Review Considerations on Disease State Donor Programs

1. Review Considerations onDisease State Donor Programs Hoi-may Wong, BS, MT(ASCP)SBB Consumer Safety Officer CBER, OBRR, DBA September 16, 2009

2. Outline • Define disease state donor and collection program • Examples of disease state donor collection programs • Supplement contents • Review process • Approval

3. Disease State Donor We consider a disease state donor to be an individual who • has a chronic illness, • is recovering from the illness, or • has recovered from the illness and possesses or lacks a specific trait, protein or antibody

4. Disease State Donors Collection Program • Source Plasma from these donors contains IgG and/or IgM antibodies • Used in the manufacture of noninjectable or in-vitro diagnostic reagents • Collection programs: - auto-immune - hematologic/oncologic - infectious diseases (not high risk) - allergies

5. Auto-immune Collection Program Examples: • Rheumatoid Factor • Anti-nuclear antibody (ANA) • Anti-DNA antibody • Heterophile antibody • Anti-mycoplasma • Anti-mitochondrial antibody • Anti-cardiolipin • Cold Agglutinins

6. Hematologic/Oncologic Collection Program Examples: • HLA antibodies • Multiple myeloma antibodies • Hemophilia A or B • von Willebrands Disease • Anti-platelet antibodies • Coagulation Factor deficiency (V, VII, VIII, IX, etc) • Fletcher Disease

7. Infectious Diseases Collection Program Examples: • Syphilis • Lyme Disease • Anti-Streptolycin-O antibody • Rocky Mountain Spotted Fever • Chagas Disease (alternative procedure to 21 CFR 640.63(c)(9)) Allergy Collection Program Example: • Elevated IgE

8. Disease State Donors Collection Program • Prior Approval Supplement (21 CFR 601.12(b)) • Submission contents - Form FDA 356h - Cover letter - SOPs - Informed consent form - Labels

9. Supplement • Cover letter has typically included a detailed description of the following: - specific disease state condition being collected - description of the property being harvested - IgG and/or IgM antibody - intended use of the plasma - collection facilities (address and registration number)

10. Supplement • Standard Operating Procedures must specify 21 CFR 606.100(b)(1): - Donor suitability criteria Donor may not qualify as an acceptable donor under 21 CFR 640.63 when the donor, for example: • is under the care of a physician for the disease • has a medical diagnosis, bleeding disorder or procedures related to the disease • is taking medications or clotting factor concentrates for disease treatment • is a Multiple Myeloma donor who has an abnormal SPE

11. Supplement • Standard Operating Procedures must specify 21 CFR 606.100(b)(1) (cont.): - Donor reaction management (21 CFR 606.100(b)(9)) - Product handling, segregation, storage and shipping (21 CFR 606.100(b))

12. Supplement • Typically, Standard Operating Procedures have included the following: - Donors have written permission from their personal physician for the collection volume and schedule - Donors have been evaluated by center physician prior to donation This responsibility may not be delegated to a physician substitute

13. Supplement • Typically Standard Operating Procedures have included the following (cont.) - Situations when additional evaluation and medical examination is indicated - Laboratory assays for monitoring donor’s disease condition - Criteria for discontinuing donor in the program

14. Supplement • In addition to the requirements in 21 CFR 640.61, the approved Informed Consent Form has typically included: - Statement that the donor’s plasma is collected because it contains a specific property - Statement that the repeated plasmapheresis procedure may exacerbate the donor’s disease condition - Should acknowledge that the donor has obtained permission from the personal physician to participate in the program -

15. Supplement Label submission • Form FDA 2567 • Typically, include the antibody or the disease state • Should contain one of the following caution statements: - “Caution: For Use In Manufacturing Noninjectable Products Only” - “Caution: for Further Manufacture Only into In-Vitro Diagnostic Reagents for which There Are No Alternative Sources” - “Caution: For Research Use Only”

16. Supplement Label submission (cont.) • IgM antibody collection are typically labeled as “Biohazard” • Syphilis reactive collection must state “Use only for the Manufacture of Positive Control Reagents for the Serologic Test for Syphilis” (21 CFR 640.70(a)(9))

17. Supplement Review • Regulations • Precedent reviews • Case by case review

18. Approval letter Approval letter specifies the following: • Disease state collection program • Facility • SOPs It also includes the following statement: Please be advised that CBER is presently reviewing its policy on disease state collections which may necessitate revisions to your current Standard Operating Procedures, in order to be consistent with future recommendations.