October 26, 2017 PAP-Q4-17-NO-001
Manufacturing and quality issues have been at the heart of many drug recalls and shortages, which have a huge negative impact on the pharma industry’s ultimate customer — the patient. While state-of-the-art technologies are often employed in pharmaceutical discovery efforts, they are not regularly implemented on the plant floor. Traditional manufacturing approaches are, however, clearly no longer sufficient to meet the challenges posed by today’s complex drug substances and formulated products. Changes occurring in the pharmaceutical industry are also driving the need for a move away from traditional manufacturing practices to new manufacturing platforms and technologies that will allow accelerated development and production. Some of these changes will be incremental innovations that modernize existing systems. Others will involve the introduction and implementation of novel technologies and operational methodologies. Most pharmaceutical companies recognize the need for innovation and are actively pursuing the implementation of advanced technologies and solutions, such as continuous process and single-use systems.
One of the biggest hindrances to adoption of emerging technologies in the pharmaceutical industry is concern over regulatory agency acceptance. Realizing the crucial need for modern manufacturing technologies and their potential to improve the robustness, flexibility and quality of pharmaceutical production processes, FDA’s Office of Pharmaceutical Quality (OPQ) within the Center for Drug Evaluation and Research (CDER) “is determined that regulatory agility is warranted to facilitate — and not hinder — company efforts to adopt novel or otherwise unfamiliar technologies.”1 OPQ established the Emerging Technology Program (ETP), which is run by the Emerging Technology Team (ETT) and published draft guidance for industry — Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base.
Companies making regulatory submissions, including investigational new drug applications (IND), original or supplemental new drug applications (NDA), abbreviated new drug applications (ANDA) or biologic license applications (BLA), or application-associated Drug Master Files (DMF) to CDER, are suitable for the ETP program if they include a proposed technology with potential to improve product safety, identity, strength, quality and purity, and that includes one or more elements subject to quality assessment for which FDA has limited review or inspection experience.
Some examples of emerging technologies considered by the ETT include continuous manufacturing, additive manufacturing, ultra-long-acting oral formulations, model-based control strategies, next-generation sequencing, predictive modeling for process monitoring, isolators for aseptic filling, and novel container and closure systems for injectables.2
There are several other technology-based trends that will transform the pharmaceutical industry, according to Bertalan Mesko, a recognized author and speaker who considers himself to be the “Medical Futurist.” Bertalan’s top-ten list of disruptive technologies includes the following:3
David Epstein, an Executive Partner at Flagship Pioneering and Chairman of the Board of Rubius Therapeutics, noted in a March 2017 interview with Martin Dewhurst, a Senior Partner in McKinsey’s London office, that cellular therapies, improved diagnostic tests based on whole-genome screening and new ways of performing remote patient monitoring in the home were beginning to impact the industry.5 He also observed that there is enormous waste in current health practices that digital solutions should address, noting: “There are some incredible innovations out there — technology that enables a different level of efficiency, joined-up thinking within patient care.”5
In light of its consideration of 3D printing as an important emerging technology, FDA issued draft guidance on the use of additive manufacturing for drug and device production in May 2016.6 In an August 2016 interview with Pharmaceutical Technology magazine, Kristofer Baumgartner, a spokesperson for CDER, indicated that existing approval pathways are “flexible enough to address new technologies, small batches, orphan/expedited review, and personalized medicines,”7 including those involving 3D printing.
Features of 3D printing — portable equipment, the ability to produce customized final dosage forms with multiple ingredients, perhaps in multi-layered tablets — make the technology ideal for personalized medicines.7 CDER/OPQ’s Office of Testing and Research’s Division of Product Quality Research has established a manufacturing science research program with the goal of enabling innovation and advancing the understanding of the risks and benefits of novel technologies, including 3D printing, according to Baumgartner.7
Several academic groups are investigating the use of additive manufacturing for the production of living cells, tissues and organs, the synthesis of small molecule APIs and the formulation of solid-dosage drugs.8 The technology is at the early stages for these applications, however, and much more work must still be done. “Printing technologies will be able to become manufacturing tools of the future if the capabilities of the printers are continuously developed. This also means that a wider range of printable materials has to be developed to broaden the possibilities to create multifunctional drug delivery systems and medical devices,” according to a blog posted by the American Association of Pharmaceutical Scientists.9
There is significant potential for nanotechnology to be applied in the pharmaceutical industry, from smart materials for tissue engineering to intelligent tools for drug delivery. Grand View Research estimates that the global nanomedicine market is growing at a compound annual growth rate of 11.2%, and will be valued at $350.8 billion by 2025.12
In many cases, nanotechnology is being investigated as a means for improving efficiency and reducing cost while providing novel functionality. In drug discovery, for instance, nanotechnology is enabling high-throughput screening via miniaturization of analytical tools. It is also enabling the design of lab-on-a-chip diagnostic tests for point-of-care use and greater resolution and accuracy in medical imaging.10
In drug delivery applications, nanosuspensions, nanoemulsions and nanomicells are used to synthesize various nanoparticle-based materials for the formulation of advanced drug products. Using these technologies can improve drug performance by increasing bioavailability and stability, prolonging activity, reducing dosing frequencies and allowing for drug targeting.12
The importance of emerging technologies for contract manufacturers and research organizations was clearly highlighted in the 2017 Nice Insight surveys of top executives in the pharma industry. Cost was initially the main driver for outsourcing. In 2016, it was the desire to improve quality. In 2017, however, the top reason for outsourcing by survey respondents to both CDMOs13 and CROs14 was access to specialized technologies. The surveys also revealed that contract service providers that can offer novel and proprietary technologies in conjunction with the ability to form long-term, strategic partnerships, acting as extensions and providing comprehensive, efficient, responsive and affordable support, are most successful at attracting and retaining desirable pharmaceutical industry customers.
Mr. Walker is the founder and managing director of That’s Nice LLC, a research-driven marketing agency with 20 years dedicated to life sciences. Nigel harnesses the strategic capabilities of Nice Insight, the research arm of That’s Nice, to help companies communicate science-based visions to grow their businesses. Mr. Walker earned a bachelor’s degree in graphic design with honors from London College of Communication, University of the Arts London, England.