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 3 rd 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

Labelling Table

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

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