Selecting a Contract Development and Manufacturing Organization (CDMO) partner impacts not only your current drug development but also other drugs you have in the pipeline.
Since more and more candidate compounds are poorly water-soluble, the need for specialized technology to address complex molecules isn’t nice to have, it’s a necessity. But with increasingly specialized science and technology, keeping drug development and manufacturing in-house isn’t viable—and neither is choosing the wrong CDMO company.
Many compounds require specialized handling, especially those that include highly potent active pharmaceutical ingredients (HPAPI) which require highly specialized assets and expertise. Choosing a specialized CDMO with a proven track record (and clients who will back them up) is the cornerstone to your drug product’s success.
The leadership of CDMO companies is also critical in order to focus on understanding the drug sponsor’s product profile and commercial objectives in early drug development stages to provide a clear view of the ultimate goal rather than a focus on delivering a drug product according to specifications. This leads to a higher-end product, as well as a look ahead at the potential complexities involved with your drug substances that could cause issues and threaten timelines. Selecting the wrong CDMO could lead to missed milestones, production delays, lost funding, and even halt your drug development completely.
8 Warning Signs of CDMO Companies
We’ve all experienced it before…the nagging feeling in the back of our minds that something doesn’t seem quite right. Maybe it’s a promise that sounds too good to be true, a tight deadline that you haven’t heard a word on lately, a lack of experience or completed projects to assure you that they have the expertise, limited future planning for production scale-up, a proposal that sounds nice but doesn’t seem to have a good grasp of your priorities or operational procedures that seem light.
Choosing the right CDMO company can help you battle a steadfast concern in developing pharmaceuticals: unpredictability. A specialty CDMO company can focus on purity, potency, safety, and stability from Discovery all the way to commercialization, all while tapping into cutting-edge technology and carefully collected data analytics while using streamlined processes.
As you evaluate CDMOs to partner with, watch out for these common pitfalls:
1. You (or your CDMO) need to bring in a large number of partners. The more players in the pharmaceutical development field, the higher the risk of inefficiencies, communication issues, and delays in decision-making. This can lead to timeline delays, additional costs, and redundant work. If a CDMO doesn’t have the specialized equipment and expertise often needed for orphan and rare drugs, identifying and moving to a new partner can extend timelines. Using an end-to-end CDMO can mean the difference between making it to market quickly and efficiently or not making it at all.
2. You’re spinning your wheels trying to move from formulation development to drug product. When you use the same CDMO companies for formulation development and drug product work, the work can overlap, which reduces testing requirements from transfers and eliminates delays from releasing materials for drug product manufacturing.
3. Your CDMO doesn’t collect enough information. An experienced CDMO will know what chemistry, manufacturing and controls (CMC) information to collect, as well as how much information is needed for a successful biologics license application (BLA) or new drug application (NDA).
4. Inaccurate supply forecasts. Producing and storing biologics comes with an expensive price tag which is why accurate forecasting is needed. Estimating the right amount of supply can mean the difference between wasted resources and a months-long empty pipeline while you wait for more materials.
5. A lack of urgency to adhere to timelines. Each stage of the development and commercialization process is critical. Timing of clinical studies, regulatory filing dates, and commercial launch dates can have a domino effect. Development timelines must also be met to help secure funds from investors. In addition, having a flexible CDMO that can adjust their schedule to meet customer needs is important to reduce risks in processing and bioprocessing.
6. Unwillingness to use anything but their own proprietary technologies. Flexibility is necessary especially when it comes to cell lines, manufacturing technology, and formulations to avoid increased costs from royalties and licensing fees, process changes, and impact on product quality. A customized approach that is based on each molecule and project rather than a proprietary process or technology means a more efficient, and potentially faster, path to market.
7. The CDMO company doesn’t offer analytics services in-house. With the need to rely on one or more third-party vendors for analytics services, drug sponsors risk adding months to their timelines with the potential for shipping errors or testing site delays.
8. Responsiveness and transparency are lacking. CDMO companies offering frequent check-ins, and those who welcome drug sponsors on-site, provide the communication and transparency needed to keep the project moving forward, as well as to quickly address any issues that may arise and threaten timelines.
CDMO Warning Letters, Errors, and Other Issues
While careful consideration of your CDMO selection is critical to the success of your drug development process, mistakes and errors happen.
Your CDMO could receive a warning letter from the FDA, which can be issued when a CDMO has violations or FDA-documented concerns from a previous visit (routine or surprise) that have not yet been addressed. The warning letters are typically issued seven months after the inspection when the issues in question are identified. The impact of the warning letter on the drug sponsor is a potential CDMO shutdown if violations are not taken care of, which could significantly derail your timeline, or worse, cause your drug component to be completely abandoned due to lack of additional funding and time.
Take time to do your due diligence and ask the right questions:
• Do the issues identified by the FDA directly impact your product? Will you need to recall it to ensure patient safety?
• Do you have a backup CDMO? Is your process so unique that other CDMO companies could take it on, should you need to transfer?
• Ask to be included in updates on how they plan to address their infractions.
In addition to warning letters from the FDA, simple human errors—such as using the wrong adenoviral vector in preparing a vaccine—can cause delays or bottlenecks in manufacturing when batches or processes need to be restarted for quality control.
What to Look for in a CDMO
When evaluating and hiring a CDMO, look at their depth of experience, leadership, and approach to drug development and manufacturing. Make sure your CDMO uses advanced technology, has the technical expertise your drug needs, as well as access to an end-to-end suite of services and resources.
Key considerations for forging a successful relationship with a CDMO company:
1. Your potential CDMO partner presents a timeline that meets your needs and is achievable. While shorter-than-expected timelines sound nice in theory, in reality, they can be nearly impossible to deliver on, especially if your CDMO hasn’t baked adequate time in for potential issues, as well as testing. Ask about their availability and their approach to handling issues as they arise to ensure they can handle potential changes.
2. An experienced team of experts with strong early-phase development experience. The experience of their scientists and engineers will mean they have well-established processes in place to identify potential problems, the ability to solve complex molecular challenges, and make sure it doesn’t impact production. An experienced CDMO can also help you manage the complexity of regulatory reviews and clinical trials.
3. Their approach to technology is forward-thinking and flexible. It’s important to find a CDMO that balances expertise in their own proprietary technologies (which could be limiting and add more time to your drug development) and cutting-edge technology that could streamline development and enhance manufacturing. Look for a CDMO that develops a strategy to align with development and production processes and considers both fit-for-purpose and fit-for-future.
4. They have solid supply chain relationships and experience, as well as the capacity to scale up. A CDMO with multiple manufacturing facilities is more likely to have the capacity to scale up production. And with supply chain connections paired with multiple facilities, the CDMO has access to and can store a large amount of commonly used raw materials, making them readily available if and when needed for your project.
5. One that seeks out ways to improve. A CDMO that is serious about operational excellence has dedicated team members in charge of managing its continuous improvement program. They also likely use templated documentation paired with real-time data management to make adjustments as soon as they are needed.
6. Their track record speaks for itself. Do they have many warning letters? What type of projects and clients have they worked with in the past? A solid track record showcases their abilities and success in developing drugs.
How a Specialty CDMO Company Can Save the Day
A specialty one-stop shop CDMO that offers tailored formulation solutions will ensure a rapid, successful transition of compounds from preclinical to clinic. In addition, a tailored formulation strategy can more successfully address small-molecule solubility and bioavailability challenges.
The key is an approach to formulating a specific molecule and not taking a one-size-fits-all approach. A formulation partner that understands the rational design of dosage forms based on compound properties, possesses different technologies to address varied compound challenges, and offers flexibility in terms of time and deliverables, will be an ideal partner.
Ascendia Pharmaceutics offers tailored formulation approaches, leveraging its suite of technology platforms: NanoSol®, EmulSol®, and AmorSol®. The technologies are used to formulate biological therapeutic entities that could help address delivery issues associated with solubility, stability, and permeability. Ascendia often uses its technologies to solve more than 90% of difficult-to-formulate compounds by enhancing the bioavailability and solubility of compounds for different methods of administration.
Formulation Development Tailored to Your Needs
With the unpredictability that comes with developing pharmaceuticals, selecting a CDMO with the ability to provide a multi-faceted approach is critical. This is particularly important early on because the formulation that will work best with the molecules is unknown. CDMO companies with experience in a variety of formulation technologies can better optimize drug development. Ascendia Pharma has a broad array of technologies, which allows our team to try multiple approaches in parallel, thereby saving valuable time. It also allows us to optimize solid dispersion approaches to advance a drug more efficiently to the next stage.
Make sure your CDMO company has a state-of-the-art facility with the equipment necessary to offer drug development options. Additionally, the CDMO must operate under current good manufacturing practice (cGMP), which is necessary for compliance with regulatory guidelines. CDMO companies need rigorous procedures in place and must ensure these principles are always followed to meet this standard. Ascendia Pharma has Class 10,000 (ISO 7) and Class 100 (ISO 5) cleanrooms for conducting cGMP manufacture of sterile injectable products, and Class 10,000 (ISO 7) manufacturing suites for the production of oral dosage forms.
The leadership team of CDMO companies is also a key component of your selection process as its team will have the knowledge and experience to provide proof-of-concept efficiently during the first-in-human stage to help keep costs in check. In addition, selecting a CDMO with a track record in your specialty will help prevent costly mistakes, missed deadlines, and other issues. Ascendia Pharma has a track record of providing low-cost alternatives in small-scale early development for injectables.
Ascendia specializes in the invention and development of specialty pharmaceutical products and novel formulation technologies (including nano-formulations), providing pharmaceutical companies with rapid, comprehensive, and cost-effective solutions to improve drug bioavailability and solubility. We’re ready to hit the ground running – contact us today!