FACT and JACIE Remained Committed to Publishing the Eighth Edition Hematopoietic Cellular Therapy Standards Despite Worldwide Pandemic
As an international Standards Committee, the FACT-JACIE Hematopoietic Cellular Therapy (HCT) Standards Committee is accustomed to remote collaboration. Its ability to work primarily online was brought to the test during the COVID-19 pandemic in 2020, and the committee rose to the challenge! The eighth edition FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration and its accompanying Accreditation Manual were published on May 17, 2021.
“Even with the challenges of a pandemic combined with very rapid advances in the field, amiable dedicated colleagues allowed successful completion of the task,” says Dr. Paul Eldridge, Chair of the Standards Committee. “I want to express my thanks and gratitude to everyone.”
Dr. Kim Orchard, Co-Chair of the Clinical Standards Subcommittee, adds, “The preparations for the eighth edition of the Standards proceeded with only minimal delays due to the COVID-19 pandemic. Credit is due to all those involved who continued to review and prepare the Standards despite the impact on their work and personal lives.”
“It was a challenge to continue with everything during the pandemic,” according to Dr. Nina Worel, Co-Chair of the Collection Standards Subcommittee. “Not so much with the FACT-JACIE team working on the eighth edition as the time schedule is perfect. We are used to working remotely and the meetings always close on time, but this time there were a lot of other additional meetings that were remote.”
“We managed to have the second face-to-face meeting of the combined FACT and JACIE teams just before the full impact of the first wave occurred, and all subsequent meetings were held by remote means which were already planned,” says Dr. Orchard. “Credit is due to all those involved who continued to review and prepare the Standards despite the impact on their work and personal lives.”
The objective of the FACT-JACIE Standards is to promote quality medical and laboratory practice in hematopoietic progenitor cell transplantation and therapies using hematopoietic derived cellular products. FACT-JACIE Standards are unique in depth and breadth, being applicable to all phases of cell collection, processing, storage, transportation, and administration, and to all phases of clinical application including standard of care therapies and products, products administered under regulatory-approved clinical trials, and licensed (or other regulatory approval) products.
The scope of the Standards includes hematopoietic progenitor cells (HPCs), nucleated cells or mononuclear cells from any hematopoietic tissue source collected for therapeutic use other than as HPCs, immune effector cells (IECs), and genetically modified cells.
The HCT Standards Committee consists of 64 expert members among a Steering Committee and five subcommittees that reviewed clinical, collection, processing, quality, and immune effector cell (IEC) requirements. These members reside in 14 countries, contributing a truly international perspective to the Standards.
Following months of initial reviews and revisions, the HCT Standards Committee considered approximately 770 comments, submitted by 78 participants from 20 countries, during the public comment period. Additionally, other experts from FACT and JACIE participated in discussions related to new developments in the field, including Dr. John Snowden, member of the JACIE Committee and secretary of the European Society for Blood and Marrow Transplantation (EBMT), the FACT Immune Effector Cell Task Force, and others. These experts provided the HCT Standards Committee advice to consider when finalizing the Standards, with revisions ultimately drafted by the Standards Committee and approval granted by the FACT and EBMT Boards of Directors.
“It was really exhausting [with the other remote meetings]. However, we managed to finalize a great new edition of Standards for best quality in cellular therapy for our patients,” says Dr. Worel.
“It was a pleasure to work with committee members on the new edition of standards,” says Dr. Eldridge. “The opportunity to learn from such a diverse group of international experts is amazing.”
The eighth edition Standards become effective on August 16, 2021. All organizations accredited under these Standards are expected to be in compliance with the requirements by that date. Although there may be a few inspections remaining to be completed under the previous edition due to COVID 19-related delays, all other inspections scheduled after this date will be under the eighth edition.
The FACT-JACIE Standards Committee, led by Paul Eldridge, PhD, is finalizing the eighth edition FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration (HCT Standards). The updated editions will be published by May 17, 2021. Following a 90-day transition period, the requirements will be effective on August 16, 2021. To receive announcements of the publications and direct links to the new Standards, Accreditation Manual, and associated documents, subscribe for the FACT newsletter by creating an account at www.factwebsite.org.
FACT committee representatives are also nearing completion of the draft second edition FACT Standards for Immune Effector Cells. Publication of these Standards is planned following publication of the HCT Standards. This change in schedule will allow FACT to place priority on updating related accreditation documents for programs accredited under the HCT Standards, whose inspections were disproportionally affected by COVID-related delays.
New Editions of FACT-JACIE Hematopoietic Cell Therapy and FACT Immune Effector Cell Standards to be Published in May
The FACT-JACIE Standards Committee, led by Paul Eldridge, PhD, is completing the final review of the draft eighth edition FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration. FACT committee representatives are also nearing completion of the draft second edition FACT Standards for Immune Effector Cells.
FACT thanks the many participants of the public comment period for providing useful feedback on the drafts. Approximately 770 comments, submitted by 78 participants from 20 countries, enriched the Standards development process and edits have been made in response when appropriate. FACT will provide a response to comments at the time of final publication of the Standards.
The updated editions will be published by May 17, 2021. Following a 90-day transition period, the requirements will be effective on August 16, 2021. To receive announcements of the publications and direct links to the new Standards, Accreditation Manual, and associated documents, subscribe for the FACT newsletter by creating an account at www.factwebsite.org.
Feedback on draft Standards is a critical step of updating requirements to remain relevant and useful to the current state of cellular therapy. Comments will be accepted on two sets of draft Standards through August 30, 2020. This is a direct way to make your thoughts known on any requirement because each comment is reviewed by the Standards Committee. Do you support the new requirements? Is there a standard that you find to be unclear? Let us know!
The following are descriptions and pertinent links for the two drafts available for review. As a peer-driven organization, we look forward to your feedback!
For questions or assistance, please contact Andra Moehring, MHA, Standards Development Manager.
FACT – JACIE International Cellular Therapy Standards
The Foundation for the Accreditation of Cellular Therapy (FACT) and the Joint Accreditation Committee of ISCT-EBMT (JACIE) published the draft Eighth Edition FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration for inspection and public comment. These Standards apply to all phases of collection, processing, storage, and administration of hematopoietic cellular therapy products. This includes hematopoietic progenitor cells (HPCs), mononuclear cells (MNCs), and immune effector cells (IECs) derived from marrow, apheresis, or cord blood.
Comments regarding the draft Eighth Edition FACT-JACIE International Standards can be submitted by accessing the Comment Form. Comments will be accepted through August 30, 2020.
FACT Standards for Immune Effector Cells
The Foundation for the Accreditation of Cellular Therapy (FACT) published the draft Second Edition FACT Standards for Immune Effector Cells for inspection and public comment. These Standards apply to immune effector cells used to modulate an immune response for therapeutic intent, such as dendritic cells, natural killer cells, T cells, and B cells. This includes, but is not limited to, genetically engineered chimeric antigen receptor T cells (CAR-T cells) and therapeutic vaccines.
Comments regarding the draft Second Edition FACT Standards for Immune Effector Cells can be submitted by accessing the Comment Form. Comments will be accepted through August 30, 2020.
By: Andra Moehring, MHA, FACT Standards Development Manager
The FACT-JACIE Standards Steering Committee initiated the development of the Eighth Edition FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration this summer.
On July 2, 2019, FACT-JACIE Steering Committee members met in Barcelona, Spain to review the Standards Development process and timeline, and discuss specific issues that require review and consideration for this edition.
During the meeting, the committee reviewed and discussed feedback submitted by our colleagues via the FACT-JACIE Standards survey that was distributed in April 2019. FACT and JACIE appreciate the time and effort that went into providing feedback to help us improve our Standards. The survey was completed by 106 total respondents, in 19 different countries, who provided over 800 comments. Thank you for your feedback!
The subcommittees will begin their review next month, and will provide our colleagues with another opportunity to submit feedback during the public comment period scheduled for April 2020.
Final publication of the Eighth Edition FACT-JACIE International Standards is scheduled for March 2021.
By Andra Moehring, MHA, FACT Standards Development Manager
Dr. John Hansen, physician scientist and emeritus faculty member of Fred Hutchinson Cancer Research Center, died of pancreatic cancer on July 31, 2019. Dr. Hansen was well known for his innumerable contributions to the field of blood and marrow transplantation, his pioneering research and discoveries in Immunogenetics, his pivotal role in establishment of global registries of potential unrelated stem cell donors, and his generosity in mentoring others.
Dr. Hansen was also a founding member of the volunteer expert panel that became FACT’s Histocompatibility Committee, responsible for development of the guidelines by which to measure organizations that accredit histocompatibility services in hematopoietic cellular therapy. FACT accreditation of clinical transplant programs and cord blood banks requires histocompatibility laboratories to meet appropriate standards. As FACT extends accreditation services globally, these histocompatibility guidelines are critical to advancing quality care for patients. Dr. Hansen’s foundational contributions and willingness to share his expertise will continue to impact patients and the cellular therapy field worldwide.
FACT continues to develop its international collaborations through regional initiatives aimed at providing educational assistance and accreditation activities tailored to the needs of the global communities.
FACT-JACIE Stepwise Accreditation in Latin America
In an effort to provide an incremental approach to accreditation, FACT and JACIE have partnered to offer a stepwise accreditation program in Latin America. This stepwise approach to accreditation would enable programs to focus on their quality systems first and ensure operations for patient and donor safety. The second phase would build on the established foundation to develop a complete quality management program and provide for efficacious care. The final step evaluates the effectiveness of the quality program, ensures reporting to the appropriate regulatory and accrediting agencies, and evaluates clinical outcomes. The first FACT-JACIE Stepwise Inspection is scheduled to be conducted in Argentina on November 20-21, 2018.
A broad group of ten participating bone marrow transplant centers throughout India is participating in the new India Working Group designed to address the regional needs of the country. The centers are completing self-assessments of their programs to identify any potential barriers to compliance with FACT Standards, clarify the intent of requirements, and assess their readiness for accreditation.
A FACT Standards and Accreditation Workshop was held on November 2, 2018 during the annual meeting of the Asia-Pacific Blood and Marrow Transplantation Group (APBMT) in Taipei, Taiwan. Presentations included the importance of integrating a quality management system throughout the clinical, collection and cell processing activities; the accreditation experience of the National University Health System in Singapore; the incentives for seeking international accreditation from the Tata Medical Center in Kolkata; and the need for standardization and accreditation in China.
Following the execution of a formal Memorandum of Understanding (MoU) in August, FACT and the Sociedade Brasileira de Transplante de Medula Óssea (SBTMO) created a FACT-SBTMO Task Force. The first meeting of the Task Force was conducted on October 17, 2018 to review the strategic goals and operational aspects of the joint FACT-SBTMO Accreditation Program. A survey of the Brazil transplant centers will be distributed in November to gather data related to the volume and type of transplants performed, program structure, personnel, facilities, and quality management systems. The information will be used to identify areas of educational need and ascertain readiness for accreditation.
The 20th year of FACT successfully built upon its history of successes to advance cellular therapy and regenerative medicine. As physicians and scientists continue to make advancements, opportunities arise for FACT to play a supporting role to educate all programs on new approaches and therapies. The following are highlights from 2016:
1. FACT Celebrates 20th Anniversary
FACT celebrated its 20th year as the leading organization in standards setting and accreditation for cellular therapy, hematopoietic stem cell transplantation, and regenerative medicine. FACT welcomed visitors to a dynamic exhibit booth at the BMT Tandem Meetings and the ISCT Annual Meeting to celebrate with the organization. Attendees who wore their commemorative FACT 20th anniversary pin received gifts and were entered in a daily drawing for prizes.
FACT also hosted anniversary receptions at these meetings, and many FACT colleagues, volunteers, and friends enjoyed hors d’oeuvres and refreshments as FACT celebrated two decades of working together in the community to improve patient care and safety. Guests enjoyed watching a short video highlighting FACT’s past 20 years, and saw some familiar faces who have been an integral part of FACT since its beginning.
2. FACT Commences Review of Corrective Action Plans for Low One-Year Survival
The FACT Clinical Outcomes Improvement Committee began formally reviewing corrective action plans submitted by Clinical Programs that did not meet expected one-year survival as outlined by comparative data. The emphasis of the committee is to help programs identify ways to improve their outcomes for patients. After several months of reviewing corrective action plans, the committee has articulated its expectations for these plans using six guidelines:
- The corrective action plan must identify specific causes of death.
- The corrective action plan must provide quantitative data.
- The assessment must identify reasonable causes of the low one-year survival rate.
- The corrective action plan must address the identified causes.
- There must be a measurable outcome improvement.
- The program must provide updates on corrective actions at the time of inspection, at the time of annual reporting, or as otherwise directed by the committee.
3. FACT Presents Comments at FDA Hearing
The Food and Drug Administration (FDA) hearing to obtain comments on the four draft guidance documents relating to the regulation of human cells, tissues, and cellular and tissue-based products (HCT/Ps) occurred on September 12-13, 2016. Dr. Phyllis Warkentin spoke on behalf of FACT and presented the following comments to the FDA:
- FDA should fulfill its responsibilities to protect patients in search of cellular therapies. FACT supports its parent society, the International Society for Cellular Therapy (ISCT), in its position on unproven therapies and agrees on the importance of providing adequate education for patients. Development of professional standards and voluntary accreditation can play an important role in providing a bridge from basic research to clinical application.
- The tiered unified approach to HCT/P regulation fails to acknowledge the complexity of some tissues with multiple native functions and many cell types. It is difficult to strictly categorize complex tissues such as adipose tissue as only structural or cellular. Dr. Warkentin offered solutions for applying regulations to such tissues.
- There appear to be some inconsistencies in the definitions and examples of homologous use that would benefit from clarification.
- FACT suggests that the Agency expand upon its expectation for cord tissue, to include which regulations apply and when they apply, based upon the processes in place.
- International harmonization is important to facilitate product development and world-wide availability of cell-based therapies for patients.
4. Sixth Edition NetCord-FACT Cord Blood Standards Published
NetCord and FACT published the 6th edition NetCord-FACT International Standards for Cord Blood Collection, Banking, and Release for Administration and its accompanying Accreditation Manual on July 1, 2016. These Standards became effective after 90 days, and all accredited cord blood banks were required to comply with the requirements by that time.
These Standards cover 1) collection of cord blood cells, regardless of the methodology or site of collection; 2) screening, testing, and eligibility determination of the maternal and infant donor according to Applicable Law; 3) all phases of processing, cryopreservation, and storage, including quarantine, testing, and characterization of the cord blood unit; 4) making the cord blood unit available for administration, either directly or through listing with a search registry; 5) the search process for selection of specific cord blood units; 6) reservation and release of cord blood units for clinical use; and 7) all transport or shipment of cord blood units, whether fresh or cryopreserved.
5. Draft 1st Edition Immune Effector Cell Standards Published for Public Comment
FACT published a draft of the 1st edition FACT Standards for Immune Effector Cells for inspection and public comment in July 2016. Interim standards for the 6th edition FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration were also proposed to include immune effector cell programs within blood and marrow transplant units. These Standards are intended to promote quality in administration of immune effector cells and will be incorporated into a voluntary FACT accreditation in this field.
The Standards apply to immune effector cells used to modulate an immune response for therapeutic intent, such as dendritic cells, natural killer cells, T cells, and B cells. This includes chimeric antigen receptor T cells (CAR-T cells) and therapeutic vaccines.
Commenters included, among others, pharmaceutical companies, the FDA, the American Society of Cell & Gene Therapy (ASGCT), and the Society for Immunotherapy of Cancer (SITC). A total of 131 comments were received, and reviewers generally expressed support for the Standards and posed worthy questions to consider.
6. CYCORD is First Cord Blood Bank in Cyprus to Earn FACT Accreditation
CYCORD Public Allogeneic Cord Blood Bank in Cyprus received internationally recognized FACT accreditation. CYCORD, directed by Paul Costeas, PhD, is the first and only cord blood bank in Cyprus to be recognized by FACT. The bank received accreditation on June 13, 2016, and is accredited for banking cord blood for both public and private family use.
7. Universidad Autónoma de Nuevo León, Servicio de Hematología Hospital Universitario is First Cellular Therapy Program in Mexico to Earn FACT Accreditation
Universidad Autónoma de Nuevo León, Servicio de Hematología Hospital Universitario in Mexico received internationally recognized FACT accreditation. Universidad Autónoma de Nuevo León, Servicio de Hematología Hospital Universitario, directed by David Gomez-Almaguer, MD, is the first and only cellular therapy program in Mexico to be recognized by FACT. The program received accreditation on September 6, 2016, and is accredited for Adult and Pediatric Allogeneic and Autologous Hematopoietic Progenitor Cell Transplantation, Peripheral Blood Cellular Therapy Product Collection, and Cellular Therapy Product Processing.
8. StemCyte India Therapeutics is First Cord Blood Bank in India to Earn FACT Accreditation
StemCyte India Therapeutics Cord Blood Bank, directed by Bhavin Kapadiya, MD, is the first and only cord blood bank in India to be recognized by FACT. The bank received accreditation on December 21, 2016, and is accredited for banking cord blood for both public and private family use.
9. FACT Hosts Quality Initiatives with Parent Organizations
FACT hosted a Quality Boot Camp at the annual meeting of the American Society for Blood and Marrow Transplantation (ASBMT). The goal of the boot camp program is to strengthen quality assurance activities through pre-meeting exercises and an in-person workshop. Members of the FACT Quality Committee encouraged registrants in the months leading to the in-person workshop to review specific aspects of their quality programs. Quality experts then presented important concepts and led roundtables that allowed participants to ask questions and help each other reach their goals during the boot camp. FACT also partnered with ISCT at their regional meeting to co-host sessions in the Quality and Operations Track. Presentations focused on outcome analysis from the processing perspective and the anatomy of an audit.
10. New Webinar Collaboration Between ASHI and FACT
FACT and the American Society for Histocompatibility (ASHI) began collaborating to offer webinars on transplant immunology. Establishing best practices in transplant immunology in different parts of the world requires both deep understanding of the unique challenges that face different parts of the world, and building on the experiences of well-established labs and international histocompatibility professional societies.
11. FACT Joins Standards Coordinating Body as a Charter Member
The Advancing Standards in Regenerative Medicine Act directs the Secretary of the United States Health and Human Services Agency to establish a public-private Standards Coordinating Body in Regenerative Medicine and Advanced Therapies. The Standards Coordinating Body (SCB) includes membership of the entire cross-section of regenerative medicine stakeholders. FACT was pleased to join as a charter member, and will organize its efforts as part of a consortium of non-government stakeholders that seeks to partner with one or more government organizations and regulatory agencies to coordinate consensus standards development efforts. More specifically, the SCB seeks to enable more efficient and successful clinical and commercial development of cellular/gene and regenerative medicine therapies through coordinating and prioritizing development of national/international standards for measurement assurance (among other objectives).
The FACT-JACIE Standards Committee will begin drafting the 7th edition International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration in June. FACT and JACIE invite you to complete a short survey focusing on general concepts of interest. You are also encouraged to promote this survey in your national or regional professional society. The results of this survey will be reported to the Standards Steering Committee for review and consideration. Input from programs, facilities, and individuals performing cellular therapy helps maintain the clarity, usefulness, and relevance of the Standards. Responses will be accepted through May 15, 2016.
Study Finds Transplant Centers Accredited Under FACT-JACIE Standards Comply Significantly Better with Related Donor Care Standards
In an article published in Biology of Blood and Marrow Transplantation (BBMT), European Society for Blood and Marrow Transplantation (EBMT)-member transplant centers accredited under the FACT-JACIE Hematopoietic Cell Therapy Standards were found to comply significantly better with related donor care standards. Results described in European Group for Blood and Marrow Transplantation Centers with FACT-JACIE Accreditation Have Significantly Better Compliance with Related Donor Care Standards (Anthias, O’Donnell, et al, 2016, doi: http://dx.doi.org/10.1016/j.bbmt.2015.11.009) show practice at these accredited centers was closer to recommended standards compared with non-accredited centers, including the use of eligibility criteria and avoiding conflicts of interest between transplant recipient and donor needs.
The study did find some areas of related donor care with room for improvement. Where standards do not exist, neither accredited and non-accredited centers met accepted best practice, illustrating that a risk of undue pressure on related donors and a risk of donation-associated adverse events is still present. The authors recommend measures to address these risks through enhanced regulatory standards and initiatives to standardize care of related donors.