Contract Pharma: How have pharma/biopharma industry changes impacted CDMOs over the years?
JoyL Silva: With the growing number of options available, selecting the right CDMO partner is an even more critical decision for drug developers. The top five end-to-end CDMOs still only comprise 15 percent of the market.1 Beyond these, there are about 300 to 400 others vying for contract work.2 This makes the process of finding the right contract manufacturer and best fit for particular projects relatively complex.
The demand for contract partners able to fulfil end-to-end drug strategies makes up only a portion of pharma’s demand for contract development and manufacturing services. Even though end-to-end CDMOs are often consulted for their breadth of services (i.e., early development, clinical to commercial, finished drug product), CDMO services and capacity are in demand to support drug strategies in other, more focused ways; as a reliable commercial capacity second source supplier or to assist a customer with a specific development request.
Not all customers need or require end-to-end solutions and what shapes demand for contract services in general is as diverse as the global pharma industry is today.
That means that there is still plenty of demand for a wide range of CMO and CDMO manufacturing and development services, especially those offering particular experience and expertise.
For the foreseeable future, pharma’s innovators will continue to demand a wide range of CDMO services, while seeking expert and collaborative partners with the experience to make even the most ambitious drug strategies possible.
CP: What global market changes have had the greatest impact on the industry and CDMO services?
JS: Several important trends are shaping the CDMO landscape and influencing how pharma is engaging the industry.
For one, aseptic drug manufacturing and sterile fill-finish operations are proving to be extremely challenging for the industry. It’s a global issue and proving to be a tremendous ‘disruptor’ with sterility and quality excursions threatening critical supplies of certain therapeutics including vaccines, antibiotics and sterile liquids like saline.
The ascent of biopharmaceutical science prompted dramatic change. The increasing global consumption of biopharmaceuticals has led to a growing demand for outsourcing partners capable of making these hard-to-make large-molecule drugs in sufficient volumes to reach underserved patient groups around the world.
Innovation in drug form and drug delivery are creating complexities for the industry as well. Influenced by a variety of pharmacokinetic and pharmacodynamic characteristics of today’s formulations, contract manufacturers are being tasked to develop and manufacture even more sophisticated API/delivery/device combinations to serve bioavailability challenges, unmet patient needs while delivering better dose compliance therapeutic effect among other goals.
Similarly, biopharma’s drug innovators are also seeking highly competent partners to develop and commercialize their very small batches of novel, hard-to-make biopharmaceutical APIs and drug products. Many of today’s therapeutics require specialty partners with the skills and experience to develop and manufacture innovations successfully.
Now CDMOs are needed as technological leaders and strategic collaborators to form strong, sustainable partnerships. Our job is to help our customers understand the optimal routes for their drug strategies and uncover the best tactics to get a reliable supply of their products to patients.
CP: What are some of the major regulatory changes that have impacted the industry over the years?
JS: One major regulatory driver impacting drug strategies over the past 20 years has been the FDA’s unwavering focus on patient safety and the therapeutic effectiveness and value of medications. Recent guidance on continuous manufacturing and quality by design manufacturing concepts for example, is prompting innovation and new capital investment to assure quality and lower manufacturing costs.
In 1990, Congress amended the Federal Food, Drug and Cosmetic Act to introduce the concept of combination products and to clarify specific control strategies for these types of products. In general, a combination product is a product made up of two or more FDA-regulated components that are intended for use together.
Drug, biologic and device combination products can make treatments safer, more effective and/or more convenient for patients. Obtaining approval for a combination product, however, involves complexities beyond a typical drug or device development program. Not only are the regulations for combination products complex, but they are also not yet globally harmonized. Close attention to the evolution of combination product regulations around the world is needed if your business is supporting this type of development program.
Since about 2008, the US pipeline of drugs submitted for approval has steadily filled with novel New Drug Applications (NDAs) followed by a flood of FDA approvals. In 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) was enacted by congress which accelerated the trend. The law created the Breakthrough Therapy Designation (BTD) to identify promising new drugs earlier in clinical development with the potential to demonstrate substantial improvement over existing therapies treating serious chronic and life-threatening disease states. Over the past 10 years, the use of expedited approval pathways has significantly increased.
In a recent article written by FDA’s Janet Woodcock, M.D., (Director, Center for Drug Evaluation and Research) and Peter Marks, M.D., Ph.D., (Director, Center for Biologics Evaluation and Research)3 it was noted that a misconception that FDA’s increasing use of Expedited Approval programs over the last decade, may be driven by a loosening of their approval standards. They mention that the reality of the situation is that the FDA’s standards have not changed, but instead, the increased use of expedited approval pathways is directly related to the increasing numbers and scope of these programs provided by Congress, as well as the kinds of medicines that are being developed, and the types of diseases that are being studied. The article shares a few facts to illustrate the rapid evolution underway in drug discovery and development:
· Only 157 orphan drugs (those that treat rare diseases) were approved in the ten-year period, 1999 through 2008, whereas 436 have been approved in the 10-year period, 2009 through 2018. Orphan drugs are often candidates for expedited programs.
· The portfolio of cancer drugs, many for people lacking other options, has rapidly grown to currently comprise more than a third of novel drug approvals.
· In the last two years, FDA has approved the first four cell and gene therapy products, and now has more than 800 active investigational new drugs of this type under review — signalling the leading edge of a wave of these new therapies.
As the regulatory environment continues to evolve, it is critical to rely on a partner that can cope with the changes and innovate successfully enough to keep up. Our focus on intelligent collaboration with our customers is helping to ensure successful outcomes of their drug development strategies—something that many rely on, especially patients who have the ultimate need for these important medicines.