President’s Letter
Last year, FACT celebrated its 20th anniversary and spent the year reflecting on its history and celebrating its accomplishments. This year, the FACT Board of Directors participated in a strategic planning retreat to envision future successes and what FACT needs to do to achieve them. The two-day retreat was filled with questions, laughter, debate, and discussion. All of this culminated into defining objectives and strategic goals for the years 2017 through 2020 that we are excited and eager to pursue.
Though FACT is poised to be a player in many exciting developments in the field of cellular therapy, we have not lost our focus on our mission: to improve the quality of cellular therapy through standards, accreditation, and education for the benefit of patients. Indeed, every new initiative we begin will ultimately become a routine part of fulfilling our mission through our core services. Many of our defining objectives and strategic goals relate to organizational infrastructure to maintain our strength and flexibility to address emerging issues as they come.
Our ability to respond to the needs of the field, using new and improved resources to do so, directly impacts the care our patients receive. By doing this, we also strengthen our relationships with like-minded organizations and develop new collaborations with colleagues in different capacities. This allows us to push the envelope on our ability to evaluate and encourage quality practices with synergistic efficiency. Our clinical outcomes improvement and data management initiatives, both made possible by the efforts of the Center for International Blood & Marrow Transplant Research (CIBMTR), harness the power of data to improve patient survival and research. Our close collaboration with our peers in the Latin America Blood and Marrow Transplantation Group (LABMT) is improving the quality of transplantation in new regions of the world. Our new accreditation program for immune effector cellular (IEC) therapy, largely created in response to requests from commercial biological product manufacturers, has been mutually beneficial and educational and, hopefully, will improve access to new and lifesaving cellular therapies. Our work with the Cardiovascular Cell Therapy Research Network (CCTRN) is leveraging our experience and the CCTRN’s cardiovascular expertise to evaluate how FACT can help even more patients in more specialties.
Sincerely,
Dennis Gastineau, MD
FACT Announces 2017-2020 Strategic Plan
FACT’s strategic plan anticipates and addresses opportunities and challenges for the next several years. The strategic plan also identifies several “Defining Objectives.” Although all the goals in a strategic plan are important and meant to be accomplished, several are designated as highest priority. Accomplishing these priority goals defines FACT’s success over the next period of time.
The three defining objectives and additional goals for the 2017-2020 period are:
Defining Objective #1: INSPECTIONS
The highest possible level of excellence and consistency in inspections of programs and facilities.
Defining Objective #2: IMMUNE EFFECTOR CELL THERAPY
Rapid mobilization of an accreditation service for immune effector cellular therapy programs.
Defining Objective #3: FINANCES
Sufficient financial resources to sustain operations and build reserves for the development of mission-directed products and services and for surviving an economic downturn.
Strategic Objective #4: REGENERATIVE MEDICINE
Continued promotion of the FACT Common Standards for Cellular Therapies, and readiness to introduce disease- or medical specialty-specific standards when appropriate.
Strategic Objective #5: CLINICAL OUTCOMES IMPROVEMENT
Cellular therapy programs that know how to prevent, investigate and correct deficiencies in clinical outcomes.
Strategic Objective #6: STANDARDS
Clear and user-friendly FACT standards and effective transition between editions of standards.
Strategic Objective #7: ACCREDITATION
Consistency in the awarding of FACT accreditation.
Strategic Objective #8: CORD BLOOD BANKING
Recognition of FACT as the premier accreditation for both public and private cord blood banks.
Strategic Objective #9: EDUCATION
Recognition that education is as important as standards and accreditation within FACT’s mission to promote quality in cellular therapy.
Strategic Objective #10: ORGANIZATIONAL EFFECTIVENESS
Organizational health is one of FACT’s greatest strengths.
Resources Continuously Added to FACT Website
Topics include clinical outcomes, immune effector cellular therapy, patients and families, and more
To support FACT-accredited organizations and the FACT mission to improve cellular therapy, resources are continuously added to the FACT website. This article highlights just a few of the informational webpages that provide links to journal articles, instructions, examples, and more.
FACT supports blood and marrow transplant (BMT) programs’ efforts to evaluate one-year survival data to improve patient outcomes, advance the field, and maintain payer and public confidence. FACT requires programs to submit a corrective action plan when one-year survival does not at least meet expected outcomes as demonstrated in comparative data. Several resources are available to assist programs with identifying trends in cause of death, the root causes, and corrective and preventive actions. This page includes links to comparative data sources (especially helpful to autologous-only and non-U.S. programs), educational resources, and example corrective action plans. The page also lists the guidelines for corrective action plans for quick reference.
The main objective of FACT’s Immune Effector Cell Standards is to promote quality practice in immune effector cellular therapy. FACT is committed to supporting efforts to make quality immune effector cellular therapy accessible to patients much like it did for bone marrow transplant and cord blood banking. Several resources are available to assist with understanding immune effector cells and implementing FACT Standards. Resources include FACT Standards for Immune Effector Cells, educational on-demand webinars, frequently asked questions, and journal articles. Examples of guidelines and procedures used by organizations for managing immune effector cell programs and patients will soon be available.
Education and assistance for cellular therapy patients and their families are key to promoting desirable clinical outcomes. Direct links to a variety of organizations and informational sources are listed for several topics, including donor registries, information and support, cord blood banking and donation, and clinical trials and access to cell therapies.
Although quality management is relatively new to cellular therapy programs and cord blood banks, the principles of quality assurance and quality control have long been incorporated. For the FACT accreditation process, the real turning point for emphasis on quality management activities was with the release of the third editions of the Cellular Therapy Standards and Cord Blood Standards, which included greatly expanded Quality Management sections. Since that time, FACT has developed and introduced quality-based educational materials to assist your organization with developing and enhancing your Quality Management Program.
Many New Developments in FACT Standards Development Activities
The FACT Standards Committees have been busy reviewing feedback, discussing new developments in cellular therapy, and editing drafts for several different sets of Standards. Updates for each set of Standards are provided below. As progress continues, important updates will be announced via weekly emails and future Just the FACTs newsletters.
FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration, 7th Edition
FACT and JACIE are finalizing the 7th edition Hematopoietic Cellular Therapy Standards, which is scheduled for publication in March 2018. 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, and administered by a blood and marrow transplant (BMT) team.
After March 1, 2018, only Compliance Applications under the 7th edition will be accepted and only inspections under this new edition will be conducted after the effective date of May 30, 2018. Programs currently pursuing renewal or initial accreditation under the 6th edition must remain mindful of these dates and ensure timely submission of pre-inspection materials and completion of the inspection.
The FACT Accreditation Services department is contacting accredited and applicant programs who will be beginning the accreditation process at the time of publication to discuss the transition. We understand the effort required to complete the accreditation process and will be ready to assist programs with timely submission of the Compliance Application in accordance with the new edition.
The FACT-JACIE Standards Steering Committee meets in Orlando to review the 7th edition draft Standards.
FACT Standards for Immune Effector Cells, 1st Edition
The FACT Standards for Immune Effector Cells apply to immune effector cellular (IEC) therapy programs that are independent of a transplant program. Standards specific to IEC therapy are also contained within the FACT-JACIE Hematopoietic Cellular Therapy Standards for programs that perform both transplant and IEC therapy. To ensure both sets of Standards include the most up-to-date requirements in this new field, requirements will be published in an interim version of the 1st edition Immune Effector Cell Standards. Once effective, the updated version of the Standards will be the basis of inspections going forward.
A list of the small number of changes to the Immune Effector Cell Standards will be provided at the same time the 7th edition Hematopoietic Cellular Therapy Standards are published in March 2018.
FACT Common Standards for Cellular Therapies, 2nd Edition
The FACT Common Standards for Cellular Therapies is currently undergoing revision. The Common Standards Committee consists of members representing a wide variety of specialties to ensure the Common Standards continue to represent the basic fundamentals applicable to any type of cellular therapy. This includes hematopoietic progenitor cell (HPC) transplantation, IEC therapy, cardiovascular medicine, cord blood banking, cell collection, and cell processing with minimal and more-than-minimal manipulation. A draft for public review and comment is expected in April 2018.
NetCord-FACT International Standards for Cord Blood Collection, Banking, and Release for Administration, 7th Edition
The Steering Committee for the 7th edition of NetCord-FACT International Standards for Cord Blood Collection, Banking, and Release for Administration will initiate the development process at the 2018 BMT Tandem Meetings in February.
FACT and WMDA-NetCord invite you to complete a short survey focused on general concepts of interest regarding the Standards. The results of this survey will be reported to the Standards Steering Committee for review and consideration as it begins to draft the next edition. Your input helps maintain the clarity, usefulness, and relevance of the Standards. Responses will be accepted through December 29, 2017. The 7th edition is scheduled for publication in October 2019.
The Role of Medical Records During On-Site Clinical Program Inspections
Last year, FACT and CIBMTR announced their collaborative data assessment program, designed to reduce duplicative efforts, enhance quality improvement efforts, and provide support to accredited Clinical Programs. Not only has this program intensified support and improvement of Clinical Programs’ data management and reporting processes, it saves time for programs audited by CIBMTR by reducing the need to make Transplant Essential Data (TED) forms and source documentation available to FACT inspectors during the on-site inspection.
Despite the reduction in records to produce for the data audit, there is still a critical need for access to medical records during on-site inspections. Compliance with many standards can be verified through medical records including:
- Donor and recipient informed consent;
- Donor eligibility evaluation and determination;
- Compliance with established policies, procedures, and guidelines;
- Verification of preparative regimens and recipient identity against protocols;
- Detection, evaluation, reporting, correction, and prevention of adverse events and other occurrences; and
- Verification of corrective action plan implementation.
Pre-selected and organized medical records facilitate inspector review. Pre-select records that represent a variety of situations applicable to your program, including:
- Allogeneic, autologous, and haploidentical transplants;
- Transplants using cells derived from peripheral blood, bone marrow, and cord blood;
- Cellular therapy using novel products such as immune effector cells (IECs);
- Adult and pediatric patients; and
- Adverse events, positive microbial cultures, and ineligible donors. (Yes! Showing inspectors medical records that represent less than ideal, but inevitable, circumstances will improve the results of your inspection by allowing inspectors to verify compliance with all standards.)
(A note about electronic medical records (EMR): Because it takes time to navigate electronic systems, it will also take time for the inspector to become familiar with your EMR. Create printed shadow charts and/or plan to navigate the system for your inspector. It is a good idea to communicate with your inspector in advance regarding his/her preferences.)
With the time saved by eliminating the need to produce accessible copies of TED forms, spend time selecting medical records from a variety of situations, evaluate your processes and make improvements where necessary. Use this opportunity to show your inspector how you continuously improve your program. That is, after all, the real purpose of FACT accreditation.
Inspection of Fixed or Non-Fixed Cord Blood Collection Sites? That is the Question for FACT.
Cord blood banks accept the noble challenge of collecting what many still unfortunately consider medical waste – placental and umbilical cord blood – and transforming it into a lifesaving therapy. In many cases, this is accomplished by establishing formal relationships with specific hospitals and other birthing units, with a written agreement between the collection site and the bank for the collection of cord blood units. The agreement describes the interaction between the collection site and the bank for all aspects of the collection process including, at a minimum, personnel training, record keeping, collection, storage, and transportation or shipping of a cord blood unit.
There are also non-fixed collection sites, where the collection of cord blood is initiated by the infant donor’s mother or family. For these sites, banks must document that a health care professional has agreed to perform the collection in accordance with the cord blood bank’s collection procedures and must provide training that covers each aspect of the collection process. Cord blood collection at these sites are typically infrequent.
The NetCord-FACT International Standards for Cord Blood Collection, Banking, and Release for Administration make very few distinctions between fixed and non-fixed collection sites, because both types have a direct impact on the quality of the cord blood unit ultimately given to a patient. Therefore, because they perform a critical step of the cord blood banking process, facilities that collect cord blood units for an applicant cord blood bank are inspected during the accreditation process.
There are several models used by cord blood banks to collect placental and umbilical cord blood, and FACT and WMDA-NetCord acknowledge the need for banks to institute models that work best for them. Banks submit information about all collection sites to FACT; with that information, FACT determines what collection sites will be inspected as part of the accreditation process. Collection sites are selected depending on a number of variables to allow verification of compliance of all processes used by the bank. Examples of variables include:
- Distance from the bank,
- Mode of transport from the collection site to the bank (e.g., private courier, donor family, commercial shipper),
- Travel time between the collection site and bank,
- Temporary storage location between the collection site and bank,
- Average number of units collected per year,
- Method of collection (in utero, ex utero, or both),
- Type of unit (e.g., unrelated allogeneic, directed allogeneic), and
- Collecting professional (e.g., bank employee, obstetrician, collection site employee).
Sometimes, cord blood banks consider a relationship with a collection site to be non-fixed, but FACT still must inspect those sites because of their responsibilities. For example, collection sites that collect a large number of cord blood units a year, store collection kits, obtain informed consent, or perform other responsibilities may be inspected. Inspectors have identified areas for improvement at such collection sites, and we believe that the processes banks implement to address these issues will result in higher quality units. Many of the deficiencies are easily resolved by the bank, and place little burden on the collection sites themselves; sometimes they make the process better for the sites. For example, a high microbial contamination rate may be attributed to the collection process. The bank can decrease the contamination rate by providing clearer Standard Operating Procedures (SOPs) and training regarding preparation of the needle site and handling of equipment.
We are a FACT-Accredited Transplant Program Providing Immune Effector Cellular Therapy.
What Do We Need to do to Meet Accreditation Requirements?
This question is frequently asked and for good reason. FACT-accredited blood and marrow transplant (BMT) programs that provide immune effector cellular (IEC) therapy must not only comply with the standards specific to IECs, but they must also apply all FACT Standards to their IEC programs as applicable. If just beginning IEC therapy, programs must be in compliance with the Standards as part of starting the new activity.
First, get to know yourself.
Ask the following questions:
- How many different IEC products are administered by our program? Are they industry-sponsored trials or investigator-initiated trials? Do we plan to administer licensed products?
- Who is responsible for infusing the IECs and treating the patient, and where is this physically performed (e.g., Do BMT attending physicians administer the products? Are the products administered on the BMT unit or elsewhere?).
- Who collects and manufactures the products? Is it collected in-house? Is it manufactured at an external company? Does the processing facility ever have control of the product?
- How is chain of custody established? Is an intermediary facility (e.g., hospital pharmacy, blood bank) ever involved?
- Are there any protocols established that include addressing issues related to IECs, including toxicities?
- Are physicians and staff trained in administering IECs, recognizing expected complications, and addressing adverse events?
- What data is collected, how is it managed, and how is it analyzed? What happens when an issue is detected?
- How is the IEC program integrated into the quality management (QM) program?
- Who is leading the IEC program? Is it the BMT Program Director or someone from a different service (such as leukemia)?
Second, talk to your Accreditation Coordinator at the FACT Office.
The value of the FACT Accreditation Coordinator cannot be overstated. With information gathered from the questions above, you can discuss your program’s model with the coordinator and determine next steps. Potential next steps may be:
- If preparing for a renewal inspection, submit all required documentation for immune effector cellular therapy in the Compliance Application and prepare for the inspection.
- If in the middle of the accreditation cycle, discuss your options. To receive an accreditation certificate for immune effector cellular therapy you must be inspected. You may choose to request an add-on inspection mid-cycle, or you may choose to wait until the renewal inspection.
- If completing the annual reporting process, report that you provide IEC therapy and attest whether you have reviewed the new standards and comply with them. Again, this will not result in IEC accreditation being listed on the FACT website as discussed above.
Third, perform a gap analysis of the Standards to determine compliance and correct any deficiencies.
Determine any gaps in compliance with the Standards. What processes need to be established, updated, or documented? Management of IEC products and their donors and recipients should become a routine part of the program; they will not be new to the program forever. There is no need to reinvent the wheel. In fact, establishing separate processes solely for IECs could put the program at risk for nonconformities and errors. Determine where the IEC program may need to be incorporated into existing processes, such as:
- Immediate access to drugs to treat cytokine release syndrome (note that this has been reported for haploidentical transplants and is not specific to IEC therapy),
- Nurse training (additional training modules may be required to train nurses as new therapies are provided), and
- Audits and outcome analysis (incorporate newly required audits and analyses into the existing schedule and perform them according to established procedures; remember that the analysis required at 30 days is required of all cellular therapies, not just IECs).
To be accredited for IEC therapy, programs must have mechanisms to comply with all standards related to toxicities even if they currently do not administer notably toxic IECs such as chimeric antigen receptor (CAR) T cells. For example, if a program only administers mesenchymal stromal cells (MSCs) for graft versus host disease (GVHD), which is not known to be as toxic, it still must provide staff training and develop policies for addressing known toxicities of a variety of IECs. This is to ensure transparency, credibility, and understanding of what FACT accreditation for IECs means. Due to the rapid growth in this area of cellular therapy, it is likely that programs will increasingly be adding new types of IECs to their repertoire. With this approach, not only will FACT accreditation remain clear and meaningful, accredited programs will be prepared to continue their ability to offer new therapies to patients.
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.
Outcomes
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.
Audits
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.
FDA Publishes Final Guidance for Reporting HCT/P Deviations
The Food and Drug Administration (FDA) announced the availability of a final document entitled, “Deviation Reporting for Human Cells, Tissues, and Cellular and Tissue-Based Products Regulated Solely Under Section 361 of the Public Health Service Act and 21 CFR part 1271; Guidance for Industry.”
The guidance document provides certain establishments that manufacture non-reproductive human cells, tissues, and cellular and tissue-based products (HCT/Ps), regulated solely under the Public Health Service Act (PHS Act) and under FDA regulations, with recommendations and relevant examples for complying with the requirements to report HCT/P deviations.
Far-Flung FACTs: Interviews with FACT-NetCord Accredited Cord Blood Banks Around the World
FACT interviewed personnel at cord blood banks that are FACT-NetCord accredited in geographically unique locations and published corresponding articles in the Telegraft, the bi-monthly online newsletter of the International Society for Cellular Therapy (ISCT). The articles describe the unique challenges the banks face in their geographic regions, and the benefits they receive from FACT-NetCord accreditation. Interviews with three cord blood banks have been published:
Juliette Liatsou, MSc, Quality Manager of CYCORD Cord Blood Bank, in Nicosia, Cyprus
Meral Beksac, MD, PhD, Director of Ankara University Cord Blood Bank, in Turkey
The Telegraft provides those in or interested in the cell therapy community with current information on new developments, items of interest, regulatory updates, summaries of work being done in both academic and industry labs around the world, and much more. Special issues are also published as required to cover developments of particular importance or interest to the ISCT membership.
