preparing for inspection: managing regulations and practices surrounding donors with positive...

Preparing for Inspection: Managing Regulationsand Practices Surrounding Donors With Positive

Infectious Disease TestingJillian Ferschke*

Division of Transfusion Medicine, UMass Memorial Medical Center, Worcester, Massachusetts

Federal and local regulatory agencies mandate that all blood collection facilities test each allogeneic blood dona-

tion for evidence of infectious diseases. When a donation tests positive or reactive for any of the required screen-

ing tests, facilities are required to take appropriate action by deferring donors and removing potentially infectious

products from inventory. Each required action must be performed in accordance with posted regulations and

documented for record retention. Donor deferral records related to positive or reactive infectious disease testing

are particularly vulnerable targets of inspection. There are currently numerous regulations and requirements for

handling donors who test positive or reactive in infectious disease screening tests. Each of these regulations must

be somehow organized and incorporated into written departmental procedures for staff to follow with confidence

and accuracy. UMass Memorial Medical Center has implemented a process that equips staff members with the

knowledge and confidence to respond in an organized way to an inspection of donor deferral records and related

activities. The extraction of regulatory detail from written procedures into job aids and tools for staff to follow

with ease and confidence ensures an inspection with zero findings in this area. J. Clin. Apheresis 23:191–195,

2008. VVC 2008 Wiley-Liss, Inc.

Key words: donor deferral; reentry; lookback; donor notification; inspection

INTRODUCTION

The UMass Memorial Medical Center Blood DonorProgram collects �3,500 allogeneic and autologous don-ations per calendar year. Approximately 1% of these don-ations are accompanied by positive or reactive tests forone or more of the required infectious disease markers.The United States Food and Drug Administration (FDA)mandates that blood collection facilities follow postedguidelines for establishing procedures for handling boththe donor and their prior donations when current testingis positive or reactive for an infectious disease.

Because of the ever increasing number of tests thatare required for blood donors, and the ongoing need toensure a safe blood supply, numerous FDA guidelinesand memoranda have been issued. It is the responsibilityof the blood collection facility to review each postedguideline and integrate each requirement into their pro-cedures to ensure compliance. In addition to FDA, thereare other accrediting agencies that also have guidelinesor recommendations for handling positive or reactivetest results. Each of these additional requirements mustbe incorporated into the same procedures to remain incompliance with all regulatory agencies.

The clock starts ticking as soon as a blood establish-ment is notified that a current donor tests positive orreactive for one or more infectious disease screeningtest. Regulatory agencies require that certain actions beperformed within a set number of calendar days from

the date that the blood establishment became aware ofthe donor’s test results. Prior donations from the donor,if still in inventory, may require market withdrawaland must be placed in quarantine until confirmatoryresults are received [1,2]. Depending on the confirma-tory results, when applicable, the donor may requiredeferral from donation for a period of time and notifiedof both the deferral status and current test results [2,4].Previously quarantined products may be destroyed orreleased from quarantine and placed back into bloodinventories based on the confirmatory testing. For con-firmed cases of Hepatitis C, Human ImmunodeficiencyVirus, and other viruses a lookback must be performedto notify recipients from prior donations of the donor’scurrent test results and advise them regarding addi-tional testing or counseling [3–6,10]. The prior dona-tions involved in a market withdrawal or lookback aredefined by a time frame set by the regulatory agencies.

From the Proceedings of the 29th Annual Meeting of the American

Society for Apheresis, Galveston, Texas, April 2008.

*Correspondence to: Jillian Ferschke, Division of Transfusion Medi-

cine, UMass Memorial Medical Center, 55 Lake Avenue North,

Worcester, MA 01655, USA.

E-mail: [email protected]

Received 29 September 2008; Accepted 29 September 2008

Published online 29 October 2008 in Wiley InterScience

(www.interscience.wiley.com).

DOI: 10.1002/jca.20177

VVC 2008 Wiley-Liss, Inc.

Journal of Clinical Apheresis 23:191–195 (2008)

This time period varies and is dependent on the spe-cific test results and infectious disease.

Developing an efficient process for complying withregulatory requirements related to donor deferral, noti-fication, and reentry testing is necessary to ensure notonly compliance but also the safety of our bloodsupply. UMass Memorial has recently restructured itsprocesses for compliance with regulatory requirementsin the area of donor deferral to achieve a high level ofconfidence that all actions comply with regulatoryrequirements.

MATERIALS AND METHODS

To initiate restructuring of the donor deferral processkey staff members were asked for suggestions toimprove the current procedures. Suggestions included amore focused procedure and tools to streamline ourresponses to the regulatory requirements. Other sugges-tions included a process that was quick and easy toupdate due to the ever increasing number of requiredtests. Staff members were also concerned with thelength of the procedure: the previous version was over20 pages in length and had a separate section for eachinfectious disease screening test. Some staff membersresisted learning and performing the old process due tothe complexity of the written procedure and lack ofsupporting documents.

The next step was to create a flow diagram of theentire process from receipt of positive or reactive infec-tious disease test results through product disposition ofprevious donations, receipt of confirmatory results, do-nor deferral, notification and recipient tracing. Guide-lines and regulations were studied intensively to ensurethat all requirements were recognized and included inthe flow diagram (Fig. 1) [1–14].

Once the flow diagram was developed, it was usedas an outline for the procedure. A written procedurewas developed to provide detailed instruction for per-forming each step of the diagram. Excluded from theprocedure were time frames for deferral, quarantiningin-date products, requirements for recipient tracing andnotification, and reentry for specific test results. Byexcluding this detail, an umbrella procedure could bedeveloped to provide instruction that was uniformregardless of the infectious disease test result.

In concert with the procedure, a worksheet wasdeveloped to walk staff through each essential step ofthe process to ensure all steps are completed. Theworksheet was designed for one donation per sheet,and it provided space for documentation of specificrequirements related to test results with sign off aseach step is completed. Review processes were incor-porated into the written procedure and documented onthe worksheet.

To define time frames and specific infectious dis-ease detail a group of tables were developed to housethe detailed information that was excluded from thewritten procedure. A separate table was developed foreach infectious disease that donations are tested for.

To create the tables, a list of all potential test resultcombinations (screening and confirmatory results) wasdeveloped for each infectious disease. Potential resultswere listed vertically as row headers. The columnheaders depicted the different actions for lookback, do-nor eligibility, notification, and reentry. Once a stand-ard template was developed, all of the requirementswere filled into the table (Fig. 3). Time frames forquarantine of in-date products, product withdrawal, andrecipient tracing were extracted from FDA and AABBrequirements and entered into the table [1–4]. For con-flicting regulations, the stricter requirement was cho-sen. Once a draft of each table was developed, theMedical Directors reviewed to determine if strictertime frames or requirements were necessary for UMassMemorial Medical Center.

Once the procedure and supporting documents werecreated, validation activities were executed to ensurethat the procedure was clear, concise, and worked inconjunction with related departmental processes. Theassociated tools were validated separately and in con-junction with the written procedure to ensure that theycould be used for their intended purposes. Validatingthe accuracy of the tables was particularly important,staff members were required to review each referencedregulation and ensure that the requirement was accu-rately documented with the tables.

RESULTS

The written procedure provides staff with instruc-tions for all aspects of handling the donor and priordonations when a screening test is positive. By exclud-ing the specific time frames and requirements for eachindividual infectious disease result, the procedurelength is cut in half and allows staff to quickly finddesired instruction or information.

The flow diagram is a useful training tool (Fig. 1).The overall process for donor deferral can be over-whelming at first glance, by using the flow diagram itenables trainees to review the general process and thenrefer to the procedure for specifics.

To assist in writing the procedure, a timeline wasdeveloped that maps the required time frames in whichblood establishments must complete appropriate actiononce a screening test is resulted as positive or reactive(Fig. 2).

A template table was developed to be used for eachindividual infectious disease. As shown in Figure 3; thetemplate table provides space under the ‘‘Test Result’’column header to list each potential infectious disease

192 Ferschke

Journal of Clinical Apheresis DOI 10.1002/jca

result. Screening results are entered into the first col-umn followed by confirmatory results in adjacent col-umns (additional columns are inserted as necessary).The third column ‘‘Donor Testing History,’’ allows forspecifics related to prior donations. For example: in theevent that a donor tests reactive for the antibody to theHepatitis B Core Antigen (Anti-HBc) the donor ishandled differently if this is the first or second reactivedonation for the test [11,12].

The ‘‘Consignee Notification’’ columns relate to thedonor’s prior donations. Based on screening results,collection facilities may be required to notifying theircustomer facilities to quarantine prior in-date products.Once confirmatory results are received, market with-drawal, or recipient tracing may be required. These

columns display time frames for which prior donationsare impacted. Staff members are required to refer tothe written procedure for specific instructions on per-forming consignee notification.

The next set of columns, ‘‘Managing Donor’’defines the period of time that a donor must bedeferred and whether notification of the donor isrequired. A time frame is entered into the ‘‘Deferral’’column and a ‘‘Yes’’ or ‘‘No’’ is entered into the‘‘Notification’’ column.

The ‘‘Donor Re-entry Evaluation’’ columns depictfollow-up actions if the donor is eligible for reentry.The ‘‘Re-entry Testing’’ column displays each test thatthe donor must test negative for to be eligible for reen-try into the allogeneic donation population. Reentry

Fig. 1. The flow diagram illustrates each essential step of the process for handling positive or reactive infectious disease results. The dia-

gram provides a useful training tool and job aid.

Positive Infectious Disease Tests in Donors 193


Fig. 3. Template table used for entering specific requirements for each infectious disease.

Fig. 2. Time frame requirements for performing appropriate action once a donation tests positive or reactive for an infectious disease.

Fig. 4. (a) Table generated for Syphilis test results. This table is to be used in conjunction with a written procedure when determining how

to handle a donor that tests positive for a syphilis screening test. (b) Table generated for HTLV I/II results. This table is to be used in con-

junction with a written procedure when determining how to handle a donor that tests positive for an HTLV I/II screening test.

194 Ferschke


testing can only be performed once the donor has com-pleted the required deferral period. Once reentry testingis resulted, the ‘‘Re-entry Results’’ and ‘‘Status’’ col-umns can be used to determine the donor’s donationstatus. The ‘‘Re-entry Results’’ column will list allpossible results from reentry testing and will have acorresponding status listed in the ‘‘Status’’ column.Figures 4a and 4b provide examples of tables createdfor Syphilis and HTLV I/II, respectively. As shown inthe figures, the table can be formatted by merging orsplitting boxes to allow for variations specific to eachinfectious disease [8,9,13,14].

The validation activities provided documentation tosupport the implementation of the new process. Staffmembers reviewed the written procedure and support-ing documents and found them acceptable for imple-mentation. Validating each infectious disease tableagainst the related regulation ensured compliance. Staffmembers find the tables extremely helpful when deter-mining how to handle a donor that tests positive orreactive for one or more infectious disease test. Insteadof flipping through pages of a written procedure fol-lowed by an interpretation of the written text, they areable to find regulatory requirements specific to theirdonor’s results within one row of a table.

CONCLUSIONS

A streamlined, written procedure enable staff mem-bers to be more confident and accurate, when handlinga donor with positive or reactive infectious diseaseresults. Regulatory requirements are easily updated bysimply editing boxes within a table instead of rewritingseveral sections or pages of a procedure.

The improvement process is an ongoing endeavor.Since implementation of the first versions of the proce-dure and accompanying documents, there have beenzero findings from regulatory agencies related to donordeferral records. Additionally, several staff membershave been trained and are competent in performing theprocedure.

REFERENCES

1. AABB. Standards for Blood Banks and Transfusion Services,

24th ed. Bethesda, MD: AABB; 2006.

2. AABB. Technical Manual, 15th ed. Bethesda, MD: AABB; 2005.

3. AABB. Association Bulletin #06-08: Information Concerning

Implementation of a Licensed Lest for Antibodies to Trypano-

soma cruzi. Bethesda, MD: AABB; 2006.

4. Code of Federal Regulations. Title 21 CFR 610.46, 630.6, 640.4

and 640.41. Washington, DC: US Government Printing Office,

2007.

5. Food and Drug Administration. Federal Register: Part III

Department of Health and Human Services 21 CFR Parts 606

and 610: Current Good Manufacturing Practice for Blood and

Blood Components; Notification of Consignees and Transfusion

Recipients Receiving Blood and Blood Components at Increased

Risk of Transmitting Hepatitis C Virus Infection (‘‘Lookback’’);

Final Rule. Rockville, MD: Department of Health and Human

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6. Food and Drug Administration. Guidance for Industry: Look-

back for Hepatitis C Virus (HCV): Product Quarantine, Con-

signee Notification, Further Testing, Product Disposition, and

Notification of Transfusion Recipients Based on Donor Test

Results Indicating Infection with HCV. Rockville, MD: US

Department of Health and Human Services; 2007.

7. Food and Drug Administration. Guidance for Industry:

‘‘Assessing Donor Suitability and Blood and Blood Product

Safety in Cases of Known or Suspected West Nile Virus Infec-

tion.’’ Rockville, MD: US Department of Health and Human

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8. Food and Drug Administration. Guidance for Industry: Revised

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on Screening Tests for Syphilis. Rockville, MD: US Department

of Health and Human Services; 2003.

9. Food and Drug Administration. Guidance for Industry: Donor

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10. Food and Drug Administration. Revised Recommendations for

the Prevention of Human Immunodeficiency Virus (HIV) Trans-

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11. Food and Drug Administration. Recommendations for the Man-

agement of Donor and Units that are Initially Reactive for Hep-

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ment of Health and Human Services; 1987.

12. Food and Drug Administration. Recommendations Concerning Test-

ing for Antibody to Hepatitis B Core Antigen (Anti-HBc). Rockville,

MD: US Department of Health and Human Services; 1991.

13. Food and Drug Administration. Recommendations for the Quar-

antine and Disposition of Units from prior Collections form

Donors with Repeatedly Reactive Screening Tests for Hepatitis

B Virus (HBV), Hepatitis C Virus (HCV) and Human T-Lym-

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14. Food and Drug Administration. HTLV-I Antibody Testing.

Rockville, MD: US Department of Health and Human Services;

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Positive Infectious Disease Tests in Donors 195


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