COVID-19 vaccine: Crucial updates on interchangeability, dosage intervals, vials affect pharmacies and patients

Revised CDC clinical recommendations specify that intervals of 6 weeks between COVID-19 vaccine doses are OK when delays are unavoidable and that the Pfizer–BioNTech and Moderna vaccines are not interchangeable, barring exceptional circumstances. In other news that affects pharmacists and patients, FDA has updated the labeling for the Pfizer–BioNTech vaccine to permit immunizers to use needles or syringes with low dead volume to extract a sixth dose out of the manufacturer’s vials; using standard needles or syringes, a vial only yields 5 doses.

More flexibility on dosage intervals
CDC’s updated guidance on vaccine dosage intervals still emphasizes that first and second doses should be administered as close as possible to the recommended interval—21 days for Pfizer–BioNTech and 28 days for Moderna. But there is some wiggle room: When adhering to that time frame is not possible, the agency said, pharmacists and other immunizers can administer a second dose of either currently available vaccine up to 6 weeks—42 days—after the first.

There are limited data showing that mRNA COVID-19 vaccine doses administered beyond that gap remain effective, CDC said; however, patients who receive their second dose more than 6 weeks after their first don’t have to start over.

Despite its earlier resistance to more flexible interval lengths, FDA has now stated that “slight delays” between doses shouldn’t affect the vaccines’ capacity to protect against COVID-19.

While CDC again urged sticking to recommended intervals between doses, its new guidance also states that second doses administered no more than 4 days earlier than recommended—i.e., 17 days for Pfizer–BioNTech and 24 days for Moderna—are valid. Second doses inadvertently administered before the 4-day grace period should not be repeated but are strongly discouraged.

No mix and match
The CDC guidance also put to bed the interchangeability question: Pfizer–BioNTech and Moderna vaccines are not interchangeable. The safety and efficacy of “mixed-product series” have not been sufficiently evaluated.

Pharmacists and other immunizers should utilize any and all possible strategies to ensure patients receive the correct vaccine products and the correct time, CDC said. These include providing patients with vaccination record cards, reporting immunizations to state and local immunization information systems, and/or, if they have access to them, documenting immunizations in patient medical records.

The agency’s guidance offered tips that can help pharmacists and other immunizers meet this goal and forestall lost information. They can ask patients to make a backup copy of their vaccination record cards by, for example, taking a photo of it with their phones, and remind them to bring the card to their appointment for their second dose. Another tip recommends scheduling the appointment for their second dose before the end of the first appointment.

Immunizers can also tell patients about VaxText, a free service that sends text reminders to schedule their second dose of the COVID-19 vaccine. VaxText doesn’t collect private health information or any other information that could personally identify its users. It does, however, ask for the date and manufacturer of the patient’s first dose; knowing the manufacturer helps the system determine whether patients should receive their second dose in either 21 (for Pfizer–BioNTech) or 28 (for Moderna) days. Patients can sign up by texting ENROLL to 1-833-VaxText (829-8398).

The interchangeability answer includes a “but.” CDC acknowledged in its guidance that in rare cases, despite best efforts, it will not be possible to track down patients’ first-dose vaccine product, or that product will have become unavailable.

In these and only these exceptional situations, patients can complete the vaccination series by receiving a dose of any mRNA COVID-19 vaccine product within at least 28 days of the first dose. These patients do not require additional doses after that.

The last drop
Pfizer–BioNTech COVID-19 initial vaccine’s EUA indicated that each vial contained five doses. After pressure from the manufacturer, FDA has now updated the products labeling information to reflect that immunizers can extract a sixth dose if they use low dead space syringes. The change has implications of how much vaccine pharmacies order, since the sixth dose will ostensibly increase their supply, and the needles and syringes they use. It also affects Pfizer’s 200 million–dose commitment to the U.S. government.

A New York Times report said that pharmacist immunizers made the “happy discovery” that Pfizer’s vaccine vials could yield an additional dose if they use the special needles, which minimize the amount of product that remains in the syringe after the drug is injected. Pfizer seized on the idea and pressured FDA to change its EUA, and ultimately got its way. The manufacturer reaps a financial benefit because it will count these “sixth doses” toward its committed 200 million doses—it could mean they can fulfill the agreement while producing fewer vials of its vaccine. It will start subtracting the sixth dose from their commitment even before the supply of low dead space needles and syringes is large enough to give all immunizers access to the vials’ extra dose.

The “sixth dose” can benefit pharmacies, because they now have more doses on hand than they ordered. But the caveat that extracting the sixth dose requires low dead-volume needles or syringes is a major complication. The special needles are not standard, not on hand in all pharmacies or other vaccination sites, and are in shorter supply overall. And according to a New York Times report, some pharmacists report that they cannot even reliably capture an extra full dose.

According to Reuters, CDC has said it is working to provide immunizers with new 6-syringe kits to accompany Pfizer vaccine orders that include at least 3 that are low dead space; the 3 special syringes will make it possible to extract a sixth dose from each vial. The agency aims to eventually make kits in which the majority of their 6 syringes will be of the low dead space variety.

FDA has previously warned that because the vials do not contain preservatives, immunizers should not combine leftover product from separate vials to make a full 0.3 mm dose.

More from CDC
The revised guidance also addresses the vaccination of patients who have or who have already had COVID-19.

Data show that the vaccine is safe for patients in whom there is evidence of prior infection, and CDC does not recommend viral testing “to assess for acute SARS-CoV-2 infection or serologic testing to assess for prior infection.”

That said, patients who currently have COVID-19, whether infected before any dose of the vaccine or between doses of the vaccine, should defer vaccination until they have recovered and fulfilled isolation recommendations. And since the latest evidence shows that patients are at low risk for COVID-19 reinfection in the months after recovery—although the risk can grow over time—can choose to temporarily delay the vaccine while supplies remain limited. Receipt of the vaccine should not affect treatment of patients who develop COVID-19 after receiving the vaccine.

Finally, patients with injectable dermal fillers may experience swelling at the filler injection site after receiving a dose of the COVID-19 vaccine; but, as long as they have no other contraindications, they should be immunized anyway and don’t require further precautions. CDC said swelling has shown to be temporary and resolved with treatments including corticosteroid therapy; patients should contact their health care provider if they experience swelling.

CDC also updated information on vaccine excipients.

Resources pharmacists need
APhA has a new resource to arm pharmacists to face COVID-19 vaccination head on. Know the Facts on Minimizing COVID-19 Vaccine Dose Variability reference provides tips and information on maximizing doses from vaccine vials.

USP recently published a toolkit, COVID-19 Vaccine Handling: Operational Considerations for Healthcare Practitioners, that features additional guidance on preparation and handling, including guidance on pre-drawing vaccine doses and storing within syringes.