Where is the pharma manufacturing industry headed in 2022 and beyond? From both a facility design and materials perspective, we’re at the cusp of some changes, whether prompted by an increased interest in mRNA and the supply chain implications of that interest, or by the realities of delays in the outsourcing of manufacture.
Fortunately, any problems arising from these changes will likely only be problematic for a few years as new technologies and processes come online. In the meantime, it’s important to take note of industry directions to ensure that your business is prepared to handle any potential impacts.
Let’s take a closer look at four trends that will generate the greatest attention in the near future.
1. Multi-modality is key for new facility design
Companies no longer build facilities dedicated to one modality, let alone one product. Future products are part of the planning process now, emphasizing flexible manufacturing suites that still adhere to regulatory guidelines.
A few years ago, pharma companies were outsourcing production to Contract Development and Manufacturing organizations (CDMOs). Today, however, there is a capacity crunch with CDMOs to manufacture viral vectors and other modalities. Companies that may have relied on a CDMO in the past now realize that they need to bring that manufacturing in-house or face a two-plus year waiting list.
With the sheer number of modalities currently in clinical trials, as well as those coming down the pipeline, it’s a guessing game as to which products will make it to full-scale commercial manufacturing. Multi-modality design provides manufacturers the necessary flexibility to get their products to clinical trials by making materials in accordance with Good Manufacturing Practices (GMP) with the capacity for commercial throughput levels.
For the foreseeable future, we can expect upfront design for smaller-scale, with the flexibility to increase production many times over if a given product is commercialized.
2. RNA therapies continue to grow in popularity
With the mass production success of COVID-19 vaccines over the past two years, expect to see more emphasis on mRNA therapies across the board — with a corresponding increased emphasis on the design, engineering and construction of mRNA facilities. An mRNA approach can allow pharma companies to realize lower costs, faster speed to market and smaller-scale production demands.
Growing cells takes time. So whether it’s a viral vector, a monoclonal antibody (mAb), or any type of process where the product is reliant on cells, manufacturing time is measured in weeks or months. However, mRNA therapies benefit from being a cell-free process, so the manufacturing timeframe is much faster — on the order of days, not weeks or months.
Although considered a biologic, mRNA is more akin to a reaction; that's how the mass production of COVID-19 vaccines happened so quickly. If the industry had focused on a more traditional biologic, we would probably still be waiting.
That speed to market advantage will drive continued interest in RNA therapies for some time to come. But that increased interest comes at a price — which brings us to our next trend.
3. Industry-wide short-term plasmid shortage
Traditionally outsourced due to cross-contamination concerns, plasmids are the raw material for both viral vector and in vitro-transcribed (IVT) mRNA manufacturing. The increased demand for these therapies is leading to an industry-wide shortage of plasmids that may continue for the next couple of years, if not longer. This could lead to slowdowns in the completion of facilities for which plasmids are necessary for production.
Plasmid manufacturing has historically been avoided because pharma companies didn’t want to bring microbial fermentation into mammalian cell culture facilities because of the potential for cross-contamination of cells. Demand began to increase with the rise of viral vector and gene therapy facilities, and has been further complicated by increased interest in mRNA manufacturing.
This increased demand has led to an industry-wide shortage of the plasmid starting material and has prompted a growing number of viral vector facilities to consider manufacturing plasmid in-house to avoid potential supply-chain issues.
Fortunately, this shortage may only last a few years, as new technologies are introduced, limiting the need for plasmids. In the case of viral vector manufacturing, for example, transient transfection is the de facto standard today, but there are other technology platforms in development that appear to be more efficient, cost-effective, and do not require plasmids, such as producer cell lines.
We may be at the start of an inflection point where demand exceeds supply, but in coming years, expect increased in-house plasmid manufacturing with the potential for new technologies and facilities to lessen the reliance on plasmids altogether.
4. Stainless steel is here to stay
For the past decade, facility design began to eclipse stainless steel systems in favor of single-use. In fact, many current startup facilities with lean budgets aren’t even addressing the infrastructure or utility systems needed to support stainless manufacturing technologies.
Single-use is still seen as the most cost-effective and fastest way to get to market. Increasingly, however, there is interest in bringing stainless steel into select operations because it makes the most sense for the specific application. In some instances, using stainless steel may be something as small as bringing in a stainless steel centrifuge instead of relying on depth filtration alone. In other cases, however, such as when dealing with solvents in mRNA and lipid nanoparticle development, single-use is not compatible with the process, so stainless steel must be used entirely.
The clear direction for facility design moving forward will be to utilize a hybrid that embraces single-use for speed, cost effectiveness, and lower risk of contamination, while still incorporating stainless steel for applications that simply cannot be done any other way.
Understanding these trends, and planning accordingly, will be essential to avoid any potential manufacturing problems in the years to come.