Risk-Based Qualification of Cellular Starting Material Collection Sites: Tools to Determine Scope of Manufacturer Audits and Reduce Duplicative Efforts.

Cellular and Gene Therapy product (CGT product) manufacturers are required by regulations to qualify sites performing cell collection and processing as part of their manufacturing processes. The use of audits to qualify a site is part of the traditional supplier quality models for drug products. Due to the rapid growth of the CGT industry in recent years, healthcare institutions and manufacturers are finding it difficult to manage the increasing workload and resources needed to support audits when they are applied to the provision of Cellular Starting Material (CSM) collection from patients/subjects for the purpose of manufacturing. To alleviate this audit burden, several manufacturers have applied risk-based approaches to determine the needs and scope of audits. The authors of this commentary recommend that all manufacturers utilize a risk-based assessment program when appropriate and explain the use of tools created to facilitate a risk-based approach to streamline and reduce duplicative audits. This approach and tools, created by The NextGen Industry Working Group (IWG) site certification workstream with representation from pharmaceutical and biotech companies, health care institutions, accrediting organizations, and other stakeholders, is aligned with proposals from other multistakeholder groups, including the ASTCT 80/20 Task Force. The tools aim to streamline the site qualification processes performed by each manufacturer, offering a standardized approach to audits or gap analysis assessments. Offering an abbreviated audit model for sites that have already attained accreditation through agencies such as the AABB (Association for the Advancement of Blood & Biotherapies) and FACT (Foundation for the Accreditation of Cellular Therapy), helping the manufacturer to focus on product-specific requirements rather than re-evaluating systems that have already been audited in great detail by other parties.

A robust quality infrastructure is key to safe and effective delivery of immune effector cells: how FACT-finding can help.

ABSTRACT: Immune effector cells (IECs) include a broad range of immune cells capable of modulating several disease states, including malignant and nonmalignant conditions. The growth in the use of IECs as both investigational and commercially available products requires medical institutions to develop workflows/processes to safely implement and deliver transformative therapy. Adding to the complexity of this therapy are the variety of targets, diseases, sources, and unique toxicities that a patient experiences following IEC therapy. For over 25 years, the Foundation for the Accreditation of Cellular Therapy (FACT) has established a standard for the use of cellular therapy, initially with hematopoietic cell transplantation (HCT), and more recently, with the development of standards to encompass IEC products such as chimeric antigen receptor (CAR)-T cells. To date, IEC therapy has challenged the bandwidth and infrastructure of the institutions offering this therapy. To address these challenges, FACT has established a programmatic framework to improve the delivery of IEC therapy. In this study, we outline the current state of IEC program development, accreditation, and solutions to the challenges that programs face as they expand their application to novel IEC therapy.

Standardization, workforce development and advocacy in cell and gene therapies: a summary of the 2020 Regenerative Medicine InterCHANGE.

Cell and gene therapy is a promising and disruptive new field of medicine for diseases lacking effective treatments. Collaboration among stakeholders has become critically important as investigators, health care providers, manufacturers, couriers, data registries, regulators and payers all become more invested in the success of this field. Many organizations have collaborated with each other to increase clarity, advocate for improvements and share lessons learned. These efforts appear to be making an impact, although the potential for duplicative efforts could slow progress. The second Regenerative Medicine InterCHANGE, hosted by the Foundation for the Accreditation of Cellular Therapy, took place at the Phacilitate Leaders World/World Stem Cell Summit conference in Miami, Florida, on January 24, 2020. Participants from several organizations outlined needs to advance cell and gene therapies. Efforts to address these include standardization, workforce development and advocacy. This article summarizes the major challenges and opportunities discussed during the InterCHANGE.

Integration of Publicly Reported Center Outcomes into Standards and Accreditation: The FACT Model.

The rapid evolution of blood and marrow transplantation (BMT), coupled with diverse outcomes associated with heterogeneous groups of patients, led to the formation of 2 important organizations early in the development of the field: the Center for International Blood and Marrow Transplant Research (CIBMTR) and the Foundation for the Accreditation of Cellular Therapy (FACT). These organizations have addressed 2 of the 9 elements identified by the National Quality Strategy (NQS) for achieving better health care, more affordable care, and healthy people and communities: a registry that promotes improvement of care and accreditation based on quality standards. More recently, a federally mandated database in the United States addresses the third element of the NQS: public reporting of treatment results. Here we describe the current process by which FACT incorporates patient outcomes reported by the CIBMTR into standards for accreditation, the requirements for accredited programs with performance below expected outcomes to maintain accreditation, and preliminary findings of an assessment of corrective action plans intended to improve outcomes.

Definitions of histocompatibility typing terms.

Histocompatibility testing for stem cell and solid organ transplantation has become increasingly complex as newly discovered HLA alleles are described. HLA typing assignments reported by laboratories are used by physicians and donor registries for matching donors and recipients. To communicate effectively, a common language for histocompatibility terms should be established. In early 2010, representatives from Clinical, Registry, and Histocompatibility organizations joined together as the Harmonization of Histocompatibility Typing Terms Working Group to define a consensual language for laboratories, physicians, and registries to communicate histocompatibility typing information. The Working Group defined terms for HLA typing resolution, HLA matching, and a format for reporting HLA assignments. In addition, definitions of verification typing and extended typing were addressed. The original draft of the Definitions of Histocompatibility Typing Terms was disseminated to colleagues from each organization to gain feedback and create a collaborative document. Commentary gathered during this 90-day review period were discussed and implemented for preparation of this report. Histocompatibility testing continues to evolve; thus, the definitions agreed on today probably will require refinement and perhaps additional terminology in the future.

Definitions of histocompatibility typing terms: Harmonization of Histocompatibility Typing Terms Working Group.

Histocompatibility testing for stem cell and solid organ transplantation has become increasingly complex as newly discovered human leukocyte antigen (HLA) alleles are described. HLA typing assignments reported by laboratories are used by physicians and donor registries for matching donors and recipients. To communicate effectively, a common language for histocompatibility terms should be established. In early 2010, representatives from clinical, registry, and histocompatibility organizations joined together as the Harmonization of Histocompatibility Typing Terms Working Group to define a consensual language for laboratories, physicians and registries to communicate histocompatibility typing information. The Working Group defined terms for HLA typing resolution, HLA matching and a format for reporting HLA assignments. In addition, definitions of verification typing and extended typing were addressed. The original draft of the Definitions of Histocompatibility Typing Terms was disseminated to colleagues from each organization to gain feedback and create a collaborative document. Commentary gathered during this 90-day review period were discussed and implemented for preparation of this report. Histocompatibility testing continues to evolve thus, the definitions agreed upon today, likely will require refinement and perhaps additional terminology in the future.