Vaccines, Blood & Biologics
Questions and Answers on FDA Guidance Entitled "Recommendations for Deferral of Donors and Quarantine and Retrieval of Blood and Blood Products in Recent Recipients of Smallpox Vaccine (Vaccinia Virus) and Certain Contacts of Smallpox Vaccine Recipients"
Why do we recommend temporary blood donor deferrals for people who have received the smallpox vaccine?
Smallpox vaccine consists of a live virus, called vaccinia. Vaccinia virus is related to smallpox (variola) virus, and this relationship allows the healthy vaccinee to develop an immune response that will also protect against smallpox. After vaccination, the vaccinia virus grows in the skin, causing a clear, then cloudy blister, a sore and later a scab. By a week or two, the vaccinee develops an immune response against vaccinia, and once the scab has fallen off, the vaccinia virus has been eliminated from the body. Because vaccinia is a live virus, it might be able to enter the bloodstream. Although early studies with a different vaccine virus demonstrated bloodstream infections in some vaccinees, no modern studies have been done to find out if vaccinia enters the blood of vaccinees during the active infection. Until we are sure whether or not this is the case, FDA is taking this step as a prudent measure to prevent possible transmission of vaccinia to blood recipients. Unlike healthy people, some blood recipients who have immune system problems may be especially susceptible to severe, even life-threatening vaccinia infections.
What are the new temporary blood donor deferrals for people who have received the smallpox vaccination?
- For vaccinees without severe complications: Deferral until after the vaccination scab falls off, or 21 days, whichever is longer.
- Rationale: People who have been vaccinated may have live vaccinia virus until the immune response is complete (usually by 14-21 days), and until after the vaccine scab has fallen off. Vaccine scabs have been shown to contain infectious virus.
For vaccinees with severe complications: Deferral for 14 days after complete resolution of severe complications.
Rationale: Rarely, vaccinated people develop more extensive infections that can last longer than usual and can be serious. These include localized and progressive spread of infection beyond the vaccination site that may involve the eyes or non-adjacent parts of the skin, as well as widespread infections that may affect internal organs including the brain. A physician would diagnose these conditions. Since in these cases, vaccinia levels in the body may be higher than after uncomplicated vaccination, we recommend deferral of donors for 14 days after complete resolution of these severe vaccine complications.
Which contacts of vaccinees would be temporarily deferred from donating blood?
Only people who have developed active vaccinia infections, inadvertently contracted from a vaccinee, should be deferred. Occasionally, people who have had close physical contact with vaccinated people, their bandages, or clothing, develop vaccinia infections on their own skin. Most of the time, these infections progress in a manner similar to vaccination, i.e., blisters form, scabs form, and the vaccinia virus is eliminated, much like events that occur after an intentional vaccination. However, the person with "contact vaccinia" can, just like a vaccinee, rarely experience a severe complication of vaccinia infection. We recommend temporarily deferring blood donors who have inadvertently caught vaccinia from a vaccinee, as follows:
For symptomatic contacts of vaccinees, who have only localized skin lesions, and not severe complications: Deferral until after the scab(s) fall off.
Rationale: Just like vaccinees, people who have inadvertent vaccinia infection of the skin may have live vaccinia virus in the body until the immune response is complete (usually by 14-21 days), and until after the scab(s) have fallen off. Vaccine scabs have been shown to contain infectious virus.
- For symptomatic contacts of vaccinees with severe complications: Deferral for 14 days after complete resolution of severe complications.
- Asymptomatic contacts of vaccine recipients do not need to be deferred.
What if vaccinia scabs were scraped off or otherwise removed?
In most people, scabs fall off on average around 3 weeks after vaccinia infection. However, on occasion, a scab, containing virus, may persist for up to 6 weeks. If a scab is prematurely removed, it is possible that vaccinia infection could still remain in the skin for a longer period. As a precaution, we recommend longer deferral periods if scabs have been prematurely removed.
How will these donor deferrals affect the blood supply?
At present, because vaccination plans are limited to healthcare workers, FDA does not anticipate a major impact on blood supply. The government is working with blood organizations to develop plans for ensuring an adequate blood supply should mass vaccination occur. It is suggested that all vaccinees save the written record of their vaccination. Saving this record will help to determine vaccination status, and donor eligibility in the event of a smallpox outbreak.
How can I help prevent potential blood shortages in case of widespread smallpox vaccination?
You can donate blood prior to vaccination. You may donate again 56 days later; by that time, it is likely that you will again be eligible, since most vaccinations will have healed within 21-22 days.
Is FDA studying whether or not vaccinia may be transmitted by blood?
Scientists at FDA, as well as industry scientists, are currently studying blood samples from people who recently received smallpox vaccination, to determine whether, and how often, vaccinia may appear in the blood of normal vaccinees. Results of these scientific studies may help to refine the current donor deferral recommendations.
Questions Specific to Blood Centers
The new guidance recommends that blood centers ask a new question about smallpox vaccination or close contact with a vaccinee in the past eight weeks. The current Uniform Donor History Questionnaire (UDHQ) asks the donors about any vaccination in the past four weeks. Is this sufficient? If not, how long do we have to implement the new question?
No, the current UDHQ does not provide ample deferral time for the smallpox vaccination in all cases. In some instances, delayed immunity or disruption of a smallpox vaccination scab can delay healing of the vaccination site for at least 6 weeks. FDA recommends that the specific question related to smallpox immunization described in the guidance should be implemented for all donors as soon as possible.
Can we use alternate question wording and/or procedures to the ones recommended in the FDA guidance?
Yes, you may implement alternate questions and/or procedures as directed below:
Licensed blood establishments:
If licensed establishments wish to implement alternate wording and/or procedures that are different from the ones recommended in the guidance, they must report this to us under 21 CFR 601.12, Reporting Changes to an Approved Application. The supplement to request an alternate wording and/or procedure to the smallpox vaccination guidance must be submitted as follows:
- The licensed blood establishment must submit a form FDA 356h "Application to Market a New Drug, Biologic or an Antibiotic Drug for Human Use."
- The submission must include the Standard Operating Procedure manual for this procedure and the revised donor history questionnaire.
The submission may be made as a Changes Being Affected (CBE) under 21 CFR 601.12(c)(5), provided the alternative wording and/or procedure is consistent with those listed below. This is to allow for immediate implementation.
- Extension of the deferral period to two months for both vaccine recipients and symptomatic contacts of vaccine recipients
- No examination of vaccine scabs of recipients or of contacts who have contracted vaccinia virus infection
- Revision of the current UDHQ vaccination question to ask about vaccinations within the past 8 weeks, provided that the donor is also asked about contacts with a vaccine recipient
- If the alternate wording and/or procedure is different from the one described above, the submission must be made as a Prior Approval Supplement (PAS) under 21 CFR 601.12(b).
Unlicensed blood establishments:
Unlicensed blood establishments may either implement the procedures described in our smallpox vaccination guidance document or an alternate procedure. They are not required to report these changes to FDA. We will examine the smallpox vaccination deferral policies during FDA inspections. However, if unlicensed blood establishments wish to implement a procedure that is different from the procedures described in our smallpox guidance document or as described above, we encourage them to discuss the alternate procedure with FDA.
Can the new donor questions be asked orally, or must they be asked in writing?
You should ask the new questions in the same fashion as you ask the current questions. If you have all questions in writing or available electronically, then the new questions should be added to the written or electronic questionnaire, as soon as possible. Until new donor questionnaires are available, as an interim measure, you may ask questions orally, as long as you document the responses.
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