Proposed changes to Draft Leukocyte Reduction
Guidance - Validation and Quality
Control
|
Issue |
Current Draft Guidance |
Proposed Change |
Comments |
|
Validation and
QC of incomplete filtration rate |
Not included |
Incomplete filtration rate should be £0.5% (excluding incomplete filtration due to
identified donor factors) |
a. |
|
Post-filtration WBC content |
1 x 106residual WBC |
5 x 106residual WBC |
|
|
Validation
of WBC content |
95% of
products have £ 1 x 106 residual WBC with
95% confidence (0 failures/SOP @N=60 consecutive counts) |
95% of products have £
5 x 106residual WBC with 95% confidence (0 failures/ individual
SOP @n=60) |
b. |
|
Elements of
process variations defined by individual SOP |
Time after
collection, filtration temperature, elapsed filtration time, filter type,
(lot #) |
To be updated based on new filter performance data |
c. |
|
Recommended QC procedure for residual WBC content |
5 WBC counts @
week/3 months |
1% of total process (³ 5 counts/week for each
SOP used during that week.) For each
12 weeks of individual SOP use, 95% of products should meet 5 x 106 residual WBC standard @ 95%
confidence. |
|
|
Rationale and
references for validation, QC recommendations |
Not detailed |
To be incorporated |
b. |
|
Process
failure definition and corrective action |
Investigation
of failure followed by corrective action and re-validation of process. |
With observed process failure (SOP
specific), initiate failure investigation and begin counting consecutive
n=60. If no further failure, QC
resumes after corrective action. If further failure observed during
consecutive counting, process is out of control. Donor-specific
variation ¹ process failure |
d. |
|
Identification
and follow-up of donor-specific factors that cause incomplete filtration
or ³5 x 106residual WBC |
Not detailed |
Donor record should be flagged. Upon second occurrence of incomplete
filtration or inadequate WBC removal, donor not eligible for WB
donation. |
|
|
Consignee
notification |
Not detailed |
Out of control process only. |
Defined by
Center SOP |
|
Options for
alternate QC |
Not specified |
Alternate validation/QC approaches to
reach 95%/95% standard allowed. Submit to FDA as PAS. |
|
Comments (Validation and Quality
Control):
a. Rates of
incomplete filtration and post-filtration residual WBC content are to be
considered as two distinct outcomes for purposes of validation and quality
control. Guidance will recommend the
use of validated blood mixing devices or manual procedures to reduce rates of
incomplete filtration due to clotting.
b. Counting recommendations and results
indicated provide 95% confidence that 95% of products meet defined standard.
This is based on exact binomial distribution. Exact binomial distribution is
used for dichotomous outcome (pass/fail) where failures for period of
evaluation expected to be < n=5. Counting can be simplified by only
determining when a count exceeds 5 x 106 residual WBC (vs.
actual enumeration).
c. Guidance will
recommend bounds of these process conditions that should have separate
validation. Filter lot validation is the
responsibility of the filter manufacturer, however users have experienced
lot-related failures. Guidance will discuss and indicate that centers
experiencing lot variations should notify filter manufacturer and FDA Division
of Hematology.
d. Incomplete filtration or poor WBC removal
due to defined donor factors does not constitute a process failure, since donor
factors are currently not predictable. However, donors contributing to
incomplete filtration or poor WBC removal should be flagged for investigation.
After a second occurrence, these donors should be considered ineligible for
further donation of filtered products unless a validated procedure is used to
prevent such failure.
Proposed changes to Draft Leukocyte Reduction
Guidance - Non-QC Issues
|
Use of
leukocyte-reduced blood products for patients for which CMV may be harmful. |
Count residual
WBC in all leukocyte-reduced blood products used for CMV-susceptible
patients. |
Remove recommendation for counting residual WBC in blood products
used for CMV-susceptible patients. Encourage centers to maintain validated
inventory where feasible. Discuss advantages of supporting susceptible
patients with leukoreduced products that are also CMV seronegative. |
Dual inventory
may not be logistically feasible at
all sites. Product COI
specifies that leukoreduced product "may reduce risk of CMV transmission
by transfusion"; Non-validated products to be used at physician's
discretion. |
|
HbS
screening of donors |
Recommended |
No recommendation. However discussion
of process control will include HbS screening as one way to reduce
failures. |
BPAC
unanimously failed to endorse HbS screening recommendation |
|
Use of
validated mechanical mixing device or validated manual mixing procedure during
collection. |
Not specified |
Recommended |
Inadequate
mixing during collection is a source of small clots which block filter |