Publicação
Risk Management of Elemental Impurities in Drug Products
| Resumo: | Impurities are unwanted chemicals present in small amounts in pharmaceutical products, that are not active pharmaceutical ingredient (API) or excipients, and can change the toxicological profile of pharmaceutical products and hence quality, safety and efficacy (QSE) (1)(2). “Guideline for Elemental Impurities” (ICH Q3D) suggests the application of the risk management methodology presented in ICH Q9, “Quality Risk Management”, aligned with the goals of Quality by Design (QbD), to understand and control the sources of elemental impurities in products. A great variety of systems, techniques and tools (STT), which can be used in quality risk management (QRM) are available. However, each one has its strengths and weaknesses and should be applied in different situations. A great number of factors need to be considered once selecting a STT, the decision about which one is the most appropriate can be very complex and difficult. In overcoming this problem, a comprehensive analyse of the available STT was done. The factors to consider in the selection were organized in a developed methodology that intends to facilitate the choice in a rational way. Despite the fact that the industry continues to place a high reliance on Failure Mode and Effect Analysis (FMEA) as a primary system for QRM, the application of the developed methodology, through a case-study of Oxybuprocaine Hydrochloride 4mg/ ml, manufactured by Laboratório Edol, demonstrates that FMEA has significant number of limitations and is not the most appropriate system for the risk assessment of elemental impurities. It was also analysed that the most appropriate systems for risk management of elemental impurities is Hazard Analysis and Critical Control Points (HACCP). Nevertheless, each specific case needs to be considered. FMEA and HACCP combined with a flowchart and an ishikawa diagram were applied to Oxybuprocaine Hydrochloride 4mg/ ml and the results were compared. The difficulties in the application of FMEA showed that HACCP is easier adapted to this case. |
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| Autores principais: | Silva, Patrícia Pereira da |
| Assunto: | Elemental impurities Quality risk management Systems Tecnhiques and tools Failure mode and effect analysis Hazard analysis and critical control points Teses de mestrado - 2018 |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Impurities are unwanted chemicals present in small amounts in pharmaceutical products, that are not active pharmaceutical ingredient (API) or excipients, and can change the toxicological profile of pharmaceutical products and hence quality, safety and efficacy (QSE) (1)(2). “Guideline for Elemental Impurities” (ICH Q3D) suggests the application of the risk management methodology presented in ICH Q9, “Quality Risk Management”, aligned with the goals of Quality by Design (QbD), to understand and control the sources of elemental impurities in products. A great variety of systems, techniques and tools (STT), which can be used in quality risk management (QRM) are available. However, each one has its strengths and weaknesses and should be applied in different situations. A great number of factors need to be considered once selecting a STT, the decision about which one is the most appropriate can be very complex and difficult. In overcoming this problem, a comprehensive analyse of the available STT was done. The factors to consider in the selection were organized in a developed methodology that intends to facilitate the choice in a rational way. Despite the fact that the industry continues to place a high reliance on Failure Mode and Effect Analysis (FMEA) as a primary system for QRM, the application of the developed methodology, through a case-study of Oxybuprocaine Hydrochloride 4mg/ ml, manufactured by Laboratório Edol, demonstrates that FMEA has significant number of limitations and is not the most appropriate system for the risk assessment of elemental impurities. It was also analysed that the most appropriate systems for risk management of elemental impurities is Hazard Analysis and Critical Control Points (HACCP). Nevertheless, each specific case needs to be considered. FMEA and HACCP combined with a flowchart and an ishikawa diagram were applied to Oxybuprocaine Hydrochloride 4mg/ ml and the results were compared. The difficulties in the application of FMEA showed that HACCP is easier adapted to this case. |
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