Inspection of Collection Facilities
Collection Standards: C1 General
• Apply to all CTPs collected from living donors
• Facility must apply with all applicable laws e.g. HTA
• Facility, CFD, CFMD and one staff member in place at least 1 year
• Minimum 10 PBSC or 1 BM collection in preceding year (re-accreditation 40 PBSC / 4 BM in 4 year cycle)
C2: Collection Facility
• Appropriate, designated areas for collection, storage of product, supplies and equipment
• Suitable and confidential space for donor examination and evaluation
• Process to control storage areas to prevent mix-up, contamination and cross contamination during quarantine, prior to release and for non-conforming products
• Transfusion Service - irradiated and CMV appropriate blood products
C3: Collection Facility Director
• Medical or relevant** degree + training / exp
• May also be the MD if appropriate
• 1 year’s CTP collection experience
• Performed or supervised min 10 CTP apheresis
collections in last 3 years
• Figure for marrow is 10 in their career
C3 Collection Facility Medical Director
• Licensed physician + appropriate postgraduate training (may also be CFD)
• Responsible for care of patients and donors and evaluation, management of complications
• 1 year in cell therapy product collections
• Numbers of collections as for the CFD
Paediatric Donors/Patients
• For CF performing paediatric apheresis there shall be documented training and experience in these procedures (C3.3.2)
• Collection methods for paediatric donors shall employ appropriate adjustments to the procedure (C8.13)
C4 Quality Management Plan (QMP)
• This a key document and often deficient
• CFD responsible for QMP• Organisational chart of key
personnel and functions – how do they interact to implement the QMP
• Personnel requirements including qualifications, training, competency
• Document control – development, approval, review etc for SOPs, worksheets, forms and labels
C4 Quality Management Plan (QMP)
• Written agreements with 3rd parties –
responsibility of facility to establish
and maintain; ensure external entities
comply with laws/regulations
• Documentation and review of products
and outcomes e.g. engraftment
• Conduct of audits
• Management of CTPs with positive
microbial cultures
C4 Quality Management Plan (QMP)
• System for - errors, accidents, adverse events and complaints
• Process for product tracking• Process for continuous
operation of electronic records
• Qualification of equipment, supplies and reagents
• Validation of processes
C5 Policies and Procedures
• List of what must be addressed eg donor consent, product collection, labelling
• 17 are listed but this doesn’t mean there have to be 17 SOPs
• There must be - SOP for SOPs - Standardised format - System of numbering, titling • Each individual procedure shall
include – purpose, equipment, description of procedure and references
C6 Donor Evaluation and Management
• Consent – clear, able to ask questions etc
• Suitability – includes ABO and pregnancy testing, risks of CVCs, anaesthesia and G-CSF
• Use of non-conforming donors, communication to physicians
• Evaluation and testing for IDMs
C7 Labelling
• Labels - held upon receipt/printed on demand reviewed against a copy or template
• Obsolete labels destroyed• Archive representative labels for 10
years• Biohazard labels - risk factors or
marker positive• Label Table: will defined whether
information should be affixed (AF), attached (AT) or in accompanying documents (AC)
• Labelling of concurrent plasma and samples
C7 Biohazard labels
• Biohazard label if screening indicates presence of a communicable disease, risk factor or clinical signs of one
• Creates 3 categories of product labelling:
- warning tests reactive for… - warning advise patient of
communicable disease risk - not evaluated for infectious
disease risk
Table 1 Label content adapted from FACT-JACIE
Element Partial label Label at completion of collection
Label during processing
Label at completion of processing
Label at distibution
Innerand outer shipping container
Unique identifier of product AF AF AF AF AF
Proper name of product AF AF AF AF AF
Recipient name and identifier AF (if
applicable)
AF (if applicable)
AF (if applicable)
AF (if applicable)
AF
Date, time collection ends and (if applicable) time zone
AF AC AC
Approximate volume AF AC AC Name and volume or conc. of anticoagulant and other additives
AC AC AC
Donor identifier and (if applicable) name AF AT AT
Identity and address of collection facility or donor registry
AC AC AC
Recommended storage temperature AT AT AT
Biohazard label AC
(if applicable)
AC (if applicable)
AC (if applicable)
AC (if applicable)
Identity and address of processing facility AF AF
ABO and Rh of donor AC AC
RBC compatibility testing results AC AC
(if applicable)
Statement “Properly identify intended recipient and product”
AC AC
Statement “Warning; this product may transmit infectious agents”
AF AF
Expiration date AF (if applicable)
AF (if applicable)
Expiration time AF (if applicable)
AF (if applicable)
Statement “For autologous use only” or Statement “For use by intended recpient only”
AF (if applicable)
AF (if for allogeneic recipient)
AF (if applicable)
AF (if for allogeneic recipient)
Statement “Do not irradiate” AT AT
Statement ” Not for infusion’”including reason
AT
(if applicable) AT
(if applicable)
Name and address of receiving institution AF
Name and phone number of contact person at receiving institution
AF
Statement“Medical Specimen” AF
Statement “ Do not X-Ray” Af
Name,address and phone number of shipping facility
AF
LabellingTable
C8 Process Controls
• Done according to written procedures
• Written order from a physician• Document interim assessment of
donor suitability immediately before
• Blood count within 24 hours - criteria
• Suitably qualified anaesthetist• Central lines - licensed, qualified
physician• G-CSF - experienced physician• Procedures have acceptable
viability/recovery
C 9, 10 Storage, transportation and shipping
• Policies for storage prior to transportation to a processing lab – control storage areas
• Procedures must protect: product and staff
• Sealed in secondary container• Shipped to PL at defined
temperature• Outer container if sent to non-
contiguous facility• Required accompanying records
C11 Records
• Facility records relating to QC etc - 10 years
• Patient records - min 10 years after infusion and as according to ‘governmental laws’
• Research records - min 10 years after infusion
• Where divided must show extent of each facility’s responsibility
• Electronic records• Expanded requirements for
donor records
C12: Direct Distribution to Clinical Programme
• Where cells are directly distributed to clinical facility without going through a processing facility, then requirements for labelling, documentation, distribution, transportation and record keeping in Section D7,8,10 and 12 apply
Collection Facilities – Most Common Deficiencies
• Policies and procedures• Engraftment data• QMP• Review of new/revised
policies
Occasional Use of BM
• The clinical facility must use a collection facility that confirms to the standards– The Clinical Program shall have access to licensed
physicians who are trained and competent in bone marrow harvesting and a bone marrow collection facility that meets these Standards.
• For accreditation of Bone Marrow Collection, BM Collection Facility must perform at least 1 BM harvest in the year prior to initial accreditation and 4 harvests in each 4 year accreditation cycle thereafter.
• What happens if the centre collects BM but not often enough to apply for accreditation for BM collection?
Bone Marrow Collection
• May be forgotten if very few harvests
• Minimum is 1 in 12 months before initial accreditation and 4 per 4-yr re-accreditation cycle
• SOPs• Staff competency and
experience
• Centre can opt to collect elsewhere
C2 Collection Facilities - Problems
• Staff not aware of emergency facilities
• No suitable space for donor examination
• Lack of proper disposal of apheresis kits
(biohazard)
• Prophylactic platelets given to healthy donors
• No evidence of training and compliance with
Biological Safety Regulations
C3 Personnel
• Inadequate documentation of
training, proficiency and continued
competency
• MD not responsible for donor
evaluation and safety
• MD does not have appropriate
contract with facility
• No record of how many
procedures are done
C4 QM - BM Harvest
• No procedure / documentation relating to validation of equipment / procedures
• Expiration dates and lot numbers of the reagents / equipment used for BM harvest not recorded
• Records of collection not regularly reviewed by CF Director - evidence of appropriate meetings
• Lack of quality audit procedure - AE, yields
• Reporting AE’s to clinical unit - SOP
C4.000 QM- Peripheral Blood
• Collection outcomes e.g.
yields and AE’s not regularly
reviewed by CF Director
• The QMP should describe the
validation of significant
apheresis procedures
• The QMP should give the
range of expected
outcomes/results
C5 Collection SOPs
• No SOP for donor screening, consent, training, BM collection, storage or transport
• SOPs present but inadequate e.g. no acceptable results and tolerance limits, no instruction for action if these are not met
• Range of expected results, ranges and end points not defined in SOP for stem cell collection
• No examples or worksheets and labels
• No arrangements for biannual review
• No procedure for recording deviation from the SOPs relating to stem cell collection, or whether and how such deviations are approved
SOP Illustration:BM Harvest
Code: SOP/BRI/SB/004/02 Copy No:
Replaces: SOP/BRI/SB/004/01 Issuing Dept: STEM CELL
Summary of Significant Changes (Changes are indicated by a vertical line in the right handmargin):
New data sheet DAT/BRI/SB/047 Bone marrow harvest volumes
Purpose and Scope Items RequiredOne of the many factors that are linked to asuccessful graft after bone marrow transplantation isthe number of nucleated cells harvested per kilogrambody weight of the recipient. It is widely reported thatfor allogeneic transplant a dose of 3 x 108/kg bodyweight is required.
Haplotype mismatched transplants require highertarget cell doses to overcome graft rejection, theseare usually not available from a single bone marrowcollection so the harvest team will collect themaximum volume available without risking donorwellbeing.
1. Anticoagulant collection medium – seeSOP/BRI/SB/051 – Preparation of Bone MarrowCollection Medium
2. Heparin (1000in/ml in 5ml ampoules)3. Scales4. DAT/BRI/SB/004 – Equipment Required for Bone
Marrow Harvesting5. DAT/BRI/SB/005 – Equipment Diagrams for Bone
Marrow Harvesting6. DAT/BRI/SB/006 – Bone Marrow Harvest Volume
Charts7. FRM/BRI/SB/010 - Haemopoietic Progenitor Cells
Labels8. FRM/BRI/SB/011 – Bone Marrow Harvest Form9. SOP/BRI/SB/008- Information And Handling
Instructions For Cryopreserved AllogeneicHaemopoietic Progenitor Cells
10. DAT/BRI/SB/047 - Bone marrow Harvest volumes
Definitions Grade/Qualifications Needed andResponsibilities
EDTA EthyleneDiamineTetraAcetic Acid -Anticoagulant works by chelation of Ca+ions
ACD Acid Citrate Dextrose AnticoagulantBMS Biomedical Scientist
Trainee/BMS trained in laboratory and operatingtheatre aseptic technique and known to the collectionteam at the harvesting hospital. Responsible forobtaining written confirmation of current virologystatus of the patient before the harvest and, afteragreement with the harvest clinicians, monitoring thevolumes and doses being harvested, and setting theend point of the collection when there are noimmediate clinical considerations about patientsafety.
Author A N Other Effective Date DRAFT
SAFETY PRECAUTIONS AND HAZARDS
See relevant Health & Safety procedures.All blood and derivatives must be treated as potentially infective.NBS staff attending marrow harvests are not trained or authorised to move patientsunder general anaesthetic in the operating theatre.Use a trolley for transporting the harvest box to reduce manual handling injury.
INSTRUCTIONS
At NBS - Bristol Centre
1. Assemble equipment required at the harvest - see DAT/BRI/SB/004 for variants.
2. Take the bone marrow harvest volume data sheet if required (DAT/BRI/SB/047)
3. From the details supplied on the patient referral form (national form 2E), preparesufficient labels (FRM/BRI/SB/010).
4. Go to harvesting hospital in good time.
At Harvesting Hospital
5. If written confirmation of the patients current virology status has not beenreceived in advance of the collection, request that the consent form (nationalform 2B) is completed and that samples are taken for mandatory testing beforethe collection begins.
6. Follow local theatre rules on theatre dress, scrubbing and gowning.
7. Confirm the correct identification of the patient with the anaesthetist orharvesting physician who should sign the Bone Marrow Harvest form(FRM/BRI/SB/011) accordingly.
In Theatre
8. Arrange required equipment for placing on a sterile field.
9. Provide scrub nurse with heparin to prepare syringe rinse bowls containing 20units/ml in 0.9% saline.
10. Arrange a non-sterile trolley for the scales, if needed. A sterile tray will beprovided for the scales.
Once scrubbed and gowned assemble collection pack, anticoagulant (SeeSOP/BRI/SB/051) , taps and sampling site couplers as shown in relevant equipmentdiagrams in DAT/BRI/SB/005.
C6 Donor Selection & Management
• No written orders for collection• Absence of written consent • No arrangements for
assessment of (interim) donor suitability
• No formal policy / SOP for assessment of venous line placement
• Assessment of venous line placement not documented in patient/donor record
• IDM testing
C6 Donor Selection & Management
• No evidence that donor
informed of abnormalities
and arrangements for
follow-up
• No secondary bag for
transportation
• No SOP for transport to
processing lab
D7 - LABELS
• Responsibility for label
production and control
unclear
- new SOP
• Lack of unique alphanumeric
identifier
• Must give proper name e.g.
Human HPC-Apheresis
• CF and PL need to agree HPC
identifiers
Autologous Collection Label
• Unique alphanumeric number• Product name• Date and time• Name and volume of AC and other
additives• Name of collection facility• Recommended storage temperature• Biohazard label if required
C9.000 Records
• Facilities for patient record
storage inadequate
• No records for ... personnel
training
• No copy of collection record
(safety, purity)
sent to Clinical Unit
Transportation
• No SOP covering transportation from the
apheresis unit to the processing facility
• Lack of stated temperature for transport
• Lack of secondary container