Like a fine wine, some Just the FACTs newsletters get better with time. They are useful reminders and references for navigating ongoing requirements, and we are excited to introduce a new feature titled, “From the Archives.” We will re-publish and update articles that address common questions that FACT continues to receive in order to share the knowledge far, wide, and into the future.
Our first featured article is, The X Factor: What is GxP and What Training is Required?” This article was originally published in July 2021 and addresses many questions FACT has recently received.
Enjoy the article!
The X Factor: What is GxP and What Training is Required?
The eighth edition FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration requires that physicians and staff in Marrow Collection Facilities, Apheresis Collection Facilities, and Processing Facilities have annual training in current GxP appropriate to the processes performed in accordance with Applicable Law. (See Standards CM3.3.4, C220.127.116.11, and D18.104.22.168).
What is GxP?
The Standards define GxP as, “Good practice following various quality standards and regulations. The “x” is variable, with further definition of good practices defined by different Applicable Law and industry standards. The type of work that is being performed will define which GxPs should be followed.”
Different facilities will follow different GxPs based on the activities they perform. These may include, but are not limited to, Good Manufacturing Practices (GMPs), Good Tissue Practices (GTPs), Good Documentation Practices (GDPs), Good Clinical Practices (GCPs), and Good Laboratory Practices (GLPs).
What GxPs require annual training per the Standards?
FACT requires training in all GxPs that are required by law. Accredited facilities must determine which GxPs apply to the activities they perform and for the types of cellular therapy products for which the cells will be used. Facilities must:
- Perform an assessment of all activities and determine which GxPs are required by law for each of those activities.
- Document this assessment so 1) the program has a defined list of GxPs that require training and 2) inspectors can verify appropriate training is performed.
- Develop training for each GxP identified as applicable to the activities performed. It can be within existing training or separate.
- Document completion of the training by each relevant physician or staff member.
There are some GxPs that will most likely always apply to certain situations. All Apheresis Collection and Processing Facilities will have activities applicable to GTPs and GDPs. All Marrow Collection Facilities will have activities applicable to GDPs, but may also perform activities related to GTPs depending on the type of cellular therapy products for which they are collecting. Collection and Processing Facilities may also need to follow GCPs or GLPs.
The extent and level of GMPs implemented in Collection or Processing Facilities is dependent on the type of manufacturing that is performed and for whom. For example, Collection Facilities may need to follow GMP requirements related to the transportation of starting material to a third-party manufacturer of a more-than-minimally manipulated cellular therapy product. Often, such processes would be dictated by the manufacturer. Processing Facilities manufacturing investigational and licensed cellular therapy products that are more-than-minimally manipulated or for non-homologous use will need to follow GMPs.
How much training is required each year?
Comprehensive training on every aspect of GxPs each year is not expected; rather, there must annually be some training based on a GxP topic.
Many of the procedures performed by personnel already require training in GxPs to perform the work; therefore, GxP training is not required to be separate. However, documentation must provide evidence that the GxPs were included. For example, training in environmental control could include an overview of GTPs or GMPs, the relevant requirements based on the work to be performed, and the specific tasks performed by personnel.
Training resources for GxPs from reputable sources are plentiful online via the websites of regulatory agencies, quality management societies, and professional societies. It is also acceptable to share training resources among the clinical, collection, and processing functions of an integrated cellular therapy program. Some organizations have asked if training required as part of Risk Evaluation and Mitigation Strategies (REMS) implemented by manufacturers of commercially available cellular therapy products (such as CAR-T products) would suffice for GMP training. GMP training would not be expected in REMS programs because they address specific risks associated with a final product ready for administration rather than the manufacturing of the product (for example, cytokine release syndrome following CAR-T administration).