As a public service, paindr.com will continue to post content that focuses on practical, clinical, scientific, and/or political matters related to COVID-19. Here today are PharmD Candidates Allison Gamelli and Amy Mataraza under the mentorship of Dr. Jacqueline Cleary and yours truly. Here’s what they had to say…
In the fight against COVID-19, recent news has surrounded pharmaceutical companies Pfizer/BioNTech and Moderna who have both released data for vaccines that are over 90% effective. Both vaccines are mRNA vaccines – they introduce an mRNA sequence that codes for the viral spike protein that COVID-19 uses to enter host cells. The mRNA code for the spike protein allows the immune system to create antibodies without causing disease because no infectious material has been introduced. Additionally, AstraZeneca/Oxford has thrown their hat into the vaccine ring with their viral vector delivered vaccine against COVID-19. “Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (in vivo) or in cell culture (in vitro). Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect.” This vaccine candidate uses an adenovirus vector to deliver the COVID-19 spike protein to which the immune system develops antibodies. Once antibodies have been produced, despite the delivery system, the immune system will be able to recognize the spike protein and mount an immune response to clear it. This vaccine also does not cause disease.
Pfizer/BioNTech’s vaccine – BNT162b2 – was shown in clinical trials to be 95% effective in preventing COVID-19 infection compared to placebo in ages 12 and up.1 The vaccine is a 2-dose series given intramuscularly 21-days apart.1 Pfizer/BioNTech faces challenges with their vaccine in terms of storage and distribution (Table 1).1,2,3,4,5 They have developed a temperature-controlled, thermal shipping container that utilizes dry ice and keeps the vaccine stored at -70°C +/- 10°C.2 The containers are equipped with thermal and GPS sensors to track temperature and location in real time and can maintain temperature for 10 days unopened.2 Pfizer/BioNTech estimates they can distribute 50 million doses of BNT162b2 by the end of 2020 and 1.3 billion by the end of 2021.2 They plan for a “just in time” shipping model that uses both road and air modes of transportation to get the vaccine to its destination in 1-2 days; BNT162b2 has to be shipped directly to its site of administration.2 The vaccine comes as a preservative free multidose 2mL vial that contains 5 doses. Each tray holds 195 vials (975 doses) and Pfizer/BioNTech is expected to release a smaller 25-vial tray (125 doses) in early 2021.4
Moderna’s vaccine – mRNA-1273 – was shown in clinical trials to be 94.1% effective in preventing COVID-19 infection compared to placebo in adults over age 18.6 Like BNT162b2, mRNA-1273 is a 2-dose series given intramuscularly; the difference is the doses of mRNA-1273 are given 28 days apart.7 Moderna’s advantage in this race is the storage requirements for mRNA-1273, which also makes distribution easier (Table 1).6,7,8 Moderna estimates 20 million doses by the end of 2020 and 50 million-1 billion in 2021 to be available for distribution.8 Getting mRNA-1273 to its final destinations is much simpler – most pharmaceutical distribution companies have the capability to store and ship products at its required temperature worldwide; this will allow more flexibility to facilitate wider-scale vaccination and save hospitals, physician’s offices, and pharmacies the added cost of purchasing expensive equipment. Each box of mRNA-1273 will contain ten multidose vials each containing 10 doses of vaccine.7
AstraZeneca/Oxford’s vaccine – AZD-1222 – has been shown to be approximately 70% effective overall compared to placebo in adults over age 18.9 This vaccine is also a 2-dose series given intramuscularly 30 days apart.9 AZD-1222 was trialed using two different dosing regimens, the first one was a half dose followed by a full dose which was 90% effective and the second one was 2 full doses which only showed to be 62% effective.10 Trialing different doses was not the company’s original plan – the half dose that some patients in the UK was given was inadvertent, however because it was the first dose given and patients were going to receive a booster in 30-days, the trial continued.10 The advantage that AstraZeneca/Oxford has with AZD-1222 is that its adenovirus vector formulation allows for simple storage and distribution (Table 1).9,10,11 Additionally AstraZeneca/Oxford is the only one of the three vaccine developers that monitored for asymptomatic infections, by collecting weekly swabs from some participants to determine whether they had the coronavirus but did not become ill. The data show that the low-dose vaccine regimen was about 60% effective at reducing asymptomatic infections.10 AstraZeneca/Oxford has not estimated the number of doses they will be able to provide at the time of this blog but have committed to broad and equitable access to their vaccine.9
The following table is available HERE as a PDF.
|COVID-19 Vaccine Candidates: A Summary1,2,3,4,5,6,7,8,9,10,11|
2 doses, 21 days apart
Ø 3 storage options
1. Ultra-low temperature freezers – store vaccine up to 6 months
‣ Transfer vaccine from shipping container to freezer in less than 10 minutes
2. Standard refrigerator – store vaccine at 2-8°C for up to 5 days undiluted
3. Shipping container refilled with dry ice – store vaccine for up to 30 days
‣ Replace dry ice within 24-hours of receipt
‣ With each re-icing the shipping container maintains ultra-low temperature for 5 days when limited to 2 openings per day (60-90 seconds each time)
Ø Cannot be re-frozen once thawed
|Ø Estimate 50 million doses by the end of 2020 and 1.3 billion doses by end of 2021
Ø Temperature-controlled thermal shipping containers that use dry ice to maintain temps -70° C +/- 10°C
Ø Shipping containers have GPS-enabled thermal sensors to track location and temperature
Ø “just-in-time” system to ship directly to points of use
Ø Road and air modes of transportation – will get to destination in 1-2 days
2 doses, 28 days apart
Ø Store in standard freezers (-20°C) for 6 months
Ø Store at standard refrigerated temperatures (2-8°C) for up to 30 days
Ø Stable at room temperature for up to 12 hours
Ø Stability allows for easy storage at most pharmacies, hospitals, or physicians’ offices
|Ø Estimate 20 million doses by end of 2020 and 50 million to 1 billion doses by end of 2021
Ø Most pharmaceutical distribution companies have the capability to store and ship products at -20°C worldwide
Ø Working with CDC, Operation Warp Speed and McKesson for distribution
AstraZeneca & Oxford – AZD-1222
2 doses, 30 days apart
|Ø Stored and handled at normal refrigerated temps (2-8° C) – stable for 6 months||Ø Stability in standard refrigerators make for easy distribution
Ø Broad and equitable access to vaccine
Table 1: Summary of Storage and Distribution Considerations for COVID-19 Vaccine Candidates
Ultra-low temperature freezers, while commercially available, cost between $10,000 and $15,000 per unit which can be a huge expense for the storage of a single product.12 The CDC recommends against making this expensive purchase, saying that other vaccine options with better storage requirements will also be available but hospitals who have the funds are ignoring this guidance and purchasing the freezers.12 While large, urban hospitals in the U.S. are rushing to purchase these units, smaller, rural hospitals cannot afford them which may leave their residents without the vaccine. Those in rural areas may be in the most need of the vaccine, as they often have a higher percentage of elderly, low-income residents, and a higher percentage of the community has multiple chronic health conditions making them more vulnerable to COVID-19.12 Wealthy hospitals and health systems who have purchased freezers now have the advantage when it comes to gaining access to the first wave of vaccines to be distributed and for large academic medical centers, the freezers may prove to be an investment as their only other real use is for research.12 Additionally, many community pharmacies do not have the funds or the space to put this type of freezer unit in all pharmacy locations, which will again limit vaccine access.12 Those who cannot afford deep freezers are left with less desirable storage options for BNT162b2 – refilling the dry ice in the shipping container or standard refrigeration which may limit distribution to those locations causing them to have an inconsistent supply. Additionally, it is estimated that shipping of BNT162b2 will be in batches of 1000-5000 doses to start with and in a rural area without a deep freezer, the community will only have 30 days to administer all of the doses before they are no longer usable.12 Moderna’s mRNA-1273 and AstraZeneca/Oxford’s AZD-1222 are better candidates for the rural and less wealthy communities, however mRNA-1273 is estimated to have less available doses overall which may limit access to that vaccine and AstraZeneca has not released specifics regarding their distribution plans other than their pledge of broad access. Dry ice in the shipping containers brings its own risks and red tape as dry ice is considered a hazardous substance when shipped by air or water, but not when driven.13 Prior to emergency use authorization being granted, Pfizer/BioNTech shipped its first batch of vaccine from Belgium to the United States via United Airlines. The FAA granted United Airlines permission to move 15,000lbs of dry ice per flight which is five times more than is normally allowed due to its hazardous nature; it can reduce the amount of oxygen in the air as it converts back to carbon dioxide gas.13 Refilling dry ice presents its own challenges because dry ice can only be handled using specific protective equipment and the possibility of a shortage is high; the perpetual need to purchase dry ice adds additional overhead costs and if a shortage occurs, entities that need it may be priced out of being able to store the vaccine.
Pharmacists in the community are the most accessible healthcare providers and all 50 states allow pharmacists and pharmacy interns to administer vaccines. There are even a handful of states that allow for certified and trained pharmacy technicians to administer immunizations and several other states have begun considering it.14 However there are local regulations limiting which immunizations may be administered within a pharmacy and to specific age groups, commonly restricting children under the age of 18 years. The United States Department of Health and Human Services (HHS) declared that vaccines may be administered to the age group of 3-18 years by pharmacists and pharmacy interns under standard protocol procedures and bypassing a patient specific prescription from the child’s pediatrician.15 The HHS is concerned that vulnerable children who have not received routine vaccinations due to limited pediatrician availability during the COVID-19 outbreak pose a threat to public health.15 The American Medical Association (AMA) has publicly opposed this declaration as they believe children will forgo routine pediatrician checkups that are necessary to monitor growth and development.16 The federal government has acknowledged the accessibility of pharmacists and how essential they are to enhancing public health. The US government has partnered with pharmacy chains covering about 60% of the pharmacies in the US to provide rapid access to the vaccine once it becomes available.16 The HHS declared that this vaccine would come at no cost to the patients of partnered pharmacies to promote widespread access to the vaccine and they encourage pharmacies who are not currently partnered with them to join.16 The CDC released a COVID-19 Vaccination Program Interim Playbook that outlines a phased approach to vaccine distribution.17 Phase 1 consists of two parts: 1A and 1B. In phase 1A, healthcare workers in closed settings who have the potential for direct or indirect exposure will vaccinated first, followed by other essential workers and people at higher risk of severe COVID-19 infection in phase 1B.17 Phase 2 will expand access to a broader network of healthcare settings, including doctor’s offices and community pharmacies.17 Phase 3 will expand distribution even more as they expect to see a sufficient supply to meet the demand and this is where vaccination of the majority of the general population will occur.17 Currently there are no estimates on how long the initial two phases will take as this will depend on manufacturing and distribution of approved vaccines.
Pfizer/BioNTech’s request to the FDA for emergency use authorization for BNT162b2 was granted on December 10, 2020 and disbursement was immediately arranged.18 The vaccine was authorized for administration in individuals age 16 and up.19 To prepare the vaccine for administration, vials should be removed from frozen storage and allowed to thaw for up to 3 hours in a standard refrigerator or 30 minutes at room temperature.4 Using either thawing method, vials must be at room temperature before dilution and must be diluted within 2 hours of thawing.20 Each 2 mL vial containing 0.45 mL of frozen drug product will need to be diluted with 1.8mL of 0.9% sodium chloride for injection; Pfizer/BioNTech is not supplying the diluent.4, 20 After dilution, the 0.3mL (30mcg) dose of vaccine must be administered within 6 hours; any diluted vaccine remaining in the vial after 6 hours must be discarded.4,20 Common reported side effects were pain at the injection site, fatigue, and headache and more people experienced these side effects after the second dose than after the first dose.20 The timeline required to prepare BNT162b2 for administration may be a barrier to patients requesting a vaccine anytime they come into the pharmacy, especially if the vaccine is being stored in the shipping container which can only be opened twice per day. It is possible patients will have to make vaccine appointments or pharmacies may only be able to offer the vaccine during certain times which is different than the “on demand” model patients are used to for other vaccines.
Moderna’s mRNA-1273 was submitted to the FDA for emergency use authorization on November 30, 2020 and is scheduled to be discussed for approval on December 17, 2020. The vaccine being evaluated for approval in adults age 18 and up.21 This vaccine does not require the same amount of attention and finesse when it comes to administration. Once thawed, the preservative-free vaccine can remain in the refrigerator for up to 30 days and at room temperature for up to 12 hours if none of the doses have been drawn out of the 10-dose vial.7,21 There is no dilution required and each 0.5mL (100mcg) dose can be drawn up on demand and administered.7, 21 After the first dose has been withdrawn, the vial should be held between 2° to 25°C and discarded after 6 hours.21 Reported side effects include injection site pain, muscle aches, and headache.21 While the need to use all 10-doses within 6 hours following the removal of the first dose may limit vaccination times to certain blocks throughout the day, there is more flexibility in terms of having thawed vaccine available for administration because there is no time sensitive dilution and sealed vials are stable in the refrigerator for 30-days.
There are still some information we do not have about the COVID-19 vaccines. Can a vaccinated person still transmit COVID-19 without getting sick themselves? How long does the immunity last following vaccination – will the vaccine be “one and done” or will it require annual (like influenza) or other interval vaccinations? While there are still unknowns, the development of these vaccines is a great advancement for public health and giant step forward in the fight against COVID-19.
As usual, comments and educational pearls from our readers are encouraged and welcomed with enthusiasm.
Amy Mataraza is currently completing her Advanced Pharmacy Practice Experience (APPE) rotations and anticipates graduating with her PharmD from Albany College of Pharmacy and Health Sciences in May 2021. She currently works at Walgreens Pharmacy and plans to pursue a career in community pharmacy. Amy’s interests lie in immunization and tobacco cessation education. Amy enjoys cooking, gardening and walking with her dog, Kizzy.
Allison Gamelli is completing her APPE rotations and is expected to graduate from Albany College of Pharmacy and Health Sciences in May 2021. She currently works as a pharmacy intern at St. Peter’s Hospital in Albany. Following graduation, Allison plans to complete a PGY1 pharmacy practice residency and explore a PGY2 in one of her areas of interest – critical care and emergency medicine. Allison also enjoys spending time with family and friends, reading, and day trips with her spouse and their dog, Kahla.
- Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine. 2020Dec10. [cited 2020Dec13]. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
- Pfizer and BioNTech Conclude Phase 3 Study of COVID-19 Vaccine Candidate, Meeting All Primary Efficacy Endpoints [Internet]. Pfizer. 2020 [cited 2020Nov24]. Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine
- Hesman Saey T. Here’s why COVID-19 vaccines like Pfizer’s need to be kept so cold [Internet]. Science News. 2020 [cited 2020Nov24]. Available from: https://www.sciencenews.org/article/coronavirus-covid-19-why-vaccines-cold-freeze-pfizer-moderna
- Hering, D, Cane, A. Pfizer COVID Vaccine Update. [WebEx Event] 2020Dec8. Pfizer/BioNtech. [cited 2020Dec12].
- COVID-19 Vaccine U.S. Distribution Fact Sheet [Internet]. Pfizer. 2020 [cited 2020Nov24]. Available from: https://www.pfizer.com/news/hot-topics/covid_19_vaccine_u_s_distribution_fact_sheet
- A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19 – Tabular View [Internet]. ClinicalTrials.gov. 2020 [cited 2020Nov24]. Available from: https://clinicaltrials.gov/ct2/show/record/NCT04470427?term=mrna-1273
- Moderna Announces Longer Shelf Life for its COVID-19 Vaccine Candidate at Refrigerated Temperatures [Internet]. Moderna, Inc. 2020 [cited 2020Nov24]. Available from: https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-longer-shelf-life-its-covid-19-vaccine
- Moderna’s COVID-19 Vaccine Candidate Meets its Primary Efficacy Endpoint in the First Interim Analysis of the Phase 3 COVE Study [Internet]. Moderna, Inc. 2020 [cited 2020Nov24]. Available from: https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy
- AZD1222 vaccine met primary efficacy endpoint in preventing COVID-19 [Internet]. AstraZeneca. 2020 [cited 2020Nov24]. Available from: https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html
- Deloria Knoll M, Wonodi C. Oxford–AstraZeneca COVID-19 vaccine efficacy [Internet]. 2020 [cited 2020Dec13]. Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32623-4/fulltext
- Blankenship K. AstraZeneca hopes warmer storage needs for COVID-19 vaccine will be an advantage against mRNA competitors [Internet]. FiercePharma. 2020 [cited 2020Nov24]. Available from: https://www.fiercepharma.com/manufacturing/astrazeneca-hopes-warmer-storage-needs-for-covid-19-vaccine-will-be-advantage-against
- Goldhill, O. ‘We’re being left behind’: rural hospitals can’t afford ultra-cold freezers to store the leading COVID-19 vaccine [Internet]. 2020 [cited 2020Dec1]. Available from: https://www.statnews.com/2020/11/11/rural-hospitals-cant-afford-freezers-to-store-pfizer-covid19-vaccine/
- Kansteiner, F. Signed, sealed, delivered: Pfizer marks first ‘mass air shipment’ of COVID-19 shot amid cold chain scrutiny [Internet]. FiercePharma. 2020 [cited 2020Dec1]. Available from: https://www.fiercepharma.com/manufacturing/first-pfizer-doses-from-belgium-touch-down-at-o-hare-international-report
- Guidance for PREP Act Coverage for Qualified Pharmacy Technicians and State-Authorized Pharmacy Interns for Childhood Vaccines, COVID-19 Vaccines, and COVID-19 Testing. 2020 Oct 20 [cited 2020 Dec 3]. Available from: https://www.hhs.gov/sites/default/files/prep-act-guidance.pdf
- Andis Robeznieks. AMA opposes HHS move to expand Pharmacists’ scope of practice. [Internet]. AMA. 2020 Aug 25 [cited 2020 Dec 3]. Available from: https://www.ama-assn.org/practice-management/payment-delivery-models/ama-opposes-hhs-move-expand-pharmacists-scope-practice
- Trump Administration Partners with Chain and Independent Community Pharmacies to Increase Access to Future COVID-19 Vaccines. [Internet]. 2020 Nov 12 [cited 2020 Dec 3]. Available from: https://www.hhs.gov/about/news/2020/11/12/trump-administration-partners-chain-independent-community-pharmacies-increase-access-future-covid-19-vaccines.html
- COVID-19 Vaccination Program Interim Playbook. [Internet]. 2020. [cited 2020 Dec 3]. Available from: https://www.cdc.gov/vaccines/imz-managers/downloads/COVID-19-Vaccination-Program-Interim_Playbook.pdf
- Pfizer and BioNTech Celebrate Historic First Authorization in the U.S. of Vaccine to Prevent COVID-19 [Internet]. Pfizer. 2020 [cited 2020Dec14]. Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-celebrate-historic-first-authorization
- Hinton D. Emergency Use Authorization FDA; 2020. Available from: https://www.fda.gov/media/144412/download
- Fact Sheet for Healthcare Providers Administering Vaccine – EUA of the Pfizer-Biontech COVID-19 Vaccine to Prevent Coronavirus Disease 2019. [Internet]. 2020. [cited 2020Dec13]. Available from: https://www.fda.gov/media/144413/download
- FDA Briefing Document: Moderna COVID-19 Vaccine. 2020. Available from: https://www.fda.gov/media/144434/download