Orally inhaled and nasal drug products

U.S. Food and Drug Administration (FDA), Extra 6 Safety thresholds and best practices for extractables and leachables in orally inhaled and nasal drug products, PQRI Leachables and Extratables Working Group, available http //www.pqri.org/pdfs/ LE Recommendations to FDA 09-26-06.pdf. 

Leachables in orally inhaled and nasal drug products (OINDP) are compounds which are present in the drug product due to leaching from container closure system components. Extractables are compounds that can be extracted from OINDP device components, or surfaces of the OINDP container closure system when in presence of an appropriate solvent(s) and/or condition(s). Leachables are often a subset of, or are derived directly or indirectly from, extractables. Extractables may, therefore, be considered as potential leachables in OINDPs. Some leachables may affect product quality and/or present potential safety risks, therefore regulatory guidance has provided some recommendations regarding the analysis and toxicological safety assessment (i.e., qualification) of such compounds. 

Inhalation drug products, also referred to as orally inhaled and nasal drug products (OINDPs including inhalation aerosols and solutions, nasal aerosols and sprays), have a high likelihood of packaging component-dosage form interaction,and therefore have individual USFDA guidance documents. As an example, consider the metered dose inhaler (MDI), shown... 

However, Norwood and Qiu observe that for orally inhaled and nasal drug products (OINDPs), FDA guidance documents require a greater degree of excipient characterization and stricter quality control... 

IPAC-RS Foreign Particles Working Group (Dec 2004) Foreign particles testing in orally inhaled and nasal drug products. Pharm Res 21 (12) 2137-2147... 

OINDP Orally Inhaled and Nasal Drug Products ... 

Protein and peptide therapeutics currently represent eight of the top 100 prescription pharmaceuticals in the U.S., and biotechnology products are projected to account for 15% of the total US. prescription drug market by 2003. Of the protein and peptide products now on the market, many are administered as daily injections, though several are delivered by noninvasive routes. For example, desmopressin is delivered as a nasal spray, and deoxyribonuclease I is administered by inhalation. Although cyclosporin A is orally active, as yet there are no general means to confer oral bioavailability to peptides and proteins. A major advance in delivery of peptides was achieved with the introduction of a monthly injectable, biodegradable microsphere formulation of LHRH. 

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