Content 14 Sterile Formulation 616 Michael J. Akers, Curtis S. Strother, Mark. Walden 1.0 INTRODUCTION 616 2.0 STERILE BULK PREPARATION 617 3.0 ISOLATION OF STERILE BULK PRODUCT 6l8 3. 1 General Consideratio 618 4.0 CRYSTALLIZATION 619 5.0 FILTERING/DRYING 619 6.0 MILLING/BLENDING 620 7.0 BULK FREEZE DRYING 620 .0 SPRAY DRYING 9.0 EQUIPMENT PREPARATION 10.0 VALIDATION 11.0 FILLING VIALS WITH STERILE BULK MATERIALS. 623 1. 1 Vial and Stopper Preparatio 11.2 Filling of Vials ,624 12.0 ENVIRONMENT 12. 1 Aseptic Area 12.2 Controlled Areas 12.3 Monitoring the Environment 12.4 Evaluation of the air 12.5 Evaluation of Surfaces 12.6 Evaluation of Water 12.7 Evaluation of Compressed Gases 12.8 Evaluation of Personnel .630 13.0 EQUIPMENT LIST 63l REFERENCES 633 15 Environmental Concerns.................. 635 Elliott Goldberg and maung k Min L0 ENVIRONMENTAL REGULATIONS AND TECHNOLOGY 635 1. I Regulatory Concerns 635 635 2.0 LAWS REGULATIONS AND PERMITS 2.1 Air 636 2.2 Water 638 2, 3 Solid Waste 2.4 Occupational Safety and Health Act (OSHA) 641 2.5 Environmental Auditing 2.6 National Environmental Policy Act 646 2.7 Storm Water RegulationsContents xxiii 14 Sterile Formulation ............................................... 616 Michael J. Akers, Curtis S. Strother, Mark R. Walden 1 .O INTRODUCTION ....................................................... 2.0 STERILE BULK PREPARATION .............................. 3 .O ISOLATION OF STERILE BULK PRODUCT ................ 6 18 3.1 General Considerations ........................................... 4.0 CRYSTALLIZATION ................................ 5 .O FILTERINGAIRYING ...................................................... 6 19 6.0 MILLINGBLENDING .............................. 7.0 BULK FREEZE DRYING ......................... 8.0 SPRAY DRYING ............................................................. 621 9.0 EQUIPMENT PREPARATION ........................................ 622 11.1 Vial and Stopper Preparation .................................... 623 1 1.2 Filling of Vials .......................................................... 624 10 .O VALIDATION ........................................................... 11.0 FILLING VIALS WITH STERILE BULK MATERIALS .623 12.0 ENVIRONMENT .................................. 12.1 Aseptic Areas ......... 12.2 Controlled Areas .................. 12.3 Monitoring the Environment ........................ 12.4 Evaluation of the Air ............. 12.5 Evaluation of Surfaces .......... 12.6 Evaluation of Water ............... 12.7 Evaluation of Compressed Gas 12.8 Evaluation of Personnel ................ ........................ 628 ................... 630 13.0 EQUIPMENT LIST ..................... REFERENCES ................................................................... 633 15 Environmental Concerns .................................... 635 Elliott Goldberg and Maung K. Min 1 .O ENVIRONMENTAL REGULATIONS AND TECHNOLOGY .......................... ............... 635 1.1 Regulatory Concerns ................................................... 635 1.2 Technology ............................. 2.0 LAWS, REGULATIONS AND PE 2.1 Air ............................... 2.2 Water ............................... 2.3 Solid Waste ............................. 2.5 Environmental Auditing .. 2.6 National Environmental P 2.4 Occupational Safety and Health Act (OSHA) .............. 641 2.7 Storm Water Regulations ............................... 643 . 646 ............................... 647