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

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

3. CBER 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. CBER 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. CBER 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. CBER 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. CBER 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. CBER 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. CBER 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. CBER 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. CBER 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. CBER 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. CBER 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. CBER 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. CBER 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. CBER 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. CBER 17 Supplement Review Regulations Precedent reviews Case by case review

18. CBER 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.