Six BioManufacturing Trends to Watch in 2022

The COVID-19 pandemic shed a light on the strengths and shortcomings of the global biotech infrastructure in relation to pandemic readiness and general support of biotech innovation.

Governments and industry have taken notice and billions of dollars in new funding is being poured into the BioManufacturing sector at unprecedented rates:

• Fifty-six synthetic biology companies pulled in just over $3 billion of equity investment in the first half of 2020[1]
• San Biotechnolgy, a Seattle based BioManufacturing company designs cells to treat cancer, central nervous system diseases, heart disease, and genetic disorders, raised $700 Million in a Series A raise[2]

What is BioManufacturing?  At its core, BioManufacturing uses of living systems (traditionally microorganisms) and more recently, cell culture combined with advanced manufacturing approaches to produce biological molecules.  Historically this has been the focus of industrial microbiology processes (like fermentation). In the 1970’s BioManufacturing harnessed the power of molecular biology, genetically modifying microorganisms like E. coli to produce recombinant molecules and drugs (i.e. insulin and growth hormone). The first commercial recombinant insulin (Huamlin®) became available in 1982[3].

As science and technology continue to advance, next generation BioManufacturing is turning to the development of customized next-gen healthcare products, such as cell therapies, engineered tissues, pharmaceuticals, and medical devices (like 3-D printed tissues and organs-on-a-chip), as well as drug discovery and testing platforms.

Six BioManufacturing Trends to Watch in 2022: 

1. Building Good Manufacturing Practice (GMP) Facilities and Expertise:

Vaccines, therapies (drugs, cells and antibodies), and diagnostics rely on GMP facilities for the manufacture of their critical reagents. Expect to see major investments and further build out of capabilities in order to support research and development with facilities, manufacturing, engineering, and regulatory capacity to enable GMP BioManufacturing.

Expansion of GMP capabilities starts with construction of facilities, but also requires development of expertise and quality management systems (QMS) to support operations. Part of this trend will be the installation of fill/finish facilities of which there is a worldwide shortage. A rapid market entry of essential vaccines, therapies and diagnostics can only be accomplished if extensive and experienced regulatory leadership and GMP training are a component of this capacity build up.

2. Distributed Production:

There is a growing trend towards the production of raw components that make up the vaccines, therapies, and diagnostics across a distributed system instead of centralized manufacturing facilities. This approach has several key benefits. First of all, it makes for a more flexible environment in which multiple initiatives can be explored simultaneously without manufacturing constraints. Exploration of expanded initiatives leads to a higher chance of finding the innovations that work best.

Also, a more distributed approach de-risks supply chain issues experienced so frequently during this pandemic (which is exacerbated by global supply system). Pooling of smaller manufacturing batches would alleviate some of the quality control testing and ensure homogeneity in the manufactured lot. Building a multitude of smaller production centers with centralized testing abilities is critical to rapid development, quick rollout, and a de-risked supply chain for critical materials.

3. Near Patient Production (NPP) by scaling out instead of up:

BioManufacturing technologies will rapidly develop and mature over the next decade, as global powers expand their own BioManufacturing capabilities. A prudent response plan should future-proof efforts by considering a shift from centralized production to near-patient customized production.

This approach is supported by a more recent trend to “scale out” instead of “scaling up”. In manufacturing terms “scaling up” poses extreme challenges for biological systems (cells, viruses, microbes, yeast, etc.), that are pivotal in the production processes. Consequently, it takes a significant amount of time to arrive at a process that yields the required amount of material. Instead, “scaling out” makes use of many simultaneous, single-use, consumables that are readily available. Once a vaccine, therapy, or diagnostic is found to be effective, there would be no major delays caused by “scaling out” and multiple centers would have the ability to produce the components.

More specifically, many of the critical raw components that make up the vaccines, therapies, and diagnostics we know today, rely on cell-based production systems. For example, all the approved antibodies required for COVID-19 therapies and diagnostics are generated using cells. Additionally, all the vaccines that are currently approved make use of cell lines in their production processes. Developing smart, home-grown, single-use, cell-based production systems for cells that are adherent or grow in suspension would not only enable rapid rollout of COVID-19 solutions, but also facilitate groundbreaking cancer treatments e.g. Chimeric antigen receptor-T (CAR-T cells) and other personalized medicine.

4. The Holistic Approach:

Personalized medicines are changing the way many diseases are identified, classified, and treated. Improved BioManufacturing technologies (such as 3D bioprinting and stem cell therapy technologies) will have an important role in personalized medicine. Personalized biopharmaceutical products are (as the name implies) tailored to each patient with highly specific manufacturing requirements. Advanced BioManufacturing technologies will be required to produce these products and the parallel development of effective drug delivery systems and drug device combination products will be required to support this type of approach.

Investment in BioManfacturing processes and systems will lead to technology improvements that will ultimate lead to reduced production costs, and increase the availability of BioManufacturing capabilities. Ultimately it is hoped that this will lead to democratizing and increasing the access to this next-gen medical breakthrough, making personalized medicine available to all.

5. Advancements in Bio Reactor Technology:

Bioreactors are a critical component in the BioManufacturing process. Improvement, innovations, and research and development spending in the bioreactor engineering field are projected to explode in the coming years. Additional demands brought on by the increasing complexity of the biology (i.e. tissue and whole organ engineering) and use cases (i.e. point of care treatment) are going to drive demand. In 2018 the U.S. bioreactor market was valued at over $230 million. It is projected to achieve 17%+ CAGR to exceed $2.2 billion by 2025[4].

Expected areas of advancement of bioreactor design will likely include:

• Addressing the technological challenge of mass transport (conditions under which cells are able to grow and metabolize)
• Designing bioreactors for large-scale production process (product handling, sterility control, minimal footprint, and maximal automation)
• Incorporation of disposable, sterile bag systems or other elements to improve sterility and de-risk batch contamination
• Improved design to ease the assembly and use in a clean room environment
• Automation improvements in tissue engineering systems are an important feature. Apart from reducing labor costs, automation greatly reduces the number of errors that have to be investigated, requiring time, effort, and cost.
• Continued incorporation of specialized scaffolds, or solid support, for differentiated cell proliferation
• Allow for the in situ addition of cryopreservation strategies to facilitate direct to clinic transfer and application of the Biopharmaceutical
• Improved human factors and industrial design (skill sets from GMP production tend to not translate easily to clinical applications), leading to more user-friendly bioreactors to come online in the near future

As the lines between BioManufactured treatment therapies and medical devices become blurred with the increasing trends towards deployment near patient, future bio reactor design considerations should consider design under ISO 13485 to streamline downstream regulatory approval and medical device applications.

6. Implications for Medical Devices:

Medical devices have played a pivotal role in this pandemic. Ventilators help to keep patients alive in Intensive Care Units, and diagnostic platforms and Personal Protective Equipment (PPE) have proven critical in controlling the spread of COVID-19. A global response to a future pandemic will inevitably require new innovative medical device solutions. Medical devices do not only play a role in controlling a pandemic, but can also play a role in monitoring and preventing a pandemic from occurring. Regular testing and monitoring of patients with potentially novel diseases will sound the alarm bells earlier, giving governments more time to respond.

There has been increased focus on performing diagnostic testing outside the traditional confinement of the laboratory, and these innovative solutions greatly reduce the time it takes to receive test results. The development of at-home monitoring of diseases with data logging in a central database will provide an incredible resource for public health, and this initiative has just started.

Medical devices play a critical role in the clinical studies that support the release of treatments and the administration of therapies. Beyond the challenges of COVID-19, many novel BioManufactured therapies rely explicitly on product delivery in specific tissues (spine, CNS etc.). With combination products, such as tissue engineering approaches that include cells, biodegradable scaffolds, advanced materials, and nanomaterials, the administration approach of novel treatments will become more complex and will inevitably require medical devices for effective delivery.

Since the first recorded recipe for beer making in Mesopotamia ~6,000 years ago[5], BioManufacturing has been an important aspect of humanity’s development and success. The future of BioManufacturing will continue to be a corner stone of our civilization and is key in the development and release of new products, treatments, and technologies that will aid pandemic readiness, but also revolutionize cancer treatments, gene therapy, personalized medicine, etc. in generations to come.