FACT accreditation is a credential that has its greatest value in the peer-to-peer exchange of ideas to confirm and improve quality in patient care and laboratory services. Successful accreditation is awarded with two tangible items: an Accreditation Certificate and a final Accreditation Report. Although the certificate gets more prominence, often framed and mounted as a visual symbol of quality, the final report is a detailed accounting of what accredited programs implemented to reach compliance with all FACT Standards.
Each Accreditation Report provides important information related to an accredited program’s journey to initial or renewal accreditation. The final report includes:
- The name and location of the program
- The date of the on-site inspection
- The clinical, collection, processing, and/or banking sites and services associated with the accreditation
- Key personnel
- Identification of the FACT inspection team
- A description of the program
- Deficiencies and variances cited by the inspection team and approved by the Accreditation Committee
- Required responses to provide evidence of correction of each deficiency or acknowledgement of each variance
- The program’s responses documenting completion of corrective actions and compliance with Standards
- FACT’s response, or determination regarding the adequacy of the program’s corrective action
- Details of any additional follow up reports or documentation due to FACT
After completing the rigorous accreditation process, programs may debrief the contents of the Accreditation Report and then file it away, turning attention to its many other important duties until annual reporting is required. However, the final report is a valuable tool that can be used throughout the accreditation cycle.
Programs that have corrected deficiencies and submitted adequate evidence of correction and compliance with standards should be very proud of the work they have invested into improvement. Lessons learned throughout this process can be applied to the entire program. For example:
- How will we evaluate our corrective actions to confirm long-term effectiveness?
- What other strengths and weaknesses did we discover while correcting deficiencies?
- Are there further root cause analyses we should perform to prevent similar deficiencies?
- Can we apply the same process to evaluate other aspects of our program?
Ideas generated from this review of the Accreditation Report may be useful to maintaining the Quality Management program via audits, process development, personnel training, and other quality concepts.
External Confirmation of Quality
Apheresis collection facilities, cell processing facilities, and clinical services are each important in the context of blood and marrow transplantation, where accreditation covers the entire scope of the therapy from patient selection and treatment, through product selection, collection, processing, and administration. These same services participate in clinical trials often including products developed and manufactured by industry partners. These facilities recognize the importance of standards, have achieved voluntary FACT accreditation, and have played a major role in delivering new products to patients. They have used their quality programs and processes to quickly adapt to increasing numbers of products, procedures, and manufacturers. However, facilities have individually and collectively expressed concern regarding the growing number of on-site audits. The increased burden of preparing for, participating in, and responding to audits requires more resources to be diverted to these activities rather than toward patient care.
Commercial manufacturers who produce cellular therapy products for clinical trials or under an approved regulatory license may wish to leverage FACT accreditation to streamline audit activities, verify quality practices, and reduce the burden on health care entities. To do this, manufacturers may request a copy of the final FACT Accreditation Report. FACT does not provide Accreditation Reports to any entity except the accredited program. Accredited programs are not restricted from sharing these reports and may choose to provide them to manufacturers leveraging FACT accreditation, however, they are not required to do so.
Accredited programs or their hospital administration may be hesitant to disclose deficiencies cited during an on-site inspection. However, FACT accreditation is a voluntary, peer-based quality improvement process, during which some deficiencies can be expected at any program. The documented deficiencies demonstrate the rigor of the inspection process. The final report includes the description and documentation of the program’s corrective action, FACT’s determination of the adequacy of the response, and any additional follow up that may be indicated. Responses to deficiencies are an opportunity to proudly share a program’s process improvements. Programs should inquire of any commercial manufacturer regarding the confidentiality of information they provide to increase confidence in the use of the FACT report.
If a program chooses to provide the final Accreditation Report to a commercial manufacturer, it will likely be able to participate in an abbreviated site audit because the Accreditation Report can be used to confirm the quality systems in place meet FACT Standards. If a program chooses not to provide the report, it may be required to undergo a full site audit that will include requirements duplicative to the FACT Standards.
The American Society of Gene & Cell Therapy (ASGCT) has partnered with FACT and the American Society for Transplantation and Cellular Therapy (ASTCT) to bring you the two-part webinar series, “Centers’ Experience with Implementing Commercial CAR T-cell Products.”
The first webinar will be on Thursday, July 25, 2019 at 11:00 am ET. Part one includes information from two centers regarding their journey to successful implementation of commercialized CAR T-cell products. Clinicians will address the challenges faced during the site on-boarding process, where they are in this process, commonly faced impediments to timely delivery of therapy to patients, and suggestions for centers initiating implementation of commercial CAR T-cell products. Topics in this webinar will include required training, maintenance of chain of custody, and mechanisms for reporting outcomes data. FACT accreditation will also be covered.
Part two will take place in September of 2019 and will include the perspective of a hospital administrator in regard to the following:
- Agreements with Manufacturers
- FACT accreditation
Although clinical research has been a major part of the blood and marrow transplant (BMT) field since its inception, recent developments have prompted questions regarding the scope of FACT Standards. The number of programs participating in research of new cellular therapy products beyond minimally manipulated hematopoietic progenitor cells (HPCs) is increasing. Furthermore, two immune effector cell (IEC) products are now commercial and treated as “standard of care.”
FACT Standards apply to both clinical research and standard of care cellular therapy products. If an accredited program provides both types of products, then it must comply with FACT Standards for both. There is not an option to be accredited for only one or the other.
Both cellular therapy products administered within the context of clinical research, and products administered within regulatory licensure (such as Kymriah® and Yescarta®), must comply with FACT Standards as they are applicable to the requirements. Products must be collected and processed using controlled and documented procedures; personnel must be trained and competent; recipient and donor health must be evaluated and managed; facilities, equipment, supplies, and reagents must meet specifications; and records must be created and maintained.
Both clinical research and licensed cellular therapy products must be incorporated into the program’s quality management (QM) program. As more products are administered, this is challenging due to the involvement of additional providers and companies, increasing data collection and reporting requirements, varying protocols, and more. These challenges, though, are the very reasons why a QM program can help the program! Evaluating, creating, and documenting procedures and protocols, training staff on those procedures, and maintaining a centralized mechanism to access documents and records will assist the program with maintaining control of its services.
The FACT Immune Effector Cell Task Force acknowledges these challenges and seeks to provide resources and education to assist programs experiencing the growing types of products administered. For example, see the article from a past Just the FACTs newsletter regarding reporting adverse events for commercial products and the IEC resources webpage. The task force is also hosting a webinar on January 30, 2019 to describe programs’ approaches to using nonconforming commercial products. These resources are based on real-world program experiences, and we appreciate the questions and feedback programs have provided FACT as we all learn more about these exciting new developments in cellular therapy.
David Porter, MD, Director of Cell Therapy and Transplantation at Penn Medicine (second from left), Member of FACT’s IEC Task Force, presents “CAR-T Cells: On the road to a cure” at the University of Nebraska Medical Center Hematologic Malignancies Research Meeting. With him are Julie Vose, MD, MBA, James Armitage, MD, and Phyllis Warkentin, MD.
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.