In last’s year’s manufacturing outlook we delved into biopharma’s manufacturing capacity crunch. While lack of manufacturing capacity remains a challenge for the industry, the future of biopharma manufacturing has never looked so bright, and there is a variety of reasons why. For starters, when it comes to innovation in manufacturing, biopharma companies continue to push the envelope. Want proof? Take a quick review of the ISPE Facility of the Year Awards (FOYA), an annual program recognizing state-of-the-art projects by biopharma manufacturers. There you’ll see some old standbys (e.g., Abbott, Bristol-Myers Squibb, and Lilly) being recognized for operational excellence (OPEX), facility integration, and process innovation, but you’ll also encounter some lesser-known names. For example, Kalbio Global Medika’s young team (average age of 24) received an honorable mention for its 40,000-square-foot biotechnology manufacturing build in Jakarta, Indonesia. Nephron Pharmaceuticals Corp., another honorable mention, is a woman-owned business that also happens to be the world’s largest blow-fill-seal manufacturer.
Another reason for optimism is the volume of incredible technological innovations beginning to make their way into biopharma manufacturing operations. Beyond those technologies, though, is the talent that will ensure proper implementation. With that in mind, for this year’s manufacturing outlook we assembled the biggest and most diverse group of biopharma manufacturing thought leaders ever. You’ll hear from Big Pharma, virtual biopharma, and U.S. regulatory leadership, as well as international perspectives, for what to expect in biopharma manufacturing for 2018 — and beyond. So let’s begin.
WHAT INNOVATIVE SOLUTIONS TO THE CURRENT BIOPHARMA INDUSTRY MANUFACTURING CAPACITY CRUNCH NEED TO BE IMPLEMENTED TO MEDIATE THE PROBLEM?
Paul McKenzie, Ph.D.
EVP Pharmaceutical Operations & Technology
As the pipelines of innovators continue to diversify across modalities, every company will face the challenge of building needed capabilities for all modalities, while maintaining existing capacities and capabilities consumed by the current portfolio. In addition to this diversification, the productivity of more mature modality platforms is increasing significantly, driving current facilities to be underutilized or in need of redesign. This inflection point will create the need for different partnership models amongst innovator companies, as well as between innovator companies, CMOs, and laboratory organizations. Since owning everything will be a significant financial burden, the onus will be on each company to clearly delineate what it can manage and access through these partnerships.
WHAT DISRUPTIVE TECHNOLOGIES WILL TRANSFORM BIOPHARMA MANUFACTURING IN THE NEXT THREE TO FIVE YEARS?
Wolfram Carius, Ph.D.
Head of Pharmaceuticals Product Supply
Gene and cell therapy seem to be at the edge of having a transformative impact on different therapeutic areas such as oncology, immunology, or hematology. This will intensify beyond the five-year horizon as advanced technologies like CRISPR-Cas9 or viral vectors will accelerate innovation tailored to patients. This too, will significantly transform the value chain and operating model in the market within the biopharma industry. Drug-device combinations, be they for diagnostics, IT support (e.g. monitoring compliance), or drug application, also will increase, making an end-to-end setup of our organizations ever more important. At the same time, both improvements and step changes through advanced analytics and artificial intelligence (AI) also will reach the pharmaceutical sector, not just in clinical development but probably also initially in supply chain and quality and then in technical development and manufacturing. Big Data managed along the entire supply chain will provide real-time transparency, and many supply chain process steps could be performed by self-learning computer systems. Robotics and evolution toward real-time controls through advanced analytics will further improve cGMP compliance and product quality by speeding up process robustness and quality control, thus also accelerating technical development and manufacturing, which will be on a steady, critical path for new product launches.
WHAT BIOPHARMA MANUFACTURING TRENDS DO YOU FIND MOST EXCITING?
Manufacturing & Supply
GSK When we couple modular design with continuous manufacturing, then we can truly create a flexible pharmaceutical manufacturing space that is genuinely transformative. The footprint and equipment scale of these modular-design continuous plants will be completely different from what we know today and will enable significant reduction in operating costs while virtually eliminating plant changeover time loss and freeing up capacity. Our networks will become far more flexible, and construction costs will decrease. Within the next 10 years, we could even see portable manufacturing facilities.
The opportunities for continuous processing in API manufacturing are particularly interesting and should provide far more robust and reproducible manufacturing platforms with significant scope for automation. Coupled with online analysis, which can shorten batch release times and improve data integrity, continuous processing will significantly reduce processing time.
WHAT MANUFACTURING TRENDS FROM OTHER INDUSTRIES WILL BEGIN TO SPILL OVER INTO BIOPHARMA IN 2018 AND BEYOND?
Pharma is still behind many other industries regarding investments in technology involving how businesses are run, compared with how products are made. We see the potential for continued investment and improvement here, learning from the fast-moving consumer goods and electronics industries which have demonstrated a proclivity for using much of today’s innovation (e.g., cloud computing and the Internet of Things) to increase visibility to data and other trends to facilitate fast and more agile decision making across supply chains.
WHAT ARE THE TOP EMERGING INNOVATIONS THAT WILL IMPACT BIOPHARMA MANUFACTURING WITHIN THE NEXT FIVE YEARS?
EVP Global Industrial Affairs
Certainly the way data can be exploited through cloud computing and the Industrial Internet of Things, for example, to enhance more effective and quicker decision making is a definite benefit. However, there is a perception that the biopharma industry has been behind the times in adopting some new approaches, but we should bear in mind that these emerging innovations come with unique risks that need to be managed carefully. For example, despite the obvious benefits of cloud computing, particularly in clinical research, it is imperative we keep any patient-sensitive data secure. How much risk a company is willing to take in this respect is likely to vary from one organization to another. While we should always proceed in new ways of working with necessary caution, it is certainly an exciting time to be involved in biopharma manufacturing, as ultimately all of these technologies will feed on one another as they mature.
WHAT IS YOUR VISION FOR HOW THE GLOBAL BIOPHARMA MANUFACTURING INDUSTRY COULD LOOK IN 2028 AND BEYOND?
Chun Zhang, Ph.D.
Head of Process Development & Manufacturing
The industry will consist of several segments tailored to product platforms such as proteins, cell therapies, and gene therapies. They also will consist of different scales to meet the diverse product needs, ranging from blockbuster to individualized medicine. Large manufacturing plants are more cost-effective for commodity-type products, while smaller modular facilities will be tailored for niche products. Continuous manufacturing will be widely adopted and greatly enhance productivity and product quality, and true integration of information and data will enable rapid analysis and fast decision making. There will be much closer collaboration between manufacturers and suppliers in precompetitive consortia to drive standardization and automation, and as a result, supply chains will be more integrated and efficient in reducing inventory hold.
WHAT’S GOING TO BE BIG IN BIOPHARMA MANUFACTURING IN 2018?
Clearly, the impact of Hurricane Maria on Puerto Rico and the importance of risk-mitigation and business- continuity strategies will be a topic of discussion in the biopharma industry well into 2018. After an event of this magnitude, the relevance of having well-rehearsed crisis- management and business-continuity plans rises to the top of everyone’s list. Hurricane Maria tested the resilience of our industry’s global supply chain, and from the lessons learned, industry needs to consider what improvements are to be made.
WHAT ARE YOU DOING THAT WILL HAVE A BIG IMPACT ON YOUR MANUFACTURING ORGANIZATION IN 2018 AND BEYOND?
SVP & Head Biologics & Sterile Operating Unit
Investing in the infrastructure necessary to explore new processing and analytical technologies is a top priority. In order to define the technology/process of the future, investment is needed now to determine the selection of “intensification strategy.” Factors being considered include existing manufacturing capacity, prior knowledge of existing technologies, size of company and portfolio, potential market for the product, and the stage of product lifecycle. The impact of the selected technology will then be weighed against the risk of successful implementation. Areas of focused innovation include process intensification, chemically defined simplified media, robust scalable harvest technologies, standardized modular approaches, and single-use technologies.
As the Director for the CDER and an FDA employee since 1986, Janet Woodcock, M.D., holds a special place in the world of biopharma manufacturing. Under her leadership, we have witnessed the introduction of risk management as a new approach to drug safety, the “Critical Path” Initiative to move medical discoveries from the laboratory to consumers more efficiently, and the “Pharmaceutical Quality for the 21st Century Initiative,” the FDA’s highly successful effort to modernize drug manufacturing and its regulation. Here is Dr. Woodcock’s biopharma manufacturing outlook for 2018 — and beyond.
WHAT DISRUPTIVE TECHNOLOGIES WILL TRANSFORM BIOPHARMA INDUSTRY MANUFACTURING IN THE NEXT THREE TO FIVE YEARS?
We will continue to see the adoption of continuous manufacturing technologies. These technologies may soon begin to integrate drug substance and drug product manufacturing in the small molecule space and upstream and downstream processing in the biological product space. This should be a positive trend as it can potentially enable higher product quality, lower manufacturing costs, smaller facility footprints, and improved agility. Coupled with this, we also may see advancements in process analytical technology (PAT) and model- based control strategies enabling real-time monitoring of product quality at unprecedented frequencies and real-time product release decisions without end product testing. Also on the horizon are new dosage forms enabled by additive and other manufacturing technologies that can accommodate specialized patient needs. For example, this might include easy-to-swallow drugs or drugs with specifi c release rates. These technologies may even be mobile or on-demand. These smaller manufacturing platforms may enable on-site drug manufacturing at pharmacies, hospitals, or sites of public health emergencies. The rise of digital medicine also could allow us to more closely link drug quality to individual patient impact than ever before.
WHAT IS YOUR VISION FOR HOW THE GLOBAL BIOPHARMA MANUFACTURING INDUSTRY COULD LOOK IN 2028 AND BEYOND?
Currently, the pharmaceutical manufacturing industry is still entering the stage of automation, while other industries are entering the stage of cyber-physical systems or Industry 4.0. Some in the FDA recently described a future vision of pharmaceutical quality and a potential path to get there. That future is Six Sigma pharmaceutical quality (i.e., no more than 3.4 defects per million opportunities). A path to get there includes economic drivers, performance-based regulation, Quality by Design (QbD), advanced manufacturing technologies, and continuous improvement and operational excellence (OPEX). To realize this future there need to be economic factors that recognize and incentivize quality. The regulatory approach must shift from predominantly management- based regulation to performance-based in order to give industry the necessary flexibility to improve quality. The adoption of emerging manufacturing technologies, including continuous manufacturing and advanced PAT, can enable higher quality. The knowledge gained from a QbD approach forms the basis for establishing a control strategy for these technologies. Finally, continuous improvement, OPEX, and a culture of quality must be part of the overall effort to drive quality in an organization. It is not unreasonable to think that the pharmaceutical manufacturing industry could follow this path to Six Sigma quality over the next decade.
WHAT ARE YOU DOING THAT WILL HAVE A BIG IMPACT ON YOUR MANUFACTURING ORGANIZATION IN 2018 AND BEYOND?
The CDER has an Emerging Technology Program to promote early engagement with firms to discuss potential challenges in implementing innovative approaches to pharmaceutical product design and manufacturing. We recently issued a final guidance for industry, “Advancement of Emerging Technology Applications for Pharmaceutical Innovation and Modernization,” with recommendations for firms that are interested in discussing these emerging technologies with the FDA. We recognize that adopting innovative approaches can present technical and regulatory challenges, including concerns about delays in the regulatory assessment process. With early engagement, the FDA can move more quickly to assess and act on applications involving new technologies. Along with this initiative, we have made an effort to provide staff with the knowledge necessary to handle such applications. Much of this knowledge stems from our research in both PAT and manufacturing science, which provides learning opportunities for our staff involved in application assessment. We’ve also taken steps to more fully integrate the human drug-assessment programs with facility evaluations and inspections. This enables better alignment between our field professionals and the staff who evaluate the products manufactured in the inspected facilities. The Emerging Technology Program could have a big impact on manufacturers in 2018 and beyond due to the potential for early face-to-face meetings even before identifying a lead drug molecule. These interactions then continue to provide regulatory feedback and facilitate the preparation of a regulatory submission.
Insights From A Biopharma Manufacturing Trailblazer
Across races, females are earning more undergraduate degrees than their male counterparts, including disciplines of science and engineering. Why then are 38 percent of female engineers opting to leave their field? According to a national study, 30 percent of respondents cited an organizational climate characterized by nonsupportive supervisors or co-workers and general incivility, while nearly half left due to working conditions. So despite there being more women in biopharma manufacturing leadership roles, there aren’t as many as there should be. This issue isn’t related to female self-confidence or leaving the workforce for motherhood; it’s a field that lacks a strong network of female leaders, necessitating aspiring women to have to blaze their own trail.
Chhaya Shah, one of two women trailblazers to participate in this year’s manufacturing outlook, has had to overcome her share of adversity. For example, when she moved to the United States from India at the age of eight, she did not speak any English. Yet Shah went on to graduate from high school with honors. In her graduating class of over 3,000 students at Wilkes University, there were only three women (including her) in the college’s engineering program. Shah has spent 19 years in biopharma manufacturing with the likes of Becton Dickenson, Abbott, Wyeth, and Shire, before taking on her current role as SVP of manufacturing and technical operations at Synergy Pharmaceuticals (NASDAQ: SGYP). Her perspectives are as diverse as her experiences — and they do not include a mention of the need for more women in biopharma leadership.
IS THERE A CURRENT BIOPHARMA MANUFACTURING TREND THAT HAS BEGUN TO DIE?
The traditional hierarchical organizational structure is not likely to last much longer. More companies are moving toward a teambased organizational structure. Top-down hierarchical organizations were originally designed for accountability. However, for successful organizations to compete and win in today’s global market, they must be designed for speed, agility, and adaptability. As organizations make the transition to a team-based approach, they find smaller teams (i.e., five to seven people) to be a more natural way for employees to work. Whatever a hierarchical organizational chart says, real, day-to-day work is done in networks. Therefore, the organization of the future is a network of teams that are accountable for results and given the freedom to drive the required decision making to achieve them. Top-performing companies are built on systems that encourage teams and individuals to meet each other, share information transparently, and move from team-to-team depending on issues to be addressed. Different networks may have different specialties, such as innovation or getting a product to market quickly, but the principle is the same. Launching a product is a great example of where you need a team that is agile, networked, effective, effi cient, and sharing a common goal. New organizational models also will require new approaches to leadership, and leaders of a teambased approach will need skills in the area of talent development, negotiation, resilience, and system thinking.
WHAT REGION OTHER THAN THE U.S. WILL HAVE THE BIGGEST IMPACT ON BIOPHARMA MANUFACTURING IN THE NEXT THREE TO FIVE YEARS?
Brazil, Russia, India, and China (BRIC) will likely continue to have a significant impact on biopharma manufacturing over the next several years. As the pharma market has flattened in the U.S. and many EU countries, the BRIC market has thrived due to improved standards of living, more citizens with access to health coverage, and an increased need for medicines related to noncommunicable diseases (e.g., diabetes, cancer, and cardiovascular problems). Pharmaceutical sales have doubled in these markets over the last five years, and projections show continued growth through 2020. Additionally, BRIC nations are looking at biosimilars as their chance to compete for a bigger chunk of the global pharmaceutical market. Many pharma companies have moved manufacturing locally or have partnered with companies in BRIC nations to improve access for their products, while also achieving more cost-effective and efficient supply. This has posed some challenges to industry, as GMP manufacturing expertise and the infrastructure in these markets have struggled to keep pace with the high demand. The companies that are most successful in meeting these challenges will reap the biggest rewards.
WHAT NONBIOPHARMA MANUFACTURERS WILL HAVE THE BIGGEST IMPACT ON THE INDUSTRY’S MANUFACTURING IN THE NEXT THREE TO FIVE YEARS?
Those working in the areas of artificial intelligence (AI) and robot manufacturing will have the biggest impact. This trend has been growing and will become more prevalent as biopharma manufacturers eventually have most of their tasks conducted through automated systems (i.e., even more than we do currently). Robots will conduct testing on production lines, enter results, and even conduct dual-quality checks. This trend already has been used in various other industries (e.g., automotive and electronics), and the cost savings are significant. Pharmaceutical companies will likely follow this trend and invest more in automation and robots and, in turn, move their human capital toward innovation vs. manufacturing. The advantages of complete robot manufacturing are evident: Errors are reduced, contamination limited, and overall assurance of a repetitious manufacturing process becomes more reliable.