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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Guidance for Industry: “Lookback” for Hepatitis C Virus (HCV): Product Quarantine, Consignee Notification, Further Testing, Product Disposition, and Notification of Transfusion Recipients Based on Donor Test Results Indicating Infection with HCV

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Additional copies of this guidance are available from Office of Communication, Outreach and Development (OCOD) (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448, or by calling 1-800-835-4709 or 301-827-1800, or email ocod@fda.hhs.gov, or from the Internet at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

For questions on the content of this guidance, contact OCOD at the phone numbers listed above.

 

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research (CBER)
August 2007
Updated December 2010



Guidance for Industry

“Lookback” for Hepatitis C Virus (HCV):
Product Quarantine, Consignee Notification,
Further Testing, Product Disposition,
and Notification of Transfusion Recipients
Based on Donor Test Results

Indicating Infection with HCV

 

NOTE:  Changes have been made to update the guidance dated August 2007:

  • Figure 1 and Table 1 of the guidance have been revised to reflect new technologies for anti-HCV testing, and corresponding changes have been made to the text.
  • The guidance has been updated to note that Title 21 Code of Federal Regulations 610.48 (21 CFR 610.48) (historical lookback) requires blood establishments to have completed a number of actions by February 19, 2009, based on the review of historical testing records.  Note that the recommendations for implementing historical lookback as reflected in Figures 2-4 and Tables 2-5 have been relocated to the new Appendix to this guidance.
  • In section IV, “January 1, 1988” was revised to “February 20, 2008”.
  • The recommendation with respect to notification by transfusion services, as consignees, was expanded to include a recipient’s physician of record, as appropriate, consistent with the regulations.
  • The time frames in which blood establishments must perform appropriate procedures after a donor tests reactive for evidence of HCV infection were clarified.
  • A number of nonsubstantive changes were made throughout the document for clarification purposes.

 

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research (CBER)
August 2007
Updated December 2010



Table of Contents

I.      INTRODUCTION
II.      BACKGROUND
III.     DEFINITIONS
IV.     LOOKBACK REQUIREMENTS
V.      CURRENT RECOMMENDATIONS
VI.     BLOOD AND BLOOD COMPONENTS INTENDED FOR MANUFACTURE INTO NON-INJECTABLE PRODUCTS
VII.   REFERENCES
APPENDIX


Guidance for Industry

 “Lookback” for Hepatitis C Virus (HCV): 
Product Quarantine, Consignee Notification,
Further Testing, Product Disposition, and
Notification of Transfusion Recipients
Based on Donor Test Results
Indicating Infection with HCV

This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic.  It does not create or confer any rights for or on any person and does not operate to bind FDA or the public.  You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations.  If you want to discuss an alternative approach, contact the appropriate FDA staff.  If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.

 

I.          INTRODUCTION

Multiple layers of safeguards, including donor screening and testing, are used to reduce the risk of transmitting infection through blood transfusion.  However, a person may donate blood early in infection, during the period when the viral marker is not detectable by a screening test, but the infectious agent is present in the donor’s blood (the “window period”).  For example, if an individual donates blood on a number of occasions and each donation tests nonreactive for antibody to HCV, but the donor returns and tests repeatedly reactive for antibody to HCV at a later date, prior collections from such a donor could be at increased risk for transmitting HCV.  In addition, a recipient of a transfusion of blood or blood components collected during the “window period” from a donor who is now repeatedly reactive would not know that he or she might be at increased risk of infection with HCV through the transfusion, unless he or she is notified.  Furthermore, untested collections from donors who later were found to be repeatedly reactive when tested for antibodies to HCV since 1990 (when antibody tests for HCV became available) might have been at increased risk for transmitting HCV due to a chronic infection in the donor.

Chronic hepatitis due to HCV is a major health problem in the U.S.  The infection is usually clinically silent until the liver is seriously damaged.  As a result, infected people usually are unaware of their disease.  Although transfusion-transmitted infections account for only a very small proportion of HCV infections, it is possible to identify and “lookback” at prior donations that might have been collected during the “window period.”

This guidance document provides recommendations for complying with 21 CFR 610.47 and 21 CFR 610.481 to (1) blood establishments that collect blood or blood components, including Source Plasma and Source Leukocytes, (2) hospitals, and (3) other consignees.  This guidance does not apply to autologous donations, pooled blood components intended solely for further manufacturing into products that are manufactured using validated viral clearance procedures, and blood and blood components that were intended for manufacture into non-injectable products subject to the labeling described in Section VI.

This document supersedes the guidance document of the same title, dated August 2007.  The August 2007 document superseded the HCV sections of the Food and Drug Administration (FDA) memorandum of July 19, 1996, entitled “Recommendations for the Quarantine and Disposition of Units from Prior Collections from Donors with Repeatedly Reactive Screening Tests for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Human T-Lymphotropic Virus Type I (HTLV-I).”  The August 2007 guidance document also superseded the September 1998 guidance entitled “Guidance for Industry:  Current Good Manufacturing Practice for Blood and Blood Components:  (1) Quarantine and Disposition of Units from Prior Collections from Donors with Repeatedly Reactive Screening Tests for Antibody to Hepatitis C Virus (Anti-HCV); (2) Supplemental Testing, and the Notification of Consignees and Blood Recipients of Donor Test Results for Anti-HCV.”  Additionally, the August 2007 guidance finalized FDA’s draft guidance dated June 1999 entitled “Guidance for Industry:  Current Good Manufacturing Practice for Blood and Blood Components:  (1) Quarantine and Disposition of Prior Collections from Donors with Repeatedly Reactive Screening Tests for Hepatitis C Virus (HCV); (2) Supplemental Testing, and the Notification of Consignees and Transfusion Recipients of Donor Test Results for Antibody to HCV (Anti-HCV).” 

FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities.  Instead, guidances describe FDA’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited.  The use of the word should in FDA’s guidances means that something is suggested or recommended, but not required.

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II.        BACKGROUND

Lookback related to HCV testing has been discussed at open public meetings, including meetings of FDA’s Blood Products Advisory Committee (BPAC), on multiple occasions since October 1989.  As a response to these discussions, FDA provided detailed guidance in the July 19, 1996, memorandum on the quarantine and disposition of certain prior collections of blood and blood components from donors who subsequently test repeatedly reactive for anti-HCV.  The 1996 memorandum recommended that blood establishments notify consignees (such as the transfusion service, physician, or fractionator) for the purpose of quarantine and eventual disposition of products made from prior collections.  Prior to recent advances in medical diagnosis and therapy, FDA did not recommend notification of recipients of blood from donors who subsequently test positive for anti-HCV because no clear consensus on the public health benefit (i.e., disease prevention and treatment) of such action had emerged.

Improvements in the management and treatment of chronic hepatitis C have occurred over time, and there is a strong correlation between a positive test for anti-HCV in a supplemental assay (e.g., the Chiron RIBA HCV 3.0 SIA2 ) and HCV infection (Refs. 1-4).  Prior collections from donors later found to be repeatedly reactive for anti-HCV might also be at increased risk of transmitting HCV.

At public meetings on April 24 and 25, 1997, and August 11 and 12, 1997, the Public Health Service (PHS) Advisory Committee on Blood Safety and Availability recommended notification of recipients of transfused blood and blood components that are at increased risk of transmitting HCV infection based on donor screening with a licensed multiantigen screening test (Enzyme Immuno Assay (EIA) 2.0 or EIA 3.0) since 1992.  Consistent with these recommendations, in March 1998, FDA issued guidance for implementation and public comment regarding recipient notification (63 FR 13675, March 20, 1998).  In response to comments received, FDA issued a revised guidance for implementation in September 1998 (63 FR 56198, October 21, 1998).

At public meetings on November 24, 1998, and January 28, 1999, the PHS Advisory Committee on Blood Safety and Availability reconsidered the issue of recipient notification related to repeatedly reactive results on the single antigen (EIA 1.0) screening test that was licensed in 1990.  The PHS Advisory Committee recommended the expansion of the targeted HCV lookback program to include recipients of blood and blood components from donors subsequently identified as repeatedly reactive by the EIA 1.0 screening test.  In addition, the PHS Advisory Committee considered that, in cases where no supplemental test result is available, it is reasonable to perform lookback for EIA 1.0 based on a signal to cutoff ratio of the screening test of greater than 2.5 (S/CO > 2.5) to capture the vast majority of the true positives and minimize unnecessary recipient notifications based on false reactive screening test results. 

In accordance with the recommendations from the PHS Advisory Committee, FDA issued a draft guidance on HCV Lookback dated June 1999 for public comment (64 FR 33309, June 22, 1999) and published a proposed rule entitled “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 HCV Infection (“Lookback”) (65 FR 69378, November 16, 2000).  In the Federal Register of August 24, 2007, (72 FR 48766), FDA published the final rule entitled “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”)” and a companion guidance document, dated August 2007 (72 FR 48658).  The August 2007 guidance provided recommendations for complying with 21 CFR 610.47 and 21 CFR 610.48.

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III.       DEFINITIONS

Alternative Test:  A licensed test for anti-HCV that is of equal or greater sensitivity in comparison to the licensed HCV EIA 3.0.

Blood and Blood Components:  Whole Blood and blood components, including Source Plasma and Source Leukocytes.

Lookback: 

  • The identification of blood and blood components from prior collections from a donor with:
  • a repeatedly reactive antibody screening test for anti-HCV; or
  • a reactive NAT3 for HCV; or
  • other reliable test results or information indicating evidence of HCV infection (provided the testing was performed using a test approved by FDA by a laboratory compliant with the Clinical Laboratory Improvement Amendments of 1988, or has met equivalent requirements as determined by the Centers for Medicare and Medicaid Services in accordance with the provisions of 42 CFR part 493); and
  • subsequent actions, such as:
  • quarantine of such blood and blood components that are not expired;
  • notification of consignees to quarantine such in-date blood products;
  • further testing of the donor;
  • destruction or relabeling of potentially infectious prior collections;
  • release from quarantine of blood and blood components that do not present a greater risk of infection; and (if appropriate)
  • notification of recipients of identified blood and blood components, or the recipient’s physician of record.

Lookback Donations:  Collectively, the blood and blood components from prior collections from the same donor.

Reactive NAT3 for HCV:  A result for an HCV RNA test that uses only one set of primers specific for HCV that is performed initially on an individual donation, or is performed as a discriminatory NAT subsequent to a reactive multiplex NAT, which tests for multiple viruses, including HCV RNA.

Repeatedly Reactive Screening Test:  The result when an initially reactive screening test is repeated in duplicate samples on the same test run and one or both samples are reactive.

NOTE:  In the HCV Lookback regulations, 21 CFR 610.47 and 610.48, we refer to screening tests as “reactive” instead of “repeatedly reactive” to accommodate the different testing algorithms established for NAT and other screening tests.  However, in this guidance we refer to reactive antibody screening test results for anti-HCV as “repeatedly reactive” to accurately reflect the established testing algorithm for anti-HCV.

Transfusion Recipient Notification:  The actions taken by a hospital, transfusion service, or recipient’s physician of record to notify recipients that they received a transfusion of a Lookback Donation that is at increased risk of transmitting HCV infection.

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IV.         LOOKBACK REQUIREMENTS

In this guidance, FDA addresses lookback related to donor screening by a licensed anti-HCV test and NAT.  Under 21 CFR 610.47 and 21 CFR 610.48, blood establishments must search records of prior collections from donors whose test results on current or historical review donations show evidence of infection with HCV (either repeatedly reactive on screening tests for anti-HCV or reactive on NAT for HCV RNA).  Blood establishments must search their records to identify prior collections dating back 10 years (for current donations) or dating back to January 1, 1988 for historical review donations.  If an establishment maintains computerized electronic records relating to collections made before February 20, 2008, the blood establishment must perform a historical review search of those records dating back indefinitely, as far back as they exist in computerized, electronic form (21 CFR 610.48(b)(1)(i)).  The blood establishment must search records of prior collections, if available, back to the date 12 months prior to the donor’s most recent nonreactive licensed multiantigen screening test for anti-HCV (if applicable), if that is a shorter period, since prior infection in the donor is highly unlikely based on the known duration of the window period (see 21 CFR 610.47(a)(1)(i) and 21 CFR 610.48(b)(1)(iii)(A)).  FDA believes that this date (12 months prior to the last nonreactive multiantigen screening test for anti-HCV) will antedate the window period for infection in that donor.

FDA believes that results for NAT are of value in (1) lookback related to current collections when a NAT result exists and (2) in historical lookback, when a NAT result, including NAT performed under an Investigational New Drug Application (IND), exists in the record of the previous donation(s).  Blood establishments should consider a reactive NAT result to be presumptive evidence of ongoing HCV infection.  A reactive NAT must serve as a basis for initiating lookback (i.e., both quarantine and recipient notification) (21 CFR 610.47(a)(1)).  Note that certain licensed HCV NAT have been labeled with a “limited supplemental claim.”  When current donor test results are repeatedly reactive on an anti-HCV screening test and reactive on HCV NAT, the reactive NAT acts as a positive supplemental test and it is not necessary to perform a licensed multiantigen supplemental test for anti-HCV.  However, a nonreactive NAT should not be a reason for not performing lookback for a donation that is repeatedly reactive on an anti-HCV screening test.  This recommendation is based on current research that indicates that in about 15-25% of cases of HCV infection, viremia may be intermittently detectable (Ref. 5) or resolved (Ref. 6).

Blood establishments must initiate lookback based on a reactive NAT although a screening test or supplemental test for antibodies to HCV performed on the same collection is nonreactive (21 CFR 610.47(a)(1)).  In this situation, blood establishments must search records of prior collections for the 12 months prior to the date of the NAT-reactive donation
(21 CFR 610.47(a)(1)(ii) and 21 CFR 610.48(b)(1)(iii)(B)), since this configuration of test results is consistent with recent HCV infection in the donor (Ref. 7).

Blood establishments that collect blood or blood components, including Source Plasma and Source Leukocytes, must establish, maintain and follow appropriate procedures4 for the following actions within specified timeframes after a donor tests reactive for evidence of HCV infection (21 CFR 610.47(a)); or during an historical record review, after identifying donors who tested reactive for evidence of HCV infection (21 CFR 610.48(b)):

  • quarantine prior collections that remain in inventory;
  • notify consignees to quarantine prior collections;
  • further test the donor and notify consignee of test results; and
  • destroy or relabel potentially infectious prior collections.

Under 21 CFR 610.47(b) and 21 CFR 610.48(c), transfusion services, as consignees, must establish, maintain and follow an appropriate system for the following actions within specified timeframes, when notified by the collecting establishment:

  • quarantine prior collections that remain in inventory;
  • destroy or relabel potentially infectious prior collections; and
  • notify transfusion recipients who received blood or blood components from a donor who is later determined to be infected with HCV, if appropriate, or the recipient’s physician of record, as appropriate.

NOTE:  Recommendations for implementing historical lookback required under 21 CFR 610.48 are included in Figures 2-4 and Tables 2-5, located in the Appendix.

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V.        CURRENT RECOMMENDATIONS

Current lookback recommendations are provided in Figure 1 and Table 1 to assist blood establishments in complying with the regulations in 21 CFR 610.47.

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VI.       BLOOD AND BLOOD COMPONENTS INTENDED FOR MANUFACTURE INTO NON-INJECTABLE PRODUCTS

There may be some limited uses for quarantined prior collections identified in the lookback either for current donations or for historical review donations that are not suitable for release from quarantine for their original intended use.  We recommend that you do not use such prior collections for transfusion or for manufacturing into injectable products.  You should destroy these prior collections as a general practice; however, in limited situations, release for research or for further manufacture is acceptable.  If released for research or for further manufacture into in vitro diagnostic reagents, you must relabel the prior collections with a “BIOHAZARD” legend (21 CFR 610.40(h)(2)(ii)(B)).  In addition, we recommend that you relabel the prior collections with two of the following statements:

-     “Collected from a donor who subsequently tested reactive for anti-HCV or HCV RNA.  An increased risk of transmission of HCV is present.”

and either

-     “Caution:  For Further Manufacturing Into In Vitro Diagnostic Reagents For Which There Are No Alternative Sources.”

      or

-     “Caution:  For Laboratory Research Use Only.”

If you release the units for further manufacture into injectable products, the units must include a statement on the container label indicating the exempted use specifically approved by FDA
(21 CFR 610.40(h)(2)(ii)(D)).


Figure 1 Lookback for Hepatitis C Virus (HCV) Based on Current Donor Test Results Using a  Licensed Screening Test for HCV Antibody or a Licensed or Investigational NAT for HCV RNA
 

Table 1          Current Review

You must take the following steps when donor test results for antibody to Hepatitis C Virus (anti-HCV) by a licensed screening test are repeatedly reactive, or a licensed or investigational HCV RNA Nucleic Acid Test (NAT) is reactive.  You must identify and quarantine prior collections, notify the consignees and request them to quarantine prior collections.  Then…

 

 

If the initial test is a licensed …

 

And the additional testing1  is a licensed or investigational  …

 

Then …

 

 

 

 

Notify
Consignee of test result

Destroy/
Relabel prior collection

Transfusion services notify recipients or recipient’s physician of record

Release prior collection

 

Anti-HCV

 

NR

NAT

Reactive

 

X

 

X3

 

X3

 

 

 

Anti-HCV

 

 

RR

Appropriate  Multiantigen Supplemental Test

Positive

 

 

X

 

 

X

 

 

X

 

NAT

Nonreactive

 

 

Anti-HCV

 

 

RR

Appropriate Multiantigen Supplemental Test

Positive

 

 

X

 

 

X

 

 

X

 

NAT2

Reactive

 

 

Anti-HCV

 

 

RR

Appropriate Multiantigen Supplemental Test

Indeterminate

 

 

X

 

 

X

 

 

NAT

Nonreactive

 

 

Anti-HCV

 

 

RR

Appropriate  Multiantigen Supplemental Test

Indeterminate

 

 

X

 

 

X

 

 

X

 

NAT2

Reactive

 

 

Anti-HCV

 

 

RR

Appropriate Multiantigen Supplemental Test

Negative

 

 

X

 

 

 

 

X

NAT

Nonreactive

 

 

Anti-HCV

 

 

RR

Appropriate  Multiantigen Supplemental Test

Negative

 

 

X

 

 

X3

 

 

X3

 

 

X4

NAT2

Reactive

1Appropriate additional testing includes all the antigens contained in the screening test that was performed
2Certain licensed HCV NAT have been labeled with a “limited supplemental claim.”  When current donor test results are repeatedly reactive on an anti-HCV screening test and reactive on HCV NAT, the reactive NAT acts as a positive supplemental test and it is not necessary to perform a licensed multiantigen supplemental test for anti-HCV.
3Collections during the 12 months prior to the date of the donation testing NAT reactive
4Release collections from more than 12 months prior to the date of the donation testing NAT reactive
NR means nonreactive
RR means repeatedly reactive 

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VII.     REFERENCES

1.  Sayers, M.H., and Gretch, D.R.  Recombinant immunoblot and polymerase chain reaction testing in volunteer whole blood donors screened by a multi-antigen assay for hepatitis C virus antibodies.  Transfusion 33:809-813 (1993).

2.  Kleinman, S. et al.  Increased detection of hepatitis C virus (HCV)-infected blood donors by a multiple-antigen HCV enzyme immunoassay.  Transfusion 32:805-813 (1992).

3.  Yun, Z. et al.  Detection of Hepatitis C Virus (HCV) RNA by PCR Related to HCV Antibodies in Serum and Liver Histology in Swedish Blood Donors.  J Med Virol 39:57-61 (1993).

4.  Dow, B.C. et. al.  Relevance of RIBA-3 Supplementary Test to HCV PCR Positivity and Genotypes for HCV Confirmation of Blood Donors.  J Med Virol 49:132-136 (1996). 

5.  Alter, H.J. To C or Not to C:  These Are the Questions.  Blood 85:1681-1695 (1995).

6.  CDC.  Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease.  MMWR Morb Mortal Wkly Rep 47 (RR-19) (1998).

7.  Schreiber, G.B. et al.  The Risk of Transfusion-Transmitted Viral Infections.  N Engl J Med 334:1685-1690 (1996).

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APPENDIX   

Recommendations for implementing historical lookback required under 21 CFR 610.48 are included in Figures 2-4 and Tables 2-5.

Licensed Screening Test for HCV Antibody or a Licensed or Investigational NAT for HCV RNA

 

Figure 3 Lookback for Hepatitis C Virus (HCV) Based on Historical Donor Test Results Using a Licensed EIA 2.0 or EIA 3.0 Test for HCV Antibody or a Licensed or Investigational NAT for HCV RNA (Cont.)

Figure 4 Lookback for Hepatitis C Virus (HCV) Based on Historical Donor Test Results Using an EIA 1.0 for HCV Antibody 

Table 2             Historical Review

You must take the following steps when donor test results for antibody to Hepatitis C Virus (anti-HCV) by a licensed screening test are repeatedly reactive, or a licensed or investigational HCV RNA Nucleic Acid Test (NAT) is reactive.  You must identify and quarantine prior collections, notify the consignees and request them to quarantine prior collections.  Then …

 

If the historical initial test is a licensed …

 

And the historical additional testing1  is a licensed or investigational  …

 

Then …

 

 

 

 

Notify
Consignee of test result

Destroy/
Relabel prior collection

Transfusion services notify recipients or recipient’s physician of record

Release prior collection

 

EIA 2.0 or
3.0

 

RR

 

NFT

 

Sample available

 

See Table 4

 

EIA 2.0 or 3.0

 

RR

 

RIBA 2.0

 

Positive

 

X

 

X

 

X

 

NAT

Reactive, Nonreactive or NP

 

EIA 2.0

 

RR

 

RIBA 2.0

 

Negative

 

X

 

 

 

X

NAT

Nonreactive or NP

 

EIA 3.0

 

RR

 

RIBA 2.0

 

Negative

 

X

 

X

 

X

 

NAT

Nonreactive or NP

 

EIA 2.0

 

RR

RIBA 2.0

Negative

 

X

 

X2

 

X2

X3

NAT

Reactive

 

EIA  3.0

 

RR

RIBA 2.0

Negative

 

X

 

X

 

X

 

NAT

Reactive

 

EIA 2.0 or 3.0

 

RR

RIBA 2.0

Indeterminate

 

X

 

X

 

X

 

NAT

Nonreactive or NP

 

EIA 2.0 or 3.0

 

RR

RIBA 2.0

Indeterminate

 

X

 

X

 

X

 

NAT

Reactive

 

 

EIA 2.0

 

 

RR

RIBA 2.0

Indeterminate

 

 

X

 

 

 

 

X

(MTA)
EIA 3.0 or alternative

 

Nonreactive

NAT

Nonreactive or NP

 

 

EIA 2.0

 

 

RR

RIBA 2.0

Indeterminate

 

 

X

 

 

X

 

 

X

 

(MTA)
EIA 3.0 or alternative

 

Reactive

NAT

Nonreactive or NP

 

EIA 2.0 or 3.0

 

RR

RIBA 2.0

Indeterminate

 

See Table 3

NAT

Nonreactive or NP

RIBA 3.0

 

EIA 2.0 or 3.0

NR

NAT only

Reactive

X

X2

X2

 

1Appropriate additional testing includes all the antigens contained in the screening test that was performed
2Collections during the 12 months prior to the date of the donation testing NAT reactive
3Release collections more than 12 months prior to the date of the donation testing NAT reactive
NR means non-reactive
RR means repeatedly reactive
MTA means may test again
NFT means not further tested
NP means not performed

 

Table 3         Historical Review

You must take the following steps when donor test results for antibody to Hepatitis C Virus (anti-HCV) by Licensed HCV EIA 2.0 or EIA 3.0 are repeatedly reactive, or a licensed or investigational HCV RNA Nucleic Acid Test (NAT) is reactive.  You must identify and quarantine prior collections, notify the consignees and request them to quarantine prior collections.  Then …

If the historical initial test is a licensed …

And the historical additional testing1 is a licensed or investigational …

Then …

  

Notify
Consignee of test result

Destroy/
Relabel prior collection

Transfusion services notify recipients or recipient’s physician of record

Release prior collection

EIA 2.0 or 3.0

RR

RIBA 3.0

Positive

XXX 

NAT

Reactive, Nonreactive or NP

EIA 2.0 or 3.0

RR

RIBA 3.0

Negative

X  X
NAT

Nonreactive or NP

EIA 2.0 or 3.0

RR

RIBA 3.0

Negative

XX2X2X3

NAT

Reactive

EIA 2.0 or 3.0

RR

RIBA 3.0

Indeterminate XX  

NAT

Nonreactive or NP

EIA 2.0 or 3.0

RR

RIBA 3.0

Indeterminate XXX 

NAT

Reactive

1Appropriate additional testing includes all the antigens contained in the screening test that was performed
2Collections during the 12 months prior to the date of the donation testing NAT reactive
3Release collections more than 12 months prior to the date of the donation testing
NAT reactive
RR means repeatedly reactive
NFT means not further tested
NP means not performed

 

Table 4               Historical Review

You must take the following steps when donor test results for antibody to Hepatitis C Virus (anti-HCV) by Licensed HCV EIA 2.0 or EIA 3.0 are repeatedly reactive, or a licensed or investigational HCV RNA Nucleic Acid Test (NAT) is reactive.  You must identify and quarantine prior collections, notify the consignees and request them to quarantine prior collections.  Then ...

 

If the historical initial test is a licensed …

 

And the historical additional testing1 is a licensed or investigational …

 

Then …

 

 

 

 

 

Notify
Consignee of test result

Destroy/
Relabel prior collection

Transfusion services notify recipients or recipient’s physician of record

Release prior collection

 

 

EIA 2.0

 

RR

 

RIBA 2.0

 

 

See Table 2

 

 

RIBA 3.0

 

 

See Table 3

 

 

EIA 2.0

 

RR

EIA 3.0 or alternative

 

Nonreactive

 

X

 

 

 

X

 

 

EIA 2.0

 

RR

EIA 3.0 or alternative

 

Reactive

 

X

 

X

 

X

 

 

 

(NFT)

 

 

 

EIA 2.0

 

RR

EIA 3.0 or alternative

 

Reactive

 

See Table 3

 

 

RIBA 3.0

 

 

 

EIA 3.0

 

RR

RIBA 3.0

 

 

See Table 3

 

 

EIA 2.0 or 3.0

 

RR

NAT

Nonreactive

 

See Table 3

 

(MTA)
RIBA 3.0

 

 

 

EIA 2.0 or 3.0

 

RR

 

NAT

Nonreactive or Reactive

 

X

 

X2

 

X2

 

X3

 

 

(NFT)

 

 

 

EIA 2.0 or 3.0

 

RR

 

NAT

 

Reactive

 

See Table 3

 

(MTA)
RIBA 3.0

 

 

 

EIA 2.0 or 3.0

 

RR

 

(NFT)

 

No Sample
Available

 

X

 

X

 

X

 

1Appropriate additional testing includes all the antigens contained in the screening test that was performed
2Collections during the 12 months prior to the date of the donation testing NAT reactive
3Release collections more than 12 months prior to the date of the donation testing NAT reactive
RR means repeatedly reactive
MTA means may test again
NFT means not further tested


 

Table 5             Historical Review

You must take the following steps when donor test results for antibody to Hepatitis C Virus (anti-HCV) by Licensed HCV EIA 1.0 are repeatedly reactive.  You must identify and quarantine prior collections, notify the consignees and request them to quarantine prior collections.  Then …

 

If the historical initial test is a licensed …

 

And the additional testing1 is a licensed or investigational …

 

Then …

 

 

 

 

 

Notify
Consignee of test result

Destroy/
Relabel prior collection

Transfusion services notify recipients or recipient’s physician of record

Release prior collection

 

EIA 1.0

 

S/CO
£ 2.5

(NFT)

 

 

X

 

X

 

 

 

EIA 1.0

 

S/CO >2.5 or cannot be calculated

(NFT)

 

 

X

 

X

 

X

 

 

EIA 1.0

 

RR

EIA 2.0 or 3.0 or alternative

Reactive

 

X

 

X

 

X

 

(NFT)

 

 

EIA 1.0

 

 

RR

EIA 2.0 or 3.0 or alternative

Reactive

 

 

See Below

(MTA)
RIBA 2.0 or 3.0 or NAT

 

 

EIA 1.0

 

RR

EIA 2.0 or 3.0 or alternative

Nonreactive

 

X

 

 

 

X

 

EIA 1.0

 

RR

NAT

Reactive

 

X

 

X

 

X

 

(NFT)

 

 

 

EIA 1.0

 

 

RR

NAT

Reactive

 

 

(MTA)
RIBA 2.0

Negative

X

X2

X2

X3

Indeterminate

X

X

X

 

(MTA)
RIBA 3.0

Negative

X

X2

X2

X3

Indeterminate

X

X

X2

 

 

EIA 1.0

 

RR

RIBA 1.0, 2.0, or  3.0; or Neut-Peptide EIA

Positive

 

X

 

X

 

X

 


Table 5 (Continued)      Historical Review

You should take the following steps when donor test results for antibody to Hepatitis C Virus (anti-HCV) by Licensed HCV EIA 1.0 are repeatedly reactive.  You should identify and quarantine prior collections, notify the consignees and request them to quarantine prior collections.  Then …

 

If the historical initial test is a licensed …

 

And the additional testing1 is a licensed or investigational  …

 

Then …

 

 

 

 

Notify
Consignee of test result

Destroy/
Relabel prior collection

Transfusion services notify recipients or recipient’s physician of record

Release prior collection

 

EIA 1.0

 

RR

RIBA 1.0 or 2.0; or Neut-Peptide EIA

Indeterminate

 

X

 

X

 

X

 

(NFT)

 

 

EIA 1.0

 

RR

NAT

Nonreactive

 

X

 

X

 

X

 

(NFT)

 

 

 

EIA 1.0

 

 

RR

RIBA 1.0 or 2.0; or Neut-Peptide EIA

Indeterminate

 

X

 

 

 

X

 NAT

Nonreactive

(MTA) EIA 3.0 or alternative; or RIBA 3.0

 

 

See Table 3

 

EIA 1.0

 

RR

RIBA 1.0 or 2.0; or Neut-Peptide EIA

Indeterminate

 

 

X

 

 

 

 

X

 

NAT

Nonreactive or NP

(MTA) EIA 3.0 or alternative; or

Nonreactive

RIBA 3.0

Negative

 

EIA 1.0

 

RR

RIBA 3.0

Indeterminate

 

X

 

X

 

 

 

EIA 1.0

 

RR

RIBA 2.0 or 3.0

Negative

 

X

 

 

 

X

NAT

Nonreactive or NP

 

EIA 1.0

 

RR

RIBA 2.0 or 3.0

Negative

 

X

 

 

 

X3

NAT

Reactive

 

EIA 1.0

 

RR

RIBA 1.0 or Neut-Peptide EIA

Negative

 

X

 

X

 

 

(NFT)

 

 

 

EIA 1.0

 

 

RR

RIBA 1.0 or Neut-Peptide EIA

Negative

 

 

See outcomes above

(MTA) EIA 2.0 or 3.0 or alternative; or RIBA 3.0; or NAT

 


 

1Appropriate additional testing includes all the antigens contained in the screening test that was performed
2Collections during the 12 months prior to the date of the donation testing NAT reactive
3Release collections more than 12 months prior to the date of the donation testing NAT reactive
NR means non-reactive
RR means repeatedly reactive
MTA means may test again
NFT means not further tested


Footnotes

1 Section 610.48 (21 CFR 610.48) requires blood establishments to have completed a number of actions by February 19, 2009, based on the review of historical testing records.  Recommendations for implementing historical lookback required under 21 CFR 610.48 are included in Figures 2-4 and Tables 2-5, located in the Appendix.

2 The Chiron Corporation (Emeryville, CA) RIBA HCV 3.0 SIA is a strip immunoblot assay based on recombinant antigens of HCV.

3 This guidance does not address testing, product disposition, donor management, and lookback for individual donor samples that test reactive on a multiplex NAT or a minipool that test reactive on a multiplex NAT.  In addition, under 21 CFR 610.47 and 610.48, lookback is required for individual donor samples that test reactive on a multiplex NAT but nonreactive for both HIV-1 and HCV when tested using discriminatory HIV-1 NAT and discriminatory HCV NAT.  See “Guidance for Industry:  Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV):  Testing, Product Disposition, and Donor Deferral and Reentry” dated May 2010, for FDA recommendations in these circumstances.  The document may be accessed at http://www.fda.gov/downloads/biologicsbloodvaccines/
guidancecomplianceregulatoryinformation/
guidances/blood/ucm210270.pdf
accessed December 20, 2010.

4 See 21 CFR 606.100(b)(19)(i) through (vi) and 606.160(b)(1)(viii) for requirements for standard operating procedures and records concerning the activities performed under 21 CFR 610.46, 610.47, and 610.48.