Problems in scale-up of biotechnology production processes.

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.