NEWS MEDIA CLINICAL CONFERENCES CME/CE RESOURCES SUBSCRIBE BIOSIMILAR APPROVALS

Biosimilar mRNA Vaccines, Part 2: Fast-to-Market

Approach!
August 7, 2021
Sarfaraz K. Niazi, PhD

The road to production of biosimilar messenger RNA (mRNA) vaccines could be very swift compared with the experience for other
biologics. With fewer intellectual property restrictions, small manufacturers could step right in, according to Sarfaraz K. Niazi,
PhD.

In my first article on the topic, I created a new term, “biosimilar mRNA vaccine,” to suggest that
chemically synthesized messenger RNA (mRNA) vaccines can be approved as biosimilars under
the 351(k) provision by the Center for Drug Evaluation and Research (CDER) rather than as
standalone or “novel” 351(a) drugs under the Center for Biologics Evaluation and Research
(CBER).

However, there are pros and cons to both pathways to

approval. In the biosimilar pathway, a 12-year
exclusivity protection will apply if the reference vaccine x
is revised to address new mutations. This would require
biosimilar developers to file a new biologics license
application (BLA).

The analytical similarity testing can also be challenging

depending on which is considered the active
ingredient: the mRNA or the translated protein. In a
Sarfaraz K. Niazi, PhD
standalone approval, complete testing will take a
longer time and cost. However, given the recent
guideline on COVID-19–related products, the FDA is willing to consider standalone filing with the
same concessions as are allowed in the filing of biosimilar products. It remains to be seen how
the first product filing will be treated.

Today, the world needs about 8 billion doses to create herd immunity worldwide; the WHO and
other global agencies are urging that vaccines be supplied to countries that could not afford the
cost of the first wave of COVID-19 vaccines. Although there is a surplus of vaccines in the United
States, 75% of the world’s population is still waiting for shots. To meet this challenge, we will have
to develop a novel pathway to secure faster entry into the market for the COVID-19 mRNA
vaccine.

In this article, I present a path that manufacturers could follow for quick access to the market
(Figure). To make the best use of the available technology, a creative and well-organized
approach is required:

The chemical synthesis of mRNA is much simpler than manufacturing antibodies and other biological products.
Therefore, the production facility setup is a lower-cost step. Additionally, since the vaccine dose is small
(micrograms), we need to manufacture smaller quantities (eg, 30 kg to make 1 billion Pfizer vaccine doses).
Therefore, an adequate, 6000-square-foot facility can quickly be installed using modular systems within 3
months.
The only biological step in the production is the creation of DNA from a genetically modified Escherichia coli;
thus, this step is not rigorous. A 30 L bioreactor can easily produce 250 million doses per year. Comparing this
with production of an antibody such as bevacizumab, a similar number of doses would require 250,000 kg of
drug substance. If this antibody process produces 5 g/L of culture media, it would take a 100,000 L bioreactor to
produce 5 kg of vaccine, and it would take 5000 batches to produce the required quantity.
Whereas a certain minimum number of reference product samples are required for testing, there are some
ethical constraints in using a commercial vaccine in short supply for research purposes; however, enough
sample material for testing could be obtained by pooling vaccine from used vials.
With a vaccine design that duplicates the reference vaccine, a contract research organization could be employed
to manufacture an initial product sample.
The mRNA vaccine manufacturing process, as with other biological drugs, is heavily patent protected. The onus
of proving infringement lies with the claimant. Most significantly, Moderna owns several mRNA-vaccine patents
and has allowed their use without claiming infringement. So, a copy of the Moderna vaccine should not be
subject to any intellectual property (IP) infringement, notwithstanding any IP Moderna is using under a license.
By now, this would be the third month of planning, and the facility would be outfitted. After that, the
manufacturer would be scheduling the first meeting with the FDA to discuss the regulatory review plan,
including analytical, in vitro, and animal model testing for antibody production.
The sooner a manufacturer decides on the scale of production, the sooner cost estimates can be prepared. For
example, producing 1 billion doses of a COVID-19 vaccine will require about 31 kg of mRNA, and the cost will be
about $0.68 per dose in a bulk form and about $1 in finished form. About 68% of the cost is associated with the
chemicals required to make mRNA, and the rest is packaging. These costs will be lower if the vaccine is
manufactured outside the United States where the labor costs are lower. At this point, roughly 6 months would
have passed, and it would be time to file the BLA if the intention is to secure FDA approval; otherwise, the
unpackaged vaccine will be ready for export. FDA approval is not needed to export in bulk if the vaccine is not in
package form for administration.
Distributing and selling the COVID-19 vaccine requires collaboration with global health agencies, like the WHO.
Many countries will prefer to receive the vaccine in bulk to package it, to save cost. Although FDA approval is not
required for bulk export, Good Manufacturing Practice compliance is required. In my opinion, everything will go
faster if a manufacturer seeks FDA approval. There are many global concerns interested in developing mRNA
vaccines that are now providing many funding resources, making this a lucrative business opportunity.

Biosimilar mRNA vaccines, approved under 351(k) or a modified 351(a), can fulfill the present and
future needs of accessible life-saving vaccines across the globe. The original developers are not
able to offer these products at an affordable cost for many reasons, including their capital
investment and their need to show a robust profit because they are publicly traded companies.
Since the dose of the vaccine is minimal, the production costs are also low. If the cost of an
amount provided as bulk is about $0.68 and sold at $3 per dose, it can generate an income of
billions of dollars. Still, the reference vaccine producer will not enter these markets, or else they
will lose their most profitable business, supplying to richer countries at almost 10 times the price
they would get from developing country patients.

Most people in the poorest countries will need to wait

another 2 years before being vaccinated against COVID-
19. Around 11 billion doses are required to fully
Biosimilar mRNA vaccines, approved under
vaccinate 70% of the world’s population against COVID- 351(k) or a modified 351(a), can fulfill the
present and future needs of accessible life-
19. However, the most effective mRNA vaccines are not
saving vaccines across the globe.
going to be available to developing countries. Pfizer has
cautioned its investors that the rewards of producing a
vaccine for low-income and mid-income countries will be
nonexistent to very low. The position taken by Pfizer is in
stark contrast to Moderna, which has allowed the use of its pending intellectual property
(patents). However, with intervention from the US government and the World Trade Organization,
Pfizer will allow the use of the IPs if the intent is to distribute these vaccines to the developing
countries.

Therefore, I am encouraging companies to consider this remarkable opportunity to help in

ending this pandemic and saving millions of lives.

Related Content:
Development | Business & Practice | Regulatory | Clinical | Business & Practice | Policy

Opinion: A Modified 351(a) Rumors of HHS Biosimilars Advocacy Groups Call for Zero
Licensing Pathway for Coding Change Spark Concerns Co-Pay Policy on Biosimilars
Biosimilars