【文章內(nèi)容簡介】 Endotoxin testing 146 Michael E. Dawson 7. The pendial sterility tests 187 Scott . Sutton 8. Industrial sterilization technologies: principles and overview 195 Anne F. Booth 9. Steam sterilization 221 James AgaHoco 10. Gas, vapor, and liquid chemical sterilization 241 fames Agalloco 11. Dry heat depyrogenation and sterilization 255 Deborah Havlik and Kevin Trupp 12. Radiation sterilization 268 Barry P. Fairand and Dusan Razemxii CONTENTS 13. Filters and filtration 297 Maik \N. Jornitz and Theodore H. Meltzer 14. Processing of small volume parenterals and large volume parenterals 334 Donald A. Eiseiihauer, Roland Schmidt, Christine Martin, and Steven G. Schultz 15. Freezedrying: principles and practice 353 Steven L. Nail and Larri/ A. Gatlin Index 383Contributors James Agalloco Agalloco amp。 Associates, Belle Mead, New Jersey, . D. Scott Aldrich Ultramikro, LLC, Richland, Michigan, . Anne F. Booth Booth Scientific, Inc., Hendersonville, North Carolina, . Mark Caldwell Jacobs Engineering Group, Inc., Conshohocken, Pennsylvania, . Michael E. Dawson Associates of Cape Cod, Inc., Falmouth, Massachusetts, . Donald A. Eisenhauer Abbott Laboratories, North Chicago, Illinois, . Barry P. Fairand Sterigenics International, Dublin, Ohio, . Larry A. Gatlin PK, LLC, Groton, Connecticut, . Deborah Havlik Ramp。D Microbiology, Hospira, Inc., Lake Forest, Illinois, . Bob Helt Jacobs Engineering Group, Inc., Conshohocken, Pennsylvania, . Beth Holden Jacobs Engineering Group, Inc., Conshohocken, Pennsylvania, . Maik W. Jornitz Sartorius Stedim North America, Inc., Bohemia, New York, . Joseph J. Manfredi GMP Systems, Inc., Fairfield, New Jersey, . Christine Martin Abbott GmbH amp。 Co. KG, Ludwigshafen, Germany Francesca McBride Jacobs Engineering Group, Inc., Conshohocken, Pennsylvania, Theodore H. Meltzer Capitola Consultancy, Bcthcsda, Maryland, . William H. Miele Pfizer Global Manufacturing, Kalamazoo, Michigan, . Jeanne Moldenhauer Excellent Pharma Consulting, Mundelein, Illinois, . Steven L. Nail Baxter Pharmaceutical Solutions, Bloomington, Indiana, . Dusan Razem Ruder Boskovic Institute, Zagreb, Croatia Roland Schmidt Abbott GmbH amp。 Co. KG, Ludwigshafen, Germany Kevin Schreier Jacobs Engineering Group, Inc., Conshohocken, Pennsylvania, . Steven G. Schultz Abbott Laboratories, North Chicago, Illinois, . Scott V. W. Sutton Microbiology Network, Inc., Rochester, New York, . Kevin Trupp Global Sterilization Engineering, Hospira, Inc., Lake Forest, Illinois, .1 Aseptic manufacturing facility design Mark Caldwell, Bob Helt, Beth Holden, Francesca McBride, and Kevin Schreier INTRODUCTION Sterile products may be in liquid or powder form (among others) as drug products and may be presented in formats including ampoules, vials, prefilled syringes, presterilized bottles, and blowfil 1seal containers. Product form and presentation influence processing conditions, equipment selection, and therefore, facility design. The sterile envelope refers to all the steps carried out during and following the final sterile filtration step through process pletion, which occurs after filled product containers are sealed and a risk of environmental contamination to the product is eliminated. These steps include: ? Adjuvant, buffer and media formulation ? Addition of excipients ? Adjustment of concentration to achieve target potency ? Sterile filtration ? Component preparation ? Filling, stoppering/plugging, and sealing of product in final dosage containers The design of the facility must meet all applicable regulatory guidelines, and meet GMP and safety guidelines. Current Good Manufacturing Practice (GMP) requires that areas of operation used for aseptic processing must prevent contamination from particles and microbes that may be present in the air, on product contact surfaces, or shed from personnel (15). When processing biological products, such as live virus vaccines, attenuated vaccines and viral vectors, the Giohazard nature of these products place extra demands on the facility. Potent pounds, like some biological products, also pose a risk to the operator and environment. Therefore, the facility and process design must also ensure both product and personnel safety. This chapter establishes a basis for pliance with the global regulatory expectations for facility design, equipment interfaces, and utility requirements applicable to sterile processing and the manufacture of sterile products (610). FACILITY DESIGN DRIVERS As each facility is being designed, process requirements specific to each product must be considered. Each different type of product has different facility needs. Also, the number of products to be manufactured and the xiv CONTRIBUTORS production campaign strategy will impact the facility design. Product Types Chemical Bulk Drug Substances (API) Sterile chemical bulk drug substances are derived from chemical reactions. Facilities producing sterile API will be required to provide protection of the product during synthesis, isolation, and bulk filling. An adjuvant produced by precipitation is an example of a sterile API. Potent Compounds Potent pounds are classified as those chemical drug substances that are considered to be toxic to human s when exposure limits are exceeded, and may cause allergic reactions, birth defects, cancer, or other conditions. For this reason, it is required to ensure protection of operators working with potent pounds, ensure containment of all operations, and prevent release of products into the environment. It is acceptable to permit production of potent pounds in multiproduct facilities, provided the suite is segregated from other operations.2 VOLUME 2: FACILITY DESIGN, STERILIZATION AND PROCESSING Following filling, it is remended to wash the exterior of vials produced in potent pound