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Review Considerations onSource Plasma

Vaccination ProgramsJudy Ellen CiaraldiBS, MT(ASCP)SBB, CQA(ASQ)

CBER, OBRR, DBA

September 16, 2009

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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

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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)

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Submitting Vaccination Programs

Vaccination programs have been approved by CBER

Vaccination programs are “site-specific” approvals

Contractual arrangements are possible– Perform injections– Collect plasma

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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

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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

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Submission ContentThe 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

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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

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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

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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

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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

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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))

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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

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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

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Informed ConsentIn 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

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Immunization FormsThe 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))

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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)

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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

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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

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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

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References Blood Memorandum: Physician

Substitutes (8/15/88)– http://www.fda.gov/BiologicsBloodVaccines/GuidanceComp

lianceRegulatoryInformation/OtherRecommendationsforManufacturers/MemorandumtoBloodEstablishments/default.htm

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.htm