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