Practical Application of Phase-Appropriate GMP & Quality Principles to Clinical Development of ATMPs

There has been a surge in clinical development of Advanced Therapy Medicinal Products (ATMPs), also known as Cellular and Gene Therapy (CGT) Products in the USA. Many startup companies, hospitals, universities, and now even large biopharmaceutical companies, are planning or have already entered into manufacturing these genetically engineered virus and human cell products for clinical studies. While the ground rules for good manufacturing practices (GMPs) and Quality of recombinant protein and monoclonal antibody manufacturing and control are well established, for the ATMPs these are still under development.

ATMP manufacturing and control presents unique GMP and Quality challenges, such as the heightened concern about the safety and consistency of the starting material, the safety and quality of the raw materials added during processing, the need to protect against adventitious agent contamination during the entire manufacturing cycle, the limitations of the analytical methods available to characterize these virus and cell products, and the reality that the administered clinical medicinal product is a complex living organism.

Patients in these clinical development programs need to be protected by common sense GMPs and Quality. The available regulatory authority guidance documents (both EMA and FDA) for ATMPs will be thoroughly examined. In addition, the core principles presented in PDA’s 2016 Technical Report 56 ‘Application of Phase-Appropriate Quality System and cGMP to the Development of Therapeutic Protein Bulk Drug Substance (API)’ will be adapted to ATMPs.