Irradiated Blood Components

1
Irradiated Blood Components

• Jennifer Jones
• Consumer Safety Officer
• CBER, OBRR, DBA
• September 16, 2009

2
Outline

• Irradiation Source
• Radiation Dose
• Submission Contents
• Standard Operating Procedures (SOPs)
• Records
• Labeling

3
Irradiation Source

• Cesium-137 sealed source irradiator
• Cobalt-60 sealed source irradiator
• Linear accelerator
• X-ray irradiator

4
Radiation Dose

• 2500 cGy targeted to containers central portion
• 1500 cGy minimum dose at any other point of the
  container
• If product is irradiated more than once, document
  total (additive) dose
• An indicator should be used with each batch that
  is irradiated
• Follow manufacturers instructions for use,
  including temperature control

5
Submission Contents

• Cover letter
• Form FDA 356h
• SOP for manufacturing irradiated blood products
• Typically, SOPs for equipment maintenance and
  personnel training

6
Submission Contents (cont.)

• Labels for each product with Form FDA 2567
• Two months of irradiation records
• Most recent dosimetry map
• Contractor information, if applicable
• Contractor who performs irradiation must register
  with FDA

7
SOPs

• Description of the irradiator (e.g., radiation
  source)
• Description of the dose delivered to the center
  of the container
• Length of time required to deliver irradiation
• Maximum irradiation dose limits
• Description of procedures for re-irradiation, if
  applicable

8
SOPs (cont.)

• Indication of the maximum number of units to be
  irradiated at one time
• Description of procedures for monitoring to
  determine actual dose delivered
• Validation
• Initially
• Annually for Ce-137
• Semi-annually for Co-60
• After mechanical repairs
• Use Thermoluminescent Dosimeter (TLD) chips or
  other direct methods of measurement

9
SOPs (cont.)

• Dating period for Red Blood Cell products
• Not more than 28 days from the date of
  irradiation but no more than the dating period of
  the original product
• Dating period for platelets remains unchanged

10
SOPs (cont.)

• Maintenance of irradiator
• Procedure for personnel training
• Staff safety
• If contract facility used for irradiation, your
  SOPs should
• Describe what steps are performed by you and by
  the contractor
• Ensure manufacturing steps are performed
  according to your specifications and are in
  compliance with all applicable regulations

11
SOPs (cont.)

• Quality control (QC) (review considerations)
• Irradiator
• Daily QC (e.g., check of turntable rotation)
• Monthly comparison of irradiator timer and
  back-up timer, if available, with certified stop
  watch
• Irradiation indicators
• Shipping and storage temperature checks
• Expected results of each new lot
• Investigation of failures and corrective actions

12
Records

• Strength of source
• Irradiation Records
• QC
• Equipment maintenance

13
Irradiation Records/QC

• Operator ID
• Site of irradiation
• Date and time of irradiation
• Duration of irradiation

14
Irradiation Records/QC(cont.)

• Level/dose of irradiation
• Documentation of QC for irradiator and
  irradiation indicators

15
Labeling

• Container Label (21 CFR 606.121)
• Container label must include proper name of
  product, and modifier, if applicable (e.g., RBCs,
  Irradiated)
• Change expiration date for RBCs if appropriate
• Circular of Information should include
• Indications for use in treating patients at risk
  of transfusion-associated GVHD
• Side effects and hazards of irradiating RBCs
• Higher supernatant potassium levels than
  non-irradiated RBCs due to cell membrane damage

16
Labeling (cont.)

• Circular of Information (cont.)
• Removal of residual supernatant plasma prior to
  transfusion may reduce risks associated with
  elevated plasma potassium
• License Number should not appear on the container
  unless the product has been licensed by the FDA

17
Where to obtain information

• FDA Memorandum, July 22, 1993 Recommendations
  Regarding License Amendments and Procedures for
  Gamma Irradiation of Blood Products
• http//www.fda.gov/BiologicsBloodVaccines/Guidance
  ComplianceRegulatoryInformation/default.htm

18
Where to obtain information (cont.)

• For the Submission of Chemistry, Manufacturing
  and Controls and Establishment Description
  Information for Human Blood and Blood Components
  Intended for Transfusion or for Further
  Manufacture and for the Completion of Form FDA
  356h (May 1999)
• http//www.fda.gov/BiologicsBloodVaccines/Guidance
  ComplianceRegulatoryInformation/default.htm