leukocyte-reduced blood components lore fields mt(ascp)sbb consumer safety officer, dba, obrr, cber...

Leukocyte-Reduced Blood Components

Lore Fields MT(ASCP)SBB

Consumer Safety Officer, DBA, OBRR, CBER

September 16, 2009

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Outline

• Resources for FDA Review Criteria• FDA Review Checklists• General Content of Leukocyte Reduction

Submissions• Review Considerations for Specific Products

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Resources for FDA Review

• Recommendations in FDA guidance documents

• Device Operator’s Manuals• Package Inserts for Reagents and Supplies• Published scientific literature

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FDA Guidance Documents usedfor 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

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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

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FDA Apheresis Review Checklists

• Leukocyte Reduction Review Checklist: General

• Quality Control (QC) Sheets• Device Manufacturer’s Instructions for Use and

Product Specifications

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FDA Apheresis Review Checklists

http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/RegulationoftheBloodSupply/ReviewChecklist/default.htm

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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.

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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)

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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

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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

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General Submission Content

• Records and Forms – we recommend the following:– Product processing, collection information– Product quality control records

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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

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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

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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

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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)

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General Submission ContentJust remember with labeling:

Leukocytes Removed

Leukocytes Poor

Leukocytes Depleted

Leukocytes Reduced

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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

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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

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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

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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

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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

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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

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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

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Review Considerations for Platelets, Pheresis

• Monthly quality control (submit 2 months)

– Other as specified by device manufacturer

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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

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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

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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

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Helpful Tip

Percent recovery is calculated with an absolute Red Blood Cell volume.

Volume x HCT = absolute RBC volume

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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

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Summary

• Approvals are specific for:– Apheresis instrument– Product collected– Collection facility for apheresis – Manufacturing facility for filtration