President’s Letter
FACT’s season of annual meetings is winding down, and as everyone gets back to their homes and day jobs, I hope you have time to rest and reflect on the relationships built and progress made during the past several months. FACT continues to have a presence at the annual meetings of its parent societies, ASBMT and ISCT, and those of other partner organizations, including ASFA, ASGCT, ASH, and SITC. We look forward to participating in the inaugural Cord Blood Connect congress in September, hosted by the Cord Blood Association.
The articles in this newsletter reflect many of the lessons learned and accomplishments made possible by meeting with our colleagues in person at these meetings. Some discussions were complex and nuanced, such as the BMT Time Out commendable practice identified by the FACT Clinical Outcomes Committee and advice on adverse event reporting. Some discussions were intently focused on large tasks, such as review of the draft second edition of the FACT Common Standards in preparation for the public comment period. Other events welcomed new inspectors to the FACT community and celebrated the accomplishments of outgoing Board members.
We appreciate everyone’s participation in the in-person events, and also via volunteer committee teleconferences. Please allow the energy and excitement of these meetings to influence the important work you do on a daily basis.
Sincerely,
Dennis A. Gastineau, MD
FACT President
Publication of the FACT-JACIE International Standards for Hematopoietic Cellular Therapy, Seventh Edition
By Andra Moehring, FACT Standards Development Specialist
Congratulations to Dr. Paul Eldridge, FACT Standards Chair, and the FACT-JACIE Standards Committee on publishing the seventh edition FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration on March 1, 2018. The Standards will become effective on May 30, 2018.
Committee Overview
The Foundation for the Accreditation of Cellular Therapy (FACT) has several committees to help FACT achieve its vision of being the premier organization setting standards and awarding accreditation to programs in the evolving field of cellular therapy.
The seventh edition FACT-JACIE Standards Committee is comprised of 58 representatives from around the world who worked for 23 months on the development of the Standards. The committee is divided into four subcommittees: Clinical, Collection, Processing, and Quality Management. The FACT Immune Effector Cell (IEC) Task Force was also involved in the development and review of IEC specific requirements. Everyone’s commitment, expertise, and experience is invaluable to these Standards.
The seventh edition of the Standards contains important additions and changes to requirements to reflect current processes typical in a cellular therapy program. These changes maintain the relevance of the Standards in the field of cellular therapy.
Public Comment Period
During the 90-day public comment period, 653 comments were submitted by 78 contributors residing in 12 different countries. The committee was responsive to public comments and requests made on behalf of related organizations to ensure the seventh edition is broadly accepted throughout the cellular therapy community.
FACT and JACIE greatly appreciate contributors taking the time to review the draft Standards and submit comments.
Accessing the Standards and Other Resources
The Standards, accompanying Accreditation Manual, summary of changes, and crosswalks are available on the FACT website at http://www.factwebsite.org or by using the links provided below:
FACT-JACIE Hematopoietic Cell Therapy Standards, Seventh Edition
FACT-JACIE Accreditation Manual, Seventh Edition
Changes to Seventh Edition FACT-JACIE Standards
FACT-JACIE Cellular Therapy Standards Crosswalk 6th to 7th Edition
FACT-JACIE Cellular Therapy Standards Crosswalk 7th to 6th Edition
Dr. Eldridge presented a webinar on how to “Effectively Transition to the 7th Edition Hematopoietic Cellular Therapy Standards” on March 14, 2018. Based on the questions received, a question and answer document was created to assist those who were unable to attend. If you were unable to attend the webinar, you can purchase the recording. FACT inspectors may download the recording for free!
If you have questions related to the seventh edition FACT-JACIE Standards, contact your FACT Coordinator or submit your question to askfact@unmc.edu.
Thank you for all of your contributions!
The University of Texas MD Anderson CARTOX Program is First to Achieve Accreditation Under the FACT Standards for Immune Effector Cells
By Mikaela VanMoorleghem, FACT Education and Training Coordinator
The University of Texas MD Anderson CARTOX Program received accreditation for immune effector cellular therapy by the Foundation for the Accreditation of Cellular Therapy (FACT) at the University of Nebraska Medical Center. The University of Texas MD Anderson CARTOX Program, directed by Elizabeth Shpall, MD, and Sattva S. Neelapu, MD, is the first program to be recognized by FACT for compliance with the new FACT Standards for Immune Effector Cells independent of a bone marrow transplant program. The program received accreditation on April 19, 2018.
Dr. Elizabeth Shpall states, “We are very excited to receive the accreditation for the first stand-alone immune effector cell program. It was a major effort of so many people at MD Anderson to coordinate the many different departments and clinical care teams with such broad expertise. We are very grateful for the FACT IEC Standards which we used extensively as a guide for the development and continued operation of our CARTOX program.”
Dr. Phyllis Warkentin, FACT Chief Medical Officer states, “I welcome the University of Texas MD Anderson CARTOX Program to a network of cellular therapy programs and experts that promote the highest quality in the delivery of cellular therapy and care to the patients they serve. Accredited cellular therapy programs such as the CARTOX program have met rigorous standards and I commend them on this tremendous success.”
The FACT website lists all FACT-accredited immune effector cellular therapy programs, which includes bone marrow transplant programs also providing these services.
Gratitude Expressed to Outgoing FACT Board Members
FACT is well-served by an involved, conscientious, and inspiring Board of Directors, and two outgoing Board members embodied all of those characteristics. While overcoming the snowstorms that seemed to follow the BMT community, FACT expressed its appreciation to Hugo Fernandez, MD and Gillian Woollett, MA, DPhil during the Board of Directors meeting at the 2018 BMT Tandem Meetings in Salt Lake City.
We look forward to continuing our relationship with these two outstanding individuals, who will no doubt continue to make a difference. Dr. Hernandez and Dr. Woollett, thank you for your service!
Hugo Fernandez, MD
• FACT, Board Member 2009 – 2017
• FACT, Secretary 2010 – 2016
• Chair, FACT Global Affairs Committee 2010 – 2018
• Member, FACT Technology Committee 2013 – 2018
• FACT Inspector for 20 years performing 30 clinical inspections
Dr. Fernandez’ charge as Chair of the Global Affairs Committee was to provide education, assistance, and a pathway for centers establishing new BMT programs in resource-challenged areas to achieve accreditation. Since 2010, Dr. Fernandez has worked with the committee to identify opportunities to educate the global cell therapy community about the importance of FACT accreditation in establishing quality systems as the foundation for transplant programs.
Dr. Fernandez organized educational outreach sessions in countries including:
• Africa
• Argentina
• Brazil
• Chile
• India
• Japan
• Mexico
• Peru
• Taiwan
• Vietnam
Thanks to the leadership provided by Dr. Fernandez, FACT now has accredited cell therapy programs located in seven countries (Australia, Brazil, Canada, Mexico, New Zealand, Singapore, and the United States) and counting!
Gillian Woollett, PhD
• FACT, Board Member 2009 – 2017
• FACT Public Director
• FACT Audit Committee 2009 – 2017
• Member, FACT Professional Relations Committee 2009 – 2017
• FACT Representative – ISCT Cell Therapy Liaison Committee (CTLM)
Dr. Woollett leads the FDA Policy and Regulatory Strategy Practice as a Senior Vice President at Avalere and supports clients throughout the healthcare system, from patients’ groups to biopharma companies and payers/providers.
Dr. Woollett has provided a wealth of knowledge and insight to FACT regarding:
• Scientific and regulatory policy expertise regarding medicinal products gaining FDA approval.
• USP’s Compendial Notices informing stakeholders of the changing status of USP monographs and other USP standards-setting initiatives (Dr. Woollett serves on USP’s • Nomenclature and Labeling Expert Committee),
• FDA Guidance Documents and Final Rules,
• FDA Law and Proposed Legislation, and
• FDA Center for Biologics Evaluation and Research (CBER) Guidance.
Release of Cord Blood Units that Do Not Meet Post-Thaw Specification Requirements
By Cathy Talmadge, FACT Accreditation Services Supervisor
The NetCord-FACT Standards define post-processing and post-thaw specifications for cord blood units. When a cord blood unit does not meet post-processing specifications, this is an issue that can be dealt with up front prior to storage. However, cases in which post-thaw specifications are not met are more challenging. At that point, the cord blood unit has likely been selected for a patient in need.
The NetCord-FACT post thaw criteria are >70% viability for CD34 cells, >40% viability for CD45 cells, growth for CFU, and verified identity. Release of a cord blood unit that does not meet this criteria requires exceptional release, a process for which FACT-accredited cord blood banks are required to have a policy or procedure (NetCord-FACT Standard B3.1.24). The policy should outline the process to take when a CB unit does not meet predetermined release criteria, including:
- Documenting and investigating the failed criteria, including documentation in the unit record, and
- Reporting the deviation to the requesting transplant program prior to distribution.
Agreements with families for private cord blood storage should outline the bank’s processes for nonconforming cord blood units, and the bank must comply with the agreement.
Cellular Therapy Product Storage at Collection Facilities
By Sarah Litel-Smith, FACT Accreditation Coordinator
We have noticed an uptick in the number of questions regarding storage in the collection facility. There appears to be a misconception that collection facilities do not store products if the processing facility or a courier picks up the product. However, a product is considered to be in storage when it is not under the immediate control of qualified personnel. For example, a product placed in a transport container waiting to be picked up, even for a short time, is considered to be in storage.
All apheresis collection facilities must have policies or procedures that, regardless of the amount of time the product is stored, address cellular therapy product storage and define every step of the product from the time of collection to the time of release to the courier or processing personnel.
Policies and procedures must address the following in relation to storage:
- Defined storage areas and container,
- How the integrity and potency of the cellular therapy products are maintained,
- The security of the facility,
- Facility control of temperature and humidity for storage overnight or longer,
- Storage duration, and actions to take if conditions are not met,
- Product expiration date and time,
- Mechanisms to prevent product release until release criteria are met, and
- Transport or shipping temperature range and duration.
Terminology Used in Clinical Trials versus Standard of Care
By Shannon Walsh, FACT Accreditation Coordinator
We have all used similar but distinct words interchangeably at times. It is easy to do and often times does not seem to matter. However, words and the message they deliver (whether intended or not) can be critical, especially in the area of clinical research.
With the new developments in immune effector cellular therapy and products recently approved by the FDA, such as Kymriah and Yescarta, it is even easier for the distinction between therapy and research to be blurred. These advances have been the focus of a lot of media attention, and laypeople may extrapolate the compelling human interest stories to any type of similar cellular therapy. Furthermore, some programs will be administering these commercial, licensed products to patients alongside research products. For other products still under research and not yet approved, staff must be aware of distinctions that must be clear to the prospective study subject.
In the United States, the Food and Drug Administration, Department of Health and Human Services, and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, among others, have provided regulations and guidelines to ensure the protection of human subjects in research. Part of this protection involves the careful and intentional use of words when advertising for clinical trials, communicating with prospective study subjects, obtaining informed consent, and continues throughout the subject’s participation in a trial.
Words such as “treatment”, “patient”, and “cure”, when used in relation to participation in a clinical trial, can potentially blur the lines between treatment of a patient with an approved drug and enrolling a subject in a clinical research study for the evaluation of safety and/or efficacy of a test article under investigation.
For individuals to be fully informed of research under which they are agreeing to participate, they must know that it is research and that the product is not yet an approved drug for the indication being evaluated. While it is possible that the test article may help or cure the disease, it is also possible that it may not improve the individual’s condition, may cause serious adverse reactions, or may even result in death.
Federal regulations provide additional safeguards for vulnerable populations, such as pregnant women, children, prisoners, mentally disabled, economically disadvantaged, and others. Vulnerable populations may also include the terminally ill given the gravity of their illness. There is a balance between increasing access to research trials for vulnerable populations and protecting these individuals from coercion or undue influence. Considering the relationship between a trusted physician and patient, and the hope for a cure of their illness, there is a fine line in clinical research for using accurate and intentional words to ensure full understanding, autonomy, and informed consent.
Reporting of Adverse Events Related to Licensed Cellular Therapy Products
FACT Standards require reporting of adverse events related to cellular therapy product administration. FACT does not dictate the process or timing of such reporting, but requires that the reporting meets the requirements of applicable laws and regulations. We have fielded many questions via workshops, emails, and telephone calls regarding the reporting of adverse events related to commercial cellular therapy products (e.g., Kymriah, Yescarta).
Many stakeholders in the field are working on initiatives to make data reporting, including adverse event reporting, a more streamlined process. In the meantime, the FACT Immune Effector Cell Task Force recommends that programs define a reporting process and document it in a Standard Operating Procedure (SOP). The following are some tips for creating the process:
- Know, understand, and comply with the reporting requirements outlined in the Risk Evaluation and Mitigation Strategies (REMS) for the specific product(s) you administer. List these requirements in the SOP.
- For remaining gaps in the process, define your program’s reporting elements and frequency of reporting, including:
- The types of adverse events that your program will report immediately (e.g., all events, specific grades of cytokine release syndrome) and to what source (e.g., MedWatch, manufacturer).
- The types of adverse events that your program will collate for future reporting, the frequency of reporting such adverse events, and to whom the information will be reported.
- Maintain documentation of all adverse events and reporting records.
- Develop an audit plan and schedule for monitoring compliance with REMS requirements and the program-defined process.
- Regularly check in with your manufacturer contacts for any updates to their adverse event reporting requirements.
For additional information regarding adverse event reporting, visit the REMS websites of Kymriah and Yescarta, review FDA requirements for manufacturer reporting in 21 CFR 600.80 Postmarketing reporting of adverse experiences, and Standard B4.10 and its substandards in the FACT-JACIE HCT Standards and the FACT IEC Standards.
FACT Prepares for New Portal Launch
By Alisa Forsythe, IT Business Analyst
In 2015, the FACT Technology Committee committed to replacing the FACTWeb Portal. This April, after three years, the first users logged into the new FACT Accreditation Portal. Ten different organizations were selected to serve as beta testers and complete their applications in the new portal.
Feedback on the new portal has been positive:
- “So much faster than the old portal. It is nice that the tabs do not stay open as you move along the application. […] I generally am not a fan of being a beta site, but in this case, I am glad we are as this portal is such an improvement.”
– Karen Klinker, Dana-Farber Cancer Institute/Brigham and Women’s Hospital Adult Hematopoietic Stem Cell Transplant Program
- “Easy to move between application components. Easy to see where you are within the application. Color coding is very helpful.”
– Peggy Appel, Northwest Marrow Transplant Program at Oregon Health & Science University, Legacy Good Samaritan Hospital and Medical Center and Doernbecher Children’s Hospital
- “The new portal is so easy to work with and is a vast improvement from the previous system. It is much easier and quicker to go to the next question and to maneuver around in the portal. Thank you for your hard work in developing this new portal!”
– Sue O’Donnell, The Massachusetts General Hospital Bone Marrow Transplant Program
- “This is a major improvement over the first portal. The ease of use and the speed are complete upgrades! I appreciate everything that has been put into this new portal and realize that we will continue to strive to improve it. Very pleased to have been a beta tester!”
– Kim Kasow, UNC Bone Marrow Transplant and Cellular Therapy Program
With a successful beta test underway, the new FACT Accreditation Portal is scheduled for launch this August.
Upcoming Training Sessions
Online training opportunities are now available on the FACT Event Calendar. Advance registration is required. The first training session of each type will be recorded and made available online for on-demand viewing.
- Completing an Annual/Renewal Report in the Portal
- Completing a Compliance Application in the Portal
- Performing an Inspection in the Portal
Cellular Therapy Accreditation Committee News and Notes
Article written by Suzanne Birnley, FACT Accreditation Coordinator
The Cellular Therapy Accreditation Committee reviews Accreditation Reports for programs inspected under the FACT-JACIE International Standards for Hematopoietic Cellular Therapy, the FACT Common Standards for Cellular Therapies, and the FACT Standards for Immune Effector Cells. After review, the committee makes recommendations to the FACT Board of Directors regarding an applicant’s accreditation status.
The first quarter of 2018 has been an exciting and busy one for the committee. Despite no meeting in February due to the BMT Tandem meetings, the committee was still able to review 13 programs for renewal accreditation in January and March 2018. Additionally, the committee reviewed the first program to apply for standalone accreditation under the FACT Standards for Immune Effector Cells.
The following are some notes regarding the function of the Cellular Therapy Accreditation Committee:
- At each meeting, as deficiencies indicate potential needs for revisions or additions to future sets of FACT Standards, the issues are compiled into a list for future review by the Standards Committee. This feedback from the Cellular Therapy Accreditation Committee promotes improvement and greater clarity with each publication of Standards.
- As programs complete the renewal accreditation process, in addition to the inspector’s assessment, they will be reviewed by the FACT-CIBMTR Data Audit Committee and possibly the Clinical Outcomes Improvement Committee. Recommendations related to data management and clinical outcome deficiencies are considered by the Cellular Therapy Accreditation Committee when determining the accreditation outcome for an applicant.
- One of the most commonly cited requirements is validation. A satisfactory validation will include the following at a minimum:
- An approved validation plan, including conditions to be validated
- Acceptance criteria
- Data collection
- Evaluation of data
- Summary of results
- References, if applicable
- Review and approval of the validation plan, validation report, and conclusion by the Quality Manager or designee and the Clinical Program Director/Facility Director or designee
The seventh edition of the FACT-JACIE Standards for Hematopoietic Cell Therapy was published at the beginning of March 2018. Programs must be compliant with this set of Standards by May 30, 2018. It is important for programs to remember that as they add new accredited services, such as immune effector cellular therapy or more than minimal processing, these must be implemented in compliance with the FACT Standards and reported to FACT. Additionally, if your program uses or plans to use contracted services in your organization, you are responsible for notifying FACT and monitoring the accreditation status of those service providers.
