Mabs, mRNA, and ATMPs, biopharmaceutical technology is advancing - fast. Modular building technologies are hard at work providing biotech the space it needs to grow - fast! Written by Grant Merrill

Biopharma’s growth over the last four decades has been nothing short of phenomenal. From monoclonal antibodies (MAbs) that treat arthritis to messenger RNA (mRNA) vaccines to fight the COVID-19 pandemic, biopharma’s place in healthcare has never been more prominent. Recent approvals of autologous and allogeneic therapies known collectively as Advanced Therapeutic Medicinal Products (ATMPs) further epitomise the exceptional advancements in the space.

Demand for these therapeutics will continue to rise

Because of the general effectiveness of biologics, demand for these therapeutics will continue to rise and with it, the call for a dramatic increase in manufacturing capacity to serve growing patient populations around the world. Biopharma’s response to this dramatic demand is generating an astonishing amount of capital investment in the sector and a corresponding call for millions of new square feet of cleanroom manufacturing space.

According to Precedence Research, the global biopharmaceutical market is projected to reach $ 856.1 billion by 2030 and expand at a compound annual growth rate (CAGR) of 12.5% from 2021 to 2030. Grand View Research finds the global market for ATMP’s is likely to expand at a similar rate. These analysts project a CAGR of 13.2%, and expect the market to reach $21.2 billion for this subsegment of biopharma by 2028.

Biopharma is rapidly expanding, and now accounts for approximately 20% of the global pharmaceutical industry. Among other factors, increasing awareness about the effectiveness and availability of biologic therapeutics by healthcare providers is exponentially increasing the demand for the biopharmaceuticals themselves and the cleanroom space to manufacture them around the world.

BioPlan Associates’ Technical Research Director Ronald A. Rader notes the biopharmaceutical industry’s bioprocessing sector is robust and will continue to expand in revenue, breadth, importance and diversity. With worldwide sales approaching $300 million per year and increasing at ~12% annually, Rader explains that growth in bioprocessing supplies and services will also likely keep pace noting that new capital investments in bioprocessing equipment is growing at 8.7% on average.

Respondents to BioPlan Associates annual survey “18th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production,” indicated an expected rise in cell and gene therapy facilities and products. Survey responses revealed an increase in the number of current good manufacturing practice (cGMP) facilities planned. This includes a number of modular-constructed facilities and cleanrooms—a necessity for the aseptic and contained processes required to manufacture most biologic drugs.

Greenfield manufacturing facilities are an enormously expensive proposition

Biopharma’s expanding need for capacity post-COVID is already prompting dramatic capital investment in new biologics manufacturing facilities.

Siting and constructing greenfield biologics manufacturing facilities is an enormously expensive proposition. Even modest facilities can cost hundreds of millions of dollars to design, then engineer and construct on-site. In contrast, because the patient is at the centre of the therapy, many ATMP drug development strategies require dispersed capacity and a “brownfield” approach that sites cleanroom facilities within existing buildings close to the population centres that they serve.

Building out of capital assets to manufacture biologic drug substances requires a serious financial commitment, but it’s not a blank check. Much of modern drug development and commercialisation success depends on creating the infrastructure necessary to make these drugs safely and affordably. This is especially true for regions of the world where drug manufacturing is being introduced – there is no capacity so therefore it needs to be created, often without an experienced domestic or modern construction industry behind it. Regardless, all biopharma is tasked with making drugs more cost-efficient to develop and manufacture, and that includes the expenses associated with facility design and construction.

Drug developers and their contract partners are under extreme pressure to control costs associated with the design and engineering of plant facilities. One tactic increasingly being employed by the industry’s project teams is to leverage modular concepts and technologies across the production environment.

Modular technologies deliver a cascade of cost-efficiencies to plant construction. This is especially true relative to cleanrooms and reflected in the uptick in demand for modular cleanroom technologies in support of the coming build-out strategies of the burgeoning biologics sector.

Over the past two decades, the concept of modularity in cleanroom project execution has matured. Most notably to meet the evolving, growing demand for more manufacturing space to produce emerging biologic drug products like ATMP therapies.

Traditionally, cleanrooms were built on-site using stick-built drywall construction methods. This has evolved, given the inherent quality of a pre-engineered product coupled with the flexibility of modular solutions. Modular solutions enable the amendment or expansion of facilities under clean conditions. This gives assurance to biotech firms, for example, that their facility can adapt to future needs in real time without negatively impacting ongoing operations. The end is result is a reduced burden on validation and compliance through the use of technology that is proven and repeatable.

The demand for affordable, more effective drugs as well as the need to reduce the overall costs of drug development and manufacturing have all served to turn traditional pharma facility operating models in new and challenging directions. Emerging drug development business models are also influencing the industry to improve the commercial implementation of complex cleanroom spaces and help make construction as cost-efficient as possible. These drivers have led to increasing development of modular, prefabricated cleanroom solutions that ease the complexities, time and cost of erecting them.

Although cleanroom modules encompassing an entire three-dimensional space have been implemented, the ideal modularity solution in this instance refers to a component-based wraparound facility. These leverage pre-engineered modular architectural technology along with high-performance environmental systems, all of which are fabricated in a controlled factory environment to deliver predictable results to the project.

The wraparound cleanroom solutions available today are engineered to accommodate virtually any process layout both horizontally and vertically. This approach is more flexible and cost-effective and offers higher quality with quicker validation timelines than traditional stick-built facilities.

Modularity helps streamline installation schedules and lends an element of precision that traditional methods can’t accommodate. The industry’s modular cleanroom integrators understand that critical coordination, from process systems to infrastructure tie-ins, is required to ensure there are no gaps in responsibility that can disrupt project timelines. High-quality modular solutions can mitigate the many “unpredictabilities” of project execution. Experience has shown that modular technology can help shave months off construction timetables because it streamlines installation and minimises coordination.

Commissioning is the systematic and documented approach to verifying that a cleanroom performs as intended, in accordance with the product’s process and manufacturing needs.

Whether a build-out strategy calls for piloting a facility then expanding it or siting the same facility multiple times, the integrated design, fabrication and commissioning that is inherent to modular cleanrooms sets the stage for a consistently repeatable launch.

Considering accelerating vaccine and mRNA development timelines prompted by the pandemic, not to mention the fast-track designations many of these novel therapies receive, timelines continue to shrink. Expedited approval classifications for example can accelerate Chemistry Manufacturing Control (CMC) programmes by over two years based on mean timeframes (from 7.4, down to 5.2). The pathway to operational readiness should be as short as possible because time is of the essence and a biologic-based drug strategy can ill-afford to waste any on a fast-track to treating patients.

Modular cleanroom solutions support key development and commercialisation goals, timelines and regulatory agency approval milestones. Over the past 15 years, modular cleanroom facilities have become a key enabler in the safe and effective manufacture of drugs, and with each breakthrough, proving how simply effective the solution is in helping biopharma build out capacity in a financially sustainable way. As a pioneer of turnkey cleanroom solutions, AES understands that modular approaches to cleanroom deployment can deliver significant capital expense control as well as the ongoing operational benefits biopharma needs to meet its most aggressive market objectives faster.