Announcement of the Advisory Group ‘Blood’ (Arbeitskreis Blut)
of the German Federal Ministry of Health
The following recommendation (Votum, V 34) was adopted at the
62nd session of the Advisory Group ‘Blood’ held on June 14, 2006:
Lookback Procedure
(According to Paragraph 19 of the Transfusion Act)
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Contents
Introduction
Lookback Procedure
1.
Potential infection
2.
Testing
A
Sample material
B
Testing samples of potentially infectious donations
C
Testing of specifically requested second blood samples
D
Follow-up samples
E
Retained samples from production pools
3.
Immediate measures and initiation of lookback procedures
4.
Procedures for notification and obligation to report lookback studies
5.
Notifying the donor of positive test results
6.
Donor-triggered lookback procedures by donation facilities
7.
Donor-triggered lookback procedures by plasma processing facilities
8.
Recipient-triggered lookback procedures
A
B
C
Initiation of the lookback procedure
Further measures regarding blood components
Further measures regarding plasma derivatives
Glossary
Appendices: A1 - A3 Schematic diagram of the testing procedure for HIV infection
B1 - B2 Schematic diagram of the testing procedure for HBV infection
C1 - C3 Schematic diagram of the testing procedure for HCV infection
D1 – Causality assessment of suspected HIV-, HBV- and/or HCV virus transmission via blood or blood components
D2 – Causality assessment of suspected HIV-, HBV- and/or HCV virus transmission via human plasma products.
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Introduction:
The German Transfusion Act – TFG enacted on 1 July, 1998 (BGBl. I, S. 1752-1760) and the
“First Amendment to the TFG and Legal Regulations for Pharmaceuticals” enacted on 19
February, 2005 (BGBl. I, Nr. 10, S. 234-238) lay down the requirement for lookback procedures. Directives 2002/98/EG and 2005/61/EG, which in the interim have been enacted by the
European Parliament and Counsel, also specify the requirement for comprehensive lookback
capabilities in member countries and corresponding implementation in national regulations.
Confirmation of the potential infectiousness of a donor and/or the possibility of transmission
of infection by blood or blood products must conform to the current state of scientific knowledge. Until now these requirements have been met by Recommendation (Votum) 24 of the
Advisory Group ‘Blood’ from 8 November, 2000. Introduction of new testing methods now
make necessary a revision of this recommendation in which both prior experience with these
guidelines as well as the current state of science and technology are taken into consideration.
This recommendation expressly addresses the procedures to be followed for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV). It may be
applied analogously to other potentially serious infections. A separate recommendation (Votum 33) was passed to address procedures to be followed regarding variant Creutzfeldt-Jakob
Disease (vCJD) in relation to blood, plasma and blood products.
This recommendation is composed of a first part describing lookback procedures. Appendices
A-C 1-3 provide schematic diagrams of procedures to be followed for individual infections.
These include the presently prescribed testing methods (detection of antibodies to HIV1/2 and
HIV-1-NAT, detection of antibodies to HVC and HCV-NAT, detection of hepatitis B surface
antigens (HBsAG) as well as detection of hepatitis B core antigen (anti-HBc).
The recommendation is supplemented with appendices D1 and D2 listing the criteria for
evaluating the potential for transmission of infection by blood or blood components (D1) and
plasma derivatives (D2) upon completion of a lookback study.
This recommendation supersedes Votum 24.
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Lookback Procedures
Summarizing the steps that are to be followed whenever
a.)
a donor of blood or blood components is diagnosed with an HIV, HBV or HCV infection or a reasonable suspicion for infection exists and transmission of the infection
by donations from this donor cannot be ruled out,
b.)
a recipient of blood or blood products is diagnosed with an HIV, HBV or HCV infection and there is a reasonable suspicion that the infection was transmitted by blood
or blood products,
c.)
it has retrospectively been determined that test results of viral markers that were
used as a basis for product release were falsely negative, leading to reasonable suspicion that blood products that were released may potentially result in transmission of
an infectious agent.
This procedure is performed to prevent transmission of infective agents by still unused blood
and blood products and to identify any infections that may have possibly been transmitted by
blood or blood products.
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1.
Potential infection
1.1
Repeated positive or reactive HIV-, HBV- or HCV screening results from samples of
a donation of blood must be considered grounds for suspicion of infection of the
donor. The samples may stem directly from a donation of blood or blood components, from quarantine plasma or as a result of samples obtained by specific request.
Testing may also be undertaken after the descriptions of symptoms obtained by anamnesis or by onset of illness. In addition, results from tests on follow-up samples
may result in a suspected infection, e.g. as a result of follow-up studies performed
because of retroactive doubt regarding the validity of a previously used test system.
1.2
If a sample that was repeatedly positive or reactive in the screening test is also positive, reactive or indeterminate in confirmatory tests it must be considered evidence of
reasonable suspicion of infection of the donor.
In case of reasonable suspicion of HIV or HCV infection that was initially indeterminate (see appendices A2, C2), evaluation must be based on examination of a second blood sample (see appendices A1, A3 or C1, C3). If the test results of the second
sample are again indeterminate suspicion of infection cannot be considered confirmed. In these cases lookback procedures need not be continued.
1.3
Reasonable suspicion of transmission of HIV, HBV or HCV infection to a recipient
by blood or blood products is indicated when infection has been confirmed and critical evidence exists (e.g. known negative serological evidence before treatment, clinical symptoms in temporal relationship to transfusion) indicating that the infection
was transmitted by transfused blood products.
In cases of a potential transmission of HIV, HBV or HCV infection that occurred before donor screening was implemented it is not necessary to initiate lookback procedures. Such cases need only be reported according to paragraph 63 b AMG (German
Pharmaceuticals Act) with the classification “causality cannot be determined.”
1.4
Infection of a recipient can be considered confirmed if there are:
•
repeated positive or reactive results in a serological test system
AND
•
a positive result in a confirmatory test
AND/OR
•
Detection of the viral genome in two independent test samples.
(see Appendix D1 and D2)
2.
Testing
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A
Sample material
2.1
Testing may be performed on
•
Samples obtained on the occasion of donating blood or blood components.
•
Samples obtained to assess donor suitability.
•
Follow-up samples used as partial requirement for the release of quarantine
plasma.
•
Samples that were specifically requested for viral marker testing. (2nd blood
samples)
•
Follow-up samples for blood components, obtained on donation of blood or
blood components or as part of the release of quarantine plasma and which must
be retained by the donation facility.
•
Follow-up samples obtained from production pools and retained by plasma
processing facilities.
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B
Testing samples of potentially infectious donations
2.2
If viral marker tests from a blood or blood-component donation or tests used as partial requirement for the release of quarantine plasma are repeatedly positive or reactive the results must be immediately confirmed by the recommended test procedure
for the specific virus on samples from the same donation (confirmatory tests). (Appendix A2, B2, C2).
2.3
If all results of the confirmatory test are negative the repeatedly positive or reactive
results in the first test (screening test) are to be rated as unconfirmed (false positive/false reactive).
2.4
If the results of the ancillary tests are confirmed positive or reactive, suspicion of
infection is considered justified and infection of the donor is confirmed. In cases of
inconclusive results for HIV or HCV the conditions specified in 1.2 apply.
C
Testing of specifically requested second blood samples
2.5
If suspicion of infection cannot be abrogated or confirmed by diagnostic laboratory
tests to determine the status of infection according to Appendix A2 and C2, a second
blood sample shall be obtained within 7 – 21 days 1 after the original sample was
taken. This also applies to confirmed positive or reactive results from HIV tests performed to confirm infection status before informing the donor and providing consultation. Testing of the second blood sample is to be performed by or at the request of
the transfusion facility according to the test scheme (Appendix A3, C3).
2.6
Second blood samples are tested:
• to provide further clarification or confirmation of test results
• in the case of HIV to reconfirm the infection before informing the donor and
providing consultation
2.7
Test results of additional blood samples provided in writing by external laboratories
may be used in individual cases, rather than testing second samples, under the condition that specificity and sensitivity of the test procedures used are comparable to
those used by the donation facility.
2.8
Discrepancies in test results between first and second blood samples must be further
clarified by the donation facility in order to rule out possible mix up of samples.
1
A time limit of at least 7 days should be adhered to allow detection of early seroconversions.
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D
Follow-up samples
2.9
For every donation of blood or blood components as well as for samples used as partial requirement for the release of quarantine plasma 1-2 ml of serum/plasma should
be retained, frozen at ≤ -30° C without delay and stored at ≤ -30° C for follow-up
testing. These follow-up samples should be divided into at least 2 aliquots, stored in
sealed containers in order to eliminate contamination.
2.10
Follow-up samples must be kept for at least one year beyond the shelf life of the
blood components.
2.11
Follow-up samples are tested to:
• elucidate the results of infection-marker tests made on the occasion of the donation;
• obtain further evidence of infectivity;
• demonstrate the sequence identity of the viral genomes from donor and recipient
in case of virus transmission;
• allow investigation of infectious agents that fall outside the range of routine diagnostic testing.
2.12
If the results of ancillary tests according to 2.4 make lookback procedures necessary
in order to test for potential infectivity of prior donations, the follow-up samples as
described in 3.3 and 3.4 must be retested for the virus that triggered the lookback
procedure. If possible, testing procedures should differ from those used at the time of
the donation of blood or blood components or samples used as partial requirement
for the release of quarantine plasma. Furthermore, supplemental testing must be performed (e.g. anti-HBc, anti-HBe, anti-HBs, HBV-NAT, HIV-1-NAT, HCV-NAT in
individual samples).
2.13
If a recipient has been shown to be infected, comparison of the viral genome of the
follow-up sample with that of the recipient can be performed in order to either confirm, or as the case may be, rule out the transfused blood product as the causative
agent.
E
Retained samples from production pools
2.14
Retained samples from all production pools must be divided into aliquots and stored
in adequate volumes and under proper conditions to allow follow-up testing (s. 7.3)
for at least one year beyond the expiration date of the blood product with the longest
shelf life (see Annex 14 of the GMP Guidelines 2 ).
2
Annex 14 “Manufacture of Products derived from Human Blood or Human Plasma” GMP Guidelines“
2003/94/EC “ Principles and guidelines of good manufacturing practice in respect of medicinal products for
human use and investigational medicinal products for human use”.
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3.
Immediate measures and initiation of lookback procedures
The decision making path is schematically represented in Appendices A1, B1 and
C1.
3.1.
If suspicion of infection of a donor arises (1.1) resulting from tests of a sample obtained on the occasion of blood or blood component donation or as partial requirement for release of quarantine plasma, the donation and/or the donor shall be precluded as described in Appendices A1, B1 and C1. Samples that were obtained to
qualify a donor are to be treated analogously.
3.2
If the results of tests performed according to 2.4 yield justifiable suspicion of infection for a repeat donor all prior donations must be identified without delay. This action constitutes initiation of the lookback process.
3.3
The cut-off date for identification of prior donations is the date on which the last
sample was taken in which there was no indication of infection.
The timeline for establishing the cut-off date comprises 5 years before the date upon
which the donation or sample was drawn from which the test results led to suspicion
of infection (1.1).
3.4
To be identified are the donation from the cut-off date and all prior donations
• for HIV
• for HCV
• for HBV
12 weeks
12 weeks
16 weeks
before the cut-off date. 3
3.5
All affected blood and/or all blood components still stored at the donation facility are
to be secured and isolated.
3.6
Healthcare facilities/physicians that received blood components originating from
donations identified according to 3.4 are to be notified without delay insofar as blood
components are still within their shelf life. Any remaining blood products are to be
secured and isolated.
3.7
If plasma identified according to 3.4 was sent to a plasma processing facility, the
facility is to be informed immediately concerning identified previous donations.
3.8
A donation must be considered suspicious should ex post evidence indicate the possibility of false negative results in its sample tests for virus markers that had served
as evidence in the release of donations of blood or blood components. The infection
status of the donor must be determined without delay and if necessary, risk evaluation should be undertaken in conjunction with the responsible agency. Immediate
measures must be taken accordingly.
3
Regarding plasma for fractionation see: „Note for Guidance on Plasma Derived Medicinal Products“, e.g. 6 Months
(CPMP/BWP/269/95, rev. 3)
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4.
Procedures for notification and obligation to report lookback studies
4.1
The donation facility is to maintain a notification system by which the healthcare
provider/physician is immediately informed within the framework of (3.6) cases of
justifiable suspicion of infection of a donor.
An analogous system is to be maintained for reciprocal notification between the donation facility and plasma processing facilities (3.7).
4.2
In case of a recipient with a justifiable suspicion of infection (1.3) notification is
required according to paragraph 16 of the TFG. Likewise, the obligation to report as
laid down in the German Pharmaceuticals Act (AMG) (paragraph 63b AMG, reporting severe undesirable effects to the responsible federal agency with 15 days). The
appropriate forms for these reports will be supplied by the supreme federal authority.
Reports made to the Pharmaceutical Commission of the German Medical Fraternity
are independent and inefficacious.
4.3
Reporting the initiation of a lookback procedure without delay is regulated by paragraph 19 (1) of the TFG. For donor triggered lookback procedures, the State Central
Agency for Health Protection (ZLG) has an information sheet and notification form
available for download on the Internet.
4.4
In compliance with paragraph 7 (1) of the Infection Protection Act (IfSG) any direct
or indirect evidence of hepatitis B must be reported including name to the public
health department insofar as the evidence points to an acute infection. Evidence of a
hepatitis C infection must be reported to the public health department if it is not
known whether infection is chronic. The infection must be reported including name
without delay, in any case no longer than 24 hours after diagnosis.
In accordance with paragraph 7 (3) of the IfSG, indirect or direct evidence of a Treponema pallidum or HIV infection must be reported without name to the Robert
Koch Institute within 14 days. The appropriate notification form can be obtained
from the Robert Koch Institute. Regarding the obligation of notification in accord
with the IfSG it is necessary to refer to the corresponding case definitions.
4.5
In accordance with paragraph 22 of the TFG, the organisation responsible for the
donation facility is obligated to provide quarterly and yearly an anonymised list of
the total number of donors who tested positive for an infection marker. Furthermore,
according to paragraph 22 of the TFG, these data are to be itemised according to the
criteria laid down in the appropriate notification regulation and forwarded to the supreme federal authority.
Additionally, the data summarising infections in donors of plasma for fractionation
are to be sent yearly to the European Medicines Agency (EMEA) according to the
guidelines of that agency. 4
4
also see EMEA/CPMP/BWP/3794/03
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5.
Notifying the donor of positive test results
5.1
Suspicion of infection is considered justifiable (see 1.2) if test results (Appendix A2,
B2, C2) are confirmed positive. This applies to samples taken from a blood or bloodcomponent donation, drawn in order to qualify a donor, as partial requirement for release of quarantine plasma, specifically requested, or retained as follow-up samples.
In such cases the donor is to be informed without delay by the physician appointed to
this duty by the donation facility or by the personal physician specified by the donor.
The type and amount of information presented, explanation and counselling are to be
determined and documented on the basis of the individual case. In the case of HIV,
reconfirmation of infection in a 2nd blood sample is required before informing the
donor (see Appendix A2, A3).
5.2
If an initial suspicion of infection, about which the donor was notified, cannot be
confirmed by follow-up testing the donor must be appropriately informed and must
receive consultation by the physician appointed by the donation facility.
5.3.
In case of a repeatedly inconclusive result (see Appendix A2, A3, C2, C3) for which a
justifiable suspicion of infection has not been obtained, the donor should only be informed and receive counselling after results from a 2nd blood sample are available.
The decision as to whether the donor should be temporarily or permanently deferred
shall be made by physician responsible for notification of results. (see Appendix A1,
C1).
5.4
In analogy to 5.1, if HBV laboratory diagnosis indicates a past HBV infection of the
donor (see Appendix B2), the donor should be informed and should receive counselling.
5.5
If within 5 weeks time of donation withdrawal the infection status cannot be determined, the donor shall be informed and counselling offered as in 5.1.
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6.
Donor-triggered lookback procedures by donation facilities
6.1
If justifiable suspicion of infection is determined for a repeat donor according to 2.4 a
lookback procedure must be initiated in order to determine potential infectivity of
available or transfused blood and blood products from prior donations.
6.2
Previously documented test results from samples or donations that were identified in
3.3 and 3.4 are to be reviewed.
6.3
Follow-up samples and any available test samples from blood drawn within the defined time period according to 3.4, including any that were drawn independent of the
donation are to be specifically tested for the virus that triggered the lookback process
as defined in sentence 2 of 2.12.
6.4
If these samples test negative the lookback study can be concluded.
6.5
If test results of these samples indicate that the donor was infectious at the time the
sample was obtained the cut-off date must be re-established.
6.6
If it is not possible to test the follow-up samples it is necessary to continue the lookback process, testing the recipient of the last negative prior donation and preceding
donations for a period of
• 12 weeks
• 12 weeks
• 16 weeks
for HIV
for HCV
for HBV
If the recipient of blood components from this donor is not available the lookback
process can be concluded.
6.7
If additional donations are identified according to 6.5 any remaining blood or blood
components must be secured and isolated. In addition, health providers/physicians
(3.6) and plasma processing facilities (3.7) must be notified without delay.
6.8.
The plasma processing facility that received plasma from identified donors and was
notified according to 3.7 will be informed of the re-examination of prior test results
(6.2) and of the results of follow-up samples (6.3). Notification will be made without
delay, or no later than 5 weeks after the date on which the blood was drawn that led to
suspicion of infection.
6.9.
Healthcare facilities/physicians that received blood components from identified donors
and were notified according to 3.6 will be informed of the re-examination of prior test
results (6.2) and of the results of follow-up samples (6.3). Notification will be made
without delay, or no later than 5 weeks after the date on which the blood was drawn
that led to suspicion of infection.
6.10
The healthcare facilities/physicians identify any recipients of blood components from
identified donations and take appropriate actions according to (1) 6-8 of the TFG if results from 6.9 are not negative and a justifiable suspicion exists or if evaluation of the
follow-up samples is not possible.
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6.11
If the results of follow-up tests of the recipient preclude infection (Appendix D1) the
donation facility concludes the lookback process.
6.12
If justifiable suspicion of infection is determined for one or more recipients the donation facility will use appropriate techniques (e.g. comparative genome analysis) to determine whether the transfused blood or blood components could have been the cause.
(Appendix D1).
6.13
If the cause of infection of the recipient has been confirmed to be the transfused blood
or blood components (Appendix D) the time period of the lookback will be set after
determining (3.4) a new cut-off date (3.3).
6.14
The physician who initiated the investigation must make certain that the recipient is
informed of the results of the investigation and receives consultation.
6.15
If a recipient was not found corresponding to the time period established in 3.4 and if a
new time period for lookback according to 6.5 has not been set the donation facility
will concluded the lookback process.
6.16
The healthcare provider/physician will inform the donation facility without delay
about the execution and results of follow-up investigations of recipients.
6.17
The competent government agency is to be informed of the results of the lookback
process.
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7.
Donor-triggered lookback procedures by plasma processing facilities
7.1
If a plasma processing facility is notified that it has received plasma for further processing/fractionation from identified prior donations of a donor with justifiable suspicion of infection according to 3.7, all unused identified donations must be secured and
isolated.
7.2
In addition to the measures specified in 7.1, the production pool records of all processed donations from the time period specified in 3.4 must be examined for infection
parameters (e.g. NAT results for HIV and/or HBV and/or HCV). The test program is,
if necessary, to be appropriately amended to include tests of retention samples from
production pools.
7.3
If results of tests on retained samples suggest that the donor may have been infectious
at an earlier time point the production pool records of all processed donations must be
examined for infection parameters (e.g. NAT results for HIV and/or HBV and/or
HCV). The test program will, if necessary, be appropriately amended to include tests
of retention samples from production pools.
7.4
If the results of a state-of-the-art, adequately sensitive NAT or comparably sensitive
virus detection procedure are negative for the production pool it may be assumed that
viral safety is ensured in regard to the validation of the processing method and the virus being tested. Under these circumstances no further measures are necessary.
7.5
If the NAT or comparably sensitive virus detection procedure for the production pool
is positive or cannot be performed for technical reasons (e.g. polymerase inhibition,
destruction of nucleic acid) risk evaluation according to 7.6 must be undertaken without delay.
7.6
Risk evaluation is to be based upon i) the results of experimental testing of the procedure to eliminate and/or inactivate viruses (CPMP/BWP/268/95 and
CPMP/BWP/269/95 revision 3), ii) verification of correct procedures followed in
manufacturing the batch and iii) the amount of contamination detected or suspected in
the production pools. Based upon the data available, risk evaluation is made to determine whether the tested batch meets the quality and safety requirements for use in
humans.
If there is justifiable suspicion that use of the plasma derivatives may lead to transmission of the aetiologic agent, the product may not be brought into commerce by the
pharmaceutical firm. If the products are already in circulation it is necessary to notify
the appropriate authority and after evaluation a decision must be made regarding possible recall.
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8.
Recipient-triggered lookback procedures
A
Initiation of the lookback procedure
8.1
If there is evidence of an infection of a recipient and there is justifiable suspicion that
transmission occurred via a blood product (1.3) the attending physician or the health
care facility together with the physician responsible for transfusion/transfusion specialist will initiate the lookback process.
8.2
The attending physician or health care facility will identify all blood products given
to the recipients as well as the involved pharmaceutical firms.
8.3
The pharmaceutical firm is to be informed without delay about the suspicion of infection and the transfused blood products. The pharmaceutical firm continues the
lookback process and informs the attending physician who informs and counsels the
recipient. The obligations to report must be observed as outlined in 4.
B
Further measures regarding blood components
8.4
The pharmaceutical firm that manufactured the transfused blood components arranges for identification of the affected donor.
8.5
Any remaining blood components derived from donations by the affected donor are
to be identified, secured, isolated and if necessary, retained as evidence.
8.6
The records of laboratory tests from any blood components derived from the donation other than that received by the infected recipient must be examined.
8.7
The donation facility will determine whether testing was later performed on the donor(s) that might provide evidence to rule out or make unlikely the given infection.
•
If the donor is negative for anti-HIV, HIV-1-NAT, anti-HCV and HCV-NAT 12
weeks or longer after the donation, the suspicious donation is to be considered
non infectious for HIV and HCV.
•
If the donor is negative for anti-HBc, HBsAg and HBV-NAT 16 weeks or longer
after the donation, the suspicious donation is to be considered non infectious for
HIV and HBV.
8.8
If infection cannot be ruled out according to 8.7, available follow-up samples from
the donation from which the questionable blood components were transfused must be
retested for the virus that triggered the lookback procedure as described in sentence 2
of 2.12.
8.9
If no results are obtained that help clarify the infection status, the donor must be contacted immediately for a follow-up examination. A blood sample must be obtained as
soon as possible. If the original suspicious donation was obtained more recently than
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• 12 weeks for HIV
• 12 weeks for HCV
• 16 weeks for HBV
from the time the follow-up sample is obtained, an additional blood sample will be
required. For HIV and HCV infections this second follow-up sample must be drawn
12 weeks after the original suspicious donation was obtained, for HBV infections 16
weeks are required.
8.10
If a donor is identified with justifiable suspicion of infection lookback procedure
must be carried out as outlined in Chapter 6.
8.11
If it is not possible to obtain test results of follow-up samples from the donor it is
nonetheless necessary to initiate the donor-triggered lookback procedure.
8.12
Evaluation of causal relationships is prescribed in paragraph 63b of the AMG in accordance with Appendix D1.
C
Further measures regarding plasma derivatives.
8.13
For plasma derivatives the laboratory records for NAT testing of the production
pools for HIV and/or HCV and/or HBV must be examined. If necessary, the test program must be appropriately supplemented as described in 2.12. If NAT or a comparably sensitive virus test is positive comparative sequence analysis must be performed for the isolated genomes of the plasma pool and the recipient.
8.14
The pharmaceutical firm shall inform the responsible federal authority of the results
of the analysis in compliance with paragraph 63b of the AMG.
In the name of the Advisory Group ‚Blood,
Prof. Dr. R. Burger, Chairman
Dr. R. Offergeld, Managing Director
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Glossary
AMG: German Pharmaceuticals Act
Analytical sensitivity: In this recommendation equivalent to limit of detection. According to the CTS (Common
Technical Specifications) the concentration at which 95% of all samples are reactive.
Constituents of blood: Erythrocytes, thrombocytes, granulocytes, lymphocytes, dendritic cells, stem cells,
plasma.
Blood (Whole blood): Blood containing all native components.
Blood components: Cellular blood products such as erythrocyte concentrates, thrombocyte concentrates, granulocyte concentrates, stem-cell preparations and frozen fresh plasma (FFP).
Blood products (Term used in the Transfusion Act): Blood preparations in the sense of article 4 paragraph 2
of the Pharmaceutical Act, serum from human blood in the sense of article 4 paragraph 3 of the Pharmaceutical
Act, for use in the manufacture of active principles or pharmaceuticals.
Recipient: A person (female or male) who received blood, blood components or blood products by transfusion.
HBV: Hepatitis B Virus
HBc: Hepatitis B Core antigen
HBsAg: Hepatitis B surface antigen
HCV: Hepatitis C Virus
HIV: Human Immunodeficiency Virus
Repeat donor: Donor (female or male) for whom the donation facility possesses a prior donation or laboratory
report.
Follow-up Samples: A storage sample from a donor taken on the occasion of a blood or blood-component donation that allows a retroactive look-back study by follow-up testing of the original donation for an infection
marker.
NAT: Nucleic Acid Amplification Testing
Plasma for further processing/fractionation: Plasma used in the manufacture of SD plasma or plasma derivatives.
Plasma derivatives: Blood products such as factor concentrates, prothrombin concentrates prothrombin complex, immune globulins and albumin obtained by fractionation of plasma pools and any additional purification
steps. They are subjected to procedures for virus inactivation or depletion.
Production pool: Pooled plasma from which SD plasma or plasma derivatives are manufactured.
Quarantine plasma: Frozen Fresh Plasma (FFP) that may not be brought into circulation until a donor blood
sample drawn no sooner than 4 months after the donation fulfills all of the release criteria.
Retention samples: Stored samples from production pools used for manufacture of SD plasma and plasma derivatives. These are Samples of Raw Material in the sense of the Plant Regulations for the Pharmaceutical Industry (PharmBetrV).
Lookback capability: The ability to follow every single unit of blood or blood components from the donor to
final use or vice versa, regardless of whether from the aspect of the recipient, a manufacturer of pharmaceutical
products or disposal.
17
SD Plasma: Plasma that has been processed by the solvent-detergent method for virus inactivation.
Donation: An amount of blood or blood constituents drawn from a person to be used directly as active principle
or medicinal product or for the manufacture of an active principle, medicinal or other product for treatment of
humans.
Donor: The donating person (female or male).
Donation facility: A facility in which donations are drawn or that is responsible for activities of drawing donations and, as required by the application, testing, processing, storage and distribution of donations.
TFG: German Transfusion Act
Existing results: Documents and validated laboratory results in written or electronic form that have been released by an authorized person.
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