President’s Letter
The past several months have been a metaphorical mountain climb in cellular therapy, presenting steep learning curves in immune effector cellular therapy, regulation of regenerative medicine, payment methodologies, clinical outcomes, data management, and other emerging issues. As challenging as these issues are, it is gratifying to see the entire field come together and collaborate to find solutions and implement improvements.
FACT continues its close interactions with accredited organizations, inspectors, its parent organizations the American Society for Blood and Marrow Transplantation (ASBMT) and the International Society for Cellular Therapy (ISCT), other peer societies, and regulatory agencies. The list of professionals and associations in cellular therapy is long, and the field has a strong network of collaboration.
FACT learned a lot of important lessons in 2017, and plans many process improvements and educational programs in 2018. So much of this is thanks to the support, feedback, and flexibility of our accredited programs, inspectors, and related organizations. Though challenging, the success of cellular therapy is indeed an ascent to higher quality. We should all take the time to stop and look at the view – this is an exciting time for us and for our patients.
Sincerely,
Dennis A. Gastineau, MD
FACT President
FACT Standards Committee Developments
Prepare for the Hematopoietic Cellular Therapy Standards, Seventh Edition
The seventh edition of the FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration will be published on March 1, 2018 and will become effective on May 30, 2018. At that time, FACT will also publish minimal changes to the FACT Immune Effector Cell Standards, Version 1.1, in an effort to provide consistency and transparency among all sets of FACT Standards.
After March 1, 2018, only Compliance Applications under the seventh 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 sixth 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 has contacted accredited and applicant programs who will begin 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.
As FACT is preparing for the seventh edition, we are here to help you do the same! Several upcoming events will provide information regarding changes made and how to comply:
- Cellular Therapy Inspection & Accreditation Workshop at the BMT Tandem Meetings: February 20, 2018 in Salt Lake City
- Effectively Transition to the 7th Edition Hematopoietic Cellular Therapy Webinar: March 14 (online)
- Cellular Therapy Collection Workshop at the ASFA Annual Meeting: April 25, 2018 in Chicago
- Cellular Therapy Inspection & Accreditation Workshop at the ISCT Annual Meeting: May 1, 2018 in Montréal
If you have any additional questions, please contact your FACT Accreditation Coordinator.
FACT Common Standards, Second Edition Nearing Public Comment Period
The FACT Common Standards Steering Committee will complete its initial revisions to the FACT Common Standards for Cellular Therapies, second edition at the BMT Tandem Meetings in February 2018. A draft for public review and comment is scheduled for publication in April 2018.
NetCord-FACT International Standards for Cord Blood, seventh Edition Development Process Underway
The NetCord-FACT Standards Steering Committee initiated the development process for the NetCord-FACT International Standards for Cord Blood Collection, Banking, and Release for Administration, seventh edition development, and the timeline for publishing the Standards.
The committee is excited to begin working with the subcommittees on the initial review of the documents in March. The Cord Blood Steering Committee roster can be found on the FACT website.
Article written by Andra Moehring, MHA
Transitioning to New and Revised FACT Standards: Advice from the Quality Committee
Managing change is a difficult task we are faced with on a daily basis. FACT provides guidance and resources to help navigate changes from one edition of Standards to the next. With an enthusiastic staff, a thorough plan, and the right resources, your program will be able to proactively address the changes and avoid feeling overwhelmed. The purpose of this article is to provide tips and references for transitioning to new Standards editions.
FACT releases new editions of Standards on a three-year cycle, issuing interim standards as needed. The public comment period is your first opportunity to preview changes that will be made. The draft Standards and Accreditation Manuals are made available to the public for review and comment nine months in advance of final publication. Even though the Standards are not finalized, the drafts released at this time allow your program to begin a preliminary assessment of the new edition’s potential impact on its policies and processes.
On March 1, 2018, the 7th edition of the FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration (the Standards) will be published. Immediately following publication, begin assessing the new and revised requirements and implementing changes as necessary to become in compliance before these Standards become effective on May 30, 2018.
Operational changes for FACT compliance are often most efficient if leadership-driven; therefore, the first step is to assign a leader or group within your organization who will be responsible for implementation (e.g., Program Director, Administrator, or Quality Committee). Next, a point person or group should be identified to facilitate review of existing and proposed standards along with the summary of changes provided by FACT. The Accreditation Manual should be referenced for guidance. The focus of a preliminary review will be on the intent of the new edition of the Standards.
Next, perform a gap analysis, which compares specific requirements against existing policies and procedures. Evaluate how changes in the Standards will affect current processes and determine new methods for compliance. Use the FACT self-assessment tool to effectively and efficiently track new or revised standards, gap analysis information, and follow-up plans. Developing a crosswalk between the new Standards and an organization’s relevant SOPs, forms, worksheets, and labels will assist the program with identifying deficiencies in compliance with the new edition. This gap analysis will flag concerns that will require review and discussion at an organizational level.
A gap analysis should not focus solely on the new or revised standards but also include unaffected standards. This is an excellent opportunity to proactively evaluate overall compliance with the FACT Standards and further prepare your program for future inspections. Furthermore, the program must verify that implementation of policies and procedures for new or revised standards does not adversely affect its compliance with existing standards.
Feedback from all critical stakeholders should be addressed. Ways to accomplish this is to tap into existing committee structures or by chartering working group(s) with delineated scope and schedules. Key personnel from all facilities (i.e., clinical, collection, processing, and cord blood banks) should collaborate to identify issues relevant to the group including, but not limited to:
- Which documents in each facility will need to be created or revised?
- Which personnel within each facility will be impacted (e.g., will require training and competency)?
- How will the change affect work processes?
- Are dedicated meeting(s) with affected staff required?
Some methodologies for assessing compliance and identifying noncompliance (or predicting the risk of non-compliance) with new or revised standards include procedural review, audits, and mock inspections. To evaluate potential impact on policies and processes for high-risk activities, conducting a predictive failure analysis, using a tool such as Failure Mode Effects Analysis (FMEA), may be warranted.
Effective meetings will result in the best outcomes. If possible, group members should schedule time for meetings, recognizing that regular attendance and active participation are essential. Members of each facility should prepare and present an agenda for common discussion, circulating it and any handouts for review in advance. Discussion items should be summarized with conclusions and action items should be assigned both a responsible party and a target date for completion.
Participants are responsible for identifying change(s) in the standards they are assigned, ensuring these revisions are tracked in the crosswalk with facility and organization policies and procedures. Prior to presenting at larger organizational meetings, smaller working group meetings may be helpful to agree on the plan for the standards to be discussed.
It is helpful to develop and manage an implementation plan for needed changes identified by the gap analysis. This is a dynamic activity that addresses logistical concerns and changes required, solutions to new issues, action items with due dates, and staff assignments. Again, crosswalks developed using the FACT self-assessment tool can help with organizing these activities; however, for particularly complicated action plans, a separate tool(s) may be necessary.
In addition to assistance provided by FACT staff, FACT provides a variety of useful and practical resources that may support organizations’ compliance with new, revised, and current standards. Organizations can prepare early by regularly reviewing FACT resources, including, but not limited to:
- the “Just The FACTs” newsletter,
- the LinkedIn “FACT Active Learning Forum,”
- Ask FACT and ASK-A-PEER,
- Weekly emails,
- Educational events, and the
- FACT Quality Handbook: A guide to implementing Quality Management in Cellular Therapy Organizations.
Additionally, the online FACT Cellular Therapy Library and FACT Cord Blood Library include tools for organizations including the self-assessment tool mentioned earlier, Document Submission Requirements, Summary of Changes, and numerical crosswalks between old and new Standards editions. In-person events are also offered to facilitate the Standards transition process and allow opportunities for interaction with FACT leaders. Check the FACT website’s calendar frequently, as FACT’s educational events include many sessions throughout the year such as webinars, workshops, and Quality Boot Camps. FACT recommends using multiple sources of educational resources based on your organization’s learning style and focus.
Once transition changes are identified and proposed solutions are discussed and agreed upon, these solutions must be implemented in accordance with the program’s quality management plan. Policy and procedure revisions must be documented and approved with defined effective dates. The change process must involve all affected personnel, providing them with associated documents and other resources in advance of the change to allow them time to complete required training prior to implementation. To help error-proof the process change, retired documents must be archived appropriately and outdated documents must be removed from use.
Once changes are deployed, it is prudent to review and analyze the impact of the changes on the quality management systems. Some methods to accomplish this are:
- performance of an audit for effectiveness,
- review of staff training records and/or competency testing, and
- assessing the availability of current documents at all relevant sites.
To close the loop on implemented changes, it is essential to provide feedback to responsible groups and personnel.
Armed with your plan, engaged staff, and FACT resources, the transition to the new edition of Standards will be efficient and effective. Please contact the FACT Office with any questions. The staff can refer you to the right resource to solve your problem. We all recognize that change is inevitable, but with the right resources, change can be managed.
Article written by Therese Dodd BA, MBA, RN, CPHQ, FNAHQ
New Online List of Accredited Organizations Includes Accredited Services, Search Functions
The official listing of FACT-accredited organizations is on the FACT website at www.factwebsite.org. The addition of new accreditation services (including Immune Effector Cellular Therapy) and sets of Standards led to increased diversity in the types of organizations accredited by FACT. To provide greater clarity on accredited services, and to structure the information in a useful way, FACT created a new online search of accredited organizations.
The new webpage provides a menu of filters for identifying programs based on their location, accredited services, standards set, and status as an accredited service provider. Searches can be further refined by clicking on specific elements of information to continue to narrow down the list of organizations by different criteria.
We are pleased to provide this new online search page not only to enhance the information available to FACT’s stakeholders, but to also highlight the accomplishments of our accredited organizations.
FACT Accreditation of Immune Effector Cellular Therapy Programs
It has been one year since FACT published the FACT Standards for Immune Effector Cells, and the associated accreditation program has not only begun, but has grown and matured over the past several months. Much of its success is credited to the organizations that have undergone inspections and provided important feedback and experience to FACT inspectors and committees.
As of February 12, 2018, 43 inspections of immune effector cellular (IEC) therapy programs have been conducted or scheduled. Of these, 24 have achieved accreditation. Congratulations to all of these programs. It has been an honor for FACT to assist programs with establishing and improving quality-based processes to facilitate desirable outcomes for patients receiving these new therapies.
Clinical Programs Accredited for Immune Effector Cellular Therapy as of February 12, 2018
Banner MD Anderson Cancer Center, Gilbert, AZ
Director: Rajneesh Nath, MD
Baylor College of Medicine, Stem Cell Transplant Program, Texas Children’s Hospital and Houston Methodist Hospital, Houston, Texas
Director: Helen Heslop, MD
Baylor University Medical Center, Dallas, Texas
Director: Edward Agura, MD
Blood and Marrow Transplant Program at Children’s Hospital Los Angeles, Los Angeles, California
Director: Neena Kapoor, MD
Children’s Healthcare of Atlanta Blood and Marrow Transplantation Program, Atlanta, Georgia
Director: Lakshmanan Krishnamurti, MD
Children’s National Health System Blood and Marrow Transplant Program, District of Columbia, Washington
Director: David Jacobsohn, MD, ScM
City of Hope Hematopoietic Cell Transplantation Program, Duarte, California
Director: Stephen J. Forman, MD
Colorado Blood Cancer Institute Blood and Marrow Transplant Program, Denver, Colorado
Director: Richard A. Nash, MD
Emory University Hospital Bone Marrow and Stem Cell Transplant Center, Atlanta, Georgia
Director: Amelia Langston, MD
Hamilton Health Sciences Stem Cell and Bone Marrow Transplant Program, Hamilton, Ontario
Director: Irwin Walker, MBBS, FRACP, FRCPC
Indiana Blood and Marrow Transplantation (IBMT), Indianapolis, Indiana
Director: Luke Akard, MD
Indiana University Bone Marrow and Stem Cell Transplantation Program, Indianapolis, Indiana
Director: Sherif Farag, MD, PhD, FRACP, FRCPA
Mayo Clinic Rochester Blood and Marrow Transplant Program, Rochester, Minnesota
Director: William J. Hogan, MBBCh
Medical College of Wisconsin Blood and Marrow Transplant Program Children’s Hospital of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin
Director: David Margolis, MD, MS
MedStar Georgetown University Hospital Stem Cell Transplant and Cellular Immunotherapy Program, Washington, District of Columbia
Director: Scott Rowley, MD, FACP
Northwell Health Adult HPC Transplant Program, Manhasset, New York
Director: Ruthee-Lu Bayer, MD
Roswell Park Cancer Institute Corporation, Buffalo, New York
Director: Philip L. McCarthy Jr., MD
Sarah Cannon Blood and Marrow Transplant Program, Nashville, Tennessee
Director: Carlos Bachier, MD
St. Jude Children’s Research Hospital Department of Bone Marrow Transplantation and Cellular Therapy, Memphis, Tennessee
Director: Brandon Triplett, MD
Texas Transplant Institute at Methodist Hospital, Methodist Children’s Hospital in San Antonio and South Austin Medical Center in Austin, Austin & San Antonio, Texas
Director: Paul Shaughnessy, MD
The Blood & Marrow Transplantation Program of the Holden Comprehensive Cancer Center at the University of Iowa, Iowa City, Iowa
Director: Margarida Silverman, MD
UCSF Medical Center Adult Blood and Marrow Transplant Program, San Francisco, California
Director: Lloyd Damon, MD
University of Nebraska Medical Center/Nebraska Medicine Hematopoietic Cell Transplantation Program, Omaha, Nebraska
Director: Lori Maness, MD
Westchester Medical Center, Cancer Center, Valhalla, New York
Director: Mitchell Cairo, MD
Requirements for Qualifying Third-Party Manufacturers of Cellular Therapy Products Regulated Under U.S. INDs or BLAs
In light of the recent licensing of immune effector cell (IEC) products in the United States, this is an opportune time to continue education regarding third-party manufacturers in general. The manufacturing process for many novel cellular therapy products, including research and licensed cellular therapy products, involves multiple entities: holders of Investigational New Drug (IND) applications for research or Biological License Applications (BLA) for licensure, collection facilities, and processing facilities. Clinical units may be involved with one or more of these facilities.
There are three main responsibilities when third-parties are involved in the manufacture of a research or licensed product: verify regulatory oversight, qualify the vendor or service provider, and define responsibilities.
Though many questions from organizations regarding these requirements are specific to IEC processes, the information below can also be used as guidelines for other types of cellular therapy products.
Verify Regulatory Oversight
- The participating manufacturer (e.g., collection or processing facility) is responsible for verifying that the contracting entity for whom it performs services possesses an approved IND or BLA.
- The Clinical Program is responsible for verifying the manufacturer responsible for the entire manufacturing process (e.g., a commercial manufacturer) possesses an approved IND or BLA.
Qualify the Third-Party Manufacturer
- The IND or BLA holder is responsible for verifying that any facility performing a step of manufacturing complies with GMP and GTP requirements as applicable (see 21 CFR 1271.150(c)(1)(iii)).
- If the IND or BLA is held internally by a FACT-accredited facility, then the facility must perform this qualification and provide documentation to FACT inspectors.
- If the IND or BLA is external, i.e., held by a third-party investigator or manufacturer, this qualification is outside the scope of FACT accreditation and the FACT-accredited facility is not required to provide documentation of this type of qualification to FACT inspectors.
The participating manufacturer must participate in site visits from the IND or BLA holder and provide the level of service required of that entity, including compliance with GMP and GTP requirements as applicable. FACT-accredited facilities that participate in manufacturing for external IND or BLA holders must provide FACT inspectors evidence of complying with these requirements as required by applicable laws and regulations.
- The Clinical Program must perform vendor qualification of the IND or BLA holder. It is the FDA that monitors regulatory compliance, and the Clinical Program only needs to perform vendor qualification. Programs must verify the IND or BLA holder meets its needs in regards to many areas of cellular therapy, including labeling processes (label content applied by whom and how), level of service (turnaround times, customer inquiries), and other metrics defined by the program. Documentation of this qualification must be provided to the FACT inspection team.
- It is acceptable to delegate this activity to the Processing Facility so long as there is robust communication between the program and facility, which should be obvious in documentation.
Define Responsibilities
- The level of participation of the clinical service in manufacturing an immune effector cell product varies. Regardless of where the product is collected or manufactured, responsibilities must be clearly defined.
- If a Clinical Program is responsible for collecting cells or preparing the IEC product for administration, or if independently FACT-accredited cell collection and processing facilities contract with a manufacturer, FACT Standards for collection and processing apply to the steps performed.
- If products are received directly by the Clinical Program or intermediary facility (e.g., blood bank, pharmacy) from a third-party manufacturer, the following responsibilities must be defined at a minimum: chain of custody, product storage, verification of product identity, and management of adverse events. Additional responsibilities will be included in the new edition of FACT Standards to be published in March 2018.
Exceptional Release for Investigational Cellular Therapy Products in the U.S.
FACT Standard D11.1.2* and its substandards require cellular therapy products to meet pre-determined release criteria prior to distribution from the Processing Facility. When products do not meet release criteria, the Processing Facility Director or Medical Director, as appropriate, must give specific authorization for release.
In the case of investigational products regulated by the Food and Drug Administration (FDA) under Investigational New Drug (IND) applications, the FDA expects that products will not be administered if they fail to meet the release criteria listed in the IND. The FDA recognizes that there are situations when administration of a failed lot may be in the best interest of the patient, but the FDA must be involved in the decision to administer the product. To comply with the FACT Standards, both D11.1.2 and the regulatory requirements of the FDA must be met.
*In the FACT-JACIE Hematopoietic Cell Therapy Standards, the FACT Immune Effector Cell Standards, and the FACT Common Standards.
FACT Submits Comments Regarding Draft FDA Guidance on Regenerative Medicine
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.
Cellular Therapy Accreditation Committee News and Notes
The Cellular Therapy (CT) Accreditation Committee has been busy in 2017 reviewing inspection results for 107 programs, including 5 new programs applying for their initial accreditation. The 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 following are points of interest regarding the CT Accreditation Committee:
- The committee is comprised of volunteer members from FACT-accredited programs representing clinical, collection, and processing expertise.
- Inspectors are encouraged to join committee meetings when their reports will be discussed to provide answers to committee members’ questions. This provides a helpful source of information to the committee when making accreditation outcome decisions.
- Compliance issues noted by inspectors are used for recommendations to the Education Committee to incorporate into inspector training and for FACT workshops and boot camps.
- Commonly cited deficiency data is compiled for publication along with recommendations for programs to avoid those deficiencies. The data is also considered by FACT when revising standards.
The next year looks to be busier than ever with increasing numbers of accredited programs, programs expanding their range of accredited services, and the publication of the seventh edition of the Hematopoietic Cellular Therapy Standards. Also in the coming year will be a public comment period for the next edition of the Common Standards. Additional information about the new Standards will be published leading up to March, so be sure to keep an eye on the FACT website and your email inbox for more information.
Article written by Suzanne Birnley, MS, MBA
NEW Inspector Handbook Mobile App
 The 4th Edition of the FACT Inspector Handbook is now available to download as an application on your mobile phone! The mobile application provides inspectors tips in an easy-to-read format and shares guidelines and wisdom developed by inspectors and accredited organizations since the inception of FACT.
If you have an iPhone, follow these steps: For Android users, follow these steps: |
