Throughout the regulations and guidances you will find something like this: “As with other aspects of the development program, documentation may be ‘less vigorous’ in early phases, but ‘they would still need to be adequate in order to allow for traceability of the manufacturing process.'”

Agencies, like the FDA, have consistently stated that phase 1 is less vigorous but starting in phase 2 you are fully GMP. These regulations are meant to ensure basic safety and documentation standards are met in the manufacture and testing of phase 1 clinical trial material and to encourage the design of quality into the process. It is expected that enhanced process controls and GMP standards will be employed as the material transitions into later clinical stages.

With the speed of development, and the fact early phase material can support commercialization, this phased in approach is an important balancing act in advanced therapeutics like cell and gene therapy.  It is crucial that manufacturers of phase 1 clinical trial material assess potential risks associated with their manufacturing process, facilities, equipment, methods, materials, etc. and the associated impact of these risks on the safety and quality of the material. All significant risks should then be mitigated, and appropriate controls implemented to reduce potential adverse impact for the patients and data generated.

Recognizing the difference between the elements of a strong quality system and what is needed for GMPs. Folks often confuse the two and have difficulties maturing quickly. The stuff in the orange? That’s system and is not GMP dependent.

Some GMP, such as clean room controls or starting materials controls should be robust from the beginning. Others, such as cleaning validation, are developed as you move through the phases.