1. CBER Source Plasma Labeling Judy Ellen Ciaraldi BS, MT(ASCP)SBB, CQA(ASQ) CBER, OBRR, DBA September 16, 2009

2. CBER 2 Outline Source Plasma label regulations Common information on all Source Plasma labels Source Plasma for manufacturing into injectable products Source Plasma for manufacturing into noninjectable products Source Plasma Salvaged How to submit Source Plasma labels Source Plasma label review

3. CBER 3 SP Labeling Regulations Applicable regulations – 21 CFR 610.40 – 21 CFR 610.62 – 21 CFR 640.70 – 21 CFR 640.76 Non-applicable regulations – 21 CFR 606.121 – Donor classification, machine-readable – 21 CFR 606.122 – Instruction circular – 21 CFR 610.60 – Information contained in 640.70 – 21 CFR 610.61 – Package label

4. CBER 4 Info on all SP Labels Proper name of the product, i.e. Source Plasma (640.60) – Prominent position and size – Legible type Caution statement – Follow proper name of the product – Same size and type as proper name Storage temperature Total volume or weight of product Anticoagulant name and volume

5. CBER 5 Info on all SP Labels (cont.) Donor or bleed number – Trace unit to donor and donor’s records – Pools – all donor or bleed numbers or a pool number Expiration date – 10 years – Pools – determined by collection date of oldest unit Collection method – Manual method – Automated method

6. CBER 6 Info on all SP Labels (cont.) Type of donor – Normal donor – Pre-existing disease associated antibody – Immunized donor – state immunizing antigen – Disease state donor – High-risk donor Name, address and license number – Legal entity name (vs. “dba” name) – Plasma center or corporate address – Street and city/state or only city/state address

7. CBER 7 Info on all SP Labels (cont.) Infectious disease test results – List results for tests that are completed – Identify which tests are pending Negative/nonreactive test results – “Negative by tests for antibody to HIV and HCV and nonreactive for HBsAg, HCV RNA and HIV-1 RNA ” or equivalent Positive/reactive test results – Identify which tests are positive/reactive – Biohazard symbol on unit – Identify if collected from donor with previous positive/reactive test

8. CBER 8 SP for Injectable Products Caution statement – “CAUTION: FOR FURTHER MANUFACTURING USE ONLY” Storage temperature – -20 C or colder

9. CBER 9 SP for Noninjectable Products An appropriate caution statement – “CAUTION: FOR USE IN MANUFACTURING NONINJECTABLE PRODUCTS ONLY” – “CAUTION: FOR FURTHER MANUFACTURING INTO IN VITRO DIAGNOSTIC REAGENTS FOR WHICH THERE ARE NO ALTERNATIVE SOURCES”* – “CAUTION: FOR LABORATORY RESEARCH USE ONLY” *Positive/reactive test results Storage temperature – Appropriate for final product, determined by consignee

10. CBER 10 SP for Noninjectable Products (cont.) Anti-HBc statement – Not tested for anti-HBc – Negative for anti-HBc – Reactive for anti-HBc – FDA Recommendations Concerning Testing for Antibody to Hepatitis B Core Antigen (Anti-HBc) (9/10/91) Reactive for syphilis test – “Reactive by a Serological Test for Syphilis” – “Use Only for Manufacturing Positive Control Reagents for Serological Tests for Syphilis”

11. CBER 11 Source Plasma Salvaged Relabeling if SP intended for injectable products is exposed to unacceptable temperatures Not required when – Only 1 episode of storage warmer than -20 C and colder than -5 C for less than 72 hours and units remained solid Required when – > 1 inadvertent exposure during storage of warmer than -20 C and colder than +10 C for not more than 72 hours – > 1 inadvertent exposure during shipping of warmer than -5 C and colder than +10 C for not more than 72 hours Additional statements when relabeling – “STORAGE TEMPERATURE EXCEEDED -20 C” – “SHIPPING TEMPERATURE EXCEEDED -5 C”

12. CBER 12 Submitting SP Labels Original BLA or BLA supplement for specific collection program Label for each collection program Original and copy of each label Forms 356h and FDA-2567: Transmittal of Labels and Circulars Reporting category based on collection program – 21 CFR 601.12(f)(1) - PAS – 21 CFR 601.12(f)(2) - CBE

13. CBER 13 Reviewing SP Labels Based on regulations and guidance documents Documented on label review checklist – Branch chief concurrence Label review checklist with decision sent to applicant – Approved – Approved with comments - revise on next printing or software upgrade – Not approved – revise and submit