The Food and Drug Administration published the final rule “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’)” Aug. 24, 2007, with a Feb. 20, 2008, effective date. In addition, a guidance document — “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” — was released by FDA, and a companion interim final rule was published by the Centers for Medicare and Medicaid Services. The CMS interim final rule requires hospitals that transfuse blood and blood components to have procedures for performing HCV lookback, quarantining prior collections, notifying transfusion recipients of the need for HCV testing and counseling, and extending the records retention period for transfusion-related data to 10 years.
Summary of the FDA Final Rule
The FDA rule finalized the HCV lookback requirements for establishments collecting blood or blood components, including Source Plasma and Source Leukocytes, to establish, maintain, and follow an appropriate system for identifying components previously donated from a donor who tests reactive for HCV on a subsequent donation by current testing or after a review of historical records. The historical record review includes blood and blood components that were tested using an EIA 1.0 screening test. Likewise, consignees must have systems in place to notify transfusion recipients of the possibility that they may have received blood or blood components that were at an increased risk of transmitting HCV.
The final rule made the following revisions to the Code of Federal Regulations:
· Established requirements for HCV lookback.
· Established requirements and key dates for retrospective HCV lookback:
o Historical record review must include all HCV testing from Feb. 20, 2008, back indefinitely for computerized systems or to Jan. 1, 1988, for all other records.
o Historical record review by collecting establishments must be completed by Feb. 19, 2009.
o Consignees must complete specified actions initiated by the historical record review within one year from the date of notification by the collecting establishment.
· Segregated the responsibilities of the collection establishment and consignee for clarity.
· Harmonized the lookback requirement for HIV and HCV.
Highlights of the FDA Final Rule:
21 CFR 610.46 and 21 CFR 610.47 – HIV and HCV Lookback
These regulations were modified to harmonize the requirements for the acceptable time frame for record review, quarantine and consignee notification for HIV and HCV lookback. After receiving comments regarding the proposed time frame, FDA responded that “it is important that consignee notification and quarantine of infectious blood and blood components be performed expeditiously within a reasonable time frame, and we believe that three calendar days is reasonable.” The regulations require that establishments have three calendar days after a reactive test or the establishment is made aware of other reliable test results or information to perform a review of all records required under 21 CFR 606.160 to identify blood previously donated, quarantine all in-date products and notify consignees. FDA further defined three calendar days as the period ending at the close of business three full days after a donor tests reactive. For example, if a donor tests reactive by a screening test on the first day — Friday — then quarantine by the collecting establishment and notification of consignee to quarantine must occur by close of business on the fourth day — Monday. Previously, this timeline was 72 hours.
21 CFR 610.47 – HCV Lookback
The collecting establishment has the following responsibilities:
· Perform the lookback for 12 months from the donor’s most recent non-reactive screen or 12 months from the reactive nucleic acid test (with negative antibody screen). Previously, the lookback was performed for five years prior to the repeatedly reactive test for transfusable products or six months if the product was for further manufacturing into injectables.
· Quarantine in-date blood and blood components, and notify consignees to do the same.
· Perform a supplemental test within 45 calendar days of the reactive screening test.
· Notify consignees of the supplemental result or the reactive screen result if there is no available supplemental test approved for such use by FDA within 45 calendar days after the donor tests reactive. Previously, the consignee notification was to be completed within 30 calendar days of supplemental testing.
The consignee also has responsibilities:
· Quarantine in-date blood and blood components as directed.
· Notify transfusion recipients or the physician of record, of the need for recipient HCV testing and counseling. Notify physician of record or legal representative or relative if the recipient is a minor, adjudged incompetent, or the state law permits a legal representative or relative to receive information on behalf of the recipient. Transfusion services may choose to directly notify the recipient rather than contacting the physician of record.
· Make reasonable attempts to perform the notification within 12 weeks after receiving test results. Previously, this was defined as three attempts in eight weeks.
21 CFR 610.48 – HCV Lookback: Historical
Establishments that collect blood or blood components, including Source Plasma and Source Leukocytes, must complete the following actions by Feb. 19, 2009:
· Perform the historical record review to include all HCV testing before Feb. 20, 2008, with all actions prescribed in 610.48(b) completed by Feb. 19, 2009.
· Search HCV testing records back indefinitely if computerized records are available or to Jan. 1, 1988, for all other records.
· Identify the donors and their prior donations 12 months before the most recent non-reactive screening test or 12 months before the reactive NAT (with negative antibody screen). Previously, the lookback was performed for five years prior to the repeatedly reactive test if it was for transfusable products or six months if the product was for further manufacturing into injectables.
· Within three calendar days after identifying the prior donations: 1) quarantine in-date components; 2) notify consignee to quarantine all previously collected in-date components; and 3) notify consignee of test results including supplemental results, if available at the time.
· Perform appropriate supplemental or licensed screening tests using a frozen sample from the same reactive donation or a fresh sample. The supplemental or licensed screening test must be at least as sensitive as the test of record.
· When additional supplemental or licensed screening tests are performed, consignee notification must occur within 45 calendar days of completing the further testing. Include the results for the components that were previously collected. Previously, the consignee notification was to be completed within 30 calendar days of supplemental testing.
Consignee responsibilities should be completed within one year of the date of notification:
· Quarantine as directed.
· Make reasonable attempts to notify recipients or the physician of record of the need for recipient HCV testing and counseling. Notify physician of record, legal representative or relative if the recipient is a minor, adjudged incompetent, or the state law permits a legal representative or relative to receive information on behalf of the recipient. Previously, this was defined as three attempts in eight weeks.
Any lookback action — such as record review, quarantine testing, notification and disposition — performed before Feb. 20, 2008, that otherwise satisfies the requirements under 610.47 are exempt from the historical/retrospective lookback in this section. This allows establishments to utilize the results of HCV lookback that were performed when the 1998 guidance document was released, provided the lookback meets the current requirements.
Donors who tested reactive by a screening test and negative by an appropriate supplemental test on the same donation are not subject to further action.
Summary of the FDA Guidance Document
Testing and notification algorithms are included as part of the guidance document as Figures 1 through 4. HCV lookback algorithm for samples that are currently being tested and samples that were previously tested and require a historical record review are different. The figures are stand-alone documents, and the guidance document text does not address all of the information included on the algorithms. Blood components subject to lookback are those identified from prior collections from a donor with a repeatedly reactive antibody screening test for anti-HCV, a reactive NAT for HCV, or other reliable test results or information indicating evidence of HCV infection. When performing lookback, the guidance document provides the following recommendations:
· Quarantine prior collections that remain in inventory.
· Notify consignees to quarantine prior collections.
· Perform further testing of the donor.
· Destroy or label potentially infectious prior collections.
· Notify transfusion recipients who received blood from a donor who is later determined to be infected with HCV, if appropriate.
The guidance document does not apply to autologous donations identified in the lookback process, 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.
With the release of this guidance document, the July 1999 “Draft 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)” is finalized. Additionally, it supersedes the HCV sections of the July 19, 1996, FDA memorandum, “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),” as well as the September 1998 “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.”
Sample Letters for Physician and Recipient Notification (MS Word)