G S A B C J O U R N A L O F B L O O D S E R V I C E S

Events at blood collection area due to nonconforming blood bagsand plateletpheresis kits: need for timely corrective and

preventive actions_3759 1622..1627

Anupam Verma, Deepti Sachan, Priti Elhence, Hem Pandey, and Anju Dubey

BACKGROUND: Good blood banking practice requiresthat every effort should be made to detect any deviationor defect in blood bank products and to identify anypotential risk to blood donor or recipient(s). We reportthe findings of an exercise that provide an insight intowhy feedback from the user side is crucial.STUDY DESIGN AND METHODS: Various eventsinvolving blood bags and plateletpheresis kits and thecorresponding appropriate actions instituted for reme-dial measures were recorded. These scattered eventswere recorded for 6 months following the use of a newbatch of improved blood bags with add-on features.Several events related to plateletpheresis kits fromthree different manufacturers were also recorded for1 year.RESULTS: The affected blood bags were utilized withno untoward incident. The complaint was closed follow-ing satisfactory response from the blood bag manufac-turing company that acted in a timely manner inaddressing the root causes of the problems. However,corrective and preventive actions (CAPA) could not beimplemented for plateletpheresis kits. The rate of unde-sirable events was higher with plateletpheresis kits ascompared with whole blood bags (1.75% vs. 0.06%).CONCLUSION: As defects or deviations that trigger theneed for CAPA can stem from numerous sources, it isimportant to clearly identify and document the problemsand level of risk so that appropriate investigations canbe instituted and remedial actions can be taken in atimely manner. This study demonstrates the usefulnessof a quality initiative to collate and analyze bloodproduct faults in conjunction with blood productmanufacturers.

INTRODUCTION

Problems related to blood bags and other bio-medical devices’ manufacturing defects rarelyget reported in the literature, especially if com-plaints are minor in nature. However, good

blood banking practice requires that every effort shouldbe made to detect any deviation or defect in blood bankproducts and to identify any potential risk to blood donoror recipient(s). The Guidelines for the Blood Services inthe United Kingdom (“Red Book”) stipulates that all bagdefects must be recorded and all such defects should bereported to the quality assurance manager. If the defectappears to be batch related, all blood bags and blood col-lected in them must be set aside for further investigation.1

In our country, blood bags are regulated under bio-medical devices by Food and Drug Administration, India;however, there is no system of providing feedback to iden-tify and take corrective and preventive actions (CAPA) ifthere are any such complaints. We report here the findingsof such an exercise that provide an insight into why feed-back from the user side is crucial.

FINDINGS

Recently, we encountered a few manufacturing-relatednonconforming events in 350- and 450-mL quadruplewhole blood collection bags used at our center. These bagswere from a licensed manufacturer of blood bags in India.These scattered events were noticed over a period of 6

ABBREVIATION: CAPA = corrective and preventive actions.

From the Department of Transfusion Medicine, Sanjay Gandhi

Postgraduate Institute of Medical Sciences, Lucknow, India.

Address reprint requests to: Anupam Verma, MD, PDCC,

Department of Transfusion Medicine, SGPGI, Lucknow, UP

226014, India; e-mail: aver2211@gmail.com.

Received for publication January 13, 2012; revision

received April 30, 2012, and accepted May 9, 2012.

doi: 10.1111/j.1537-2995.2012.03759.x

TRANSFUSION 2012;52:1622-1627.

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months from May 2010 to October 2010following the use of a new batch ofimproved blood bags with add-on fea-tures such as a diversion pouch andneedle cover protector. We had nevercome across any manufacturing defector other anomaly in blood bags suppliedearlier by the same manufacturer whichprompted us to start the investigation.The resident doctors at the phlebotomyarea recorded every event in the “inci-dent report form” (Fig. 1). A detaileddescription of the various events wasprepared and sent to the blood manufac-turer who responded promptly. A qualityassurance manager and his team fromthe company visited our center andcollected implicated bags, tubings,and other materials. A comprehensivereview of all the circumstances related tothe problem was then done. The coop-eration and assistance from the manu-facturing company played an importantrole in deciphering the probable causes

Fig 1. Incident report form.

TABLE 1. Details of various events and appropriate actions instituted for remedial measures involvingwhole blood bags

Description of the event Root cause(s)Corrective and preventive actions

taken by the manufacturer

1. Collection of 350 mL of blood took more than13 minutes following a single venepuncturewith frequent low flow alarms (n = 5). Aftercompletion of the unit, it was noted that therewas a kink in inflow tubing at the point ofcontact with the white clamp (Robert clamp).In one bag upon component separation,the plasma unit was red colored (plasmahemoglobin [Hb] = 0.11 gm/dL); however, therewas no hemolysis in pilot sample tubes. Onlythe red blood cell (RBC) unit was retained inthe inventory, whereas the plasma unit wasdiscarded due to red discoloration. Althoughminor kinks were seen in the majority of bagsfrom the implicated lots, however, it did nothamper collection of blood. In all bags, kinkswere seen specifically near the Robert clampin tubing from the primary bag (Fig. 2[1,2]).

From the impression of the lip of the Robertclamp on the inflow tubing, it was clear thatthe gap between the lips of the clamp wasless than normal.

The Ishikawa (Fishbone) diagram was used toidentify the potential sources of hemolysis(Fig. 3). It was revealed that due to theseverity of tubing kink, blood collection timewas increased and during stripping oftubing the refilling of blood back to thetubing was also slow. This resulted indamage of RBCs, which was likelyexacerbated during centrifugation leadingto lysis of RBCs. It was further noted thatkinks were not severe in most cases,except in two bags that showed slighthemolysis (plasma Hb within normal limits).

The condition of the clamp has beenmade a checkpoint duringinspection and packing of thecomponent by the supplier.

The locked components receivedduring molding are now beingunlocked before packing.

2. Blood bags were not filling properly as theinner surfaces of the primary bag toward thebottom of bag were sticking to each other atthe time of blood collection (n = 7) (Fig. 2[3]).However, after manipulation of these bagsat the donor bedside, there was no problemduring blood collection or separation.

Stickiness (plastic to plastic adhesion) insideprimary bag. After a detailed trace backanalysis and from manufacturing records,it was noted that the embossing valuewas nearing the lower limit (but withinspecification). This, along with possibleoverlapping of bags during sterilization,could have resulted in internal stickiness.

The rubber roller, which embosses theplastic sheeting, is replaced with anew one when the embossing valuenears its lower limit.

The position of hard components suchas needle injury protector andRobert clamp has been made acheck point before sterilization. Alsoafter sterilization, the embossing isinspected for any variation.

3. Tubing breakage observed in the bag onstripping of tubing after collection of unit(n = 4).

It was ascribed to the indentation created bythe lip of the Robert clamp.

The results of implicated tubingsamples were however complyingwith specification limits for variousparameters; hence, no specificaction was taken.

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for these events and facilitating rapid problem resolution,which are outlined below (Table 1).

The affected bags were utilized with caution.However, no untoward incident was observed in thepatients who were transfused blood components fromimplicated bags or in the donors from whom blood wascollected with the use of these bags. The complaint wasclosed following satisfactory response from the companythat acted in a timely manner in addressing the rootcauses of the problems and after encountering no furthercomplaints in the new lot of blood collection bags.

Besides these, few events due to faulty plateletpheresiskits from three different manufacturers (“A,” “B,” and “C”)have also been recorded over a period of 1 year from July2010 to June 2011 (Table 2). As it is evident from the table,the problems with the kits were not aggressively pursued

with the manufacturers and in most cases detail workupwas not done. Here, CAPA could not be implemented as nopreventive action was taken, unlike the case with wholeblood bags; however, the manufacturers replaced theimplicated kits. Although somewhat speculative, theseproblems in plateletpheresis kits could have arisen fromnonadherence to manufacturing/transportation/storagestandards. The rate of such events was much higher withplateletpheresis kits as compared with whole blood bags(1.75% vs. 0.06%).

DISCUSSION

A good supply and material management is one of theessential quality management principles. The materialsused as inputs to a process are considered “critical” if theyaffect the quality of the products being produced. Bloodbags and apheresis kits are two of such critical supplies.Each facility must define acceptance criteria for criticalsupplies and must develop procedures to control andprevent inadvertent use of such materials. Any improve-ment or an appropriate action is dependent upon athorough investigation of the reported nonconformity.Documentation is important in such cases. Control chartsalong with standard forms for the collection of blood bagfault information can be helpful to identify trends for spe-cific faults as done in a study by National Blood Services,UK.2 Also noncompliance with a standard procedure mayaggravate the problem. A standard operating procedureon blood collection incorporating the apparently “minorsteps” should be adhered to at all times. It was revealedthat this step of standard operating procedure of inspect-ing the blood bag and its associated tubing after unpack-ing was omitted by the resident doctors and nursingpersonnel in the blood donation area (Fig. 4).

The increasing complexity associated with manufac-turing of blood bags and apheresis kits has resulted inincreased scope of errors. Besides, inadequate training ofblood bank personnel can also contribute to these prob-lems, which can be improved with a reorientation trainingprogram in conjunction with the manufacturer. Even theconditions in the transport containers for the blood bagscan favor the survival and growth of bacteria, which canbe catastrophic.3 We have also previously reported aboutthe faulty blood administration sets that were responsiblefor a cluster of transfusion reactions in the recipients.4

Thus, biomedical device manufacturing companies havean important role in ensuring that appropriate CAPA aretaken to sustain quality and to promote improvementwithin the organization. CAPA management is the keyactivity of a well-established compliance and qualityprogram within good manufacturing practice involvingany manufacturing industry. However, in spite of best pos-sible efforts, sometimes deviations or nonconformancesare discovered at the source, that is, in blood bag and

Fig 2. Details of the implicated blood bags and plateletpher-

esis kits. (1) Robert clamp pinching the tubing in the fresh

blood bag; (2) indentation in the tubing of the bag; (3) sticki-

ness inside the primary bag; (4) ballooning of left waste bag

during priming in the plateletpheresis kit; (5) kink in the inlet

tubing of a single needle kit; (6) kink in the tubing at T junc-

tion of a single needle kit; and (7) leakage at umbilical joint of

the kit at the centrifuge interface of a double needle kit.

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Fig 3. Ishikawa (Fishbone) diagram for identifying potential sources of hemolysis.

TABLE 2. Events, their probable causes, and actions instituted for immediate remedial measures involvingplateletpheresis kits

Manufacturer Description of the event Probable cause(s) Action taken

“A” 1. During priming, alarm with “Kit TestProblem” display and ballooning ofwaste container were noticed (Fig. 2[4])

Air was sucked in during priming due tothe defect in the umbilicus joint of the kitat the centrifuge interface.

Procedure was aborted and thekit was discarded.Manufacturer was informed.

2. During start of the procedure at 1minute, the machine gave the “InletPressure Low” alarm.

Kink was noticed in the inlet linetubing (Fig. 2[5]).

Kink was removed manually toallow smooth flow of bloodand the procedure wascompleted.

3. Machine gave an alarm that “LeakageDetected at Centrifuge.”

Leakage at the umbilical joint of the kit atthe centrifuge interface was noticed withplasma seepage over the sensor(Fig. 2[7]).

The procedure was aborted andthe kit was discarded.

4. During priming, alarm with “CassettePressure Limit Exceeded” display wasobserved. The kit was checked for kinkand occlusion; however, machinecontinued to give repeat alarms.

A piece of broken plastic kit was foundin the cassette gasket after removingthe kit.

Kit was discarded andmanufacturing company wasinformed.

“B” 1. Installation of kit and priming wasuneventful. During procedure, leakagefrom the return chamber was noticedwith seepage of blood.

Crack in the return chamber was noticed,which could have happened duringmanufacturing, transportation, orstorage of kits.

Procedure was stopped withoutreinfusion. Kit was discardedand donor was deferred forthe next 3 months.

2. Leakage from tubing entering theplasma pump was detected duringpriming. Solution containers wereclosed and kit was removed.

Manufacturing defect at the junction oftube entering the plasma pump, leadingto leakage of saline during priming.

Manufacturer informed aboutthe defect.

“C” 1. In spite of an obvious kink in thetubing, the kit was installed, whichresulted in frequent alarms during theprocedure (Fig. 2[6]).

Kink was present at T junction, whichcaused red blood cell (RBC)contamination in the platelet collectionbag during the first cycle.

Procedure could be completedafter straightening the tubingmanually without further RBCcontamination.

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Dept of Transfusion Medicine

SGPGIMS, Lucknow

Standard Operating Procedure

Whole Blood Collection

Number Pages Authors Authorized byEffective

date

TM/D/04 01/04/2004 Dr A Sonker

Dr A Verma

Dr R Chaudhary5

Version Review

period

Date of review Reviewed by Number of copies

IV 2 yrs 31/03/2010 3

LOCATION

FUNCTION DISTRIBUTION

SUBJECT

Blood donation complex

Collection of whole blood in a suitably

labeled container with proper identification

Selection of blood bags, labeling, and

phlebotomy for whole blood donation

1. PRINCIPLE & APPLICATION

2. RESPONSIBILITY

3. REFERENCES

4. DEFINITIONS

5. MATERIALS REQUIRED

6. PROCEDURE

7. INTERPRETATION

8. DOCUMENTATION

9. END OF DOCUMENT

6.1 Selection & labeling of blood bag

Blood donation complex faculty l/C

Residentin change of donation complex

Master file

ÿ

ÿ

ÿ

For all male blood donors weighing between 45 to 60 Kg, select 350 mL quadruple blood bags,

while select 450 mL bags for those weighing above 50 Kg (for all female donors, regardless of

weight, select only 350 mL bags).

Check the bag visually for

Punctures/cracks/cuts

Discoloration of anticoagulant/additive solution

Suspended particulate matter in anticoagulant/additive solution

If the needle seal is broken

Expiry date

Any kink in the tubing

Record the result in the designated area on the donor registration card.

Make suitable entries in the Incidence Report (TM0A1.1) if applicable.

Fig 4. Excerpts of the standard operating procedure on whole blood collection highlighting salient features.

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1626 JBSM Volume 52, July 2012

apheresis kit manufacturing operation or at the user end.As defects, deviations, or any other gaps that trigger theneed for a CAPA can stem from numerous sources, it isimportant to clearly identify and document the prob-lem(s) and level of risk so that appropriate investigationscan be instituted and remedial actions can be taken in atimely manner as a part of GMP. It is equally important tocollate and analyze blood bag faults as a safety and qualityinitiative in conjunction with blood bag manufacturers.An active management is vital in this area as the pattern offault changes over time, owing to alterations in raw mate-rial and manufacturing method.2 Regulatory and non-regulatory quality standards can be followed for effectingprocess improvements. An elaborate nonregulatoryapproach to improving processes in the blood center isthrough the six sigma process.5

In conclusion, we hope that this report on noncon-forming blood bags and plateletpheresis kits will makeblood bank personnel aware of these undesirable events,which will ultimately help the donors and the patientsreceiving blood components. A national or regionalhemovigilance program is needed for countries such asIndia where all such data can be collated and used forimproving the quality of blood bags and apheresis kits.This will ultimately pave the way for good manufacturingpractice in blood banking. A successful outcome can be

achieved if all the stakeholders work as a team as exem-plified in our case where various issues with blood bagswere resolved satisfactorily.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest related

to the manuscript submitted to TRANSFUSION.

REFERENCES

1. James V, McClelland B. Guidelines for the blood transfu-

sion services in the United Kingdom. 6th ed. London: The

Stationery Office; 2002.

2. Beckman N, Nicholson G, Ashford M, Hambleton R. Blood

pack fault monitoring. Vox Sang 2004;87:272-9.

3. Szewzyk U, Szewzyk R, Stenström TA. Growth and survival

of Serratia marcescens under aerobic and anaerobic condi-

tions in the presence of materials from blood bags. J Clin

Microbiol 1993;31:1826-30.

4. Dubey A, Verma A, Sonker A, Sachan D, Chaudhary R.

Sudden increased incidence of transfusion reactions

reported from a ward: root cause analysis. Transfusion

2009;49:409-10.

5. Tata RM, Jones GD. Six sigma culture as a management

principle. Transfusion 2011;51:1604-8.

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