The acceptability of continuous cell lines: A personal & historical perspective

Area of Science:

• Biotechnology
• Cell Biology
• Regulatory Science

Background:

• Historically, only primary cell cultures were accepted for human biological product manufacturing.
• Human diploid cells (HDCs) and later continuous cell lines (CCLs) challenged this standard.
• The need for CCLs intensified with the advent of recombinant DNA technology in the 1980s.

Purpose of the Study:

• To review the historical controversy surrounding human diploid cells (HDCs) and its relevance to continuous cell lines (CCLs).
• To highlight the need for consensus on regulatory issues concerning CCLs in biological product development.
• To discuss safety concerns, acceptable DNA levels, and purity in the context of CCL use.

Main Methods:

• Historical review of cell culture acceptability in biological product manufacturing.
• Analysis of regulatory challenges and consensus-building efforts for cell line usage.
• Examination of safety data and manufacturing process capabilities for CCL-derived products.

Main Results:

• Continuous cell lines (CCLs) are now recognized as viable for producing human biological products.
• A 1986 World Health Organization Study Group recommended pursuing CCLs due to advanced manufacturing capabilities.
• Modern processes can effectively manage contaminants, addressing earlier safety concerns.

Conclusions:

• Lessons from the HDC controversy inform the acceptance of CCLs.
• Regulatory authorities, industry, and the scientific community must collaborate on rational, science-based solutions.
• The use of CCLs is crucial for developing certain biological products, supported by robust manufacturing controls.