bmt stem

1. Blood and Marrow Transplant
(BMT) Program
Annual GxP Training

2. Good Practices
in the BMT Clinical and
Marrow Collection Program
The regulations were written to guide us in doing our jobs better and to produce
safe CTPs. The FDA is responsible for ensuring the safety of our nation's blood
supply. The Center for Biologics Evaluation and Research (CBER) regulates the
collection of blood and blood components used for transfusion or for the
manufacture of pharmaceuticals derived from blood and blood components.
Blood and blood components are both biological products and drugs.
Blood establishments are now held to quality standards comparable to those
expected of pharmaceutical manufacturers.

3. • GxP is an abbreviation that stands for “good practice” following various
quality standards and regulations. The “x” is variable: GMP, GTP, GDP,
GCP
 GMP – Good Manufacturing Practice
 GTP – Good Tissue Practice
 GDP – Good Documentation Practice
 GCP – Good Clinical Practice
• The type of work that is being performed will define which GxPs should
be followed.
• There are variations based on the scope of work of different physicians
and staff members; however, even those not regularly performing
marrow collections must be trained on GxP topics.
What is GxP??

4. • The “x” is variable: GMP, GTP, GDP, GCP
1. GMP – Good Manufacturing Practice
2. GTP – Good Tissue Practice
3. GDP – Good Documentation Practice
4. GCP – Good Clinical Practice
Types of Good Practice

5. GMP – Good Manufacturing Practice
• It is required that all employees involved in the marrow collection
procedure and other relevant processes in the clinical program
comprehend the federal regulations known as Good Manufacturing
Practices (GMPs). These regulations are published in the Code of
Federal Regulations (CFR) and are legal requirements.
• Staff must be knowledgeable of the GMPs that relate to their job duties
and must practice the GMPs at all times.
What is GMP??

6. 1. Record Keeping:
2. Personnel
3. Calibration
4. Validation
5. Error Management
6. SOPs (Standard Operating Procedures) or P&P (Policies &
Procedures)
7. Process Controls
8. Labeling
9. Facilities
10. Equipment/Supplies
11. Quality Assurance
12. Auditing
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GMP Elements

7. 1. Record Keeping:
• Records should provide complete history
• Product trackability (where the product is at all times)
• Product traceability (who performed what process)
• Consistent clinical documentation practices
Examples of record keeping errors:
 Use of Whiteout
 Use of pencil or non-indelible ink
 Incomplete documentation
 Documentation after the fact
 Use of outdated or unapproved forms
 No review of records
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Exploring GMP Elements

8. 2. Personnel
Qualifications and Training
• Personnel performing specific assigned tasks are qualified on the basis
of appropriate education, training, and expertise. Credentials are
verified prior to hire.
• Personnel training is planned, organized, documented and consistent
with individual job descriptions. Education, training and experience to
perform the assigned functions
• Training includes yearly GMP training
• Relevant staff received REMS training
Competency
• Annual competency evaluation and continuing education
Continuing Education
• Relevant staff must complete at least 10 hours continuing education and
submit updated logs at the end of the calendar year
Refer to BMTP-07
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Exploring GMP Elements

9. 3. Calibration
• Documentation of calibration for relevant equipment used in the clinical
program (digital scales for marrow harvest, water baths used for thaw)
• Identification of the equipment and calibration standard used
• Performed at suitable intervals, after major service and as required by
regulation or manufacturer’s recommendations
4. Validations
• Must consistently produce a result that meets pre-established quality
and performance specifications
• Critical processes are validated
• Revalidation must take place following any significant changes in the
equipment, process, or procedure. Refer to BMTP-67
• Marrow collections are done infrequently, therefore a validation of is
completed after each marrow collection. Refer to BMTP-39
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Exploring GMP Elements

10. 5. Error Management
• We have a system to prevent errors, detect errors that have occurred,
and take appropriate corrective actions to avoid future occurrences –
Refer to BMTP-37
• Includes deviations, accidents, incidents, adverse events, complaints
and feedback
• Must report to FDA if may affect safety, purity or potency of blood
• Blood collection or transfusion related fatalities must be reported to the
FDA by phone or email within 24 hours and in writing within 7 days
Deviations should not be feared!!!
• Non-punitive
• Self-reporting is encouraged
• Designed to detect trends
• Root cause analysis
• Corrective action to adjust process or retrain personnel
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Exploring GMP Elements

11. 6. SOPs
• Maintained for all steps to be followed in manufacturing of blood and
blood products (collection, testing, storage, distribution)
• Available for use in the areas where the procedures are performed
• Only one version in use
• Are reviewed, approved, and followed by applicable staff and
departments
• Deviations investigated and documented
• Refer to AD-013 Master List of SOPs
• BMTP-04 Policies, Procedures and Document Control
• BMT SOPs are available on PULSE Intranet and in the event of
computer downtime they are available in binders in the BMT file cabinets
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Exploring GMP Elements

12. 7. Process Controls
• Change Control
 New or changed processes must be controlled and validated to
ensure new process works
 Ideally all staff trained prior to implementation
 Old versions of SOP removed and archived
 New or changed critical processes shall be validated before
implementation
 Changes are communicated to relevant employees
• Quality Control
 Ensure reagents, equipment and methods function as expected
 Results shall be reviewed and corrective action taken where
appropriate
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Exploring GMP Elements

13. 7. Process Controls continued..
• Risk Evaluation
 Risk evaluations are documented to assess new and/or significant
changes to processes for risk.
 Once a potential risk or known risk is identified, the QA Department
under the guidance of the Program Director, evaluates the level of
risk and if necessary CAPA (Corrective Action Preventative Action) is
initiated.
Refer to BMTP-60
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Exploring GMP Elements
Risk Definitions
Extreme Risk Activities in this category contain unacceptable levels of risk
High Risk Activities in this category contain potentially serious risks or the negative
event may occur frequently
Moderate Risk Activities in this category contain varying levels of risk ad varying
probabilities that something will go wrong
Low Risk Activities in this category contain minimal risk

14. 8. Labeling
 Bone marrow harvest labels, applicable warning tags and additional DIN
barcode labels are generated and maintained by the SCPL using the
validated Hema-Trax ISBT-128 labeling system
 Labels and warning tags are validated and approved by the SCPL Medical
Director prior to implementation.
 Labels and warning tags are pre-printed by the SCPL and provided to the
harvest team on or before the day of the harvest.
 Labels for bone marrow products collected in more than one container are
identical, except for an additional designation of AO, BO, CO etc…
 Unused labels are discarded upon completion of collection.
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Exploring GMP Elements

15. 9. Facilities, Equipment & Supplies
 Outpatient, Inpatient and marrow collection facilities are maintained in a
clean and orderly manner. OR cleaning is managed by EVS and the OR
team.
 There is a designated pre-op area for confidential evaluation of the
donor prior to the harvest and there are PACU rooms for post-op
recovery.
 ORs are all well ventilated, have adequate lighting and are temperature
and humidity monitored and there is adequate equipment, supplies and
staff in each OR.
 To avoid mix-ups and contamination, only one marrow collection is
scheduled on a given day.
 Supplies and reagents are visually examined prior to use for evidence of
damage, contamination and expiration.
 Equipment is validated for its intended use and maintained by
Biomedical Engineering
 Refer to BMTP-68 and BMTP-22
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Exploring GMP Elements

16. 10.Quality Assurance Program
• Required to have a QA department
• Under the guidance of the Program Director and QA Chair, the QA
Manager or designee manages the implementation and effectiveness of
the QM Plan
• Goals of The BMT QM Plan and Program:
 Reduce and prevent errors
 Collect and analyze outcome data
 Implement effective mechanisms to improve patient safety, quality of
processes and patient satisfaction
The Program Director (or designee):
 Reviews and reports quality management activities to staff, at a
minimum, quarterly
 Does not have oversight of his/her own work if performing other tasks in
the Clinical Program
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Exploring GMP Elements

17. 10.Quality Assurance Program
QA Responsibilities:
1. Develop, review and approve all SOPs
2. Develop and approve validation protocols
3. Approval of training content
4. Approval of procedures used in QC
5. Error management
6. Internal audits
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Exploring GMP Elements

18. Quality Assurance is everyone’s responsibility!!!
Many components are required to create a true quality program, quality product and
quality patient care
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Exploring GMP Elements
Quality Product
and Patient Care
Quality
Program
SOPs
Training and
Education
Clinical
Documentation
Data Collection
and Analysis
Deviations,
Reporting &
Feedback

19. 11.Auditing
Audits are completed to verify compliance with elements of the Quality
Management Program and operational policies.
Results and audit findings are documented, reviewed by the QA Committee
and are used to detect trends, identify performance improvement
opportunities and implement timely corrective action as necessary.
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Exploring GMP Elements

20. What is GTP??
• Guideline developed by the FDA specifically to establishments that
manufacture Human Cell and Tissue Products (HCT/Ps). Written to be
compatible with GMP.
• Similar to GMP but taking into consideration that the nature of the
product is very different (biologics vs drugs) and specific to tissue which
has not been significantly modified such as stem cells for transplant.
• Applies more to the Stem Cell Processing Laboratory
• Additional guidelines include:
 Donor eligibility requirements
 Focus on the prevention of the introduction, transmission or spread
of communicable diseases
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Good Tissue Practice (GTP)

21. GTP specific requirements relevant to the
Clinical/Marrow Collection Program:
 Recovery (collection) and processing of cells must occur in a way that
does not cause contamination or cross-contamination
 Must have controlled storage areas/rooms for products, supplies and
reagents to prevent mix-ups, contamination and cross-contamination
 Packaging and shipping containers must be designed to protect the
product from contamination
 Records must be retained for a minimum of 10 yrs.
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Good Tissue Practice (GTP)

22. What is GDP??
 The work done in the BMT Program affects the safety of donors, patients
and staff and for this reason it is vital that documentation is of the
highest standard.
IMPORTANT:
 Written procedures must be followed
 Consistency of clinical documentation
 Document everything
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Good Documentation Practice (GDP)

23. What constitutes GDP??
 Documentation and records should be sufficiently detailed and provide
proof that something was done
 Document in real time
 Documents must be clear and legible
 Do not leave blank spaces – write N/A if not applicable or cross out if not
relevant
 Correct errors in a legible way
 Errors must be corrected immediately
 Deviations should be captured and provide sufficient detail to tell a story
 Confidentiality is crucial. Access to certain information and records
should be restricted
 Falsification is not tolerated. Information must be true and accurate
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Good Documentation Practice (GDP)

24. What is GDP??
 Signatures must be traceable. A signature list of maintained of all
clinical employees
 Complete/submit documents on time. Many documents are used by
other departments to perform their tasks so process documents promptly
and do not allow paperwork to pile up. Your work affects others!!
 Records must be stored safely and securely and easily retrievable
 GDP applies to all types of document media; paper and electronic
 Refer to BMTP-64 and BMTP-66
 For the safety of staff, donors and patients:
Do what you document and document what you do!!
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Good Documentation Practice (GDP)

25. What is GCP??
Relevant clinical program faculty and staff involved in FDA
regulated research or internal research with
investigational drugs are required to complete CITI GCP
training
Good Clinical Practice is the compilation of accepted ethical and
scientific standards governing clinical research that ensure the
integrity of data obtained and the protection of human research
subjects.
 GCP was written and designed to address the responsibilities of
all involved in human subject research. Responsibility for
following GCPs is shared among the following:
• Institutional Review Board (IRB)
• Investigator (study team)
• Sponsor
• Monitor
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Good Clinical Practice (GCP)

26. Investigator Responsibilities:
In a nutshell:
1. Follow approved protocol according to the signed agreement ,
investigational plan and FDA regulations
 Responsible for research team’s adherence as well
2. Protect human subjects
 Ensure informed consent (both via IRB approved form and
research notes in the subject’s record)
3. Control investigational product, including disposal or return
4. Document study progress
 Maintain accurate, complete and current records
 Submit appropriate reports-progress, safety and final
 Retain records and make them available for review
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Good Clinical Practice (GCP)

27. Investigator Responsibilities:
5. Disclosure of Conflicts of Interest that affect the design, conduct,
reporting, and analysis of the research (Disclose to Sponsor and UC
San Diego Health)
6. Complete Form FDA 1572 – contract between the PI and FDA.
Investigator:
 Agrees to personally conduct or supervise the study in accordance
with the approved, relevant, current protocol
 Maintains adequate and accurate records
 Reads and understands the information in the investigator brochure
 Ensures all assisting in the study are informed of their obligations
 Ensures IRB complies with FDA requirements
 Promptly report all changes or unexpected problems to IRB
 Ensure changes are approved by IRB
 Ensure all site personnel are qualified and familiar with the product
and it’s use
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Good Clinical Practice (GCP)

28. Investigator Responsibilities per Form 1572 cont’d:
 Sufficient resources, access to patients and time
 Adequate number of qualified personnel
 Adequate facilities and equipment
 Personnel trained on protocol, investigational product, and assigned
duties and functions
 Medical decisions should be made by a qualified physician who is an
investigator or sub-investigator for the study
 Adverse events and other medical issues should be managed
adequately
 Subject’s Primary Care Physician should be notified of participation,
with subject’s approval
 Withdrawn subjects should be assessed
 Accurate documentation and records
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Good Clinical Practice (GCP)