Process Control in a Component Laboratory Dr.S.B.Rajadhyaksha, MD,DTM,PGDMLS Professor & Head Dept. of Transfusion Medicine Tata Memorial Hospital, Mumbai

Blood Components (BC) processing Biological variations between blood donors influence the component production/ quality BC are highly concentrated, not completely free of other blood elements BC processing cannot completely optimize product quality

QUALITY SYSTEM ESSENTIALS (AABB Standards) 1. Organization 2. Resources 3. Equipment 4. Supplier and Customer Issues 5. Process Control 6. Documents and Records 7. Deviations, Non-conformances, and Adverse Events 8. Assessments: Internal and External 9. Process Improvement - Corrective and Preventative Action 10. Facilities and Safety

FOR BLOOD BANKS/ BLOOD CENTRES & TRANSFUSION SERVICES NABH STANDARDS FOR BLOOD BANKS/ BLOOD CENTRES & TRANSFUSION SERVICES PROCESS CONTROL Note: Some of the following might not be applicable to the scope of all blood banks/ blood centres. 6.1 Policies and validation of processes and procedures The blood bank/ blood centre shall have policies and validated processes and procedures that ensure the quality of the blood, components and services. The blood bank/ blood centre shall ensure that these policies, processes and procedures are carried out under controlled conditions. Process or procedure steps For each critical step in collection, processing, compatibility testing and transportation of blood and components issued, there shall be a mechanism to identify who performed the step and when it was performed.

PROCESS CONTROL Defn.: Sum of actions that assures processes are operating within acceptable parameters and established practices Ensures each step is performed in a consistent manner (SOPs) Each critical step in a process should be traceable. Each staff member involved in each process along the way should be documented. 3. QA program - verify reagents and equipment functioning as intended 4. Measures to reduce chances of bacterial contamination 5. There must be a well defined process for product labeling and review. 6. Proficiency testing (e.g. EQAS) - to compare the accuracy & reliability of test methods

Process Variation Process can be out of control due to Malfunctioning equipment Defective reagents or supplies Untrained staff Incorrect procedure

Process Control Steps Produce Goods Start Provide Service No Take Sample Problem? Yes Inspect Sample Stop Process Create Find Out Why Control Chart

Collection and Processing of Components (WB and Apheresis) by Component extractor Particular component is collected

Factors Affecting the Quality of Blood Components (1) Selection of donor: Antiplatelet drug therapy, defer for 72 hours Quality of blood bag and anticoagulant used Techniques of phlebotomy Clean venipuncture - minimal tissue trauma Flow- uninterrupted, should be completed in 8-10 min Frequent gentle mixing Time period: separation within 6-8 hrs of collection Transit temperature: 20-240C for not more than 8 hours

Factors Affecting the Quality of Blood Components (2) 6. Precentrifugation: Allow for 2 hours of resting time 7. Centrifugation: calibration Critical variables – speed, temp, duration, rotor size Accurate balancing, Bag position Gentle handling, Resuspension of platelets 8. Storage temperature 4±20C = WB, PRBC 200C-240C = platelets ≤ -300C = FFP, Cryoppt 9. Uninterrupted, gentle flat bedded platelet agitator 60-70 cycles /min

Component Preparation protocol Weighing Counter balancing Expression Centrifugation

Collection and processing method of Platelet Concentrates (PC)

PRP method for preparation of platelets Whole blood Soft spin within (1800 rpm 6 hrs x 9 min at 22oC) Red cells Platelet rich plasma (PRP) Hard spin (3000 rpm x 7 min at 2 Plasma Platelet Conc. (RDP)

Platelet Preparation Buffy Coat Method

Separation of component using Automatic component extraction Conventional Quadruple Bag (TAT) Top and Bottom Bag (TAB)

Quality Control of Blood Components Should be performed on >/= 1% of all components produced per month (if fewer than 100 per month, at least 4) >/= 75% components tested must meet specifications

Sampling Mixing of product and stripping of lines Should be standardised For platelet count Samples in dry EDTA tube, to induce disaggregation Sampling methods must be validated - consistent samples, regardless of operator

Sampling …contd. NOT to be taken from the last part of the tube This section is difficult to strip properly and the last 2 cm should be cut off after stripping the rest of the line

When to Perform Quality Control For platelet products it should be done on expiry date (end of storage period) of the component On installation and after repair of equipments (refrigerator, centrifuges, deep freezers etc.) Modification in procedure for components preparation Recruitment of new personnel

Comparison of QC Parameters of Blood Components Whole Blood Derived Apheresis Derived Packed Red Cells Volume (450ml) - 280±40ml (350ml) - 220±30ml Hct 70%±5 Hb content 45g/unit Leucocyte 108 – 109 360ml 65% to 75% ≥51g/unit <5x106 Platelets (PC) Volume 50 – 70 ml Platelet count ≥ 5.5 x 1010 Leucocyte content 5.5x107 to 5.0x108 Red cell contamination 0.5ml 200 – 300 ml ≥3.0 – 7x1011 < 5.0x106 Traces to 0.5ml Plasma Volume 175 – 230 ml Fibrinogen 200 – 400mgm/unit Factor VIII 0.7 1U/ml 450 – 800ml 400 mg/unit ≥ 0.7 IU/ml

Process control is imperative Objectives: reduce lot to lot variation in BC manufacture reduce risks of Tx to as low as reasonably achievable Based on principles Continuous Statistical Process Improvement process control Innovation

Process Improvement Continuous Improvement is the Goal Data collection & analysis of performance Identification & evaluation of problems & solutions Changes to improve performance Corrective action reduces or eliminates recurrence Preventive action eliminates potential non-conformance to prevent occurrence

Statistical process control Problem solving tool in attaining process stability and improving capability by decreasing variability e.g. Control charts to identify non conforming lots or individual components and to detect trends Centered on error management - redesigning processes to prevent error from recurring

Process innovation Employs information technology to control manufacturing processes Next opportunity to improve significantly the safety and quality of blood supply

MOST COMMON LABORATORY ERROR Error Management Systems need to be in place to report & investigate quality incidents or errors Systems of correction, CAPA need to be in place of which all staff and users need to be aware of Incidents must be used to improve processes / procedures, not to punish staff Summarize the presentation, emphasizing the importance of error reporting and management and the concept of ‘improvement opportunity’ Emphasize the importance of all staff and users being fully aware of error reporting policies and systems Emphasize the importance of not punishing people for errors It is essential that errors are reported and, in a culture of fear, they will not be reported MOST COMMON LABORATORY ERROR Transcription

To summarise… Process control necessary to ensure a process is stable, predictable and with minimum variability Validation of SOPs and QC: Evaluation of performance of process Proficiency testing (EQAS): Comparison of performance to a goal Error Management/Audit: Control of non-conformances Regular monitoring and control of production /process will ensure safer and consistency of quality of Blood components