Reisman H B
Organogenesis Inc., Canton, MA 02021.
Crit Rev Biotechnol. 1993;13(3):195-253. doi: 10.3109/07388559309041319.
The unique nature of biotechnology processes adds to the complexity and difficulty of scale-up. Successful scale-up means a shortened cycle to full-scale production, competitive advantage, and cost savings. The many pitfalls as well as actual and potential scale-up problems are reviewed. Emphasis is placed on covering all areas of concern in planning, executing, and documenting key studies. Needs in technology transfer are discussed and regulatory requirements are incorporated into scale-up needs. A review of the recent literature is coupled with actual case studies; problem avoidance is stressed. Problems in asepsis, in construction, and in validation are discussed and potential solutions given. Organizational problems are noted. Finally, checklists are given for project planning, for a safety audit, and for timely attainment of successful scale-up. Eighty-two references are included.
生物技术工艺的独特性质增加了放大生产的复杂性和难度。成功的放大生产意味着缩短全面生产的周期、获得竞争优势并节省成本。本文回顾了诸多陷阱以及实际存在和潜在的放大生产问题。重点在于涵盖规划、执行和记录关键研究中所有需要关注的领域。讨论了技术转移方面的需求，并将法规要求纳入放大生产需求之中。对近期文献的综述结合了实际案例研究；强调了问题的避免。讨论了无菌、建设和验证方面的问题并给出了潜在解决方案。指出了组织方面的问题。最后，给出了项目规划、安全审计以及及时实现成功放大生产的检查清单。文中包含82篇参考文献。
