1. CBER Review Considerations on Source Plasma Vaccination Programs Judy Ellen Ciaraldi BS, MT(ASCP)SBB, CQA(ASQ) CBER, OBRR, DBA September 16, 2009

2. CBER 2 Outline Considerations on how to submit for a vaccination program when using: Licensed vaccines according to package insert Licensed vaccines not according to package insert Unlicensed vaccines Medical oversight CBER review of vaccination programs

3. CBER 3 Approved Licensed Vaccine Programs  Tetanus Toxoid  Hepatitis B  Rabies  Smallpox (Vaccinia)  Anthrax  Influenza  Varicella  Material used for immunization must be licensed or approved by CBER (640.66)

4. CBER 4 Submitting Vaccination Programs  Vaccination programs have been approved by CBER  Vaccination programs are “site-specific” approvals  Contractual arrangements are possible – Perform injections – Collect plasma

5. CBER 5 Submitting Vaccination Programs (cont.)  If using licensed vaccine according to package insert for the: – Injection volume – Administration route – Injection schedule, including boosters – Typically we have reviewed these as a CBE30 Supplement (601.12(c))  If approved for specific vaccine and changing vaccine manufacturer but using it according to package insert – If no changes to SOPs – Annual Report (601.12(d)) – If revise SOPs to incorporate new package insert – CBE30 Supplement

6. CBER 6 Submitting Vaccination Programs (cont.)  If using licensed vaccine but varying from package insert for injection volume, administration route, injection schedule, including additional boosters – We have typically reviewed these as a PAS Supplement (601.12(b)) – Injection protocol is studied under an IND  If using an unlicensed vaccine – We have typically reviewed these as a PAS Supplement (601.12(b)) – Injection protocol is studied under an IND

7. CBER 7 Submission Content The following items have typically been included in a vaccination program submission:  Forms: 356h and 2567  Applicant name and license number  Contact name and information  Facility name, address, and registration number  May reference previously approved SOPs, forms, labels (include reference number for approvals)  Medical oversight, use of a physician substitute

8. CBER 8 Submission Content (cont.) The following items have typically been included in a vaccination program submission (cont.):  Vaccination program SOPs that include – Donor selection (606.100(b)(1)) – Vaccination procedures (640.66) – Handling of adverse events (606.100(b)(9))  Contractor information  Informed consent form (640.61 & 640.72(a)(3))  Immunization forms (blank)  Labels (640.70)  Package insert for vaccine

9. CBER 9 Medical Oversight (640.62 and 640.66)  Qualified licensed physician must be on premises when immunizations are performed  Qualified licensed physician must select and schedule the injection  Qualified licensed physician must evaluate donor’s clinical response  Administration of vaccine may be performed by licensed physician or trained person under physician’s supervision

10. CBER 10 Medical Oversight (cont.)  Blood Memorandum: Physician Substitutes (8/15/88)  Appropriately trained physician substitute may perform some of the physician’s duties  Physician substitute may administer and supervise approved vaccine immunization programs (needs additional training)  Physician does not need to be on premises during injection but is still responsible for – Weekly evaluation of immunization records – Approval of injections

11. CBER 11 Medical Oversight (cont.)  CBER has approved physician substitute to assume additional responsibilities in vaccination programs as alternative procedure to 640.66 under the provisions of 640.120 when: – Donors meet all donor suitability criteria – Vaccine is licensed by FDA – Vaccine is administered according to package insert – With this approval, physician substitute may review clinical responses and schedule injections  Physician still responsible for direction and control of vaccination program and for reviewing adverse reactions

12. CBER 12 SOPs  Immunization procedures must be on file at centers where immunizations are performed (640.66)  Describe medical responsibilities (640.62)  Donor selection procedures (606.100(b)(1)) – Donors must meet all donor suitability criteria in 640.63 & 650.65 – Physical exam must occur within 1 week before first immunization unless active donor (640.63(b)(2)) – Medical staff must approve donor’s participate in the program (640.63(a))

13. CBER 13 SOPs (cont.)  Vaccination procedures typically include: – Preparation of injection – Injection volume and schedule, including any boosters allowed, administration route – When titrations will be performed – Handling and storing of vaccine vials  Adverse reactions procedures (606.100(b)(9)) – Vaccine Adverse Event Reporting System (VAERS) – Medical oversight (640.62) – Records maintained (640.72(d))  Proper documentation procedures

14. CBER 14 Contractor Information  Name and license number  Address and registration number  List activities done under contract  Where records maintained  Describe quality oversight of contractor  Both injection facility and collection center must be approved for vaccination program; both parties are participating in vaccination program

15. CBER 15 Informed Consent In addition to the requirements in 640.61, the approved informed consent should include:  Volume, route and schedule of injections  Criteria for discontinuation from program  Participate in only one immunization program at a time  May not be eligible for other donation programs  Adverse reactions consistent with package insert  Restrictions for female participants

16. CBER 16 Immunization Forms The immunization forms in approved submissions have typically included the following information:  Donor name, ID number (640.72(b))  Injection preparation – date, employee name, visual inspection  Injection – date, employee name, route, volume, facility  Vaccine - name, lot number, expiration date  Physician/physician substitute approval (640.72(a)(4))  Adverse reactions (640.72(d))  Evidence of QA review (606.100(c))

17. CBER 17 Labels  May be made into injectable and noninjectable products  Label must state immunizing antigen (640.70(a)(7))  Separate label for each vaccine and intended use (and facility, if applicable)

18. CBER 18 CBER Review of Vaccination Programs  Pre-approval inspection is – Not required if implemented in an approved center – Required if implemented in new center  Vaccination procedures should be consistent with package insert  Approved informed consents typically contain the adverse events described in the package insert  Informed consent includes recommendations in guidance document  Forms contain all information

19. CBER 19 CBER Review of Vaccination Programs (cont.)  Procedures for donor selection, adverse events and medical oversight are consistent with regulations and include all steps to be followed (606.100)  Physician substitute has necessary training (606.20) and if appropriate, 640.120 approval to select and schedule injection  Procedures for handling and storing vaccine vials are consistent with package insert  Labels consistent with 640.70 – Includes the immunizing antigen (640.70(a)(7))  All facilities (including contractors) are FDA registered (607.20) and should have acceptable compliance checks

20. CBER 20 Investigational Vaccine Programs  To distribute Source Plasma in interstate commerce collected as part of an IND program – Source Plasma procedures and labels must be approved – Labels should contain IND number – Collection must occur under cGMPs in facility with approved vaccination program  IND review may include clinical reviewers from either OBRR and OVRR  Contact Office of Communication, Outreach and Development (OCOD) for information on submitting an IND at 301-827-2000

21. CBER 21 References  Blood Memorandum: Physician Substitutes (8/15/88) – http://www.fda.gov/BiologicsBloodVaccines/GuidanceComp lianceRegulatoryInformation/OtherRecommendationsforMa nufacturers/MemorandumtoBloodEstablishments/default.ht m http://www.fda.gov/BiologicsBloodVaccines/GuidanceComp lianceRegulatoryInformation/OtherRecommendationsforMa nufacturers/MemorandumtoBloodEstablishments/default.ht m  Guidance for Industry: Informed Consent Recommendations for Source Plasma Donors Participating in Plasmapheresis and Immunization Programs (8/8/07) – http://www.fda.gov/BiologicsBloodVaccines/GuidanceComp lianceRegulatoryInformation/Guidances/Blood/ucm073433.h tm http://www.fda.gov/BiologicsBloodVaccines/GuidanceComp lianceRegulatoryInformation/Guidances/Blood/ucm073433.h tm