Category | Small molecule
When Henry Ford revolutionized manufacturing practices back in 1913 in Highland Park, MI, his main goal was simple—to make the best possible product in the most efficient and cost-effective manner. Ford’s focus on bettering the “flow” of manufacturing to enable workers/technology to work smarter and reduce waste of raw materials, changed manufacturing principles forever. These ahead-of-their-time principles have influenced many of the manufacturing practices today—including more recent, agile approaches to manufacturing for pharmaceuticals.
For many years, batch manufacturing has been a standard means of drug production. Batch manufacturing is a process where “all materials are charged before the start of processing and discharged at the end of processing.” While batch manufacturing has been the traditional approach to drug manufacturing, its systematic, step-by-step process has two major disadvantages—it wastes material and time:
“In a batch process, one manufacturing step must be completed before moving on to the next step; and similarly, one batch must be finished before starting another. Batch manufacturing is a lengthy process comprising multiple steps that require a quality check/test after each, and thus poses a serious risk of human error and product contamination. In addition, because batch processing requires multiple pieces of complicated equipment and machinery, the raw material and intermediates may need to be stored and moved from one site to another to complete the manufacturing process.”
Gautam Chauhan, M.S., and Vivek Gupta, Ph.D., St. John’s University
The traditional batch manufacturing processes results in significant revenue losses to pharmaceutical companies as it perpetuates recalls, wastes time, increases risk of contamination, and wastes valuable API. With all being said, there is an alternative to this outdated manufacturing process—continuous manufacturing. As defined by the FDA, continuous manufacturing is a process where “material is simultaneously charged and discharged from the process.” This more agile workflow can allow great assurance of quality, as well as scale up efficiencies. More simply put, continuous manufacturing:
In a market dominated by news regarding the rapid growth of biopharmaceuticals, oral solid dose (OSD) drug products still maintain a large amount of market share in the pharmaceutical industry. Unlike the ever-growing biologics market, the OSD market has been slow to adopt more modernized approaches to manufacturing. This begs the question—why has the OSD market been slow to embrace continuous manufacturing, in an industry that requires companies to be more agile?
While some OSD drugs require large-scale production, many OSD’s are manufactured in relatively small batches. This reality, combined with the common misconception that continuous manufacturing is only suited for large-volume products, is assumed to be one of the largest contributing factors of why the OSD industry has been slow to adopt continuous manufacturing. With all being said and despite this common misconception, if your company plans to scale up production of your OSD drug product—regardless of volume—continuous manufacturing may be the right move.
The Achilles heel of traditional, batch manufacturing is determining how the formulation will behave at the commercial scale—“the size of the final batch makes it impractical to fully characterize the effect of the scale-up, so a limited number of technical batches are run due to cost.” Continuous manufacturing on the other hand, runs the same small-scale process for commercial but for an extended period. This eliminates potential errors with scaling up powders—regardless of weight—and further reduces timelines and the use of valuable API.
If your company wants to pursue a continuous manufacturing strategy, it’s important to evaluate your options and whether an in-house or externalized strategy is best for your organization. Many pharma companies—particularly new and emerging ones—may have challenges with the upfront costs of human and physical capital for continuous manufacturing and the timelines for recuperation of that investment. Below are a few steps to consider if your company chooses to implement continuous manufacturing—and while these steps are simplified, they are the foundational considerations to implementing such a strategy:
Consulting with specialists and/or building your team is key to a successful continuous manufacturing strategy. A well-rounded team should include people with technical skills—from scientists to engineers, quality assurance/control specialists, and regulatory professionals. Before making the investment in continuous manufacturing, there should be no gaps in the talent necessary to run your strategy.
The team should have a full and mutual understanding of how technologies will interact with existing processes or how technologies should be built—if you’re establishing a new line. This key understanding of a continuous manufacturing strategy should be agreed upon by your team prior to any investment in capacity.
Another important consideration in developing a continuous manufacturing strategy, is determining your line’s end goal. This will not only enable your team to develop a reasonable goal but will provide a clearer picture of the various deliverables necessary to build an effective continuous manufacturing line. When determining your line’s end goal, ask your team:
Much like steps one and two, these questions and considerations must be answered and addressed well before any investment in equipment is made.
Another option for implementing a continuous manufacturing strategy for your OSD drug product is partnering with a Contract Development and Manufacturing Organization (CDMO). While many companies approach outsourcing with multiple vendors, who each specialize in the various steps of taking drug products to market—i.e., a vendor for development, a vendor for manufacturing, a vendor for distribution, and so on—it’s becoming the wisest choice to go with a single vendor. Why? Because a single vendor with a holistic, end-to-end solution can reduce timelines, rework, and cost.
With all being said, not all CDMOs are created equal—so if a CDMO approaches your company to be your single vendor for continuous manufacturing and beyond, ask them:
Lastly, when evaluating a potential CDMO, it’s important to see that they have the expertise and broad capabilities to tailor a sound and effective continuous manufacturing strategy to your unique needs. Are they able to effectively implement continuous manufacturing strategies for development and commercialization? And what about regulatory support? Do they have the expertise to manage not only manufacturing, but the required regulatory filings associated with pharmaceutical manufacturing? Do they have a good relationship with regulatory authorities to ensure manufacturing runs smoothly?
Though these questions are just the tip of the spear when it comes to what the right continuous manufacturing CDMO should look like, they will start to reveal who that CDMO is.
Thermo Fisher Scientific: Your Strategic, Continuous Manufacturing Partner – since 2017, Thermo Fisher Scientific has been a market leader in continuous manufacturing of OSD drug products for both development and commercialization.