Category | Large molecule
With the number of CDMO’s rising in the biologics manufacturing industry, it can be challenging for new and emerging biopharmaceutical companies to determine which CDMO is right for them. Deciding on a CDMO can be a daunting task, and it is crucial to find a partner who can seamlessly manage all facets of your biologics manufacturing—from delivering your products to the market quickly, to mitigating risk and giving your molecule the attention it needs.
At the cornerstone of what it means to be an efficient and effective biologics manufacturing partner, is being a true expert at bioproduction. The right CDMO will have proven expertise demonstrating their ability to scale a large bioproduction process for a cell line that:
If a CDMO isn’t yielding higher titers, manufacturing costs will increase, and cost of goods will likely impact product availability and subsequent affordability. The right CDMO will not only deliver higher titers but will also have the flexible capacity to adapt to changing demands as the molecule moves through the different stages of its development and clinical lifecycle.
Getting life-saving medicine to market quickly is critical to the success of any biopharmaceutical company. There is no time to waste and if your current CDMO—or a prospective CDMO—cannot ensure that your medicine will get to market on-time, you should consider looking for a CDMO that will. The good news is, you have many to choose from.
There is an incredible amount of regulatory guidance pertaining to the final manufacturing cell bank. The right CDMO will have an established and mature understanding of these guidelines along with procedures to mitigate risk while delivering your medicine.
The long-awaited completion of clinical and commercial milestones shouldn’t be the beginning of drawn out discussions on royalties when the focus should be on making lifesaving medicines. The right CDMO will offer a cell line that has freedom-to-operate and terms defined ahead of time.
For a CDMO to be considered a bioproduction expert, they must have the aforementioned prerequisites. In addition to these prerequisites, a CDMO must be able to oversee the entire bioproduction process—from high throughput cell line development and media optimization, cell culture development, and process scale up, to harvest and collection, purification, bulk storage, and final fill. For a CDMO to possess the expertise to oversee the entire bioproduction process, they must leverage innovative technology to optimize cell line development, continually improve performance with best-in-class workflows, and possess a vast internal roster of global bioprocessing experts and scientists. The right CDMO will also have the bench strength and business continuity strategies to continuously produce your life-improving biologics no matter what unexpected events disrupt your supply chain.
New and emerging biopharmaceutical companies should look for a CDMO who is continuously expanding their use of innovative technology. Without the continuous expansion of their current technological resources, a CDMO will not only find it challenging to help you develop your molecule, but struggle to sustain your product in the commercial market for years to come. While a CDMO’s biologics expertise is crucial for success, so is their ability to bring a wide breadth of innovative technology. When it comes to bioproduction, the right innovative technology can significantly impact the selection of your manufacturing cell line.
This poses the question, what is an example of the “right” type of innovative technology to optimize and accelerate cell line development?
Take the Berkeley Lights’ Beacon® Optofluidic System for example. This system utilizes microfluidics with Opti Electro Positioning (OEP) technology which uses light to move cells in and out of the microfluidic chambers called nanopens—allowing a CDMO the ability to process and analyze thousands of cells with more insights, at a much faster rate, versus traditional methodologies. This is a prime example where a traditional method has been modernized through miniaturization. Logistically, the Beacon® performs single cell cloning on a chip, moving single individual cells into these nanopens holding only one nanoliter of cell culture medium. This process is also visualized and monitored over time so that scientists can estimate both growth and protein production at the nanoliter scale.
Each Beacon® system holds four microfluidic chips and each chip can hold 1,750 nanopens. This provides scientists with the ability to process and analyze 7,000 nanopens at once. Being able to evaluate 7000 individual clones at once, allows for faster cell line development timelines and the screening power needed to identify the highest producer in a heterogenous population. Compared to more traditional methods such as limiting dilution cloning, the Beacon® can shorten the single-cell cloning step of cell line development from weeks to days.
When assessing your current CDMO—or assessing a potential one—be sure to ask about their technological capabilities as it pertains to cell line development. Have they invested in cutting-edge technology such as the Berkeley Lights’ Beacon® Optofluidic System? Or are they still using more traditional and lower throughput methods? When it comes down to it, you want a CDMO that invests in innovative technology to expand capabilities, while streamlining and accelerating cell line development.
When a CDMO utilizes innovative technologies targeting media analytics, they can learn a thing or two to support media optimization and get an early start on cell culture development. Understanding the target clone’s nutritional needs can improve titers and reduce unnecessary product quality variability. CDMO’s that lean into deeper media analytics, can better:
Characterize product quality to help ensure consistency throughout cell line and process development.
Identify key drivers that impact performance to help troubleshoot media formulation and process challenges.
A true bioproduction expert will masterfully balance technology and media analytics during cell line and process development. However, just using technology and analytics may not be enough for a successful cell line—Sometimes success in these facets does not translate to overall success as protein quality can be the limiting factor. However, having a best-in-class protein characterization workflow can solve all that.
Optimal workflows are how technology enables deeper cell culture media analytics—workflows should be fluid, reliable, and effective. Without best-in-class workflows, CDMOs will not only find it challenging to produce a quality product, but also struggle to get a quality product to market in timely fashion and at a lower cost.
At the forefront of tried and true workflows that assess and analyze product quality, is the Multi Attribute Methodology (MAM) workflow. The MAM workflow uses low-artifact, peptide mapping to better quantitate modifications at the amino acid level. MAM can replace multiple product assays with a single assay, resulting in lower costs and shorter timelines—providing a richer data set than the assays it is replacing.
Ultimately, the goal of biopharmaceutical development and manufacturing is delivering the highest quality product, reducing cost, and shortening timelines. If a CDMO is still approaching bioproduction with traditional, low resolution methods, they will find it more difficult to identify and quantify critical quality attributes (CQAs) that define your product. The MAM workflow allows a CDMO to better identify, quantify, and monitor multiple CQAs simultaneously. This reduces cost and time, as well as the number of operating procedures and instruments that more traditional approaches depend on.
The savvy CDMO will also have a global roster of MAM experts—ensuring the workflow is optimized to its fullest potential. How a CDMO works can dramatically affect your bottom dollar and new and emerging biopharmaceutical companies cannot afford to waste expensive new biologic entities. Similarly—and most importantly—without the balance of performance and quality, you run the risk of impacting efficacy and supply. If a CDMO does not have the proper workflow in place to ensure production continuity and clinical success, patients run the risk of not receiving life-improving and life-saving medicines.
If you find yourself assessing a potential or current CDMO, ask them about how they work—what are their workflows? If they are not using modern workflows such as MAM, it may be time to find a CDMO partner that does.
At the soul of the right CDMO, are their people. While innovative technology and modern workflows are two critical factors to the success of bioproduction, the people at the ground-level must be able to leverage these factors creatively and expertly, to ensure molecules go from development to commercialization, successfully. Technology and workflows can help supplement shorter timelines, but at the end of the day, it’s the people that make it all possible.
When a CDMO has a vast roster of global bioprocessing experts, it allows them to make better decisions when it comes to things like clone selections and process development—which is crucial in the early stages of bioproduction. A CDMOs internal bioprocessing experts accomplish this by:
Collaborating internally across multiple teams—internal collaboration helps a CDMO identify gaps to better apply and use innovative technologies.
Driving customer value—throughout the bioproduction process, the CDMO increases their value by providing customers with relevant, valuable, and forward-looking content.
Revolutionizing data management—the right CDMO will have people who use data to make decisions, enabling them to seamlessly improve process development speed and bioprocessing outcomes.
Improving single use technology (SUT)—SUT ensures that molecules are never cross-contaminated and the right CDMO will continuously improve SUT success rates and manufacturing flexibility for their customers.
This cannot happen without the people with true bioproduction expertise and experience. When evaluating a potential or current CDMO, ask to be introduced to as many of their bioprocessing experts as possible. Talk to the people at the ground-level and ask questions about their experiences and why they consider themselves to be experts. A sales rep or customer success manager should not be your only way of contact with a CDMO. The right CDMO will encourage communication between you and their bioprocessing experts.
No matter what unprecedented event—i.e., COVID-19—may disrupt the bioproduction supply chain, the right CDMO will have reliable contingency plans and business continuity procedures to ensure that production won’t be affected. Ask your current or potential CDMO if they proactively:
Identify potential risks in the supply chain? In order to curb disruptive events, CDMO’s must diligently and continually identify risks that may happen.
Assess potential risks in the supply chain? Once a CDMO identifies risks, they should be able to categorize the severity of risks in the supply chain to determine what actions are necessary to respond.
Find ways to respond to risks? For example, if they source raw materials from a vendor and that vendor must close operations due to an internal outbreak of COVID-19, do they have a backup vendor for raw materials to support production continuity?
It cannot be stressed enough—the competition in biologics and being first to market is fierce, expensive, and has long, complicated timelines. Furthermore, it’s also important to find a CDMO who will give your molecule the care and attention it needs for it to be successful. A CDMO shouldn’t view you as just another customer—but as a collaborative partner. Once that collaborative partnership expectation is established, the right CDMO will show you their proven track record, innovative technologies, broad offering of services and solutions, and wide range of global scientific experts. Only then will you be able to successfully reach that first-to-market position.