On April 18, 2018, FDA issued draft guidance on Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products—Quality Considerations. The guidance explains the chemistry, manufacturing, and controls (CMC) information that applicants should include in NDAs and ANDAs. The guidance updates and replaces the draft guidance from November 13, 1998.
Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) are drug-device combination products consisting of at least one drug substance and a container closure system. The drug is delivered via inhalation to treat respiratory diseases.
The guidance provides recommendations on critical quality attributes (CQAs) to be developed, and how those attributes relate to elements of the desired quality target product profile (QTPP). The QTPP includes the characteristics that ideally will be achieved to ensure the desired quality; for MDIs and DPIs, these elements include proposed dosage form and delivery system, strength (e.g., targeted metered dose for DPIs, targeted delivered dose for MDIs), purity, stability, and aerodynamic performance. FDA indicates that potential product CQAs for MDIs and DPIs typically comprise assay, impurities and degradants, delivered dose, aerodynamic particle size distribution, foreign particulate matter, moisture content, net content (drug substance and excipients), microbial load, and device constituent part characteristics. The guidance contains additional CQAs specific to the drug substance, excipients, and container closure systems for MDIs and DPIs.
FDA recommends considering factors during product and process development that may impact product quality, including common design and development issues and typical manufacturing operation issues. The guidance also outlines the development of a control strategy to ensure that the CQAs are within the appropriate range, limit, or distribution to assure drug substance and product quality.
The guidance identifies technical data and information that should be submitted in NDAs and ANDAs, following the format of the ICH M4Q and focusing on aspects of MDIs and DPIs that are unique to these products. For example, FDA recommends that the section on pharmaceutical development address the development process for the entire product, including the device constituent part, because an MDI or DPI is a combination product. The guidance also gives recommendations for labelling to help achieve consistency, including naming conventions, information to include on the container/carton label, as well as specifics for sections of the prescribing information such as the description, storage and handling, and instructions for use.