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Overcoming Challenges of Implementing Closed System Transfer Device Clinical In-Use Compatibility Testing for Drug Development of Antibody Drug Conjugates
- Source :
- Journal of Pharmaceutical Sciences. 109:761-768
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Closed system transfer devices (CSTD) are a supplemental engineering control designed to reduce occupational exposure of hazardous drugs and are currently implemented in accordance with evolving regulations. Owing to the novelty and complexity of these devices and their importance in clinical in-use testing, here we evaluated FDA-approved CSTD, assessing product quality through stability indicating assays to determine any drug product incompatibilities. Six devices were used in a simulated compounding and administration of a late-phase IgG1 antibody-drug conjugate (ADC) and the resulting samples were analyzed for visible and subvisible particle counts by light obscuration and micro-flow imaging, physical stability by size exclusion chromatography, and biological activities by relative potency. Potential challenges included improper fit of CSTD components, loss of product to void volume, and material incompatibility. Results showed compatibility of the ADC with the 6 CSTD evaluated. One CSTD introduced subvisible particles into the ADC during compounding that were identified through morphological assessment as silicone oil. This study highlights the importance of clinical in use testing with new devices and proposes strategies to mitigate the risk of drug product incompatibility with CSTD.
- Subjects :
- Drug
Immunoconjugates
Cell Survival
Computer science
Drug Compounding
media_common.quotation_subject
Pharmaceutical Science
02 engineering and technology
030226 pharmacology & pharmacy
Protein Aggregates
03 medical and health sciences
0302 clinical medicine
Drug Stability
Cell Line, Tumor
Occupational Exposure
Materials Testing
Void volume
Humans
Relative potency
media_common
Compatibility testing
Protein Stability
Protective Devices
021001 nanoscience & nanotechnology
Reliability engineering
Drug development
Compounding
Immunoglobulin G
Compatibility (mechanics)
Physical stability
0210 nano-technology
Subjects
Details
- ISSN :
- 00223549
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....baf9ecc5df477c805243701718c2ba9c