Leukocyte-Reduced Blood
Components
Lore Fields MT(ASCP)SBB
Consumer Safety Officer, DBA, OBRR, CBER
September 16, 2009
Outline
• Resources for FDA Review Criteria
• FDA Review Checklists
• General Content of Leukocyte Reduction
Submissions
• Review Considerations for Specific Products
2
Resources for
FDA Review
• Recommendations in FDA guidance
documents
• Device Operator’s Manuals
• Package Inserts for Reagents and Supplies
• Published scientific literature
3
FDA Guidance Documents used
for Reviews
• Recommendations and Licensure Requirements
for Leukocyte-Reduced Blood Products,
5/29/1996
• Guidance for Industry: Use of Sterile
Connecting Devices in Blood Bank Practices,
11/22/2000
• Guidance for Industry and FDA Review Staff:
Collection of Platelets by Automated Methods,
12/7/07
4
Operator’s Manuals and Package
Inserts for Reviews
• Operator’s Manuals and Package Inserts
– Apheresis instruments
– Leukocyte Reduction Filters
– Sterile connecting devices
– Residual WBC counters
– Collection bags
• How we use operator’s manuals and package inserts
– Collection procedures
– Processing procedures
– Product specifications
5
FDA Apheresis Review Checklists
• Leukocyte Reduction Review Checklist:
General
• Quality Control (QC) Sheets
• Device Manufacturer’s Instructions for Use and
Product Specifications
6
FDA Apheresis Review Checklists
http://www.fda.gov/BiologicsBloodVaccin
es/BloodBloodProducts/Regulationofthe
BloodSupply/ReviewChecklist/default.ht
m
7
Device Manufacturer’s
Instructions for Use and Product
Specifications Checklists
Devices that do not allow the calculation
of 85% recovery will have specific
instructions on a quality control plan to
follow.
8
General Content of
Submissions
• Form FDA 356h
• Detailed Description of Request
• SOPs
• Records and Forms
• Product Quality Control Logs
• Labeling
• May reference previously approved SOPs,
forms and labeling (include STN)
9
General Submission Content
• The detailed description of the request
typically includes:
– Products requested for licensure, including
anticoagulants
– Collection, processing and testing device(s)
(instrument, filter)
– List of facilities requesting product licensure
(address, registration number)
– Cell counting method and where the testing will be
performed
10
General Submission Content
• SOPs typically submitted include:
– Collection procedures, including arm prep
– Donor history forms, including informed consent
– Product manufacturing procedures, including QC,
labeling, splitting, leukocyte reduction, storage,
shipping, equipment calibration, etc.
– Failure investigation
– Quarantine and disposition of unsuitable products
11
General Submission Content
• Records and Forms – we recommend the
following:
– Product processing, collection information
– Product quality control records
12
General Submission Content
• Completed records and forms
– Relevant validation protocols and data (Validation
summary only, including failure investigations)
– 2 consecutive months quality control data
• Red Blood Cells
• Platelets, Pheresis
• Each type of device and each methodology
13
General Submission Content
• Product Quality Control Records
– Product description (eg, product name, leukocyte
reduced)
– Type of collection (eg, single, double)
– Collection and testing dates
– Product specifications
– Product testing results, including WBC counts,
platelet yields, absolute RBC volume, pH, RBC
recovery, product volume, etc.
– Interpretation of each result
14
General Submission Content
• Product Quality Control Records (cont.)
– Collection device (manufacturer, model number)
– Product identification number
– Collection center
– Technologist identified
– Monthly interpretation
– Acceptable criteria
– Evidence of QA oversight
15
General Submission Content
• Labeling
– Form FDA 2567
– Circular of Information
– Base label and product overlay labels for each product
– 21 CFR 606.121(c)(13) – machine readable information
• Unique facility identifier
• Lot number relating unit to donor
• Product code
• ABO/Rh of donor
– ISBT 128 or Codabar
– “Apheresis” in product name or attributes (if applicable)
16
General Submission Content
Just remember with labeling:
Leukocytes Removed
Leukocytes Poor
Leukocytes Depleted
Leukocytes Reduced
17
Review Considerations for
Whole Blood and Red Blood Cells
• Validation
– No recommendations in LR guidance
– establish documented evidence which provides a high
degree of assurance that a specific process will
consistently produce a product meeting its pre-determined
specifications and quality characteristics
• Monthly QC
– 1% of collections for each product type, selected at
random; if less than 400 per month, then 4 of each product
type
– 95% meet product standards
18
Review Considerations for
Whole Blood and Red Blood Cells
Whole Blood, Leukocytes Reduced and
Red Blood Cells, Leukocytes Reduced
should be prepared by a method known
to:
– leave a residual leukocyte count of less than 5.0 x
10e6 per container and
– retain a minimum of 85% of the original component
19
Review Considerations for
Platelets
• Validation
– No recommendations in LR guidance
– establish documented evidence which provides a
high degree of assurance that a specific process
will consistently produce a product meeting its pre-
determined specifications and quality
characteristics
20
Review Considerations for
Platelets
• Monthly QC
– 1% of collections for each product type,
selected at random; if less than 400 per
month, then 4 of each product type
– 95% meet product standards
21
Review Considerations for
Platelets
Platelets, Leukocytes Reduced prepared
from Whole Blood should be prepared by
a method known to:
– leave a residual leukocyte count of less than 8.3 x
10e5 per container and
– retain a minimum of 85% of the original component
22
Review Considerations for
Platelets, Pheresis
Validation Summary
95%/95% is a statistical approach to demonstrate a 95% confidence that a
product or process conforms to a prespecified standard 95% of the time
23
Review Considerations for
Platelets, Pheresis
• Validation (continued)
– Perform when the automated blood cell separator device or
filtration method is first put into use at an establishment
and/or as recommended by the automated blood cell
separator device manufacturer.
– Conduct testing on the collection (parent container) and on
the individual components from double and triple
collections.
– Other as specified by device manufacturer
24
Review Considerations for
Platelets, Pheresis
• Monthly quality control (submit 2 months)
– Other as specified by device manufacturer
25
Review Considerations for
Red Blood Cells (Apheresis)
• Validation
– No recommendations in LR guidance
– establish documented evidence which provides a high
degree of assurance that a specific process will
consistently produce a product meeting its pre-determined
specifications and quality characteristics
• Monthly QC
– 1% of collections for each product type, selected at
random; if less than 400 per month, then 4 of each product
type
– 95% meet product standards or repeat QC
26
Review Considerations for
Red Blood Cells (Apheresis)
Red Blood Cells, Leukocytes Reduced
should be prepared by a method known
to:
– leave a residual leukocyte count of less than 5.0 x
10e6 per container and
– retain a minimum of 85% of the original component
27
Review Considerations for
Red Blood Cells (Apheresis)
• Devices that are not able to provide a pre-
filtration sample.
– Devices have been cleared by FDA with an alternative
method of determining product quality.
– Results of alternative methods must still be recorded and
evaluated to ensure that 95% of the products are
acceptable.
– Methods include:
• Computer Software (part of collection device)
• Minimum absolute Red Blood Cell Volume
28
Helpful Tip
Percent recovery is calculated with an
absolute Red Blood Cell volume.
Volume x HCT = absolute RBC volume
29
Summary
• CBER reviews based on:
– Regulations and Guidance Documents
– Operator’s Manuals and Package Inserts
• Submission typically should include
information for substantive review
– Consult CBER review checklists
– Consult operator’s manuals and package inserts
30
Summary
• Approvals are specific for:
– Apheresis instrument
– Product collected
– Collection facility for apheresis
– Manufacturing facility for filtration
31