Establishing Efficiencies Between IND Requirements and FACT Standards
Many FACT-accredited cellular therapy programs participate in clinical trials, and awareness of such activities has become more pronounced with the advent of FACT’s new voluntary accreditation for immune effector cellular (IEC) therapy. Most IEC products are administered under Investigational New Drug, or IND, requirements.
There are some FACT requirements that are not typically required of INDs but could greatly enhance research, such as a quality management program, accessible procedures, and training. Likewise, some typical IND requirements could be used to also satisfy FACT requirements, and documentation created to comply with IND requirements can be used.
FACT requires outcome analysis, which is also performed in accordance with IND requirements. The program does not need to gather and report its own independent data if this is already performed by the investigator and shared with the program. This could be demonstrated through minutes from a quality meeting where outcomes were reviewed, or within signed outcome analysis reports. The key is that outcome information is reported back to the accredited center’s Quality Management (QM) program in some fashion to allow assessment of program performance (such as personnel training and competency or needed procedural improvements).
Product efficacy based on patient outcome may be difficult to document for novel cellular therapy products, and that assessment will differ for each product type. Predefined outcome criteria for investigational cellular therapy products (e.g., CAR T-cells, vaccines) may be found in the clinical research protocol and may include clinical outcomes or only safety endpoints, depending on the trial phase. Data from each investigational product does not need to be aggregated in total; for example, IECs vary widely in cell type, manipulation, protocol, and indication. However, data regarding similar products may shed important light on process improvements within the control and discretion of the program (protocols must be strictly followed per IND requirements).
Reporting of outcome data also advances the field. FACT Standards recommend that Clinical Programs collect each of the data elements contained in the applicable CIBMTR Cellular Therapy forms or EBMT forms. Use of the actual form and submission to CIBMTR or EBMT is not required unless dictated by applicable laws and regulations. FACT strongly recommends the publication of data and strongly encourages the submission of data to the CIBMTR. In the event that the Clinical Program does not submit data to these registries, it should provide reasonable explanations for not doing so. Examples of the forms currently utilized by the CIBMTR may be found on the organization’s website at http://www.cibmtr.org.
Similar to outcome analysis, audits are typically performed as directed by INDs and the results of those audits can satisfy FACT Standards if they are forwarded to the QM Program for review. If an IND does not require an audit, then an audit as required by the Standards must take place.
Policies and Procedures
Many programs utilize IND protocols to satisfy FACT requirements for SOPs. At a minimum, programs should have a local, high-level SOP that describes the big picture of the activities to perform. Actual protocols could be referenced and made available to staff, or the detailed procedural steps could be outlined in job-specific SOPs. Some manufacturers have very specific SOPs and provide them to programs, and, in these cases, there is no need to copy the SOP over to the program’s format. However, protocols are not a no-fail way of meeting the intent of the standard. Programs should ensure that the protocols include specific details for staff performance without being burdensomely long, that they are accessible to staff, and that training on the protocols has been performed.