Supply of Endonucleases

The Clinical Biotechnology Centre at NHS Blood and Transplant is an MHRA-licensed facility for the manufacture of investigational medicinal products, including advanced therapy medicinal products (ATMPs) and other biotechnology products such as plasmid DNA, viral vectors, and therapeutic proteins. The organisation intends to initiate a procurement process for the supply of advanced, high-performance, and cost-effective endonucleases to support the removal of nucleic acids from ATMPs, particularly gene therapy vectors, including adeno-associated viral (AAV) vectors and lentiviral vectors.

The endonuclease must exhibit non-specific nuclease activity against a broad range of nucleic acid substrates, including DNA, RNA, plasmid DNA, synthetically produced DNA, enzymatically produced DNA, and other nucleic acid modalities used in viral vector manufacturing. The enzyme should retain activity under physiological pH and salt conditions, while also maintaining high enzymatic performance across a broad pH and salt concentration range.

Demonstrated suitability for use in viral vector manufacturing processes employing HEK293 suspension cells cultured in stirred-tank bioreactors will be considered an advantage. Suppliers should also demonstrate that residual endonuclease can be efficiently removed from the viral vector product using a defined set of purification methods commonly applied in bioprocessing.

A key requirement is the availability of GMP-qualified and validated analytical assays for the quantification of residual endonuclease at different stages of the manufacturing and purification process. The supplier should be able to provide endonuclease in multiple quality grades, including R&D grade, GMP-compatible grade, and GMP-qualified grade.

It is also essential that these materials are available in quantities suitable for small, medium and large-scale production. Suppliers must provide comprehensive technical and scientific documentation to support the quality attributes and performance characteristics of the endonuclease.

Enzymatic activity should be demonstrated using appropriate standards or reference materials relevant to viral vector manufacturing. Overall, the endonuclease must be highly efficient, scalable, and cost-effective, and suitable for the manufacture of clinical-grade viral vectors. Appropriate analytical methods must also be available to support testing of product quality and residual endonuclease levels in drug products intended for human clinical use, in accordance with applicable national and international regulatory requirements.