how to deal with product-related mishaps...how to deal with product-related mishaps lizette...

How to Deal with Product-Related Mishaps

Lizette Caballero, BS, MT (ASCP) Lizette Caballero, BS, MT (ASCP) Laboratory Supervisor,

Florida Hospital Cancer Institute Cellular Therapy Laboratory

Orlando, FL

Presented in this Session:

• Present serious case scenarios on ‘product-related mishaps’ experienced by cell processing facilities.

• Discuss how the facility dealt with the problem.

• Suggest a list of preventive actions for each case scenario as to possibly avoid such a recurrence.

• Sharing each others ‘experiences’ provides room to learn & improve our practice.

• Expect full audience participation, so speak up!

CAPA - Corrective And Preventive Action

• In response to any trouble-shooting situation, or SOP deviation:Ø Immediate action ØNotifyØDocumentØ Investigate cause ØReport to regulatory authorities (QA, legal, etc)ØDetermine preventive actionØ Implement preventive action ØMeasurable follow-up to determine effectiveness


• Corrective Action- a term that encompasses the process of reacting to product problem, customer complaints or other nonconformities and fixing them. This process includes:– Reviewing and defining the problem or

nonconformity– Finding the cause for the problem– Developing an action plan to correct problem and

prevent recurrence– Implementing plan– Evaluating the effectiveness of the correction


• Preventive Action- a process for detecting potential problems or nonconformances and eliminating them. The process includes:– Identify the potential problem or

nonconformance– Find the cause of the potential problem– Develop a plan to prevent the occurrence– Implement the plan– Review the actions taken and the

effectiveness in preventing the problem

CAPA - Corrective And Preventive Action Procedures

– The development of an Investigationprocedure with assignments of responsibility. • A written plan helps assure that the

investigation is complete and nothing is missed. The procedure should include: an objective for the actions that will be taken, the procedure to be followed and personnel responsible.


• Performing a thorough Analysis of the problem with appropriate documentation. – This process involves collecting relevant

data, investigating all possible causes, and using the information available to determine the cause of the problem.


– Creating an Action Plan listing all the tasks that must be completed to correct and/or prevent the problem. • The plan should include, as appropriate: the

items to be completed, document changes, any process, procedure or system changes required, employee training and any monitor or controls necessary to prevent the problem or a recurrence. The action plan should identify the person or persons responsible for completing each task.


–The Implementation of the plan. •Once the plan is implemented all the required tasks described in the action plan are initiated, completed and documented.


– A thorough Follow up with verification of the completion of all tasks, and assessment of the effectiveness of the actions taken. Several key questions must be answered:

• Have all the objectives of this CAPA been met?

• Have all the recommended changes been completed and verified?

• Have appropriate communications and training been implemented ?

• Is there is any chance that the actions taken may have had any additional adverse effect on the product or service?

8:00 am

• Arrive for work half hour early, latte in hand.

• Quietly begin reviewing paperwork.

8:15 am – LN2 Tank Alarm

• LN2 tank alarm goes off.

• Enter the cryo-storage room and find LN2 tank lid OPEN!!!.

• Cassettes with products waiting to be placed in their respective location inside the LN2 tank are resting on top of the tank rack (vapor phase).

WHAT DO YOU DO?

NOTE:

•Rees-Scientific alarm didn’t go off (monitoring temperature).

•LN2 tank alarm goes off as “low liquid level for LN2 source”.

8:25 am – CORRECTIVE ACTION• Check Liquid Nitrogen Level on storage tank:

– result = within acceptable range.• Check previous 24hrs temperature readings from

Rees-Scientific printout:– result = highest temperature reported was -1210C.

• Conclusion – Tech opened lid to move cells from vapor phase into liquid phase. Got distracted and left lid open. Lid was open for approx. 12 hours. Patient had enough cells collected to be able to thaw one unit. Result= viability >80%.

• Changes in SOP made.

Question for the Audience:

• What can be implemented so this ‘incident’ does not happen again?

PREVENTIVE ACTION SUGGESTION

• Revisit Training SOP:– Staff should concentrate on task, especially when

putting away bags in LN2 storage tanks.

• Add a new step on paperwork for a tech to sign when cells are moved and a second tech to sign as the verifier for this procedure.

9:00am- NMDP Product

• The laboratory released 3 bone marrow product bags from unrelated donor to the nursing unit the night before.

• The bags were issued using a transport cooler (igloo).

• Infusion started at 7:00pm. After infusion, the nurses were instructed to return cooler to the Blood Bank (open 24 hours).


• Tech from the lab retrieves the cooler from Blood Bank and inspects the contents of the cooler.

• They discover the last bone marrow bag was still in the cooler.

WHAT DO YOU DO?

NOTE:PM nurse finished her shift and forgot to tell the incoming shift that there was the last bag inside the cooler.


• A viability test is immediately performed.• The BMT Lab calls patient's MD and reports

the incident.• Since the bone marrow had a low nucleated

cell count, the MD explained the incident to the patient and arranged for the patient to receive the last bag.

• Patient was upset and reported the incident to administration.


• What can be changed in the current policies & procedures so this ‘reported case’ does not happen again?

• Remove bags from cooler and place where accessible and visible at time of infusion.

• System for nurses where there is a change in custody during shift change or handover.

• Label Bags as 1/3, 2/3 and 3/3.

Preventive Action: Suggestions

10:00 am – Infusion

• Preparing for 1st infusion of the day, removing cassettes from LN2 storage.

• Inspect bags in lab with co-worker – identity, labeling.

• Proceed to patient’s room for thaw.• Upon removing bag from cassette, notice that

cassette is flooded with frozen blood.• Frozen chunks of cells were stuck to the cassette.

WHAT DO YOU DO?

NOTE: – Patient only has 2 bags with marginal

CD34 content.

– Physician wants to give every last drop.

10:05 am – Corrective Action

• Call for help - lab supervisor & MD. • Put frozen bag inside a sterile bag while waiting

for MD.• Return to dry shipper.• Using the end of the barrel of a 60 ml syringe,

scrape frozen cells off cassette.• Place ‘cell slurry’ in a sterile bag and thaw.• Draw up the cells from the bag using a 60 ml

syringe and blunt needle/cannula.

10:05 am – Corrective Action• Inspect bag to figure out where the leak is:

– poorly sealed segment.• Clamp the segment, double bag the product in

sterile bags and continue thawing.• Use an injection site and withdraw the product

from the bag using 60 ml syringe.• Take sample(s) for sterility.• Measure the volumes & cell doses recovered.• Infuse the cells through stopcock via IV push.


• What can we implement or introduce in our current SOPs to make problems like this example easier to solve?

• Discuss with personnel possible cause for poorly sealed segment and how to prevent:– Revisit ‘heat-sealing’ SOP.

• Introduce the use of sterile overwraps for cryopreservation/storage.

• Staff should check not only the identity & labelling, but integrity of bag(s).


11:00am Tech gets ready for Cord Blood thaw

• A cord blood unit is awaiting to be transplanted into a child with ALL. All labeling and condition of unit looked fine upon receipt.

• It is time for thawing and the unit typed is a different ABO. The tech noticed the discrepancy in typing and notifies supervisor.

WHAT DO YOU DO?

NOTE: – A rapid HLA (class I) typing showed

this unit to be 0/4 match.

11:30am Corrective Action

• A back-up unit was ordered and delivered within 24 hours.

• Transplant is done on Day +1.

• Patient engraftment is attained.


• What can be done to prevent wrong the unit from being delivered and infused?


• The use of contiguous segment testing (currently in place).

12:00 pm – Bone Marrow Processing

• Young patient (AML, <20Kg) CY/TBI treated for matched unrelated bone marrow transplant.

• Buffy Coat processing to be performed using Cobe 2991.

• During centrifugation, leakage of cells was observed out of the bag into the COBE centrifuge bowl.

• Processing was halted.

WHAT DO YOU DO?

NOTE:Removed processing bag and discovered only 10% of the original collection volume remained in bag.

12:05 pm – Corrective Action

• Recovered cells and “left over” packed RBC’s were reprocessed for a buffy coat preparation.

• Reprocessed cell dose regarded by BMT clinicians as insufficient graft dose.

• Enquiry back to NMDP to recollect from the same donor unsuccessful (waiting period of 10 days).

• Local cord blood bank had X3 units (potential 4/6 matches).

Corrective Action-continue

• Urgent tissue typing revealed 4/6 match after three days.

• Patient proceeded to an unrelated umbilical cord blood transplant.

• Potential disaster ends with a successful transplant outcome.


• How can we prevent these ‘cell processing mishaps’ from happening?

• ‘Prime and spin’ empty bag with saline before processing real sample.

• Staff should be present at all time when ‘processing’ on Cobe 2991 machine.

• Avoid using a ‘sampling site coupler’with Cobe bag when spinning.


1:30 pm – Auto HPC-A Cryopreservation

• Apheresis nurse calls the laboratory to report concern about the collection. ACD-A bag is almost full and the collection will be over in 30 minutes.

• She visually inspects the bag and notices the formation of large clots.

• Tech hangs up the phone and calls Laboratory Director in preparation for processing of grossly clotted product.

WHAT DO YOU DO?

NOTE:The ACD-A pump on the apheresis

instrument malfunctioned. Instrument didn’t detect problem, therefore the alarm didn’t go off.


• Laboratory Director gives authorization to add heparin to product to attempt break up the clots and avoid more clumping.

• The decision is made to filter product using Y-line blood filter (170µm). This procedure is accomplished successfully.

• Cryopreservation procedure continues without complications.


• No problems encountered with viability.

• Thawed product was infused – no adverse reactions or engraftment problems.

• Collection facility starts a corrective action plan with investigation of a cause for the malfunction.


• Have others experienced ‘odd’ looking HPC products? If so, has it compromised the source of cells for engraftment post processing?

2:30pm Processing of two HPC products

• The laboratory received two products and two techs are assigned to process each one.

• Each product was split into two transfer bags and then spun on a floor centrifuge.

• Tech #1 takes out 2 of the bags and expresses plasma.

2:30pm Processing of two HPC products

• Tech #2 arrives later and pulls the other 2 bags from the centrifuge cup and notices that they are two different products.

• He alerted Tech #1 who realizes that he had one bag from his collection and one bag from the other collection.

WHAT DO YOU DO?

NOTE:Tech #1 assumed that his bags were opposite each other in the centrifuge and he omitted an important step of checking prior to pulling bags out of the centrifuge.

3:30pm –CORRECTIVE ACTION

• Tech #1 had already started mixing the products after connecting them with the sterile connective device, therefore both products had to be destroyed.


• What can we do to avoid mixing products?

• Each donor is assigned a color for processing labels on the day of the first collection.

• Centrifuge one product at a time.

• When two products are being processed on the same day, have two techs do label checks at different steps.


4:00pm- Getting ready for next day auto infusion for patient with MM

• Tech goes into LN2 tank to move frozen cells from liquid phase into vapor phase in preparation for next day infusion.

• Cells cannot be found!!!!

• Tech discovered that all bags were infused 12 months ago and database was not updated.

• MD thought cells were in storage for another transplant.

WHAT DO YOU DO?

NOTE: ØPatient already conditioned but no

stem cells!!!!

4:10pm –CORRECTIVE ACTION

• MD notified.

• Patient’s sibling who resided in same city had been tissue typed in the past during consultation with physician as a possible allogeneic donor, and was a match.

• Patient undergoes an urgent allogeneic transplant at day +5.


• How do we ‘stop’ such serious events like this from happening again?

• Prior to patient conditioning, have paperwork & bags signed & checked by tech, transplant physician, pharmacists and BMT nurse confirming availability of cells.

• Have a system in place where a second tech verifies and signs updating of database.


5:30 pm

• Finishing up paperwork (LOTS of deviation reports) for the day!!

• Still have one unrelated product arriving later that day.

11:30 pm – NMDP Product

• 2nd Shift Tech in lab preparing for NMDP product arrival.

• Product arrives, QC samples taken, take product to patient room for infusion.

• Nurse starts infusion - After 20 minutes, patient complains of being cold and wet.

• Nurse notices that the blanket and floor are wet, infusion set was separated from the central line.

WHAT DO YOU DO?

NOTE: Bag was ¾ empty!!

12:05 am – Corrective Action

• Close and secure the infusion tubing.• Remove remaining cells from bag into

syringe to determine volume remaining / lost.

• Reconnect to central line and continue infusion.

• Lift blanket off patient’s central line to visualize entire line during infusion.

• Call the MD to talk to the family.


• What can be introduced or revised in SOPs for infusion so this type of situation does not happen again?


• Clinical staff are up to date with training & procedures for fresh and thawed HPC infusions.

• Add to infusion procedure checking line every 10 minutes to ensure proper flow of cells.

2:15 am – Go Home

• Crawl in bed & dream of a beautiful day in paradise!

MORE SCENARIOS• A tech does the cryopreservation procedure

and loads 4 cassettes into the control rate freezer (top loader). A different tech pulls cassettes out of the CRF after procedure ends. She pulls 3 cassettes and didn’t realize she left 1 inside. CAPA: a loading worksheet was created were the person loading writes how many cassettes are loaded and the person unloading does the same thing.

MORE SCENARIOS• PM is done on control rate freezer by a

contracted company. The program used for PM is different and is left as the default by the PM tech without the lab personnel’s knowledge. Next time a cryo is done, the tech noticed program ended in less than 20 minutes. CAPA: cassettes are moved to the mechanical freezer to finish cryopreservation. Checking of program # becomes part of the procedure.

MORE SCENARIOS• 2 cryopreserved products were noticed to

have “waves” or “ripples” in the bags, 1 bag was cracked. After investigating it was believed that the “ripples” were caused when products were placed in LN2 vapor phase on top of other cassettes holders, the LN2 tank performed and automatic fill- LN2 filling into the tank caused “vibrations” with product moving during freezing process.

MORE SCENARIOS

• Bone Marrow processing on COBE. Tech pressed super-out without first removing hemostat from line. COBE bag exploded, sending marrow “everywhere”. Unclear whether old COBE model didn’t have excess pressure detection or if it did not respond fast enough with full bag.

MORE SCENARIOS• Tech goes to place cassette in to storage

freezer slot and the slot already has a cassette present. Storage location was not updated.

• Technologist to supervisor:" I know you told us to do it, but we stopped doing that months ago.”

• We think we lost a product in the bottom of the tank. We need it today.

MORE SCENARIOS• The LN2 supplier delivered LN2 to the

bulk storage tank at too high pressure. The pipes burst and LN2 is spraying all over the room.

• Three different people checked the math but it turns out to be wrong anyway-happened with cell dosing, DMSO, purging procedures.

how to deal with product-related mishaps...how to deal with product-related mishaps lizette...

Documents