Relative Bioavailability Risk Assessment: A Systematic Approach to Assessing In Vivo Risk Associated With CMC-Related Changes
| Autor: | Shobha N. Bhattachar, Aktham Aburub, Xuan Ding, John P. Rose, David C. Sperry, Evelyn D. Lobo |
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| Rok vydání: | 2018 |
| Předmět: |
Chemistry
Pharmaceutical education Pharmaceutical Science Biological Availability 02 engineering and technology 021001 nanoscience & nanotechnology 030226 pharmacology & pharmacy Risk Assessment Risk zone Bioavailability Biopharmaceutics 03 medical and health sciences 0302 clinical medicine Pharmaceutical Preparations Risk Factors health services administration Environmental health Humans 0210 nano-technology Risk assessment health care economics and organizations |
| Zdroj: | Journal of pharmaceutical sciences. 108(1) |
| ISSN: | 1520-6017 |
| Popis: | Relative bioavailability (RBA) studies are often carried out to bridge changes made between drug products used for clinical studies. In this work, we describe the development of a risk assessment (RA) tool that comprehensively and objectively assesses the risk of noncomparable in vivo performance associated with Chemistry, Manufacturing, and Controls (CMC)-related changes. The RA tool is based on a risk grid that provides a quantitative context to facilitate discussions to determine the need for an in vivo RBA study. Relevant regulatory guidances and the required in vitro and in silico absorption modeling data, on which the RA is based, are discussed. In addition, an analysis of previously executed RBA studies at Eli Lilly and Company over a period of several years is presented. The risk grid incorporates individual risk factors for a given study and provides a recommendation on the risk associated with bypassing an RBA study. The outcome of an RA results in 1 of 3 possible risk zones; lower tier risk, intermediate tier risk, and upper tier risk. In cases where the outcome from the RA falls into the intermediate tier risk zone, further in depth data analysis is required. |
| Databáze: | OpenAIRE |
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