6th Edition FACT-JACIE International Standards for
Hematopoietic Cellular Therapy Product Collection, Processing, and Administration
Summary of Changes
This document summarizes the changes made to the 6th edition of the FACT-JACIE
International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and
Administration. This summary does not list all changes made to the Standards; refer to the final
Cellular Therapy Standards and the accompanying Accreditation Manual for all requirements.
Changes made to the 6th edition Cellular Therapy Standards and/or its accompanying
Accreditation Manual include:
Global Changes
1.
Revised Title
a. FACT-JACIE Standards are now called FACT-JACIE International Standards for
Hematopoietic Cellular Therapy Product Collection, Processing, and
Administration, also referred to as the Hematopoietic Cell Therapy Standards.
b. The purpose is to define the scope of these requirements due to an increasing
number of accredited facilities that support non-hematopoietic cellular therapies
and because FACT now has a separate set of Standards for those services (the
Common Standards for Cellular Therapies). The scope of the Hematopoietic Cell
Therapy Standards includes:
i. Collection, processing, and administration of hematopoietic progenitor
cells (HPCs), whether minimally or more than minimally manipulated, for
hematopoietic indications.
ii. Collection, processing, and administration of cellular therapy products for
donor lymphocyte infusion (DLI).
c. Facilities pursuing accreditation for hematopoietic services in addition to
collection and processing for other clinical specialties (e.g., immunology,
cardiology, neurology, etc.) may consult the Hematopoietic Cellular Therapy
Standards as a single reference point.
d. Clinical Programs for other specialties may only share an accreditation with a
hematopoietic progenitor cell (HPC) transplant program if the same physician
group serves the same patient population (for example, if an immunology
program works with the transplant program to administer CAR-T cells). If a
different patient population is served, the program likely will not be able to share
an accreditation because of differing directorship and protocols. In these cases,
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the Clinical Program will be inspected and accredited under the Common
Standards.
e. For more details for how the Standards will be applied, reference the Just the
FACTs Newsletter, Fall 2014 (Available at:
http://factwebsite.org/uploadedFiles/Just_the_FACTs_Newsletter/Fall%202014(1
).pdf)
2. New Format
a. The new format of the Standards visually groups related requirements.
b. Standards used solely for organizational purposes, but without specific
requirements, were removed to make the document briefer. Header standards
that facilitate comprehension remain.
3. Continuing Education (B3.1.6, B3.2.2, B3.5.3, B3.8.4, B3.10.2, CM3.1.5, CM3.2.2,
C3.1.5, C3.2.5, C3.3.2, D3.1.3, D3.2.3, D3.3.2)
a. Hours
i. Key personnel (directors, attending physicians, quality managers, and
designated pharmacists) must participate in at least 10 hours of
continuing education.
ii. The number of hours is now specified in response to concerns from
applicants and inspectors that “regular participation” is too ambiguous.
iii. Because there are many topics related to the required areas of education,
and because formally recognized activities (e.g., CME activities) are not
necessarily required, this is an achievable amount of activity.
b. Required areas of education include:
i. Clinical Program Director, attending physicians, and designated
pharmacists: Cellular therapy, to include (but not limited to) the field of
HPC transplantation.
ii. Quality Managers: Cellular therapy and/or quality management, to include
(but not limited to) the field of HPC transplantation.
1. Collection quality managers should also have education in cell
collection.
2. Processing quality managers should also have education in
cellular therapy processing.
iii. Marrow Collection Facility Medical Director: Cellular therapy, to include
(but not limited to) the field of HPC transplantation and marrow collection.
iv. Apheresis Collection Facility Director and Medical Director: Cellular
therapy, to include (but not limited to) the field of HPC transplantation and
apheresis.
v. Processing Facility Director and Medical Director: Cellular therapy, to
include (but not limited to) the field of HPC transplantation and
processing.
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4. Annual Review of Quality Management Program (B4.1.2, C4.1.1, D4.1.1)
a. Many applicants did not understand the purpose of the annual report on the
performance of the Quality Management (QM) Program, which is a longitudinal
review of the program.
b. The 6th edition more clearly explains this by requiring the Director to annually
review the effectiveness of the QM Program, and provide documentation of the
review findings to the Clinical Program Director (collection and processing).
5. Outcome Analysis (B4.7, C4.7, D4.7)
a. Analysis
i. Outcome analysis must include evaluation of individual cellular therapy
product data and aggregate data for each type of cellular therapy product
and/or recipient type.
1. Products must be safe for individual recipients and any adverse
events must be reviewed.
2. Aggregate data will illustrate trends that may need to be
addressed.
ii. Clinical Programs must compare one-year survival to national or
international outcome data, and should achieve survival rates within
expected ranges.
1. With the introduction of national and international comparative
outcome data, Clinical Programs have additional resources to
evaluate their one-year survival rates and improve upon them
when they fall below expected ranges.
2. Clinical Programs should begin evaluating their one-year survival
rates in comparison with published data soon, before it could have
an impact on their accreditation. This new recommendation will
also give programs, FACT, and JACIE experience with this type of
evaluation before any decisions are made to officially require
outcomes within expected ranges in future Standards editions.
3. In the U.S., the CIBMTR Transplant Center-Specific Outcome
Data must be used.
a. This report calculates center-specific expected ranges, so
all programs should feasibly be able to perform as
expected. There is no default number of programs that will
fall out of range.
4. Programs in other regions must report which data is used to FACT
or JACIE.
5. If expected one-year survival outcome is not met, the Clinical
Program must submit a corrective action plan. FACT plans to
establish a committee to create tools and resources for performing
root cause analysis.
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b. New required analyses:
i. Clinical Programs:
1. Acute GVHD grade within one hundred (100) days after
transplantation.
2. Chronic GVHD grade within one (1) year after transplantation.
3. Central venous catheter infection.
ii. Apheresis Collection and Processing Facilities:
1. Time to engraftment measured by ANC and platelet count.
6. Audits (B4.8, C4.8, D4.8)
a. Most required audits must now be performed annually.
i. Audits do not need to have the same objective every year. Different
points of processes can be audited.
7. Deviation Management (B4.10, B5.7, CM5.7, C4.10, C5.7, D4.10, D5.7)
a. There were several disparate comments regarding deviation management
requirements, indicating a general lack of clarity. The section was revised to be
more concise and streamlined.
b. The most significant change to requirements is in regards to planned deviations,
or variances.
i. Variances always require pre-approval, and that process requires less
scrutiny after the occurrence because approval was granted upfront.
ii. Pre-approvals for variances are now required in the policies and
procedures section and do not need to undergo the exact process as
required for serious adverse events, errors and accidents, and biological
product deviations in the quality management section.
c. Documentation of incidents and investigation reports now requires more detail.
8. Qualification and Validation (B4.13, C4.14, D4.14)
a. Qualification of critical reagents, supplies, equipment, and facilities used for the
marrow collection procedure is now required.
b. More specific requirements for validation studies are delineated in response to
common deficiencies found during on-site inspections. Such requirements
include:
i. An approved validation plan, including conditions to be validated.
ii. Acceptance criteria.
iii. Data collection.
iv. Evaluation of data.
v. Summary of results.
vi. Review and approval of the validation plan, results, and conclusion by the
director or designee and Quality Manager or designee.
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9. Policies and Procedures (B5, CM5, C5, D5)
a. Newly Required Standard Operating Procedures (SOPs)
i. Clinical Program:
1. Donor screening, testing, eligibility determination, selection, and
management: This was always required per B6 but more explicitly
stated in B5 in the 6th edition.
2. Management of donors who require central venous access:
Infections are a real risk and must be minimized.
3. Administration of ABO-incompatible products to include a
description of the indication for and processing methods to be
used for red cell or plasma reduction: Requirements have been in
the processing section, but it is the attending physician that
actually writes the order.
4. Duration and conditions of cellular therapy product storage and
indications for disposal: This is another requirement that has been
in the processing section; however, the attending physician
ultimately approves disposal. (See also D12.1.6)
5. Hygiene and use of personal protective equipment: This has
always been required to maintain safety of personnel, but is now
explicitly stated.
ii. Marrow Collection Facility
1. Donor testing, eligibility determination, and management: In
addition to a donor screening SOP, facilities must address donor
testing, eligibility determination, and management in SOPs in
compliance with CM6.
2. Hygiene and use of personal protective equipment: This has
always been required to maintain safety of personnel, but is now
explicitly stated.
3. Emergency and disaster plan related to the marrow collection
procedure: Although Marrow Collection Facilities work closely with
the Clinical Program, there are considerations for emergency and
disaster management with respect specifically to the marrow
collection procedure.
iii. Apheresis Collection Facility
1. Management of donors who require central venous access:
Infections are a real risk and must be minimized.
2. Administration of blood products: Apheresis Collection Facilities
often need to administer blood products to donors and this should
be performed according to an established procedure.
3. Prevention of mix-ups and cross-contamination: Apheresis
Collection Facilities often have more than one cellular therapy
product in its possession.
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4. Hygiene and use of personal protective equipment: This has
always been required to maintain safety of personnel, but is now
explicitly stated.
iv. Processing Facility
1. Recalls of equipment, supplies, and reagents: Recalls for
materials have an effect on resources for future processing, and
cellular therapy products processed with defective materials may
have been adversely affected.
b. Other changes
i. The SOP manual’s listing of current SOPs must include the title, identifier,
and version for completeness and control.
ii. Age-specific issues are now a required element of SOPs, which is
believed to assist programs to remember to consider these issues when
developing procedures.
iii. In addition to staff training, competency must be documented before a
staff member performs a new or revised procedure, if appropriate.
10. Donor Selection, Evaluation, and Management (B6, CM6, C6)
a. The Clinical Program must have written criteria for selection of allogeneic donors
who are elderly in addition to those who are minors.
b. Interpretation and translation must be performed by individuals qualified to
provide these services in the clinical setting.
i. The Standards recommend that family members and legally authorized
representatives not serve as interpreters or translators. It is expected that
every effort be made to avoid this situation, but it is also understood that
many centers treat patients who speak uncommon languages.
c. Informed consent and donor evaluation now must be obtained by a health care
professional who is not the primary health care professional overseeing care of
the recipient. This was only a recommendation in the 5th edition.
d. The informed consent process must inform the donor of the policy for cellular
therapy product discard or disposal.
e. Pregnancy tests are now required.
i. Previous editions only required a pregnancy assessment for female
donors with childbearing potential, which was often misinterpreted.
ii. Tests must be performed within seven (7) days prior to starting the donor
mobilization regimen and, as applicable, within seven (7) days prior to the
initiation of the recipient’s preparative regimen. This is particularly
important when the recipient is on a long-term (for example, 21-day)
preparative regimen.
f. The requirement for a written order from a physician specifying the timing and
goals of collection and processing is now also included in the clinical standards.
g. The requirement for verification typing of the selected donor, with results
confirmed prior to administration of the preparative regimen, is more explicitly
stated in response to many questions.
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h. Clinical Programs must have a policy for anti-HLA antibody testing for
mismatched donors and recipients.
i. Records required for donor eligibility determination must be in English or
translated into English when crossing international borders.
j. Standards throughout the document explicitly reference requirements for
incomplete donor eligibility determination in addition to ineligible donors.
11. Cord Blood Administration
a. Clinical Programs and Processing Facilities must have a procedure to confirm
the identity of cord blood units if verification typing cannot be performed on
attached segments, given Clinical Programs’ experiences with too few segments
to perform verification typing. (B6.4.12.3, D8.13)
b. Clinical Programs must consult with the Processing Facility regarding cord blood
preparation for administration. Cord blood units that have not been red cell
reduced prior to cryopreservation are now required to be washed. (B7.6.3)
c. Requirements for cord blood washing (which is required for units that were not
red cell reduced prior to cryopreservation) were intentionally duplicated in the
processing section in recognition of the relationship between clinical and
processing: physicians order the preparation and processing personnel perform
the task. (D8.4.3, D8.4.4)
12. Control of Facility Parameters (CM2.3, C2.4, D2.3)
a. Facility parameters that may affect cellular therapy product viability, integrity,
contamination, sterility, or cross-contamination during collection, including
temperature and humidity at a minimum, must be assessed for risk to the cellular
therapy product.
b. Parameters identified to be a risk must be controlled, monitored, and recorded.
c. Applicants and inspectors often questioned what parameters must be controlled,
and their opinions sometimes differed. These revisions are intended to ensure
applicants assess risks of facility parameters and document that assessment.
Such information will help inspectors make a judgment call on the adequacy of
facility controls.
13. Backup Coverage of Staff (CM3.3.2, C3.4.1, D3.4.1)
a. Facilities were often found to have minimal staff that was only sufficient should
no staff members be absent.
b. To provide sufficient coverage should staff members become unavailable,
facilities must have a minimum of one designated trained individual with an
identified trained backup.
14. Labeling (CM7, C7, D7, Appendix II, Appendix III)
a. The 5th edition required organizations to have a plan for ISBT 128 coding and
labeling technology implementation. The proposed sixth edition requires that
organizations be actively implementing ISBT 128 coding and labeling
technologies.
i. “Actively implementing” could be demonstrated by registration with
ICCBBA, identification or creation of appropriate product codes, label
designs, label validation, and/or use of scanned information.
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ii. ISBT 128 does not need to be implemented at the bedside since many
medical record systems are not compatible and significant time and
resources would be required to enable compatibility.
b. Barcoding may negate the need for verification of label information by two
people. The verification now may be conducted by two qualified people or by one
qualified person using a validated process.
c. Label Content
i. Product attributes and recipient name no longer need to be affixed when
using partial labels.
ii. Name and quantity of anticoagulant and other additives, and expiration
date and time may now accompany the product rather than be attached.
iii. The statements “Properly Identify Recipient and Product” and “For Use by
Intended Recipient Only” are no longer required.
iv. The statement “For Nonclinical Use Only” is no longer in the appendix
since the table applies to products for clinical use; however, the
requirement remains. It is now stated in the text as Standards CM7.4.6,
C7.4.6, and D7.4.7.
v. Date and time of distribution no longer need to be affixed to the outer
container label during shipping and transport on public roads.
vi. If labels are generated by ISBT 128 technologies or are approved under
an Investigational New Drug (IND) application, those requirements must
be used.
d. Requirements for Warning Labels On and Documents Accompanying Autologous
Cellular Therapy Products
i. Although United States FDA donor eligibility requirements do not apply to
autologous products, the following warning statements and
accompanying documentation do apply:
1. The statement, “FOR AUTOLOGOUS USE ONLY”.
2. The statement “NOT EVALUATED FOR INFECTIOUS
SUBSTANCES” unless screening and testing is performed in
accordance with all FDA donor eligibility requirements.
3. The statement “WARNING: Reactive Test Results for [name of
disease agent or disease]” if there are any identified risk factors or
reactive test results. Note that if identified risks/results were a
result of screening and testing that do not meet all FDA donor
eligibility requirements, this statement must be used in addition to
the statements in points 1 and 2 above.
4. Instructions for product use to prevent the introduction,
transmission, or spread of communicable diseases and for
reporting serious adverse reactions or events to the distributing
facility.
5. Documents related to identified risk factors or reactive test results
if any donor screening or testing is performed, whether or not all
FDA requirements are met.
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15. Liquid Nitrogen Safety (B2.15, D2.1.2, D2.8)
a. The number of deficiencies in regards to safety of liquid nitrogen handling and
oxygen sensors (or lack thereof) prompted more explicit requirements.
b. Clinical Program personnel are in the immediate vicinity of liquid nitrogen when a
cryopreserved cellular therapy product is brought to the clinical unit. The written
safety manual must include action in case of exposure to liquid nitrogen.
c. Processing Facilities must have oxygen sensors that are appropriately placed
and utilized in areas where liquid nitrogen is present and must also specifically
address liquid nitrogen exposure in the written safety manual.
Changes Specifically to Clinical Program Requirements
16. Clinical Program Location (B1.1 and B1.1.1)
a. Rather than specifying that clinical sites be housed in geographically contiguous
or proximate space, the Standards now state that an integrated medical team
and Clinical Program Director must be housed in a defined location and
demonstrate common activities among all sites.
b. Rationale
i. The change more clearly describes the underlining intent of the
requirement, which is that all clinical sites must have regular, documented
interaction and consistent protocols to be considered a single program.
ii. Improvements in technology (e.g., medical records and document
management systems) and infrastructure (travel opportunities) have
enabled clinical sites across greater distances to cohesively interact.
iii. When several clinical sites apply for accreditation as a single Clinical
Program, the burden is on the applicant to demonstrate compliance with
this requirement. Early consultation with FACT or JACIE is encouraged.
17. Provision of Care in Ambulatory Settings (B2.3)
a. Important services in the transplant process may be provided in ambulatory
settings, such as outpatient units, depending on the region or delivery model.
b. When the preparative regimen, cellular therapy product administration, or initial
post-transplant care is provided in an ambulatory setting, there must be a
designated area with appropriate location and adequate space and design to
minimize the risk of airborne microbial contamination.
18. Accreditation of HLA Typing Laboratories (B2.11 and B6.4.12)
a. Clinical Programs may now use HLA typing laboratories that are accredited by an
organization other than ASHI or EFI, so long as those accreditation programs are
appropriate for the care of HPC transplant recipients.
b. A joint FACT and NMDP consultative committee of HLA experts established
guidelines for what constitutes appropriate standards and accreditation.
c. For an accreditation organization to be recognized as appropriate, it must work
directly with FACT or JACIE to submit documentation and answer questions
related to those guidelines.
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d. Clinical Programs are strongly encouraged to confirm appropriateness prior to
discontinuing receipt of services for ASHI- or EFI-accredited HLA typing
laboratories. Determination of appropriateness prior to accreditation expiration
dates is not guaranteed.
e. The Guidelines for Histocompatibility Typing Standards and Accreditation
Programs will be available on the FACT website.
19. Accreditation of Techniques Used For Chimerism Testing (B2.12)
a. Rationale
i. Clinical decisions regarding the pace of withdrawal of post-transplant
immunosuppression and/or subsequent administration of donor
lymphocytes based on chimerism results may have potentially lifethreatening consequences with respect to GVHD, relapse risk, or graft
failure.
ii. Chimerism testing may be performed with a variety of methods and
interlaboratory variability may be significant.
b. The draft standard available for public comment described this requirement as
accreditation specifically for chimerism testing. There was little disagreement that
laboratory accreditation for chimerism testing is ideal; however, there were many
questions regarding what accreditation is available. The standard was revised to
require accreditation of the techniques used in chimerism.
c. EFI and other organizations provide external laboratory accreditation and quality
assurance in chimerism testing.
20. Clinical Program Director Verification of Knowledge and Skills of Transplant Team
(B3.1.5.1)
a. The Clinical Program Director has been required to verify knowledge and skills of
transplant team in previous editions.
b. The 6th edition requires that such verification occurs at least once per
accreditation cycle.
21. Training for Clinical Program Directors and Attending Physicians (B3.3)
a. New requirements for specific clinical training and competency include:
i. Administration of ABO incompatible cellular therapy products.
ii. Monitoring of pain.
b. New requirement for additional specific clinical training and competency for
programs requesting accreditation for allogeneic transplantation: diagnosis of
opportunistic infections (which includes cytomegalovirus (CMV) infection).
c. New requirement for knowledge: washing and diluting of cellular therapy
products.
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22. Clinical Program Personnel (B3)
a. New sections were added to B3 Personnel to include all key providers in a
Clinical Program.
i. Physicians-in-Training (B3.4)
1. Physicians-in-training must be licensed to practice and limited to a
scope of practice within the parameters of their licensure. They
must also be appropriately supervised.
2. Physicians-in-training must receive specific training and develop
competency in transplant-related skills, which include those listed
for attending physicians.
ii. Pharmacists (B3.8)
1. Pharmacist requirements relate to those who perform services for
the transplant program.
2. Pharmacists must be licensed to practice and limited to a scope of
practice within the parameters of their training and licensure.
3. Training must include an overview of hematology/oncology patient
care, therapeutic drug monitoring, monitoring for and recognizing
drug/drug and drug/food interactions and making necessary
modifications, and recognition of medications that require
adjustment for organ dysfunction.
4. Pharmacists should be involved in the development of guidelines
or SOPs related to pharmaceutical management of transplant
recipients.
5. Designated transplant pharmacists (i.e., those who have a
leadership role or routine involvement in the care of transplant
recipients) must meet continuing education requirements.
b. Mid-level practitioners are now referred to as Advanced Practice
Providers/Professionals, or APPs. (B3.5)
c. Consulting specialists must now also include ophthalmology,
obstetrics/gynecology, and dermatology. (B3.9)
23. Clinical Program Document Control (B4.5)
a. Clinical Program document control requirements were expanded in the 6th
edition and are similar to the requirements in the collection and processing
sections.
b. The document control system must include:
i. Policies, protocols, and Standard Operating Procedures; worksheets;
forms; and labels.
ii. Elements listed in B4.5.3.
iii. Process for regular review and assessment of records to identify recurring
problems, potential points of failure, or need for process improvement.
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24. Recipient Care (B7)
a. This section was previously titled, “Therapy Administration,” but now contains all
requirements related to the care of the transplant recipient.
b. Recipient informed consent must be obtained and documented by a licensed
health care professional familiar with the proposed therapy, and this process
must provide information regarding the risks and benefits.
c. Records must be made concurrently with each step of recipient care in such a
way that all steps may be accurately traced, and must identify the person
immediately responsible for each significant step (including dates and times).
d. Specific references to “chemotherapy” were replaced with references to the
“preparative regimen” to encompass all regimens.
e. Barcoding has become more prevalent in Clinical Programs and may negate the
need for verification of the drug and dose and recipient identity by two people.
The verification now may be conducted by two qualified people or by one
qualified person using a validated process.
f. The recipient’s medical record of the administered cellular therapy product must
include the product’s unique identifier, initiation and completion times of
administration, and any adverse events related to administration.
g. Standard of care has evolved in the assessment of recipients for evidence of
acute and chronic GVHD, need for vaccinations, and post-transplant late effects.
i. Allogeneic recipients must be assessed regularly for evidence of acute
and chronic GVHD using an established staging and grading system.
ii. There must be policies and procedures in place for allogeneic recipient
post-transplant vaccination schedules and indications.
25. Data Management (B9.1)
a. The Standards now recommend that both allogeneic and autologous data are
submitted to a national or international database even if not required by
applicable laws and regulations.
b. Collection of data necessary to complete the CIBMTR Transplant Essential Data
Forms or the EBMT Minimum Essential Data-A forms for at least one year
following administration of the cellular therapy product is recommended.
Changes Specifically to Marrow and Apheresis Collection Facility Requirements
26. Minimum Number of Marrow Collection Procedures (CM1.5)
a. The minimum number remains at a minimum average of one (1) collection
procedure per year within the accreditation cycle.
b. This requirement applies to a single team of collectors and support staff. When
different teams are used at different sites, the minimum number of procedures
must be performed at each of those sites.
c. The guidance also emphasizes that marrow collectors with little experience must
be supervised appropriately to build and maintain competency.
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27. Apheresis Equipment (C8.3)
a. Must be inspected for cleanliness prior to each use and verified daily to be in
compliance with the maintenance schedule prior to use.
b. Calibration must be performed according to a traceable standard and, when out
of calibration, there must be a defined process for action for cellular therapy
products collected since the last calibration.
28. Other Marrow and Apheresis Collection Facility Changes
a. Marrow and Apheresis Collection Facility records must identify the person
immediately responsible for each significant step (including dates and times).
(CM8.15.1, C8.16.1)
b. Marrow Collection Facilities must also control storage areas to prevent mix-ups,
deterioration, contamination, cross-contamination, and improper release or
distribution of products. (CM9.1)
i. Cellular therapy products are always undergoing some process, and
temporary holding until they are picked up by another facility is
considered storage.
c. Cellular therapy products must be transported or shipped to the Processing
Facility in a validated container. (CM10.3, C10.3)
d. Apheresis collection that is performed in outpatient units must be in a designated
area with appropriate location and adequate space and design to minimize the
risk of airborne microbial contamination. (C2.1.2)
e. Apheresis Collection Facility Directors and Medical Directors must have
performed or supervised a minimum of 5- previously 4- collection procedures in
the 12 months preceding initial accreditation and a minimum average of 5
collection procedures per year within the accreditation cycle. (C3.1.4, C3.2.4)
f. Extracorporeal photopheresis (ECP) requirements are now also included in the
apheresis section based on apheresis professionals’ request for more specific
guidelines. A written therapy plan from a physician, SOPs, and a final report of
ECP administered are required. (C8.17)
Changes Made Specifically to Processing Facility Requirements
29. Processing Facility Standards (Part D)
a. Part D was reorganized to separate the Process Controls section into more
manageable sections of like requirements.
b. New sections are named Equipment, Supplies, and Reagents (D6); Cellular
Therapy Product Transportation and Shipping (D10); and Distribution and
Receipt (D11).
30. More than Minimal Manipulation
a. Processing Facilities must qualify environmental control systems and validate
cleaning and sanitation procedures appropriate for the environmental
classification and degree of manipulation performed. (D2.4.1)
b. Processing Facilities must adhere to good manufacturing practices (GMP)
appropriate for the degree of cellular therapy product manipulation. (D8.11.1)
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31. Assays (D8.1.3.2, D8.1.3.3)
a. For HPC products intended for restoration of hematopoiesis, an assay measuring
viable CD34 must be performed. (D8.1.3.2)
b. When manipulation alters the final cell population, a validated assay must be
employed for evaluation of the viable target cell population before and after
processing. (D8.1.3.3)
32. Cellular Therapy Product Receipt (D11.4)
a. Processing Facilities must review and verify the product specifications for cellular
therapy products received by an external facility. There must be documented
evidence of donor eligibility screening and testing in accordance with applicable
laws and regulations for these products.
b. When cellular therapy products are returned to the Processing Facility after
distribution for administration and approved for return to the inventory,
documentation must include the events requiring return, the temporary storage
temperature when at the clinical facility, the results of inspection upon return, and
subsequent action taken to protect product safety and viability.
33. Other Processing Facility Changes
a. Processing Facility Directors and Medical Directors must have a minimum of two
years of postgraduate training and practical and relevant experience for the
scope of activities carried out in the facility. Some regions of the world may have
degrees that are equivalent to the doctoral degree. If a Processing Facility
Director has such a degree, significant and compelling information regarding the
degree requirements must be submitted to demonstrate equivalency. (D3.1.1,
D3.2.1).
b. Policies and procedures on the management of cellular therapy products with
positive microbial culture results must also address the identification of
individuals authorized to approve release, including the Processing Facility
Medical Director at a minimum. (D4.9.4)
c. Records of identification codes of personnel with methods to link the name
and/or signature to the identification codes is no longer required because of
improvements in recordkeeping.
d. Processing Facilities must have a written stability program that evaluates the
viability and potency of cryopreserved cellular therapy products at a minimum
annually. (D9.2.2)
i. There were many questions surrounding how stability studies must be
performed and how they could be applied to early phase cellular therapy
products.
ii. The Standards Committee felt that this requirement is appropriate, but
added guidance that includes examples of how to perform stability
studies and clarification that stability studies can be in development for
early phase products that do not yet have a definitive potency marker.
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Summary of Changes, Rev. 0
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e. Cellular therapy product inventory records no longer need to include the proper
product or specimen name since the unique identifier is the ultimate identifier.
(D9.8.1)
f. The outer container for cellular therapy product transportation or shipping must
be secured. (D10.5.3)
This outline provides a summary of the 6th edition Hematopoietic Cellular Therapy Standards and does
not include all changes or requirements. See the FACT-JACIE International Standards for Hematopoietic
Cellular Therapy Product Collection, Processing, and Administration for all current requirements. The 6th
edition is effective June 1, 2015.
5.2.003, 6th Edition Cellular Therapy Standards
Summary of Changes, Rev. 0
Page 15 of 15