final validation protocol - european blood alliance protocol revision history version status issue...

Eurobloodpack ™ Validation Protocol

FINAL

Validation Protocol

Design Right EBA 2012 Copyright © EBA 2012

Validation details

EBA validation No. 00001

Product name Eurobloodpack ™

Product description Standardised Whole Blood Collection System including Leucodepletion Filter, < > and top configuration.

Product specification Ref.

Design Specification for Standardised Whole Blood Collection Systems Including Leucodepletion Filters. V3.7 December 2011, © EBA

Product code < >

Supplier < >

Manufacturer < >

Protocol details

Title Eurobloodpack ™ Validation

Version 1.11F - FINAL

Date 1st May 2012


Version 1.11F of 63 Design Right EBA 2012, Copyright © EBA 2012

Prepared by the Workgroup on Collaborative Validations

On behalf of the EBA

EBA Contributors to this and previous versions: Workgroup on Collaborative Validations (WGCV) Members

Dr Azzedine ASSAL (Etablissement Francais du Sang) Neil Beckman (Australian Red Cross) Pia Bruce (Finnish Red Cross) Jan Ceulemans (Belgian Red Cross) Juha Eronen (Finnish Red Cross) Martin Gorham (DGP Ltd) Derek Hunter (SNBTS) Dr. Markus M. Mueller (German Red Cross) Mark Nightingale (NHSBT) Marie O’Connell (Irish Blood Transfusion Service) Janet Sampson (Welsh Blood Service) - Chair Petra Van Krimpen (Sanquin)

Blood Pack Systems Standardisation Committee (BPSC) Members

A. Chabanel (Etablissement Francais du Sang) H. Croxon (Irish Blood Transfusion Service) W. Hughes (SNITS) D. de Korte (Sanquin) R. Leimbach (Bavarian Red Cross) M. Nightingale (NHSBT) – Chair G. Nicholson (NHSBT) R. Pieterz (Sanquin) G. Rowe (Welsh Blood Service) J. Savage (NIBTS) M. Wichmann (DRK) S. Rainbird (Welsh Blood Service)

Additional authors from the Eurobloodpack Purchasing Group Technical Committee (EPG TC)

Tom Finn (IBTS) Doris Campbell (NIBTS) Josje Koolen (Sanquin) Kevin McColl (SNBTS)



VALIDATION PROTOCOL APPROVAL Dirk de Korte

Name on behalf of EPG TC Signature Date

Janet Sampson

Name on behalf of EBA WGCV Signature Date



VALIDATION PROTOCOL REVISION HISTORY

Version Status Issue date Comments/ principle changes

1.0 D Committee draft August 2009 First draft.

1.1 D Committee draft August 2009 Minor typographical amendment.

1.2 D Committee draft August 2009 EBA amendments added prior to BPSC/WGCV meeting on 18/09/09 see Appendix 1.

1.3 D Committee draft October 2009 Amendments agreed during BPSC/WGCV meeting on 18/09/09.

1.4 D Committee draft October 2009 Incorporating comments from BPSC.

1.5 D Committee draft October 2009 Incorporating further comments from EFS.

V1.0 F Final draft for comment

December 2009 Incorporating changes discussed during WGCV audio conference 03/12/09.

V1.1 F Final draft for comment

January 2010 Incorporating changes discussed during WGCV audio conference 03/12/09.

V1.2 F Final draft for issue

February 2010 Incorporating changes discussed during WGCV meeting 29/01/10.

V1.3F Final draft for issue

June 2010 Incorporating comments from Neil Beckman.

V1.4F Final draft for issue

August 2010 Incorporating Design Right and Copyright.

V1.5 Final draft for issue

August 2010

Incorporating comments from Finnish Red Cross re OQ/PQ Phase 2, DQ Regulatory requirements, update to validation standards; final formatting.

V1.6 Draft for Eurobloodpack procurement

October 2011 limited

circulation

Incorporating comments from the Technical Committee meeting of 28th September 2011.

V1.7 Draft for Eurobloodpack procurement

November 2011 Incorporating comments from the Technical Committee meeting of 4th November 2011.

V1.8F Draft for comment December 2011 Incorporating post review amendments.

V1.8.1F Final draft for issue

January 2012 Incorporating comments from the Technical Committee meeting of 6th January 2012 and minor formatting amendments.

1.9F Final draft for issue

January 2012 Deletion of confidence calculation from pack defect assessment in OQ/PQ


April 2012 Adjusted to accommodate the EBA’s revised plasma pack freezing protocol.


May 2012 Further adjusted to render generic the plasma pack freezing protocol for over-stick label adhesion testing.



CONTENTS 1.0 VALIDATION STANDARDS 2.0 VALIDATION DESIGN

Aims/ objectives Validation Phases Persons(s) responsible Proof of concept

3.0 Design qualification (DQ) 4.0 Installation qualification (IQ) 5.0 Operational and performance qualifications (OQ/ PQ) phase 1 and 2



1.0 VALIDATION STANDARDS

• EN ISO 3826-1:2003: Plastics collapsible containers for human blood and blood components Part 1: Conventional containers.

• EN ISO 3826-2:2008: Plastics collapsible containers for human blood and blood components Part 2: Graphic symbols for use on labels and instruction leaflets.

• EN ISO 3826-3:2006: Plastics collapsible containers for human blood and blood components Part 3: Blood bags with integrated features.

• EN ISO 980: 1997 Graphical symbols for use in the labelling of medical devices.

• EN/ISO 15223-1:2007/ Amendment A1:2008. Medical devices - Symbols to be used with medical device labels, labelling and information to be supplied - Part 1: General requirements.

• EN ISO 1135 – 4: 2004: Transfusion equipment for medical use - Part 4: Transfusion sets for single use.

• Commission of European Communities. Directive 2002/98/EC of The European Parliament and Council of 27th January 2003 and daughter directives. Setting standards of safety and quality for collecting, processing, testing, storage and distribution of human blood and blood components.

• Commission of European Communities. Directive 93/42/EEC of The European Parliament and Council of 14th June 1993. Medical devices.

• European Pharmacopoeia (2008). European Directorate for the Quality of Medicines of the Council of Europe (EDQM).

• Council of Europe. Guide to the preparation, use and quality assurance of blood components - 15th edition (2010).

• ISBT 128 Standard Technical Specification. ICCBBA. Version 3.5.1, January 2009. http://www.iccbba.org/technicalspecification.pdf.

• The rules governing medicinal products in the European Union. EudraLex - Volume 4 - Good manufacturing practice (GMP) Guidelines (Commission Directives 91/356/EEC, as amended by Directive 2003/94/EC, and 91/412/EEC).



2.0 VALIDATION DESIGN 2.1 Scope

• This protocol applies to conventional PVC blood pack configurations including Eurobloodpack.

• Significant product changes (e.g. plastic formulation or filter design) require re-validation. 2.2 Aims/ objectives

• To ensure that blood bags purchased by EBA members against the ‘Eurobloodpack’ specification are fit for their intended use.

• To provide comprehensive validation data acceptable to blood establishments achieved with the minimum expenditure of resource on behalf of EBA members and suppliers.

• To make validation data freely available to EBA members.

• To enable validation proposals to be discussed by EBA WGCV with Competent Authorities.



2.3 Validation Phases

Validation phase Required completion Notes

Design qualification (DQ) PHASE 0 – biochemical/ haematological parameters analysis

Required when a blood pack has not previously been assessed at DQ PHASE 0 or from previously validated packs incorporating a new plastic formulation or leucodepletion filter. To be completed to a standard that satisfies the requirements of the EBA Technical Committee including:

• UKBTS Guidelines Chapter 9 “Data Required from Manufacturers to Assess the Effect of Novel Processing Technologies on Component Quality”

The manufacturer must provide the information requested to demonstrate compliance with the chosen standard and such data must have been reviewed and found to be acceptable by the Technical Committee.

Design qualification (DQ) – physical analysis

An accredited independent ‘test house’ appointed on behalf of EBA members or alternatively, preferably two blood establishments*

Requires as a minimum the destructive testing of 20 unfilled blood packs.

Installation qualification (IQ)

All implementing blood establishments

Requires as a minimum the testing of 20 filled blood packs with at least 10 being taken to expiry for destructive testing unless data has previously been supplied by the supplier for relevant parameters at expiry of each blood component type (DQ PHASE 0).

Operational and performance qualification (OQ/ PQ) PHASE 1

All implementing blood establishments

Requires as a minimum the non-destructive testing of 125 filled blood packs which may include the 20 units at IQ.

Operational and performance qualification (OQ/ PQ) PHASE 2

Dependent on blood establishment structure (national/regional etc), policy, donation and production volumes

N.B. Some blood establishments require as a minimum the non-destructive testing of 4000 filled blood packs.

* Blood bag suppliers will be afforded the opportunity to ‘witness’ testing. Individual BEs should establish and agree with Suppliers ‘house rules’ in advance of the suppliers attendance.



2.4 Persons(s) responsible

Role Name(s) Organisation/

Position Signature

Date assigned

Coordination and administration of validation on behalf of EBA

Project Manager DQ

Project Manager IQ

Project Manager OQ/ PQ

2.5 Validation philosophy A document describing the EBA WGCV philosophy concerning validation is available from the workgroup chairperson, [email protected]. 2.6 Proof of concept The following publications are cited as proof of concept: Sterile tube welding compatibility between packs supplied to the Eurobloodpack specification

• Use of a (proposed) standard protocol to validate Terumo TSCD-II connections between dissimilar blood bag tubing. Vox Sanguinis (2006) 91, 241-269).

Universal compatibility with transfusion sets in EU

• Improving compatibility between blood packs and transfusion sets. Transfusion Medicine (2006) 16, 11-15.

• An evaluation of proposed changes to International Standards for blood bags and transfusion sets to improve their compatibility Transfusion Medicine, 2008, 18, 281-286.



3.0 DESIGN QUALIFICATION

Title Blood bag validation EBA validation No. 00001 Date commenced

Blood Establishment < > Validation Manager < > Date complete

Product description Standardised Whole Blood Collection System Including Leucodepletion Filter, < pack configuration e.g. top and top >

Product code Product lot No(s)

Details of test equipment used in the validation

Manufacturer/ model of micrometer

Manufacturer/ model of Vernier calliper

Manufacturer/ model of precision balance

Other < specify >

Details of testing levels and methods used in validation

Number of packs to be validated 20 (empty blood packs)

Status of batches supplied for evaluation ‘Pre- production pilot’ or ‘routine production batch’

Testing method Destructive

Specification Design Specification for Standardised Whole Blood Collection Systems Including Leucodepletion Filters. V3.7 December 2011, © EBA



No Description Acceptance Criteria Results Pass/Fail

Comments Signature &

Date

1 Regulatory

• Pack system is CE marked.

• Certificate of compliance with Ph.Eur (.01/2008:30101 Materials for containers and solutions for human blood and blood components; 01/2008:30203 Sterile plastic containers for human blood and blood components).

• Certificate for the adhesive used for labels applied on blood bags: suitable for intended use and toxicity studies have been conducted. (e.g. Din EN ISO 3826-1).

• Certificate of Analysis supplied is satisfactory.

2 Pack configuration

All bags, subcomponents and transfer lines are present in the pack assembly. (See Eurobloodpack Design Specification figures 1 to 3)

3 Pack volumes

All nominal pack volumes are of the required capacity

• Primary pack 600ml.

• Red cell intermediate pack 600ml.

• Red cell storage pack 600ml.

• Optimal additive pack 600ml.

• Plasma pack 600ml.





Date

4 Tubing dimensions and markings

• All tube dimensions are within length tolerance for pack configuration. Tube A = < > mm Tube B = < > mm Tube C = < > mm Tube D = < > mm Tube E = < > mm Tube F = < > mm Tube G = < > mm Tube H = < > mm Tube I = < > mm Tube J = < > mm

• All pack transfer tube internal and external diameters are within the range required for sterile tube welding/ connection. ID = X.X to Y.Y mm ED = X.X to Y.Y mm

• Cross match line has unique numbering at 40 +/- 5 mm intervals.

5 Needle and needle guard

• Needle sheath present and tamper evident.

• Visual or tactile bevel indicator present.

• Indication of needle guard locking (tactile or audible).

• Single step withdrawal of needle into needle guard.





Date

6 Sample coupler / diversion pouch

• Protective cap fitted to sample coupler.

• Sample coupler barrel extends 20mm beyond needle.

• Maximum fill volume 40ml at 9.3 kPa.

• Clamp to sample pouch non-re-openable (accidentally).

• Accommodates tubes in the range 3 ml (13 x 75 mm) to 10 ml (16 X 100 mm).

7 Anticoagulant and optimal additive

• Volume of anticoagulant 66.5 ml +/- 2 ml (or +/-10% absolute maximum at expiry).

• Volume of OAS 105 ml +/- 2 ml (or +/-10% absolute maximum at expiry).

Suitable for a blood collection volume of 475 ml +/- 10%.





Date

8 Outlet ports and cannulae (frangible closures)

• Port sleeve length >29mm.

• Insertion force for siliconised ISO 1135-4 conforming transfusion set spikes is < 35N (test 3 examples of each spike type).

• Spike does not detach when a load of 15 N is applied in the vertical plane for 15 seconds. (test 3 examples of each spike type).

• Transfer cannulae can be opened with no more than 2 movements through approximately 45o in opposite directions away from the vertical.





Date

9 Labelling/ packaging

• Base label dimensions and configuration conforms to Design Specification Appendix 1.

• Base label is tamper evident.

• No evidence of smearing of ink/ printing.

• Base label remains adhered to pack and no evidence of smearing after: ·+ 220C ± 2ºC for 1 week+ ·40C ± 2ºC for 1 week ·-800C for 1 week (post thaw)

• Boxes carry Lot/ Batch number in eye readable and barcode format.

• Storage information is present on packaging.

• Bag overwrap is easily opened (without cutting).





Date

10 Instructions for use (IFU)

• IFU written in all EU languages or pictorially.

• Instructions for all integrated features including leucodepletion filters: Recommended hold period and temperature prior to filtration. - Acceptable filtration temperature range. - Recommended filtration (gravity) height or pressure - Recommended centrifugation forces and method of folding the set for centrifugation.

• IFU carry information concerning the latex (and its derivatives) content of the product in relation to risk of allergy in patients.

• IFU are version controlled and changes identified by an appropriate means.



SUMMARY OF FINDINGS

VALIDATION OUTCOME PASS FAIL CONDITIONAL ACCEPTANCE *

* For conditional acceptance see agreed process deviations below

DEVIATIONS AND ADVERSE EVENTS

Ref. No. Details Date raised Review outcome

pass/ fail Date closed

VALIDATION REVIEW

NAME POSITION SIGNED DATE



4.0 INSTALLATION QUALIFICATION




Product code Product lot No(s)

Details of equipment used in the validation.

Manufacturer/ model of centrifuge used for processing

Manufacturer/ model of press used for processing

Manufacturer/ model of SCD used

Manufacturer/ model of tube sealer used

Other < specify >


Number of packs to be validated Minimum of 20 packs to include at least 10 blood packs kept to expiry unless the relevant storage/ component expiry quality monitoring data is supplied by the manufacturer prior to commencement of validation.

Status of batches supplied for evaluation ‘Pre- production pilot’ or ‘routine production batch’.

Testing method

• Destructive.

• As many platelet pools as possible should be prepared from these packs.

• All red cells that are that are tested destructively must be tested for haemolysis at expiry.

• Ensure that FVIII testing of plasma components is based on a sample which includes approximately equal representation by group A and O donors.



Key blood collection and processing variables defined during validation

Variable Detail/ Range

Blood donation weigher/ mixer <manufacturer> / <model>

Storage temperature at collection venue Min < > oC to Max < > oC

Storage time at collection venue Min < > hrs to Max < > hrs

Temperature during transport Min < > oC to Max < > oC

Transport time Min < > hrs to Max < > hrs

Hold temperature prior to processing Min < > oC to Max < > oC

Total hold time prior to processing Min < > hrs to Max < > hrs

Centrifuge(s) <manufacturer> / <model>

Centrifuge parameters first separation < > g mins to < > g mins

Centrifuge parameters < > separation < > g mins to < > g mins

Plasma separator(s) <manufacturer> / <model>

Sterile tube welders <manufacturer> / <model>

Other critical equipment <specify> <manufacturer> / <model>



No Description

Acceptance Criteria

Results Pass/Fail


Date

1 DQ complete • DQ satisfactory/ approved

2

Communication NB This step needs to be completed before any blood components associated with this validation are issued to hospitals.

• QA Manager and Blood Issue Manager informed of validation.

• Hospitals informed of validation and any differences in appearance and handling of packs.

• Arrangements made with Collections Manager for collection of donations into packs for validation.

• Health and Safety Advisor informed of validation to assist with full manual handling/ posture risk assessment

3 Goods Inwards Inspection

• Pack code and lot number barcodes on outer carton are compatible with host IT system.

• Clear storage instructions on outer carton

• Packaging has not been damaged or showing signs of deterioration at the point of delivery.



No Description

Acceptance Criteria

Results Pass/Fail


Date

4 Staff Training

• Approved Standard Operating Procedures available for use of packs during validation.

• Blood collection and processing staff training provided (by supplier if required).

5 Blood collection arrangements and equipment during validation

• Arrangements made with Blood Collection Manager for suitable sessions to assess packs.

• Collection teams identified.

• Calibrated tare weights available.

• Blood mixers can accommodate packs.

• Blood storage containers and arrangements are adequate.



No Description

Acceptance Criteria

Results Pass/Fail


Date

6 Pack codes and lot numbers input onto inventory control IT system.

• Local stores made aware of validation.

• Local stores input lot numbers into host IT system.

• Packs identified with status ‘undergoing validation’ and change control/ validation reference number in Stores.

• List of Collection Team provided to Stores.

• Stores only issue validation packs to identified teams.

• QA personnel with responsibility for pack defect reporting informed of new pack type.

7 IT system requirements

• IT system ‘Hierarchy Code(s)’ [blood component separation profiles] available and allocated to enable processing of donations.

• Tare weights set up on IT systems as appropriate.

• Equipment settings have been checked and confirmed as correct or are adjusted in order to accommodate tare weights and resulting component volumes.



No Description

Acceptance Criteria

Results Pass/Fail


Date

8 Processing requirements and equipment

• Temperature controlled ambient area 22ºC ± 2ºC or 4ºC± 2ºC) storage identified for overnight storage of donations prior to processing.

• Identified overnight storage area temperature mapped.

• Correct centrifuge profiles installed and calibration checked.

• Packs can be suspended at the IFU specified height for filtration.

9 Non-destructive testing of blood components

• Blood bags allow non-destructive sampling by ‘stripping’ the transfer line in order to collect a representative sample of the bag contents for quality control/ monitoring purposes.

Blood establishments should use their routine sampling method for this assessment. The BE may require an assessment on donated blood if the pack configuration differs from that already validated for non-destructive sampling (e.g. incorporates additional break cannulae or a new design).



No Description

Acceptance Criteria

Results Pass/Fail


Date

10 Quality monitoring results

Blood components meet EU Blood Safety Directive specifications.

• Red Cell components

• Platelet components

• Plasma components

Platelet pools limited in number based on the number of buffy coats produced at this stage

11 Blood sample suitability

• Serum and plasma for donor testing contain less than 2g/L of free haemoglobin as assessed by a visual comparator.

• No evidence of incomplete coagulation/ micro-clots in clotted samples.

12

Over-stick labelling including donation number, blood component type and blood group labels

Over-stick labels remain adhered to base label after:

• +220C for 1 week

• +40C for 1 week

• Rapid freezing of pack using routine process (record freezer parameters e.g. temperature and time in comments section) and then storing at <-25oC for 1 week (post thaw)

13 Reconciliation • All packs accounted for.

Manufacturing staff to complete Reconciliation Table (Appendix 5)

See Appendices for FURTHER TESTING DETAILS



SUMMARY OF FINDINGS






VALIDATION REVIEW




Appendix 1 Summary of Quality Monitoring Results – Red Cell Components (fresh product) <PRODUCT TYPE>

Leucodepleted Red Cell Component <Enter Pack type> packs n =

Volume (ml) Hct (L/L) Hb (g/unit) WBC Count (x 106/unit)

Mean

SD

Min

Max

Specification 220 - 350 n/a >40 <1

% meeting specification

Summary of Quality Monitoring Results – Red Cell Components at expiry (* only when data is not available from supplier)

Leucodepleted Red Cell Component <Enter Pack type> packs n = Volume (ml)

(if required) Hct (L/L)

(if required) Hb (g/unit) (if required)

Supernatant potassium Locally defined

Haemolysis < 0.8% of red cell mass.

Mean

SD

Min

Max

Specification 220 - 350 n/a >40




Appendix 2 Summary of Quality Monitoring Results – Platelet Pools (Fresh product) <PRODUCT TYPE>

Leucodepleted Platelet Pool n =

Volume (ml) Platelet Count (x 109/pool) WBC Count (x 106/pool)

Mean

SD

Min

Max

Specification 150 - 400 >240 <1


Summary of Quality Monitoring Results – Platelet Pools at expiry (* only when data is not available from supplier)

Leucodepleted Platelet Pool n = Volume (ml)

(if required *) Platelet Count (x 109/pool)

(if required *) pH (on day after expiry)

Mean

SD

Min

Max

Specification 150 - 400 >240 > 6.4




Appendix 3 Summary of Quality Monitoring Results – Plasma Components (fresh product) <PRODUCT TYPE>

Plasma Component Type - Leucodepleted FFP n =

Volume (ml) Plt Count (x 109/l)

FVIII (iu/ml) WBC Count (x 106/unit)

Total Protein (g/l)

Residual RBC (x 109/l)

Mean

SD

Min

Max

Specification 200 - 340 <50 >0.7 <1 >50 <6


Summary of Quality Monitoring Results – Plasma Components at expiry (* only when data is not available from supplier)

Plasma Component Type - Leucodepleted FFP n = Volume (ml)

(if required *) FVIII (iu/ml)

(if required *) Total Protein (g/l)

(if required *)

Mean

SD

Min

Max

Specification 200 - 340 >0.7 >50




Appendix 4 Summary of Quality Monitoring Results – Plasma for Fractionation

n = Volume (ml) Test 1 * Test 2 Test 3 Test 4 Test 5

Mean

SD

Min

Max

Specification


Test 6 Test 7 Test 8 Test 9 Test 10 Test 11

Mean

SD

Min

Max

Specification


* Guidance on suitable tests for plasma for fractionation (Note: Not all EBA members provide plasma for fractionation and test requirements vary): - General coagulation system: PT and APTT. - Factor VIII (after thawing) ≥ 0,7 UI/mL. - Proteins (g/L) after thawing (≥ 50). - Albumin and immunoglobulins (IgG, IgM, IgA) (g/L) after thawing. - Factor V. - Fibrinogen. - Factors: VII, II, IX, X, XI, Willebrand (antigen and activity) (% activity). - Antithrombin (% activity). - Protein C and protein S (free) (% activity). - Plasminogen and α2 antiplasmin (% activity). - Coagulation tests: TQ (%) and TCA (ratio). - Thrombin activation: fragment 1 + 2, Thrombin-anti-thrombin complex, D-dime or TAT complex. - Factor XIIa (ng/L). - Plasma haemoglobin after thawing (mg/L). - C3a (mg/l) and C5a (µg/l). - Metalloprotease (ADAMTS 13)



Appendix 5 Reconciliation (to be completed by Manufacturing staff)

Number of packs received

Number of packs used

Number of packs discarded during

validation

Number of packs discarded/ returned to supplier at end of

validation

Number of packs accounted for (should be the same as number

received)



5.1 OPERATIONAL AND PROCESS QUALIFICATION – PHASE 1




Product code Product lot No(s) Min. 2 lots of different batches of which one may be same as lot supplied for IQ

Details of equipment used in the validation





Other < specify >


Whole blood holding temperature As applicable

Number of packs to be validated 125 (filled blood packs) which may include packs bled as part of IQ

Testing method

• Non destructive - By non-invasive line sampling on 100% of all components produced including as many platelet pools as possible.

• All platelet pools produced must be tested for volume, platelet count and white cell count, with sufficient also tested for pH at expiry to ensure that at least 10 have been tested across IQ and OQ/PQ.




Key blood collection and processing variables defined during validation.

Variable Detail/ Range

Blood donation weigher / mixer <manufacturer> / <model>












White cell counting details Flow cytometer <manufacturer> / <model> Gating: Maximum age of sample:




No Description Acceptance Criteria Results Pass/Fail Comments Signature &

Date

1 IQ complete • IQ satisfactory/approved.

2a Operational suitability – Collections

Packaging

• Bag overwrap is easy to remove without cutting.

• Transport and handling of cartons meet manual handling regulations.

Needle and needle guard

• Needle sheath easy to remove.

• Needle sheath prevents bending or other damage of needle during removal.

• Visual or tactile bevel indicator easy to identify.

• Tactile or audible needle guard locking easy to identify.

• Needle can be withdrawn from the arm into the needle guard in a single step.

• Withdrawal of the needle into the needle guard can be achieved without increasing discomfort to the donor.

• Once withdrawn into the needle guard, the needle cannot be removed.

• Engagement of the needle guard requires minimal force.




Date

2a Operational suitability – Collections (continued)

• Design of the needle guard does not significantly interfere with the venepuncture process.

• The needle assembly is capable of laying flat against the arm without affecting the lie of the needle in the vein.

• Needle venepuncture does not compromise donor comfort.

• The needle does not increase the incidence of failed venepuncture or bruising above current levels.

• The needle can be fixed in position and does not rotate except when manual adjustment is required.

Sample Site Coupler and Diversion Pouch

• The break cannula to the sample site coupler or donor line is easy to break.

• Protective cap fitted to sample coupler is easy to remove.

• Orientation of the barrel can be easily identified.




Date

2a Operational suitability – Collections (continued)

• Clamp to sample pouch can only be applied in the correct position to completely occlude the line and maintain the closed system and cannot be accidentally reopened.

• Sample site coupler allows sequential filling of sample tubes without leakage.

2b

Operational suitability – Collections Donation bleed time Measure and record the donation time in minutes/ seconds for each of the 125 donations.

• Average donation time should be =/< 8 minutes (in line with ISO 3826-1 expectations).

• Data will be used to compare packs with needle variations and donor line cannulae.

Time from start of flow into main pack until donor line clamped.

3 Pack related faults at collection.

Based on 125 packs:

• Critical defects </= 1

• Non-critical defects </ = 3

Carry out a risk assessment before proceeding if limits are exceeded. Critical defects = any incident where the pack contents may be contaminated/risk to patient or donor safety




Date

4 Operational suitability -Processing

• Absence of operational problems in tube sealing.

• Absence of operational problems in automated line stripping.

• Absence of operational problems in sterile connection.

• Absence of operational problems in centrifugation.

• Absence of operational problems in use of automated processing equipment.

• Absence of operational problems in non-invasive QM sampling of components.

• Absence of operational problems in use of breakaway cannula system (This must be assessed by a trained ergonomic expert).

• Absence of operational problems in using leucodepletion aids.

• Absence of excess air in packs (up to 15ml of air per bag is acceptable – ISO3826-1).




Date

5 Filter suitability

• Filter can withstand handling during routine processing procedures.

• Filter is suitable for centrifuging (if applicable).

• End of filtration easily assessed.

• Number of slow filters or blockages comparable to or less than current filter incidents. N.B. filtration times must be recorded for each pack during validation.

6 Health and Safety

• Full manual handling/ posture risk assessment must be carried out by a trained ergonomic expert and pose minimal risk to operator and donor.

• A cannula breaker is available for this pack type (information only).

7 Filtration time – red cells

• Meets specification for filtration time of <120 mins for >95% of product.

• Time taken for filtration exceeds minimum time as stated by the manufacturer (indicator of hole in filter).




Date

8 Pack related faults during processing

Based on 125 packs:

• Critical defects </= 1

• Non-critical defects < / = 3

Carry out a risk assessment before proceeding if limits are exceeded. Critical defects = any incident where the pack contents may be contaminated/ risk to patient or donor safety.


Blood components meet EU Blood Safety Directive specifications (See referenced standards).



• Plasma components Production processes relating to use of the blood packs remain under statistical control.

10 Blood sample suitability

• Serum and plasma for donor testing contain less than 2g/L of free haemoglobin as assessed by a visual comparator.

• No evidence of incomplete coagulation/ micro-clots in clotted samples.

11 Reconciliation • All packs accounted for.





Date

12

Customer suitability (to be assessed by Blood Establishment Hospital Liaison staff in collaboration with user hospitals) Note here any specific problems with use of the packs under validation including the outcome of reviewing any severe adverse events and reactions (SAEs and SARs) attributed to the blood pack. N.B. The embedded questionnaire is to be used to collect customer feedback.

Eurobloodpack Clinical Questionnaire.doc

• Acceptable handling and storage characteristics.

• Acceptable cross-match line.

• Acceptable cross-match label application.

• Acceptable administration ports including compatibility with administration sets.

• Any other concerns that have been noted including SAE and SARs.




SUMMARY OF FINDINGS






VALIDATION REVIEW




Appendix 1 Log of Pack Related Faults at Collection

Type No of Packs Used No of Faults

Contaminated/ soiled packs

Hole in pack

Joint failure

Kinked/ bent tubing

Sampling problem

Label Adhesion Problem

Burred/ blunt needle

Cosmetic

Training Issue

Other (please specify)



Appendix 2 Log of Pack Processing Failures


Faulty filter housing

Damage during centrifugation

Heat seal failures

SCD failures

Cannula failure

Label adhesion problems

Breakage following freezing

Slow filtration




Appendix 3 Summary of Quality Monitoring Results – Red Cell Components <PRODUCT TYPE>



Mean

SD

Min

Max



Conformance to EU Specification for White Cell Count, Cpk (at 5x106/unit) and confidence limits (i.e. 95% confidence that >99% of components have <5x106WBC/unit and >90% of components have <1x106 WBC/unit *).

Number Tested

Mean WBC count (x106/unit)

Max WBC count (x106/unit)

Cpk Compliant with EU

Spec? (Yes/No)

* Alternative acceptance criteria if applied:

• E.g. EFS < 1x106 WBC/ unit for leucoreduced cellular blood components (red cells and platelets) as in the Eur Dir, with a limit quality level of 3% (95% of confidence).



Appendix 4 Summary of Quality Monitoring Results – Platelet Pools <PRODUCT TYPE>


Volume (ml) Platelet Count (x

109/pool) WBC Count (x 106/pool)

pH on day after expiry

Mean

SD

Min

Max

Specification 150 - 400 >240 <1 > 6.4



Number Tested




Spec? (Yes/No)




Appendix 5 Summary of Quality Monitoring Results – Plasma Components <PRODUCT TYPE>

Plasma Component Type - Leucodepleted FFP n =

Volume (ml) Plt Count (x 109/l)


Total Protein (g/l) Residual RBC

(x 109/l)

Mean

SD

Min

Max

Specification 200 - 340 <50 >0.7 <1 >50 <6



(Testing on Pre-Freeze Sample)

Number Tested




Spec? (Yes/No)




Appendix 6

Summary of Quality Monitoring Results – Plasma for Fractionation


Mean

SD

Min

Max

Specification



Mean

SD

Min

Max

Specification


* Guidance on suitable tests for plasma for fractionation: - General coagulation system: PT and APTT. - Factor VIII (after thawing) ≥ 0,7 UI/mL. - Proteins (g/L) after thawing (≥ 50). - Albumin and immunoglobulins (IgG, IgM, IgA) (g/L) after thawing. - Factor V. - Fibrinogen. - Factors : VII, II, IX, X, XI, Willebrand (antigen and activity) (% activity). - Antithrombin (% activity). - Protein C and protein S (free) (% activity). - Plasminogen and α2 antiplasmin (% activity). - Coagulation tests: TQ (%) and TCA (ratio). - Thrombin activation: fragment 1 + 2, Thrombin-anti-thrombin complex, D-dime or TAT complex, - Factor XIIa (ng/L). - Plasma haemoglobin after thawing (mg/L). - C3a (mg/l) and C5a (µg/l). - Metalloprotease (ADAMTS 13).







validation


validation

Number of packs accounted for (should be the same as number

received)



5.2 OPERATIONAL AND PROCESS QUALIFICATION – PHASE 2




Product code Product lot No(s) 2 lots (may be the same as PHASE 1)

Details of equipment used in the validation





Other < specify >


Whole blood holding temperature As applicable

Number of packs to be validated 4000 filled blood packs [2000 from each batch]

Testing method

• Non-destructive - As determined by EU Directive 2004/33/EC and statistical process control.

• As many platelet pools as possible should be prepared.

• All platelet pools produced must be tested for volume, platelet count and white cell count, with sufficient also tested for pH at expiry to ensure that at least 10 have been tested during this phase.




Key blood collection and processing variables defined during validation

Variable Detail / range

Blood donation weigher/ mixer <manufacturer> / <model>












White cell counting details Flow cytometer <manufacturer> / <model> Gating: Maximum age of sample:




No Description

Acceptance Criteria

Results Pass/Fail


Date

1 OQ phase 1 complete • OQ phase 1 satisfactory/

approved.

2 Operational suitability – Collections

Packaging

• Bag overwrap is easy to remove without cutting.

• Transport and handling of cartons meet manual handling regulations.

Needle and needle guard

• Needle sheath easy to remove.

• Needle sheath prevents bending or other damage of needle during removal.

• Visual or tactile bevel indicator easy to identify.

• Tactile or audible needle guard locking easy to identify.

• Needle can be withdrawn from the arm into the needle guard in a single step.

• Withdrawal of the needle into the needle guard can be achieved without increasing discomfort to the donor.

• Once withdrawn into the needle guard, the needle cannot be removed.

• Engagement of the needle guard requires minimal force.



No Description

Acceptance Criteria

Results Pass/Fail


Date

2 Operational suitability – Collections (continued)

• Design of the needle guard does not significantly interfere with the venepuncture process

• The needle assembly is capable of laying flat against the arm without affecting the lie of the needle in the vein

• Needle venepuncture does not compromise donor comfort

• The needle does not increase the incidence of failed venepuncture or bruising above current levels

• The needle can be fixed in position and does not rotate except when manual adjustment is required

Sample Site Coupler and Diversion Pouch

• The break cannula to the sample site coupler is easy to break.

• Protective cap fitted to sample coupler is easy to remove.

• Orientation of the barrel can be easily identified.



No Description

Acceptance Criteria

Results Pass/Fail


Date

2 Operational suitability – Collections (continued)

• Clamp to sample pouch can only be applied in the correct position to completely occlude the line and maintain the closed system and cannot be accidentally reopened.

• Sample site coupler allows sequential filling of sample tubes without leakage.

3 Pack related faults at collection

• Critical defects </= 400 defects per million

• Non-critical defects </ = 1000 defects per million

N.B. these are overall acceptable defect rates including production.

Carry out a risk assessment before proceeding if limits are exceeded. Critical defects = any incident where the pack contents may be contaminated/risk to patient or donor safety



No Description

Acceptance Criteria

Results Pass/Fail


Date

4 Operational suitability - Processing

• Absence of operational problems in tube sealing.

• Absence of operational problems in automated line stripping.

• Absence of operational problems in sterile connection.

• Absence of operational problems in centrifugation.

• Absence of operational problems in use of automated processing equipment.

• Absence of operational problems in non-invasive QM sampling of components.

• Absence of operational problems in use of breakaway cannula system (This must be assessed by a trained ergonomic expert).

• Absence of operational problems in using leucodepletion aids.

• Absence of excess air in packs. (up to 15ml of air per bag is acceptable – ISO3826-1).



No Description

Acceptance Criteria

Results Pass/Fail


Date

5 Pack related faults during processing

• Critical defects </= 400 defects per million

• Non-critical defects </ = 1000 defects per million

N.B. these are overall acceptable defect rates including collection

Carry out a risk assessment before proceeding if limits are exceeded. Critical defects = any incident where the pack contents may be contaminated/ risk to patient or donor safety.


Blood components meet EU Blood Safety Directive specifications.



• Plasma components Production processes relating to use of the blood packs remain under statistical control.

7. Reconciliation • All packs accounted for.




No Description

Acceptance Criteria

Results Pass/Fail


Date

8

Customer suitability (to be assessed by Blood Establishment Hospital Liaison staff in collaboration with user hospitals). Note here any specific problems with use of the packs under validation including the outcome of reviewing any severe adverse events and reactions (SAEs and SARs) attributed to the blood pack. N.B. The embedded questionnaire is to be used to collect customer feedback.

Eurobloodpack Clinical Questionnaire.doc

• Acceptable handling and storage characteristics.

• Acceptable cross-match line.

• Acceptable cross-match label application.

• Acceptable administration ports including compatibility with administration sets.

• Any other concerns that have been noted including SAE and SARs.




SUMMARY OF FINDINGS






VALIDATION REVIEW




Appendix 1 Log of Pack Related Faults at Collection


Contaminated/ soiled packs

Hole in pack

Joint failure

Kinked/ bent tubing

Sampling problem

Label Adhesion Problem

Burred/ blunt needle

Cosmetic

Training Issue




Appendix 2 Log of Pack Processing Failures


Faulty filter housing

Damage during centrifugation

Heat seal failures

SCD failures

Cannula failure

Label adhesion problems

Breakage following freezing

Slow filtration




Appendix 3 Summary of Quality Monitoring Results – Red Cell Components <PRODUCT TYPE>



Mean

SD

Min

Max





Number Tested




Spec? (Yes/No)



Appendix 4 Summary of Quality Monitoring Results – Platelet Pools <PRODUCT TYPE>


Volume (ml) Platelet Count

(x 109/pool) WBC Count (x 106/pool)

pH on day after expiry

Mean

SD

Min

Max

Specification 150 - 400 >240 <1 > 6.4


Conformance to EU Specification for White Cell Count, Cpk (at 5x106/unit) and confidence limits (i.e. 95% confidence that >99% of components have <5x106WBC/unit and >90% of components have <1x106 WBC/unit*).

Number Tested




Spec? (Yes/No)




Appendix 5 Summary of Quality Monitoring Results – Plasma Components <PRODUCT TYPE>

Plasma Component Type - Leucodepleted FFP n = Volume

(ml) Plt Count (x 109/l)


Total Protein (g/l) Residual RBC

(x 109/l)

Mean

SD

Min

Max

Specification 200 - 340 <50 >0.7 <1 >50 <6


Conformance to EU Specification for White Cell Count, Cpk (at 5x106/unit) and confidence limits (i.e. 95% confidence that >99% of components have <5x106WBC/unit and >90% of components have <1x106 WBC/unit*).

(Testing on Pre-Freeze Sample)

Number Tested




Spec? (Yes/No)




Appendix 6 Summary of Quality Monitoring Results – Plasma for Fractionation


Mean

SD

Min

Max

Specification



Mean

SD

Min

Max

Specification


* Guidance on suitable tests for plasma for fractionation: - General coagulation system: PT and APTT. - Factor VIII (after thawing) ≥ 0,7 UI/mL. - Proteins (g/L) after thawing (≥ 50). - Albumin and immunoglobulins (IgG, IgM, IgA) (g/L) after thawing. - Factor V. - Fibrinogen. - Factors: VII, II, IX, X, XI, Willebrand (antigen and activity) (% activity). - Antithrombin (% activity). - Protein C and protein S (free) (% activity). - Plasminogen and α2 antiplasmin (% activity). - Coagulation tests: TQ (%) and TCA (ratio). - Thrombin activation: fragment 1 + 2, Thrombin-anti-thrombin complex, D-dime or TAT complex. - Factor XIIa (ng/L). - Plasma haemoglobin after thawing (mg/L). - C3a (mg/l) and C5a (µg/l). - Metalloprotease (ADAMTS 13).







validation


validation

Number of packs accounted for (should be the same as number received)

final validation protocol - european blood alliance protocol revision history version status issue...

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