1. CBER Whole Blood and Blood Component Labeling Jennifer Jones Consumer Safety Officer CBER, OBRR, DBA September 16, 2009

2. CBER 2 Outline Labeling regulations ISBT 128 Request for an alternative procedure Suggestions to facilitate review Common pitfalls with ISBT 128 submissions Circular of Information (COI)

3. CBER 3 Labeling Regulations Labeling, general requirements (606.120) Certain information must be machine readable (606.121(c)(13)) – Unique facility identifier – Unit number relating to donor – Product code – Donor group and type

4. CBER 4 Labeling Regulations (cont.) Container labels (606.121) – Container label must include proper name of the product and modifier, if applicable (e.g. Irradiated, Leukocytes Reduced) – Tie tags are allowed for positive antibody screens, emergency use & additional information regarding autologous use – 606.121(j) Circular of Information (606.122) – For transfusible components only – Guidance for Industry: An Acceptable Circular of Information for the Use of Human Blood and Blood Components (12/03)

5. CBER 5 Labeling Guidance Guideline for the Uniform Labeling of Blood and Blood Components (Codabar) (8/85) Guidance for Industry: Recognition and Use of a Standard for Uniform Blood and Blood Component Container Labels (ISBT) (09/06) – United States Industry Consensus Standard for the Uniform Labeling of Blood and Blood Components Using ISBT 128 v.2.0.0, 11/05

6. CBER 6 ISBT 128 Background AABB requirement Use of ISBT 128 is governed and administered by International Council for Commonality in Blood Banking Automation, Inc. (ICCBBA) FDA recognizes as acceptable the standard for blood component and blood component container labels the ICCBBA “United States Industry Consensus Standard for the Uniform Labeling of Blood and Blood Components Using ISBT 128 v.2.0.0 dated November 2005 FDA recognizes as acceptable ISBT 128 as a labeling standard in addition to Codabar

7. CBER 7 ISBT 128 Label Submission – Firms Not Licensed Firm must request for an alternative procedure for Whole Blood and Red Blood Cells No labels should be submitted Labels for unlicensed products are not reviewed by CBER An approval letter is mailed to the firm

8. CBER 8 ISBT 128 Label Submission – Licensed Firms Prior Approval Supplement (PAS) labeling supplement Submission should include: – Labels Include at least one full-face label, the rest may be product overlay labels – Form FDA 356h – Form FDA 2567 – Request for an alternative procedure for Whole Blood and Red Blood Cells

9. CBER 9 Request for an Alternative Procedure Request an alternative procedure from 21 CFR 606.121(e)(1)(ii) under the provisions of 21 CFR 640.120 to delete the name of the applicable anticoagulant immediately preceding and of no less prominence than the proper name of the blood product Firms not licensed must request an alternative procedure Licensed firms must request an alternative procedure and submit labels for approval On the label review checklists, “Approved as a variance to 21 CFR 606.121 under 21 CFR 640.120” will be checked to indicate approval for the alternative procedure

10. CBER 10 ISBT 128 Labels Reviewed by CBER Labels submitted by licensed manufacturers Licensed products Labels that have not been previously approved Both product labels and certain other labels List of labels to submit for review on slides 12- 15 is for those facilities that have had their Codabar product labels previously approved under their U.S. License Number

11. CBER 11 ISBT 128 Labels Not Reviewed by CBER Unlicensed products Products for which the manufacturer does not hold a license New licensed products – These labels should be submitted at the time of application for that product, not with the ISBT label submission

12. CBER 12 Product Labels Reviewed by CBER WHOLE BLOOD label (for each approved anticoagulant currently in use) RED BLOOD CELLS label (for each approved anticoagulant currently in use) RED BLOOD CELLS label (for one approved additive currently in use) RED BLOOD CELLS FROZEN label RED BLOOD CELLS DEGLYCEROLIZED label RED BLOOD CELLS LEUKOCYTES REDUCED label (for one approved anticoagulant currently in use) RED BLOOD CELLS IRRADIATED label (for one approved anticoagulant currently in use) RED BLOOD CELLS LEUKOCYTES REDUCED IRRADIATED label (for one approved anticoagulant currently in use)

13. CBER 13 Product Labels Reviewed by CBER (cont.) RED BLOOD CELLS BY PHERESIS label (for one approved anticoagulant currently in use) RED BLOOD CELLS LEUKOCYTES REDUCED BY PHERESIS label (for one approved anticoagulant currently in use) FRESH FROZEN PLASMA label (for one approved anticoagulant currently in use) FRESH FROZEN PLASMA (BY APHERESIS) label (for one approved anticoagulant currently in use) CRYOPRECIPITATED AHF label SOURCE LEUKOCYTES label (for one approved anticoagulant currently in use)

14. CBER 14 Product Labels Reviewed by CBER (cont.) PLATELETS label (for one approved anticoagulant currently in use) PLATELETS LEUKOCYTES REDUCED label (for one approved anticoagulant currently in use) PLATELETS IRRADIATED label (for one approved anticoagulant currently in use) PLATELETS PHERESIS label (for one approved anticoagulant currently in use) PLATELETS PHERESIS IRRADIATED label (for one approved anticoagulant currently in use) PLATELETS PHERESIS LEUKOCYTES REDUCED label (for one approved anticoagulant currently in use) PLATELETS PHERESIS LEUKOCYTES REDUCED IRRADIATED label (for one approved anticoagulant currently in use)

15. CBER 15 Other Labels Reviewed by CBER ABO/Rh label (one of each blood type) Donation Identification Number For Autologous Use Only label with the Intended Recipient Information label Either one full face label (4 X 4) or one label of each of the 4 quadrants

16. CBER 16 Full Face Label Example

17. CBER 17 Product Overlay Label Examples

18. CBER 18 Labels Approved with Comments Labels are approved but the firm is advised to make the changes indicated on the review checklist with the next software change or revision It is not necessary to resubmit the changes to FDA for approval

19. CBER 19 Approved with Comment Examples ItemIncorrectCorrectU.S. Industry Consenus Std (v2.0.0) Rx OnlyRx Only. or Rx ONLY. Rx OnlyPg. 27 Rx ONLY or Rx only Rx OnlyPg. 27 RX ONLYRx OnlyPg. 27 Degree symbol in the temperature 1 – 6◦C1 – 6 CPg. 29 Periods after abbreviations Approx. or mL.Approx or mLPg. 51-53

20. CBER 20 Labels Not Approved Review checklist will list the necessary changes to be made For approval of these labels, the firm must make the corrections and resubmit labels to FDA

21. CBER 21 Not Approved Examples ItemIncorrectCorrectU.S. Industry Consenus Std (v2.0.0) Abbreviated legal name Community Blood Bnk of E. Anytown, Inc. Community Blood Bank of East Anytown, Inc. Full legal name is not present on label Blood BankBlood Bank, Inc. Pg. 27 License number NoneU.S. License Number 9999 Pg. 27 Divided Units Nothing present in code. For example: E4520V00 On divided units the code should have an A, B, or C indicating divided (E4520VA0) and the term Divided should be on the label in the attribute line. Pg. 18 - 19

22. CBER 22 Suggestions To Facilitate Review Review the website link provided for the guidelines and the chart of common errors found – Make any corrections necessary before sending in submission to the FDA If corrections are necessary during the review process, make them as quickly as possible and return to FDA with a completed Form FDA 2567

23. CBER 23 Suggestions To Facilitate Review (cont.) Send in a complete submission with appropriate forms and request for the alternative procedure Only send in labels for licensed products If submitting product overlay labels, send in at least one full-face label containing the facility information and caution statements in the upper-left quadrant of the label

24. CBER 24 Common Pitfalls Form FDA 2567 is not signed Cover letter does not request the alternative procedure Only product overlay labels are submitted Sending in labels for products not licensed at your firm Not sending in the intended recipient information label with autologous labels

25. CBER 25 Common Pitfalls (cont.) Not using the firm’s full legal name on the labels Printing the expiration time on all products – Only necessary if the expiration time is 72 hours or less (606.121(c)(4)) Omitting the license number on licensed products (606.121(c)(2)) Submitting the Donation Identification Number without the proper facility code

26. CBER 26 Circular of Information (COI) Part of product labeling CFR requires that it be available to medical personnel involved in transfusion processes Firms may implement the FDA accepted AABB COI (July 2002) or may create their own circular

27. CBER 27 COI Submissions COI is considered labeling When adding revisions to the current AABB COI, or when implementing future versions of AABB COI, contact your CSO to discuss the proper reporting category If preparing your own COI, submit as a PAS labeling supplement with the following items: – Copy of Circular of Information – Form FDA 356h – Form FDA 2567

28. CBER 28 When to submit your COI Each firm must submit a circular (either AABB FDA accepted version or the firm’s own version) to the FDA for approval before use is implemented Once the firm has received FDA approval, it is only necessary to submit the COI when there are revisions made to it A COI does not need to be submitted with every type of submission

29. CBER 29 Where to obtain information: Labeling Guideline for the Uniform Labeling of Blood and Blood Components (Codabar) (8/85) Guidance for Industry: Recognition and Use of a Standard for Uniform Blood and Blood Component Container Labels (9/06) United States Industry Consensus Standard for the Uniform Labeling of Blood and Blood Components Using ISBT 128 (11/05)

30. CBER 30 Where to obtain information: Labeling (cont.) Guidance for Industry: Bar Code Label Requirements Questions and Answers (10/06) http://www.iccbba.org http://www.fda.gov/BiologicsBloodVaccines/De velopmentApprovalProcess/AdvertisingLabelin gPromotionalMaterials/InternationalSocietyofB loodTransfusionISBT/default.htmhttp://www.fda.gov/BiologicsBloodVaccines/De velopmentApprovalProcess/AdvertisingLabelin gPromotionalMaterials/InternationalSocietyofB loodTransfusionISBT/default.htm

31. CBER 31 Where to obtain information: COI Guidance for Industry: An Acceptable Circular of Information for the Use of Human Blood and Blood Components (12/03) http://www.aabb.org