Guidance for Industry: “Lookback” for Hepatitis C Virus (HCV)

Name: “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

Status of Guidance: Final Guidance

Guidance Released: August 24, 2007

Link to Guidance: http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/ucm073170.htmTarget

Audience: Blood establishments, hospitals, and organizations that collect blood from people. Blood establishments are facilities that manufacture whole blood and blood components intended for use in transfusion as well as whole blood and blood components that are intended for further processing, for example, to be used in the creation of diagnostic tests for the clinical laboratory.

Definition of Terms Used in this Guidance:

anti-HCV: Antibodies to the hepatitis C virus. Anti-HCV are produced by your body when it is infected by the hepatitis C virus (HCV). A doctor can tell if you are infected with the hepatitis C virus by testing your blood for anti-HCV. All blood donations in the US are tested for anti-HCV.

Lookback: This is the name of a process used when blood from one donor is found to test positive for anti-HCV. To perform a “lookback” means to locate all prior donations of blood from the person who recently tested positive for anti-HCV.

Lookback Donations: These blood donations are the prior donations from one blood donor.

Lookback actions: After an anti-HCV-positive blood donor is identified and his/her prior blood donations are located after a historical review of blood donation records, possible actions include:

1. Quarantine the blood taken from this donor in previous blood draws. Even though the past donations from this donor did not test positive for anti-HCV, this person’s blood should not be used.
2. Notify organizations, for example hospitals, that have been recipients of this blood donor’s blood or blood products.
3. Perform additional blood testing on the donor.
4. Destroy blood from this donor that has the potential to transmit HCV to recipients of this blood.
5. Notify all people who have already received a transfusion of this donor’s blood.

Laws and Regulations Referenced:

1. 21 CFR 606.121: Title 21 - Food And Drugs Chapter I - Food And Drug Administration, Department Of Health And Human Services Subchapter F – Biologics Part 606 - Current Good Manufacturing Practice For Blood And Blood Components Subpart G - Finished Product Control 606.121 - Container label.
   
2. 21 CFR 610.40(h): Title 21 - Food and Drugs Chapter I - Food and Drug Administration, Department Of Health And Human Services Subchapter F – Biologics Part 610 - General Biological Products Standards Subpart E - Testing Requirements for Communicable Disease Agents 610.40 - Test requirements.
3. 21 CFR 610.47: Title 21 - Food And Drugs Chapter I - Food And Drug Administration, Department Of Health And Human Services Subchapter F – Biologics Part 610 - General Biological Products Standards Subpart E - Testing Requirements For Communicable Disease Agents 610.47 - “Lookback” notification requirements for transfusion services.
   
4. 21 CFR 610.48: Title 21 - Food And Drugs Chapter I - Food And Drug Administration, Department Of Health And Human Services Subchapter F – Biologics Part 610 - General Biological Products Standards Subpart E - Testing Requirements For Communicable Disease Agents 610.48 - Hepatitis C virus (HCV) ‘‘lookback’’ requirements based on review of historical testing records.
5. 21 CFR 640.70: Title 21 - Food And Drugs Chapter I - Food And Drug Administration, Department Of Health And Human Services Subchapter F – Biologics Part 640 - Additional Standards For Human Blood And Blood Products Subpart G - Source Plasma 640.70 - Labeling.
6. 42 CFR part 493: Clinical Laboratory Improvement Amendment (CLIA) Regulations – Laboratory Requirements.
   

Summary:
This guidance provides blood establishments, hospitals, and organizations that collect blood from people with recommendations of the US Food and Drug Administration (FDA) regarding procedures to follow once blood from a donor tests positive for anti-HCV.

Rationale:

Hepatitis C virus (HCV) is one of many viruses that can cause chronic inflammation of the liver. HCV is a major health problem in the US. HCV is transmitted primarily by exposure to blood, serum-derived body fluids and body fluids that are visibly contaminated with blood. Often, a person who is infected with HCV does not even know that he or she has the disease until his or her liver is seriously damaged. This feature of HCV infection means that infected people are usually unaware of their disease. HCV infections that are transmitted by blood transfusion account for a very small number of HCV infections; however, it is important to try to prevent all transmission of HCV by blood transfusion.

The risk of transmitting HCV through blood transfusion is reduced by asking the blood donor health habit questions before donation and by testing the blood donor’s blood for anti-HCV. Antibody tests for HCV became available in the US in 1990. It is possible, however, that a person may donate blood during the early part of their HCV infection. During this period, the viral marker, in this case anti-HCV, cannot be detected by a blood test even though HCV is present in the donor’s blood. The period of time during early HCV infection when HCV is present in the donor’s blood but cannot be detected by the current blood tests available, is called the “window period”. Further complicating the situation is the fact that in up to 25% of HCV infections, the anti-HCV may only be detected intermittently. Thus, recommendations regarding procedures that must be followed after a donor’s blood tests positive for anti-HCV are necessary.


Resulting Recommendations:

1. Product quarantine: Within 3 days of a donor testing positive for anti-HCV, blood establishments must review all records to identify blood and blood components previously donated by this infected donor. All blood from this donor that is in inventory at the blood establishment or transfusion service must be quarantined and not transfused into any patients.
2. Consignee notification: Blood establishments must notify all organizations, such as transfusion services, to which they have sold blood or blood products that the blood and blood products previously donated by a donor who now tests positive for anti-HCV must be quarantined.
3. Further testing: To confirm the presence of anti-HCV in the collected blood, blood establishments should perform an additional, more specific anti-HCV blood test on the first sample of blood that tested anti-HCV positive by a screening method from the infected donor. Afterwards, blood establishments must notify the transfusion services who received blood from the infected donor of the results of this confirmatory test.
4. Product disposition: Blood establishments and transfusion services and hospitals are to destroy or relabel the blood that was previously collected from the infected donor, even though that blood did not test positive for anti-HCV. This potentially infectious blood can be used in scientific research or for further manufacture into laboratory testing reagents. If the decision is made to relabel the blood, the blood must be relabeled as “Biohazard” plus “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 “For Laboratory Research Use Only.”
5. Notification of transfusion recipients: Blood transfusion services and hospitals must notify the people who received blood from a donor who is later found to be infected with HCV.