Assuntos
Contaminação de Medicamentos/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Preparações Farmacêuticas/administração & dosagem , Administração por Inalação , Administração Intranasal , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/induzido quimicamente , Humanos , Tamanho da Partícula , Preparações Farmacêuticas/química , Controle de QualidadeRESUMO
When measuring the aerodynamic particle size distribution of pulmonary drug products, the commonly used instrument is a cascade impactor. For this type of analysis, a mass balance (MB) criterion, 85-115% of label claim, has been recommended by the U.S. Food and Drug Administration (FDA) to be included in the drug product specification. Using statistical model simulations, the effect of inherent product variability on the risk to fail the proposed criteria has been assessed and compared to the corresponding risk to fail the delivered dose uniformity (DDU) test. The results clearly show that the MB criterion is at odds with typical variability of orally inhaled products and seriously contributes to the risk that a typical batch would be rejected due to natural variability of the delivered dose of the product. The MB criterion is generally more difficult to comply with compared to the corresponding delivered dose uniformity (DDU) test, indicating that the proposed FDA MB specification overrules the DDU criteria as being that controlling the DDU.
Assuntos
Aerossóis , Química Farmacêutica/instrumentação , Nebulizadores e Vaporizadores , Administração por Inalação , Aerossóis/normas , Aprovação de Drogas , Sistemas de Liberação de Medicamentos , Modelos Estatísticos , Tamanho da Partícula , Controle de Qualidade , RiscoRESUMO
The International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) presents this paper in order to contribute to public discussion regarding best approaches to foreign particles testing in orally inhaled and nasal drug products (OINDPs) and to help facilitate development of consensus views on this subject. We performed a comprehensive review of industry experience and best practices regarding foreign particles testing in OINDPs, reviewed current guidances and techniques, and considered health and safety perspectives. We also conducted and assessed results of an industry survey on U.S. Food and Drug Administration requirements for foreign particles testing. We provide here a result of our review and survey: a summary of industry best practices for testing and controlling foreign particles in OINDPs and proposals for developmental characterization and quality control strategies for foreign particles. We believe that clear consensus-based recommendations and standards for foreign particles testing and control in OINDPs are needed. The proposals contained in this paper could provide a starting point for developing such consensus recommendations and standards.
