Because of the nature of the business, every drug manufacturer faces the risk of unexpected events that can cause harm to consumers and cost the company money, resources and its reputation. Yet, in chemistry, there’s a lot of uncertainty – in how a molecule will react, how an API will perform when scaled up, including its overall impurity profile, how smoothly it passes clinical trials and when a drug product will be cleared for FDA approval.
And these types of risks, attributed to the unknown nature of molecular structure, are compounded by increasing R&D costs, looming patent expiration dates, growing competition and increasing regulatory requirements. In fact, it takes an average of 12 years for an experimental drug to become commercialized in the U.S.; and only one in 5,000 drugs make it that far.
Today, we’re also seeing that current events, such as supply chain disruption, reduced production of raw materials, transportation issues caused by closed borders and prioritized COVID-19 projects, are adding to the risk factors of most API manufacturers.
Learning How to Control Risk Where You Can
Yet it’s not always things beyond our control that create risk in API manufacturing. Human error and bad management oversight can be contributing factors. Improper corporate risk management has the potential to cause lengthy and costly delays or cause a product to fail FDA approval, or in some cases, impact the financial health of the sponsoring organization or their Contract Development & Manufacturing Organization (CDMO). To minimize these concerns, below are three best practices to consider.
- Each project should begin with a sound regulatory strategy. API manufacturers should work together with internal teams, consultants and sponsors to develop a regulatory strategy. This requires optimized process chemistry, accurate and reliable analytical methods and scientifically sound and justifiable specifications that will guide the full process-from development to manufacturing. Without a clear understanding of the goals and processes that will guide them, projects can easily go off the rails.
- Think wisely before cutting corners. Everything should be done to ensure that you can reach the finish line without changing the budget, but focusing on cutting corners almost always leads to trouble – causing the exact opposite effect, such as delays that cost more money in the long run. Many sponsors may look to save costs by using offshore manufacturers, or an inadequate facility as a way to cut corners. But often, projects need to be reshored and tech transfer alone is a major cause of risk, duplicated work, cost overruns and failed projects.
- Invest more heavily in later stages. When a project has gone through the learning stages and there are clear clinical results and solid funding, there’s a greater chance you are on the right path to commercialization. Yet, this stage of the process also means greater scrutiny by the FDA and better odds of losing a huge investment if any problems occur, so it’s important to spend more in this stage. Having said that, however, areas where you never should cut corners are in method development, full method validation and Regulatory Affairs/Quality Assurance (RA/ QA). Many projects fail in these areas because they’re not given the time or money they deserve.
Thwarting Risk in R&D
While it’s important to invest generously in the manufacturing stages to reduce risk, the R&D stages also pose many opportunities to thwart problems before they occur. Consider the following three ways
- Be strategic about sourcing. Quality raw materials can make or break your project, so it’s important to have good relationships with reputable suppliers, as well as multiple sourcing options, which we’ve seen is important during COVID-19 and supply chain disruptions. Also it is very important that the supplier can provide adequate information about the synthetic route of the raw materials and its potential impurities.
- Don’t downplay documentation. All details necessary to replicate a set of experiments should be rigorously documented, including outcomes, protocols, analysis and raw data. This data, also should include QA documents, standard operating procedures (SOP) strategy, batch records, test methods, specifications and logbooks.
- Quality management is key. Invest in the most experienced QA and Quality Control (QC) teams, who not only ensure proper quality management across processes and testing, but also handle documentation. The QA group should be the final authority, ensuring the quality of raw materials and batch quality, writing and compiling all batch records, and signing off on all certificates of analysis.
Today more than ever, API manufacturing is filled with uncertainty and rising costs, and much of it is beyond our control. Yet with strategic oversight and a commitment to quality, there are many things that can be done to proactively address risk. It requires collaboration, communication and forward-thinking that can help you anticipate the areas where things could go wrong and put measures in place to prevent them. By bracing for uncertainty, better outcomes almost always follow.
About the Author
Mehdi Yazdi, Director of Analytical Services at Seqens CDMO NA, holds a Ph.D. in Analytical Chemistry in the areas of chromatography and spectroscopy. Dr. Yazdi has over thirty years of experience in pharmaceutical industries including bulk pharmaceutical manufacturer, a CDMO Manufacturing Organization, Specialty Pharmaceutical Companies, API manufacturer, and finished dose pharmaceutical manufacturer. He began his career at Ciba-Geigy a large specialty/pharmaceutical company.
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