FDA Publishes Draft Guidance on Voluntary Consensus Standards Recognition Program for Regenerative Medicine Therapies
The United States Food and Drug Administration (FDA) is responding to needs for regulatory predictability and leverage of stakeholder efforts for standardization in regenerative medicine therapies, including cellular therapy, via a draft guidance that introduces a voluntary consensus standards recognition program.
Published in June 2022, Voluntary Consensus Standards Recognition Program for Regenerative Medicine Therapies: Draft Guidance for Industry acknowledges many unique challenges caused by the novelty of regenerative medicine therapy products. The proposed standards recognition program for regenerative medicine therapies (SRP-RMT) is intended to:
- Use agency expertise to evaluate and recognize voluntary consensus standards.
- Provide transparency to industry and other stakeholders regarding CBER’s thinking about a particular method or approach.
- Promote the visibility and use of standards applicable to the agency’s mission.
The draft guidance describes the purpose of the program, procedures for evaluating standards for recognition, documenting the use of a recognized standard, and questions and answers.
Comments on the draft guidance are due by September 14, 2022. Comments may be submitted to https://www.regulations.gov, Docket No. FDA-2022-D-0745-0001.
A public workshop to discuss the guidance will be hosted by the Standards Coordinating Body (SCB) free of charge on August 24, 2022 at 12 pm ET. Register online.
Stakeholders are motivated – and ready – to implement practical, achievable changes to advance cellular therapy and regenerative medicine. This was a theme throughout the third Regenerative Medicine InterCHANGE, hosted by FACT virtually on January 25, 2022. The event was initially scheduled to be in Miami, Florida as part of Phacilitate’s Advanced Therapies Week, but changed to a virtual format due to the ripple effect of the increase in COVID-19 cases in the previous month.
A total of 36 attendees, representing 23 organizations and various areas of subject matter expertise, participated. Participating organizations included professional societies, health care providers, industry, information technology groups, advocacy organizations, accrediting organizations, and multistakeholder groups.
The three main objectives of the event were to:
- Discuss regulatory requirements for the collection of starting material, applying approaches taken from currently licensed cellular therapies to anticipate and influence requirements for additional cell sources being investigated.
- Develop a collaborative approach to educational and training programs, building and supporting a thriving workforce by leveraging the resources of academia and industry sectors.
- Identify steps in the Investigational New Drug (IND) application, licensure, or equivalent regulatory process that could be addressed to reduce time and cost requirements in order to increase patient access to cellular therapies.
Each of these objectives were the topic of panel discussions. Panelists included a wide variety of stakeholders, whose perspectives brought fresh ideas to address challenges experienced among many different types of cellular therapy products. Audience participation was excellent, with attendees sharing ideas for many actionable solutions. A summary of the discussions and identified action items is currently being drafted.
Intermingled through the event were FACT Accreditation Success Story videos. Two videos highlighted successful multistakeholder efforts, including the ISBT 128 Standard 18 for labeling collected cells intended for further manufacture and streamlined site certification processes. The third and final video was a special message from a cellular therapy patient, shared by the Cord Blood Association, who encouraged cellular therapy professionals to continue their good work and be proud of their accomplishments.
The InterCHANGE planning committee and moderators, listed below, successfully narrowed seemingly daunting challenges into solution-driven discussions:
- Ian McNiece, PhD: Chair, FACT Regenerative Medicine Task Force and Executive Consultant at CellMED
- Joanne Kurtzberg, MD: Member, FACT Regenerative Medicine Task Force; President, Cord Blood Association; and Director of the Marcus Center for Cellular Cures and the Carolinas Cord Blood Bank, Duke
- Corinne Goldberg, MD: Medical Director, Carolinas and South Carolina Region of the American Red Cross
- David Moolten, MD: Medical Director, Penn-Jersey Region of the American Red Cross
- Colleen Delaney, MD, MSc: Vice President, Cord Blood Association and Founder and Chief Scientific Officer of Deverra Therapeutics
We look forward to sharing the full summary with the cellular therapy field in the future. In the meantime, we would like to express a hearty thank you to the following organizations for participating in the event and for all your efforts to advance quality cellular therapy for the benefit of patients.
As cellular therapies expand, accredited cellular therapy programs often become involved in the development, implementation, and performance of protocols and procedures for indications outside of hematological or malignant diseases. Accredited programs must meet the FACT Standards for these nontraditional therapies as they apply, regardless of the patient population served. The lines can become blurred when non-accredited services are also provided in the institution. While accredited Clinical Programs are expected to utilize collection and processing facilities that meet FACT Standards, the converse is not true. An accredited Apheresis Facility or Processing Facility may serve both accredited and non‐accredited clinical programs. A “clinical program” may be simply a medical service in your institution that is not part of your accredited transplant or immune effector cell program, such as neurology or nephrology.
This article will review the responsibilities of Clinical Programs, Collection Facilities, and Processing Facilities for analyzing outcomes of nontraditional cellular therapies. To start, let’s review the requirements for internal clinical outcome analysis. Standards exist in each part of the Standards (clinical, collection, and processing) and all are similar. They require that documentation and review of outcomes and efficacy are outlined in the Quality Management (QM) Plan and/or policies and procedures, that criteria are determined and reviewed at regular time intervals, and that both individual and aggregate data are evaluated for each type of cellular therapy product and recipient.
B/C/D4.7 The Quality Management Plan shall include, or summarize and reference, policies and Standard Operating Procedures for documentation and review of outcome analysis and cellular therapy product efficacy to verify that the procedures in use consistently provide a safe and effective product.
B/C/D4.7.1 Criteria for cellular therapy product safety, product efficacy, and the clinical outcome shall be determined and shall be reviewed at regular time intervals.
B/C/D4.7.2 Both individual cellular therapy product data and aggregate data for each type of cellular therapy product and recipient type shall be evaluated.
If the physicians of the FACT-accredited cellular therapy program have no responsibility for the evaluation or management of patients treated with a cellular therapy, the Clinical Program is not responsible for assessing the efficacy of that cellular therapy because it is administered outside of its control.
However, if the accredited program’s physicians are involved in management of these patients, the Clinical Program is responsible for all aspects of the cellular therapy, whether or not the patients are housed on the accredited program’s unit. If the physicians are involved in the management of these patients, the patients and products are considered part of the program and QM program.
If the patients are housed on the accredited Clinical Program’s unit but the programs’ physicians are not involved, this is essentially “renting space” and considered a “nonaccredited service” ‐ a cellular therapy program existing in the same institution but not under the FACT accreditation. This would not be part of the accredited program or its QM responsibilities.
If collection of nontraditional cellular therapy products is performed within a FACT-accredited Apheresis Collection Facility, the facility is responsible for treating them as it would any other product. All standards for collection apply, including written procedures; training; collection orders; parameters; end points of collection; labelling; transport and shipping; chain of identity/chain of custody; release criteria; and processes to prevent mix‐ups, contamination, or cross‐contamination.
As part of the accreditation process, FACT expects that all cellular therapy products collected be listed on the apheresis collection facility grid, regardless of whether the products ultimately went to the accredited Clinical Program or to patients on another service. If the Collection Facility cannot evaluate efficacy, it should at a minimum evaluate product quality by assessing some designated parameters; for example, achievement of collection goals, contamination rates (or lack thereof), proper product labeling and storage, and integrity of the product (e.g., bags are intact).
Measures of cellular therapy product efficacy may be the responsibility of the clinical teams, but the FACT-accredited Processing Facility is still responsible for providing a safe product. This includes all of the standard laboratory quality attributes: procedures; training; equipment maintenance and calibration; facility cleanliness; chain of identity/chain of custody; labeling; and prevention of mix‐ups, contamination, and cross‐contamination. If performing any processing or cryopreservation of the product, some measure of post‐processing recovery or post‐thaw viability might be used to assess product quality in addition to testing for bacterial or fungal contamination.
FACT would expect all of these cellular therapy products to be listed on the Processing Facility grid and incorporated into the QM plan and evaluated as any cellular therapy product.
The Standards Coordinating Body (SCB) is seeking input from the regenerative medicine community to update its report: Community Perspectives: Needed Standards in Regenerative Medicine. The content and potential impact of this report on the development of future standards may impact FACT stakeholders, and we encourage volunteer inspectors and personnel from accredited organizations to complete the survey. The survey will be available until November 6, 2020 at 12 pm Eastern Standard Time.
Per the SCB, this report, “is intended to align community efforts around the standards that could have the greatest benefit to the regenerative medicine field and improve the safety and quality of regenerative medicine products. Your input will ensure that the report reflects the current needs and perspectives of stakeholders in the community, helping to direct time and resources toward the highest-priority standards.”
Advanced Therapies Week, which will take place January 20-24, 2020 in Miami, Florida, will raise public awareness and support innovation in advanced therapies. Its organizer, Phacilitate, initiated this global campaign in conjunction with the Regenerative Medicine Foundation to support three areas:
- Public engagement
- Technology innovation
- Workforce development
The week will begin with a public day on January 20 at the renowned Frost Science Museum, during which interactive “activation” tables will allow members of the public to immerse themselves in concepts related to advanced therapies.
From January 21-24, the Phacilitate Leaders World and World Stem Cell Summit conferences will offer a comprehensive program with diverse tracks that address many aspects of advanced therapies – from raising capital and streamlining manufacturing processes to clinical delivery to patients. As a partner of Advanced Therapies Week, FACT participated in the development of the agenda and encourages the cellular therapy community to attend. Phacilitate has generously extended a 15% discount off the registration fee to the FACT community. To take advantage of this offer, enter the discount code FACT15 when prompted by the online registration process.
FACT will host the second Regenerative Medicine InterCHANGE on January 24, the last day of Advanced Therapies Week. During this meeting, attendees nominated by and representing organizations involved in cellular therapies will discuss solutions to the challenges identified with the development, testing, and commercialization of novel cellular therapies. In 2018, 17 organizations with complementary missions discussed specific challenges and created a list of action items based on their related initiatives. This year, over 30 organizations with broad perspectives of novel cellular therapies are invited to discuss progress on those action items and form working groups for challenges not yet addressed.
Advanced Therapies Week will also include programming for women in advanced therapies, stem cell and regenerative medicine action awards, advanced therapies 101 for the nursing professional, and a yacht party to celebrate advances in the field. The International Society Cell & Gene Therapy (ISCT), one of FACT’s parent organizations, will also be hosting a Commercialization Signature Series event.
Register for the Phacilitate Leaders World and World Stem Cell Summit conferences
Remember to enter FACT15 for a 15% discount.
The Standards Coordinating Body (SCB) and Nexight are requesting comments on a report titled, Community Perspectives: Needed Standards in Regenerative Medicine. The report outlines prioritized areas in cell therapy, gene therapy, and tissue engineering. Comments are due by June 19, 2019.
Per the SCB website, “One of SCB’s goals since its inception has been to strengthen the identification and prioritization process for advancing regenerative medicine standards through greater community engagement, a goal we outlined in Realizing the Promise of Regenerative Medicine Therapies: Strengthening the Standards Development Process. The methodology we used to create the report on needed standards allowed us to implement many of these process improvements.”
This report was drafted under contract for the United States Food and Drug Administration (FDA) and has the potential to be influential in the direction the cellular therapy field takes toward standardization. Your comments as experienced professionals are critical to charting the path.
Send comments to Sarah Lichtner at email@example.com by June 19.
The Standards Coordinating Body (SCB) was formed as an answer to the Advancing Standards in Regenerative Medicine Act, and holds contracts with the Food and Drug Administration (FDA) to advise the agency on needed standards in regenerative medicine. It formally supports many standards development efforts in conjunction with other organizations. FACT is an engaged member organization and participates in SCB projects and provides regular feedback as requested by the SCB.
Did you know that the transplant and cord blood banking communities are critical to the SCB’s efforts?
Although “regenerative medicine” is a very broad term with connotations related to “new” or “novel” therapies, many of the SCB’s projects relate to issues in which FACT-accredited organizations have decades of experience. Accredited organizations are often the facilities that collect cellular starting material, perform contract manufacturing or supportive processing and cryopreservation procedures, or clinically support specialties not yet experienced in cell and gene therapies. Even those organizations that are not directly involved have had to evaluate, resolve, and manage solutions to the very challenges newer players in cell and gene therapies are struggling with now.
Please share your experiences and expertise with the Standards Coordinating Body!
Your input will assist the SCB with its mission, inform commercial manufacturers and other specialties on inherent differences in cell and gene therapies, and promote solutions that harmonize with existing Standards and regulations. The SCB’s outputs could directly impact your daily work and, more importantly, help expedite availability of therapies to patients sooner rather than later. Express your interest in participating in SCB projects to Dawn Henke, SCB Senior Technical Program Manager, at firstname.lastname@example.org.
The following are notable SCB initiatives that are likely of interest to many FACT-accredited organizations. There are many more that may be intriguing based on professional interests. For a full listing of projects and reports, visit the SCB’s website at https://www.standardscoordinatingbody.org.
- Cell Collection Standards for Cell Therapies: FACT, SCB, commercial manufacturers, and many other organizations have heard, loud and clear, that apheresis facilities are struggling with the increasing volume of effort required of variable collection and audit requirements. This project group is currently formulating surveys to distribute to industry and apheresis facilities to learn what needs could be reconciled and then standardized.
- Cryopreservation of Cells (PDA-led project): Many commercial manufacturers have sought best practices related to cryopreservation and have had to adjust those practices to fit the needs of their particular cellular therapy products. This project group is drafting a framework on which to establish cryopreservation procedures in the hope to standardize requirements when possible.
- Transportation Requirements of Cells for Therapeutic Use: Shipping and transportation have a direct and significant influence on chain of custody and chain of identify of cellular therapy products, and is of great interest to commercial manufacturers. This project group is working to identify gaps in current Standards. Due to the emphasis on shipping and transportation requirements in FACT Standards, efforts to remain harmonization with these existing Standards will prevent conflicting requirements.
- Community Perspectives: Needed Standards in Regenerative Medicine Report: This report, based on input from many stakeholders, outlines needed standards that could have the greatest benefit to the safety and quality of regenerative medicine products. The draft is currently available, and will be updated as needed based on comments the SCB received during its recent public comment period in May 2019.
On September 17, 2018, FACT hosted a Regenerative Medicine InterCHANGE meeting in conjunction with the Cord Blood Connect congress in Miami Beach, Florida. Lessons learned from the commercialization of immune effector cells indicate that proactive change management is key to linking the needs and interests of all involved in advancing regenerative medicine. The purpose of the meeting was to create awareness and discuss challenges identified with the development, testing, and commercialization of novel cellular therapies in regenerative medicine.
The first half of the meeting was allocated to organizational introductions, during which each participating organization briefly presented information about its mission and initiatives related to regenerative medicine. Presenters mentioned several examples of collaboration with other attendee organizations, and audience members stated that the presentations enhanced their awareness and understanding of other stakeholders and their complementary objectives.
During the second half of the meeting, Dr. Ian McNiece, chair of the FACT Regenerative Medicine Task Force, moderated a discussion of challenges related to implementation of novel cellular therapies. Common themes throughout the discussion included data, standardization, accreditation, gaps in legislative policies, cost of goods and reimbursement, relationships between academia and industry, and early professional education.
The FACT Regenerative Medicine Task force will draft a summary of the meeting and distribute this document to all participating organizations for review and input. After all organizations complete this review, the summary will be distributed to stakeholders.
FACT-accredited organizations are regulated by several governmental agencies around the world in relation to quality and safety of cellular therapy products and reimbursement. When draft regulations or guidance documents are released, FACT committees review the information and submit comments as applicable to the scope of FACT accreditation. In the past decade, comments have been submitted to agencies in the United States, Australia, and Europe. The FACT Global Affairs Committee also supports cellular therapy leaders in developing countries to encourage use of FACT Standards.
So far this year, FACT has submitted comments on three topics to two agencies in the United States:
- Docket No. FDA-2017-D-6154 for “Evaluation of Devices Used with Regenerative Medicine Advanced Therapies; Draft Guidance for Industry”; submitted to the Food and Drug Administration (FDA) on February 9, 2018.
- Docket No. FDA-2017-D-6159 for “Expedited Programs for Regenerative Medicine Therapies for Serious Conditions; Draft Guidance for Industry”; submitted to the Food and Drug Administration (FDA) on February 9, 2018.
- National Coverage Analysis for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers; submitted to the Centers for Medicare & Medicaid Services on June 15, 2018.
FACT also plans to review the recently published FDA draft guidance documents for gene therapies. These comments are due by October 10, 2018. If you have input you would like FACT to consider for inclusion, submit those to Kara Wacker at email@example.com by August 31, 2018.
In November 2017, the FDA released a comprehensive policy framework for the development and oversight of regenerative medicine products, including novel cellular therapies, through the publication of four guidance documents. Two of these documents were finalized, and two are open for public comment.
Draft documents that were open for public comment until February 14, 2018 include:
- Evaluation of Devices Used with Regenerative Medicine Advanced Therapies
- Expedited Programs for Regenerative Medicine Therapies for Serious Conditions
Related documents published in final form include:
- Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception
- Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use
FACT supports the FDA’s efforts to clarify and streamline its regulation of regenerative medicine therapies, and submitted comments organized into two sections: 1) the role of FACT accreditation in advancing cellular therapy for regenerative medicine and 2) specific comments about the guidance documents themselves.
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.
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 interorganizational Donor History Questionnaire materials have been updated to reflect recommendations made by the FDA’s Guidance for Industry: “Revised Recommendations for Determining Eligibility of Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products Who Have Received Human-Derived Clotting Factor Concentrates,” published in November 2016.
The Donor History Questionnaire (DHQ) materials were developed to screen allogeneic HPC donors for communicable disease risk factors in accordance with requirements of the Food and Drug Administration (FDA), AABB, FACT, and the National Marrow Donor Program (NMDP).
The FDA does not mandate use of any particular tool to fulfill donor screening requirements for communicable disease risks and has determined that “official” recognition of DHQ materials in a guidance document is not warranted. The task force believes the DHQ materials, which are harmonized with applicable regulations and guidance documents, will optimize donor comprehension of the questions and provide donor historians with the tools needed to evaluate donor responses. Facilities should read the “User Instructions” carefully before adopting the materials for use.
When a facility implements a new version of these DHQ materials, it should follow its established change control process for the incorporation of the new DHQ materials. The change control process should address validation of the use of the new version with other existing processes and appropriate staff training.
The 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, FACT’s Chief Medical Officer, 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 our parent society, ISCT, in its position on unproven therapies and agree 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. Possible solutions to this problem include:
- Determination of “homologous use” could be not dependent on initial categorization of the whole tissue, but allow for cells and structural elements to be considered individually. The term “such HCT/P” could then be used to apply to either the cells or the structural elements, depending on intended use in the recipient.
- The term “homologous use” could be broadened to include any function or functions performed in the donor, not only the “basic function”.
- The Agency could recognize “standard of care” exceptions for certain procedures that have long been in place without such tissue regulation; those procedures in which data exist related to practitioners, procedures, and safety. Breast reconstruction is an example of this potential exception.
- There appear to be some inconsistencies in the definitions and examples of homologous use that would benefit from clarification.
- Although various phrases are used for the definition of homologous use, such as “perform the same basic function or functions” and “perform one or more of the same basic functions,” the examples seem to ignore the concept of more than one function of a tissue.
- The following example is also confusing to many: the guidance documents consider it to be non-homologous to put adipose tissue into breast tissue, since the basic function of the breast is lactation, ignoring the role of fat in support and shape. Yet it is considered to be homologous to put islets into liver, even though the primary function of liver is not glucose homeostasis.
- 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. For example, cord tissue is often collected, cryopreserved, and stored as whole tissue when the future use is undetermined at collection and storage, but it is likely intended for patient treatment. To ensure this tissue is considered to be a usable starting material in the future, the current regulatory pathway is unclear. In contrast, cord tissue may be significantly processed after collection, prior to cryopreservation and stored with the clear intent to use as MSCs or other product for an undetermined recipient.
- International harmonization is important to facilitate product development and world-wide availability of cell-based therapies for patients.
Dr. Warkentin’s full presentation is available online.
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 function of the body is defined as (1) identify opportunities for the development of laboratory regulatory science research and documentary standards that the Secretary determines would support the development, evaluation, and review of regenerative medicine products; and (2) work with such Standards Coordinating Body, as appropriate, in the development of standards described in paragraph (1).
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).
As the SCB is formalized in the coming months, FACT will announce milestones and initiatives to its stakeholders.