes (HFAs). In accordance with the Montreal Protocol on Substances that deplete the Ozone Layer, and its subsequent amendments, many industrialized countries and some developing countries have now stopped producing and importing CFC‐containing products. HFA Inhaled beclometasone is effective at a lower dosage (half dosage at least) than CFC Inhaled beclometasone.

(1) Have all important studies that you are aware of been included?

Inhaled beclometasone is in WHO essential list at the dosage of 50μg and 250μg.

(2) Is there adequate evidence of efficacy for the proposed use? Yes √ No Evidence based guidelines strongly recommend inhaled steroids in the management of persistent asthma. 100 micrograms HFA‐ beclometasone = 200 micrograms budesonide = 80 micrograms ciclesonide = 100 micrograms fluticasone.There is no good evidence that any inhaled corticosteroid is safer than others. This dosage will simplify for patients the transition from CFC to HFA: the same number of puffs will be prescribed to the patient using CFC 250μg or HFA100μg Several studies conducted by the international Union against Tuberculosis and Lung disease (The Union) and by WHO demonstrated that affordability to asthma essential drugs is one of the main obstacles for the implementation of evidence based management of asthma in developing countries. 100 micrograms HFA beclometasone will be available in the coming weeks through the Asthma Drug Facility which is a project of the International Union Against Tuberculosis and Lung Disease. Through ADF, countries will benefit from: ‐ the quality assurance system of ADF, ‐ Competitive prices (less than €2 per inhaler) ‐ Support for delivery process, ‐ Asthma training materials and information system, ‐ Technical support.

The ADF price will include the cost of the products, preshipment

inspection cost, transport and insurance cost to the recipient count ry and the ADF margin including random quality control.

(3) Is there evidence of efficacy in diverse settings and/or populations? Yes √ No

(4) Are there adverse effects of concern? Yes No √

(5) Are there special requirements or training needed for safe/effective use? Yes No√ MDI are already in use globally (6) Is this product needed to meet the majority health needs of the population? Yes √ No It would improve access and be affordable to the majority of the global population (7) Is the proposed dosage form registered by a stringent regulatory authority? Yes √ No

(8) What action do you propose for the Committee to take? I strongly propose that the 100ug beclometasone puff be included in the WHO ‐ ML

(9) Additional comment, if any. Inclusion in the WHO model List will encourage manufacture and ensure its availability. I have evidence that in some developing countries the pharmaceutical industry is manipulating the market by ensuring a steady supply of fluticasone at a higher cost and not of beclometasone which was manufactured by the same company previously. Hence making inhaled steroids unaffordable to the majority.