mRNA and viral vector vaccines and therapeutics are becoming significant players in a biopharmaceutical industry that has seen a major shift in the production of these products, clearing the way for faster manufacturing and highly effective solutions to fight viruses.

With the biopharma industry looking for innovative ways to get the COVID-19 vaccine and therapies to people worldwide quickly, mRNA and viral vectors are getting the spotlight they deserve. But with any new life-changing product comes a new set of challenges and processes.

Challenges of Viral Vector and mRNA Vaccine Manufacturing

Several challenges remain in implementing effective process validation strategies for viral vector and mRNA products.
Our experts broke down common challenges they see with viral vector and mRNA manufacturing, from maintaining proper storage to meeting a high demand from the public and government entities.

  1. Logistical Barriers
    Compared to traditional biologics, mRNA and viral vector vaccines require special logistical considerations, both during development and delivery. These products rely on raw materials with shorter shelf lives, greater temperature sensitivities, and increased complexity (safety, purity, potency) and cost.
    You must verify raw and other starting materials with your vendors before you begin manufacturing. Comprehensive verification allows you to avoid issues that could potentially disrupt your manufacturing later on.
  2. Supply Chain Issues
    With supplies and raw materials funneled to larger pharmaceutical companies to meet vaccine demand, the COVID-19 pandemic is very much still affecting the supply chain for smaller companies. These disruptions can put your production timelines at risk.
    Communicate often with your suppliers, set up contingency plans, and perform risk assessments to avoid common pitfalls.

    Related: Single-Use Systems Supply Chain Issues and the Impact of COVID-19

  3. Scalability
    Scaling up can be challenging to achieve, particularly if a product’s approval timeline is accelerated.
    Don’t underestimate the importance of determining your current scale and future scale. Investing in process development and optimization must be appropriately timed, especially if it has been granted an accelerated approval process by regulators. Always anticipate the possibility of scaling up.

Key Considerations for Manufacturing Validation

While accelerated development is exciting, compressed schedules and processes result in a greater risk for error.

As you can expect, the FDA recommends starting communications with CBER’s Office of Compliance and Biologics Quality to discuss facility preparation and inspection timing as early as possible to ensure proper validation processes are in place.

Related: Read How ICQ Prepared a CDMO for COVID-19 Vaccine Production 

The FDA does not outline specific requirements for viral vectors and mRNA vaccines outside of their standard requirements for traditional drug development.

However, early in 2020, with no FDA-approved COVID-19 vaccine yet available, the FDA released general considerations manufacturers should bake into their manufacturing process, given that many COVID-19 vaccines are viral vectors or mRNA.

We expect regulatory requirements to get more standardized as viral vector and mRNA therapeutics become more widespread and reach larger patient populations.

The COVID-19 vaccine validation process will serve as a pivotal case in how we standardized validation around these types of vaccines moving forward, considering that all current COVID-19 vaccines administered are authorized for emergency use only.

The following are several critical considerations outlined by the FDA when manufacturing viral vector and mRNA vaccines. Get the full report here.

  1. In-process control tests: The manufacturing process must be adequately validated following section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 351(a)(2)(B))and, as applicable, 21 CFR 211.100(a) and 211.110.
  2. Consistent data: Data to support the manufacturing process’s consistency should be provided, including process validation protocols and study reports, data from engineering lots, and drug substance process performance qualification.
  3. Manufacturing process: To meet process validation requirements, it should be demonstrated that commercial-scale batches can be manufactured routinely, meeting predetermined in-process controls, critical process parameters, and lot release specifications. There should include data of at least three commercial-scale batches to support the validation of the manufacturing process.
  4. Quality control: A quality control system should be in place for all manufacturing stages, including a well-defined testing program to ensure product quality throughout the formulation and filling process. This system should also include a well-defined testing program to ensure drug substance quality profile and drug product quality for release.

How Do We Ensure Quality on These Types of Products?

Process validation ensures robust, reliable, and repeatable methods. Many challenges remain in implementing effective processes as these products are highly complex and there are many unknowns.
As more viral vector and mRNA therapies receive approval for manufacturing, the commercial demand for these groundbreaking medical treatments will increase rapidly.

Is your facility ready to manufacture viral vectors and mRNAs?