Inspection of Collection Facilities

1. Inspection of Collection Facilities

2. 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)

3. 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

4. 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

5. 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

6. 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)

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. Labelling Table

15. 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

16. 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

17. 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

18. 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

19. Collection Facilities – Most Common Deficiencies • Policies and procedures • Engraftment data • QMP • Review of new/revised policies

20. 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?

21. 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 Bone Marrow Collection

22. 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

23. 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

24. 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

25. 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

26. 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

27. SOP Illustration:BM Harvest

28. 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

29. 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

30. 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

31. 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

32. 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

33. Transportation • No SOP covering transportation from the apheresis unit to the processing facility • Lack of stated temperature for transport • Lack of secondary container