Questions and Answers on Final Rule of Albuterol MDI’s
|Updated information is now available on the phase-out of Chlorofluorocarbon-containing (CFC) Albuterol MDIs. (05/30/2008)|
What did HHS/FDA do today?
The FDA announced a final rule to amend our regulation (21 CFR 2.125) on the use of ozone-depleting substances (ODSs) in medical products. This rule establishes December 31, 2008, as the date by which production and sale of single ingredient albuterol CFC MDIs must stop, by removing the essential use designation for albuterol metered-dose inhalers (MDIs) under 2.125.
What are ODSs?
ODSs are substances that deplete stratospheric ozone. They include chlorofluorocarbons or CFCs. Once released, CFCs rise to the stratosphere. Within the stratosphere, there is a zone about 10 to 25 miles above the Earth's surfaces in which ozone is relatively highly concentrated. Once in the stratosphere, CFCs are gradually broken down by strong ultraviolet light and they release chlorine atoms that then deplete stratospheric ozone. Depletion of stratospheric ozone by CFCs and other ODSs leads to higher ultraviolet B radiation levels, which in turn has increased skin cancers and cataracts, as well as caused other significant environmental damage. Albuterol MDIs have historically used the chlorofluorocarbons trichlorofluoromethane (CFC-11) and dichlorodifluoromethane (CFC-12) as propellants, both of which are potent and previously common ODSs.
What is “essential-use”?
The use of chlorofluorocarbons or CFCs, an ODS, has been generally banned in consumer aerosols in the United States since 1978. However, the Clean Air Act has permitted certain essential uses of ODSs. Since 1996, newly produced CFCs are only allowed for essential medical uses. Under 21 CFR 2.125, HHS/FDA specifies a list of drug products that are considered essential uses of ODS under the Clean Air Act, and therefore can be legally produced and used in the United States. Albuterol MDIs are currently listed as an essential use of ODSs.
What conditions had to be met for albuterol MDIs to no longer be considered “essential use”?
Under 21 CFR 2.125, several criteria must be met for a listed product to be considered no longer essential. These criteria are the following:
Sufficient non-ODS alternatives are available with the same indications and approximate level of convenience;
There is adequate post-marketing data for the alternative products.
Supplies are adequate to meet the demand;
Patients who require the product are adequately served; and
HHS/FDA initiated notice and comment rulemaking in June of 2004 to allow public input into the determination. The agency received over 75 comments. After thoroughly reviewing and evaluating the comments received, and in consultation with other federal agencies, HHS/FDA has determined these conditions will be met by December 31, 2008, which will render the use of CFCs in albuterol MDIs no longer essential.
How will the rule affect my access to albuterol MDIs?
HHS/FDA is committed to ensuring an orderly transition to the HFA albuterol MDIs, over the next three years. HHS/FDA is also committed to ensuring these products will be available to populations that need them. Currently, there are three non-ODS albuterol MDIs marketed-Proventil HFA (marketed by Schering –Plough), Ventolin HFA (marketed by GlaxoSmithKline) and a similar product from IVAX. Under 21 CFR 2.125, only Proventil HFA and Ventolin HFA can formally be considered as alternatives, because IVAX has only recently marketed its product. The final rule has an effective date of December 31, 2008. The effective date of the final rule is the date on which albuterol MDIs that contain ODSs will no longer be able to be produced, sold and marketed in the United States. HHS/FDA chose the date to assure adequate supplies would be available in the market. We are balancing our international obligations and concerns about the environment on public health with the important needs of patients who rely on these medicines and the associated public health issues.
What programs will be in place to help patients get the albuterol MDI they need, since the albuterol HFA MDI currently cost 20 dollars more per MDI than the generic CFC MDIs?
HHS/FDA is encouraged that the manufacturers of the three HFA products are implementing programs to help assure access to these albuterol MDIs for patients for whom price could be a significant barrier to access to this important medicine. These programs include MDI giveaways, coupons for reducing the price paid and patient-assistance programs based on financial need.
What is HHS/FDA’s advice to patients who use albuterol MDIs?
It is important that patients who use albuterol CFC MDIs talk with their doctors about the phase-out of the CFC products to establish the timing and manner of their move to HFA albuterol MDIs or other product/medication. This final rule goes into effect in about 40 months, and even when in effect, will not mean that albuterol MDIs will no longer be available, just that they will change. It is advisable that patients begin their own planning, and move to the HFA product in advance of the final date, since HFA supplies will be increasing over this time, and CFC supplies diminishing. While HHS/FDA have previously found the albuterol MDIs safe and effective, and through this rule found them good alternatives, they are somewhat different (in taste, delivery feel and other attributes) and patients should anticipate this as they consider their switch to the newer products. It is also important to note that while all CFC albuterols contain the same inactive ingredients, this is not true of the albuterol HFA products, so patients might wish to try the various kinds to find one that is most agreeable to them.
What will be the long-term effect of this phase-out on the price and availability of albuterol products for asthma and COPD patients?
HHS/FDA carefully thought through the rule and the effective date to assure availability of albuterol HFA products would not be an issue throughout this three-year transition. Currently, the HFA albuterol products are more expensive than the generic albuterol CFC inhalers. Three current HFA products will compete in the market place as CFC products are withdrawn, and the long-term effect of this rule on price is not certain. However, HHS/FDA carefully considered programs the albuterol HFA MDI manufacturers are establishing to assure access for patients for whom price is a significant issue, and believes these programs will help ensure patients will have adequate access by the effective date of the rule.
How does this rule affect other MDIs that contain CFCs?
This rule only affects albuterol CFC MDIs. It does not affect other currently marketed asthma or COPD CFC inhalers, which HHS/FDA separately consider as to whether and when they are no longer essential under our regulation. Notably, this action does not affect Combivent MDI, a combination product that contains albuterol as well as ipratropium, since HHS/FDA has designated it as an essential-use product distinct from the single-ingredient albuterol MDIs.
How is this rule related to the Montreal Protocol?
The Montreal Protocol on Substances that Deplete the Ozone Layer is an important international environmental treaty to which the United States is a party. The United States has generally banned the use of CFCs in consumer aerosols (like hairsprays) for decades, and eliminated almost all manufacture and importation of CFCs as of January 1, 1996. However, the Montreal Protocol permits developed countries, such as the United States, to continue to produce or import CFCs for use in medical products (principally for asthma and COPD), if the parties find such production or importation to be medically essential. The United States has received permission to do this for albuterol MDIs containing ODSs, as well as other inhalers for asthma and COPD.
What are the U.S. Government’s obligations under the Montreal Protocol?
The United States is a party to the treaty, and as such, has agreed to phase out production and importation of ODSs, including CFCs, according to the timetables agreed to by the participating countries, including the United States. Congress amends the Clean Air Act (CAA) in 1990 in response to the Montreal Protocol, and the CAA and its implementing regulations call on HHS/FDA to determine which uses of ODSs in medical products remains essential. HHS/FDA does that in 21 CFR 2.125(e).
If there have been alternatives to albuterol MDIs containing ODSs for several years, why did HHS/FDA not act sooner?
There are many reasons for this. One of the criteria for beginning the process of finding a drug to no longer be an essential use of CFCs is that there must be adequate post-marketing experience with the alternative(s). Ventolin HFA, the second product necessary for beginning this process for albuterol, only began marketing in 2002. HHS/FDA believed it needed to allow at least a year prior to initiating rulemaking on albuterol’s essentiality to ensure there was adequate post-marketing experience with both CFC-free albuterol alternatives. Another criterion is adequate supply capabilities. To date, there have not been, and are not currently, adequate supplies of the HFA albuterol MDIs to meet the needs of all asthma and COPD patients in the U.S. Finally, under the criterion of making sure that patients are adequately served by the alternatives, HHS/FDA is expected to take into account the potential for price differences to act as a potential impediment to patient access to the medications.
How was the Pulmonary Drugs Advisory Committee meeting of June 10 related to this rule?
HHS/FDA convened the June 10 meeting to discuss albuterol CFC inhalers and whether the criteria under 21 CFR 2.125 had met the two CFC-free albuterol MDIs. This meeting took place at the early stage in the rulemaking process, the day after the proposed rule was made public. HHS/FDA considered the public and advisory committee discussion in preparing the final rule.