Extractables and Leachables in Orally Inhaled and Nasal Drug Products

Orally Inhaled and Nasal Drug Products (OINDP) are a drug product class used for the treatment of Asthma, Chronic Obstructive Pulmonary Diseases (COPD), and systemic conditions such as diabetes. OINDP include Metered Dose Inhalers (MDIs), Dry Powder Inhalers (DPIs), Nasal Sprays, Inhalation Solutions and Inhalation Sprays. OINDP are unique among drug product types in that the container closure system is an integral part of the drug product and critical for drug product performance. Container closure systems can include rubber, plastic, metal and other components. Rubber components are most often used as seals, especially in Metered Dose Inhalers which include an organic propellant under pressure as part of the formulation. Since rubber and plastic incorporate chemical additives and processing aids and metal components often have organic residues on their surfaces, the potential exists for leaching of these chemicals from the components into the formulation. The USFDA and other regulatory authorities have become concerned about such organic leachables in OINDP for patient safety and other reasons. This paper presents the background of the leachables issue in OINDP, including the current regulatory environment and regulatory initiatives. Also presented are the primary issues concerning the interface between the pharmaceutical and rubber industries.