Page 51 - Assurance of Sterility for Sensitive Combination Products and Materials

CHAPTER 4

Aseptic processing

Hal Baseman
Valsource Inc., Jupiter, FL, United States

Contents
4.1 Aseptic processing of sterile combination products 40
4.2 Drug product sterility 40
4.3 Aseptic processing 41
4.4 Aseptic process design 44
4.5 Sterility by design 44
4.6 Line of sight 44
4.7 Defining aseptic process requirements 46
4.8 Basis of design 47
4.9 User requirement specification (URS) 49
4.10 Aseptic practices 50
4.11 Interventions and activities in the aseptic processing critical area 51
4.12 First air principles 52
4.13 Environmental monitoring 54
4.14 Personnel monitoring 55
4.15 Clean room design 56
4.16 Airflow or air profile visualization (smoke) studies 57
4.17 Isolators, RABS, BFS, and other advanced aseptic barrier systems 59
4.18 Critical utilities 60
4.19 Aseptic process qualification and validation 61
4.20 Aseptic process simulation design 62
4.21 Microbial contamination case study 64
4.22 Aseptic process simulation study design 66
4.23 When should aseptic process simulations be performed? 66
4.24 What process steps should be included in the aseptic process simulation? 67
4.25 How many aseptic process simulations should be run for the simulation study? 68
4.26 How should the “worst-case” parameters or conditions be included in the study? 68
4.27 How long should the aseptic process simulation be? 69
4.28 What are the aseptic process simulation acceptance criteria? 71
4.29 The future of aseptic processing 72
4.30 Conclusion: Quality risk management and risk-based critical thinking 74
References 76

Assurance of Sterility for Sensitive Combination Products and Materials © 2020 Elsevier Inc.
https://doi.org/10.1016/B978-0-12-805082-8.00004-9 All rights reserved. 39