The labeling of some COVID-19 antibody treatments specifically mentions certain materials like polyvinylchloride (PVC) administration sets and polyethersulfone (PES) filters; we do not stock PVC tubing and our filter packing does not specify the filter membrane material. Do we need to source new supplies to prepare and administer bamlanivimab and casirivimab + imdevimab?
The Emergency Use Authorization (EUA) specifically names “recommended materials” (e.g. PVC tubing and PES filters) because these were the materials in products used in the clinical trials; however as neither bamlanivimab nor casirivimab + imdevimab have known incompatibilities with conventional medial supplies and equipment, it is anticipated that standard infusion supplies are appropriate for use.¹
No, bamlanivimab and casirivimab + imdevimab may be prepared on an open benchtop using strict aseptic non-touch technique (ANTT). Preparation of a parenteral medication according to the manufacturer’s instructions is not considered compounding so long as all of the following criteria are met.²
- Aseptic technique is used, and written procedures followed to prevent contamination and/or medication errors;
- The starting components are conventionally manufactured sterile products;
- No more than 3 different sterile products are used in the preparation;
- Mixing, reconstituting, or other such acts are performed in accordance with the directions in the manufacturer labeling; and
- The prepared product is intended for immediate administration to an individual patient, ideally within one hour of beginning preparation. If circumstances prevent immediate administration, manufacturer guidelines regarding stability and storage must be followed; however, storage should not exceed 4 hours from the start of preparation.
- Product must be labeled with names and amounts of active ingredients, name of preparer, and 4-hour time period within which administration must begin.
If any of these criteria are not met, preparation must be performed in accordance with state board of pharmacy rules. In the absence of state board of pharmacy or regulatory agency guidance, preparation and storage should be performed in accordance with US Pharmacopeia (USP) General Chapter <797> pharmacy standards for compounding sterile products.
No. General Chapter <797> applies to pharmaceutical compounding of sterile preparations. Reconstituting, diluting, or otherwise preparing a parenteral medication according to the manufacturer’s instructions for immediate administration to a single patient is not compounding but rater an FDA-approved manipulation of the product.³ United States Pharmacopeia has clarified that USP <797>, including assignment of risk categories, does not apply in this case, as “preparation per approval labeling is out of the scope of the chapter.”⁴
REGN10933 is casirivimab and REGN10987 is imdevimab. In an effort to start distributing medication as soon as possible after receiving EUA, early allocations may include product originally labeled for clinical trials. For this reason, providers may receive product in with different variations of packaging and labeling. Refer to Regeneron’s Dear Healthcare Provider Letter and NICA’s Casirivimab + Imdevimab Medication Safety Alert for images of possible packaging/labeling variations and additional information about preventing medication errors.
Electronic infusion devices (pumps) should be used if available, however the COVID-19 antibody treatments can also be administered using manual flow control devices (dial-a-flow) or simply by gravity, using the roller clamp to adjust the flow. The infusions do need to be administered over 60 minutes, so gravity infusions will require the HCP to calculate the appropriate drip rate for the volume to be infused and drop factor of the administration set being used. Drip rate tables for each product can be found in NICA’s COVID-19 Antibody Treatment Resource Center.
The post-infusion observation period is required per the manufacturer and FDA’s EUA; however, competent patients always have the right to refuse treatment and cannot be held against their will. It is recommended that sites of care prepare for this possibility by developing a protocol for observation period refusal. An “Against Medical Advice” (AMA) form or similar document can be used, however the following should still be completed and documented:
- Educate patient/caregiver regarding the rationale for observation period order, providing necessary information to make an informed decision;
- Ensure patient/caregiver understands risks and is competent to make such a decision; and,
- Provide and review written discharge instruction, including signs/symptoms to report and where/how/to whom they should be reported.
Without supporting documentation, a signature alone may do little to release the facility/prescriber/personnel from responsibility for consequences of a patient’s decision to refuse medical care. Consult legal counsel for development of an organizational policy and/or form.
No. Casirivimab and imdevimab may only be administered by intravenous infusion after dilution per instructions. In an effort to start distributing medication as soon as possible after receiving EUA, early allocations may include product originally labeled for clinical trials, some of which state “for intravenous infusion or subcutaneous injection.” Refer to Regeneron’s Dear Healthcare Provider Letter and NICA’s Casirivimab + Imdevimab Medication Safety Alert for images of possible packaging/labeling variations and additional information and preventing medication errors.
Yes, Medicare will cover and pay for these infusions (when furnished consistent with their respective EUAs) during the COVID-19 public health emergency (PHE). Currently, the monoclonal antibodies are being provided to infusion sites free of charge, so there will be no drug payment associated with furnishing these treatments; however, Medicare has set a national average payment rate for the administration of COVID-19 antibody treatments of approximately $310 (exact amount will vary as rates are geographically adjusted). For more information, see the Medicare Monoclonal Antibody COVID-19 Infusion Program Instruction.
No, there is no cost sharing (no copayment, coinsurance, or deductible) for the COVID-19 antibody infusions for people with Medicare. For more information, see the CMS Coverage of Monoclonal Antibody Products to Treat COVID-19 guide.
The federal government has established the COVID-19 Claims Reimbursement to Health Care Providers and Facilities for Testing, Treatment, and Vaccine Administration for the Uninsured Program. Program funds provide reimbursements directly to providers for claims related to testing, treatment, and vaccine administration for COVID-19 for uninsured individuals. For claims for treatment for positive cases of COVID-19, a patient is considered “uninsured” if the patient did not have any health care coverage at the time the services were rendered.
Yes. The process is very similar to the way most infusion centers have established accounts with other distributors, as most do not have an on-site pharmacy and/or are not required to have a Board of Pharmacy license. The current antibody treatment distributor, AmerisourceBergen Company, requires one of the following in order to ship to a site:
- An active Board of Pharmacy license for the receiving site; or,
- A letter of affiliation (LOA) between the facility and an administering physician.
There is some misinformation floating around about the type of sites eligible to receive and administer COVID-19 antibody treatments, and some ambulatory infusion centers have mistakenly been told they are ineligible. If your infusion center is currently able to procure other provider-administered medications, you should be able to receive allocation of COVID-19 antibody treatments. Please email [email protected] if you are denied or otherwise need assistance securing allocation.
Infusion centers should first try to go through local/state health authorities to request allocation of COVID-19 antibody treatments. NICA has heard from infusion providers in several states who have be unable to reach the proper contacts to receive allocation. If this is the case click here for information about the recently established regional request system, which will assist infusion operators in obtaining COVID-19 therapeutics. Regional staff who have strong relationships with states and public health officials across the country will help facilitate allocation for infusion centers willing and equipped to administer COVID antibody treatments.
As of January 14, 2021, there are no live vaccines available in the U.S. for COVID-19 (though there are a few in development around the world). The Pfizer-Biotech and Moderna vaccines are neither “alive” (live-attenuated) nor “dead” (inactivated) vaccines; they are a new type called mRNA vaccines, which are essentially an instruction manual for building the notorious “spike proteins” on the virions’ outer surface, which gave COVID-19 its name (COVID-19 stands for “Coronavirus Disease 2019”; “corona” is Latin for “crown” or “wreath”).
No. The mRNA vaccines only contain instructions for making the spike proteins found on the outer surface of the viral particles—not the entire viral particle. The spike proteins are like the keys the virus uses to enter host cells; they are not infective or harmful on their own. Visit the CDC “Understanding mRNA COVID-19 Vaccines” page to learn more.
Autoimmune disease is not a contraindication for the mRNA vaccines. Participants with autoimmune diseases were enrolled in the clinical trials for both mRNA COVID-19 vaccines currently available and no disparities were observed.
Per the CDC, Immunocompromised individuals may receive COVID-19 vaccination if they have no contraindications to vaccination. However, they should be counseled about the unknown vaccine safety profile and effectiveness in immunocompromised populations, as well as the potential for reduced immune responses and the need to continue to follow all current guidance to protect themselves against COVID-19.
According to the CDC, antibody therapies such as IVIG are unlikely to substantially impair development of a protective antibody response, so there is no recommended minimum interval between antibody therapies and mRNA COVID-19 vaccines.
The only exception is monoclonal antibody treatment specifically for COVID-19. If a patient receives one of the monoclonal antibody treatments for COVID-19 (bamlanivimab or casirivimab + imdevimab), they should wait 90 days before receiving a COVID-19 vaccine.
For vaccines to confer protection, the recipient’s immune system needs to be able to respond appropriately. Depending on the biologic/medication a patient receives (specifically, which part of the immune system it affects), there may be circumstances where the provider recommends waiting 14 days after administration of vaccine to resume their immunosuppressing medication. For some people, the risks of delaying treatment may outweigh the benefits of allowing time for optimal vaccine effectiveness.
Ultimately, determinations regarding use and timing of vaccines and biologics (or other treatments that alter the immune system) should be an informed, shared decision between the patient and their provider. For particularly complex cases, providers can request a consultation from a Clinical Immunization Safety Assessment (CISA) Project COVIDvax clinician.