By Trisha Gladd, Editor, Life Science Connect
In today’s pharmaceutical market, biologics make up nearly 20 percent of total sales. However, by 2020, it is expected they will account for slightly more than half of the world’s top 100 selling drugs. As we move into 2016, the biomanufacturing industry will look to new technologies, processes, and relationships to support this dramatic shift in patient care. To find out what effect this will have on biopharma in the year ahead, I gathered insights from some industry experts. Below are the top five trends they think will have the greatest impact.
1. Continued Development Of Flexible Manufacturing Solutions
The biologics boom that is anticipated to take place in the next five years is a result of several manufacturing-focused trends, including the increase of product titers and yield, the adoption of single-use technology (SUT), and localization of manufacturing. Combined, these trends have created a greater interest in flexible manufacturing solutions, which, according to Parimal Desai, VP of global vaccines and biologics commercialization at Merck, is a trend we can expect to continue. “2016 will bring more focus on developing flexible manufacturing solutions to meet a wide range [high-volume to niche products] of capacity needs, as well as to address increased demands for localization of manufacturing into emerging markets. This shift will require companies to implement more continuous manufacturing and invest in single-use technologies and flexible manufacturing plants with rapid changeover procedures as well as the use of in-line process analytical technologies,” he explains.
SUT, an integral part of the flexible facility concept, also faces barriers to adoption, specifically when it comes to the standardization of both equipment and extractables and leachables testing. While Chuck Hart, director of manufacturing at Prolong Pharmaceuticals, says he expects single use to continue to grab headlines, he recognizes that understanding this and other issues is an area where focus needs to continue. Stronger partnerships between SUT vendors and biopharma manufacturers is absolutely critical, not just for the advancement of single use but also for the future of biopharma. This past year, we saw some advancement in this relationship through a project coordinated by David Wolton, a biotechnology consultant with PM Group, an international engineering design, architecture, project, and construction management firm. Wolton worked with some industry vendors to come up with the concept of offering a “store” of standardized single-use parts on supplier websites. The ultimate goal is to offer interchangeable single-use parts, so there are more choices for the buyer and increased opportunities for suppliers. Solutions provider JM BioConnect launched the first site offering standardized single-use equipment last month. Other suppliers are expected to follow in 2016.
When it comes to the standardization of extractable and leachable testing, the Extractables Work Group of the BioPhorum Operations Group (BPOG) made progress with the release of the Standardized Extractables Testing Protocol for Single- Use Systems in Biomanufacturing in November 2014. BPOG member companies are now adopting the protocol as their user requirement and are in the process of communicating this to their suppliers. BPOG will support implementation of the protocol by helping to build understanding and consistent application across suppliers. Numerous suppliers are already moving toward adoption. Compliance is expected by the first quarter of 2017. And while the focus is on implementation, BPOG's efforts to create an American Society for Testing and Materials (ASTM) extractables standard that meets the needs of biologic drug manufacturers will continue. The team is also developing a leachables testing best practice guide to compliment the extractables protocol.
Overcoming the challenges of SUT wouldn’t just accelerate its adoption; it would also establish the technology as a qualified tool in the application of continuous manufacturing, an approach that offers efficiency and agility to drug production. While some companies, such as Bayer, Genzyme, and Novartis, have manufactured a small number of products using elements of continuous manufacturing, there is still more work to be done when it comes to creating a successful end-to-end continuous process. At the 2015 BioProcess International Conference and Exhibition, Konstantin Konstantinov, VP of technology development at Genzyme, delivered a presentation on the future of continuous processing in biomanufacturing. “We’d like to see the dominant design [for continuous manufacturing] as starting from the media throughout the entire process to drug substance and perhaps even beyond to incorporate the drug product in a continuous line. However, this is not going to be enough. In order for a process like this to exist and function properly, it’s very important that it’s equipped with an integrated control system, which is often underestimated.”
Finally, we may see an increased use of prefabricated facilities, such as the KUBio biopharmaceutical factories recently introduced by GE Life Sciences. The first KUBio factory was shipped in September from Germany to China. It was bundled in 62 containers and assembled and built in 11 days. There are several benefits to these facilities, including shortened time to market and a significant reduction in costs (e.g., GE claims KUBio can reduce costs by as much as 45 percent).
2. Closer Partnerships Between Industry And Regulators
According to Desai, this trend will be key to the rapid progression of the industry and the introduction of innovative concepts in biopharmaceuticals. “With initiatives like the breakthrough therapy designation, regulatory agencies, such as the FDA, have engaged in close dialog with industry. This has truly enabled getting life-saving medicines to patients quicker while not compromising quality,” he explains. “It would be very good to see other regulatory agencies around the world also be more receptive to such discussions early in the product-development life cycle.”
"Having a single standard would simplify things significantly and would make the market even stronger."
Hart thinks 2016 will be a year that moves us much closer to regulatory standards across the globe. “The regulatory harmonization I’m seeing is very exciting,” he says. “As companies prepare for pre-approval inspection, they prepare based on the regulatory agency. For example, in the past, the EU was more interested in area cleanliness and autoclave data while the FDA concentrated on processing. Having a single standard would simplify things significantly and would make the market even stronger.” Hart says he believes the continued efforts of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) will have an even greater impact on the industry. As companies recognize regulatory efforts toward global standardization and that the FDA is truly working toward up-front partnerships, Hart expects the ability to develop world-class quality organizations within companies will become easier.
He adds that he also sees a trend with the FDA acting more as a partner than a big brother. “Instead of being perceived as a bully, the FDA seems to now be working toward up-front meetings and collaborative discussions about the path forward. In my opinion, the auditors are being trained better to really work with a company, and unless its GMP violations are egregious, the FDA works more as a partner to resolve any gaps.”
3. The Need To Foster New And Existing Talent
According to a December 2014 McKinsey & Company report, “Biopharmaceutical companies best positioned to succeed in tomorrow’s market will be those that master a broad set of technical and operational capabilities.” To accomplish this, Desai says there needs to be a sustained effort and commitment to develop and permanently embed these capabilities into an organization. For example, at Merck he says they are focusing on the development and retention of technical and scientific talent.
To master technical and operational capabilities, Merck is also focusing on developing simple and innovative business systems to enable rapid and successful decision making. “Success in this area will result in more effective management of complex technical programs and a shortened CMC [chemistry manufacturing and controls] development cycle while also ensuring that CMC deliverables are right the first time,” he continues. “It will also enable managing more programs in parallel without substantial increases in the workforce.” Finally, he believes the rapid growth in biopharma seen over the past several years will result in increased competition for a finite pool of experienced and skilled talent who are able to create and execute the strategies and tactics needed to succeed in the marketplace.
Desai says companies also should be aware of the state of new talent being recruited into industrial jobs, particularly when it comes to their training and development. “We are finding that fresh graduates do not have a good understanding of the drug development process and need a significant amount of on-the-job training.” He adds, “Academic programs should seriously consider how their curricula could cater more toward actual industrial applications.” In a recent article on OutsourcedPharma.com, Kamal Rashid, director of the Biomanufacturing Education & Training Center (BETC) and research professor at Worcester Polytechnic Institute (WPI), says an adequate source of workers is possible in the U.S. biomanufacturing industry if they can acquire additional training in specific skillsets. “For example the industry wants people who know the chemistry of a protein and how to purify it and what's involved in the post-translational modifications in the mammalian cell that's not available in microbial cells,” he says. Of course, this additional training can be both costly and time-consuming. A recent report by Eric Langer, president and managing partner of BioPlan Associates, states that this cycle can be broken by stronger relationships between employers and universities.
"2016 will bring more focus on developing flexible manufacturing solutions."
4. Industry Collaborations
As more companies enter the biologics market, the need to seek out talent and expertise not just in recent graduates but also in partners is expected to increase. According to Nice Insight’s report on 2015 outsourcing trends, 62 percent of those surveyed spent $10 million to $50 million USD (2014-2015) on outsourcing, which is a 24 percent increase over the year before. In an article published in Life Science Leader, Nigel Walker, managing director of That’s Nice, states, “The demands from industry service providers have never been greater. Some key trends driving the continuously rising outsourcing budgets include a growing pipeline of biologics, complex therapies and delivery systems, and precision-based medicines, as well as larger, more complex clinical trials, real-world evidence studies, and the need for sophisticated new technologies, all of which require advanced, integrated expertise.” He adds that this trend of turning to partners for a variety of aspects of drug development is “partly to avoid the very high capital expenditure and long lead times needed to construct, equip, and validate manufacturing facilities. Outsourcing is an efficient, cost-effective way to meet these rapidly changing industry needs.” Scott Lorimer, global VP of biologics at Patheon, says partnerships are exciting for the entire biopharmaceutical sector, not just CMOs. “These partnerships are mutually beneficial and result in drugs getting fast-tracked to the clinic, reaching the market in optimal time. By partnering with biopharmaceutical services organizations, the biopharmaceutical industry is effecting accelerated development and launch of exciting new originator medicines, biosimilars, and biobetters alike.”
Desai believes partnerships between traditional pharmaceutical companies and small biotechs may also grow in 2016. “Competition for access to innovative technologies and the next generation of therapies will result in higher valuations for new and, as yet, unproven technologies. This, in turn, will result in higher prices being paid by the traditional pharmaceutical companies for rights to these assets.” This is especially true in the area of immunotherapy, where pharma companies are all fighting for the piece of a pie that experts anticipate to be worth $80 million by 2020. A leader in the immunotherapy space, Novartis, made headlines earlier this year when it partnered with Aduro Biotech, committing to pay $200 million up front for Aduro’s Sting technology and another $500 million later in milestone payments. In June, a landmark deal was made between Celgene and Juno, with Celgene paying $1 billion for Juno’s pipeline of CAR-T drugs.
5. Presidential Election Will Increase Spotlight On Drug Pricing
The cost of pharmaceuticals is becoming more and more prevalent in today’s news coverage, and according to Hart, there should be no expectations for it to go away any time soon. “Unfortunately, with 2016 being an election year, we will continue to see a heavy push toward reduced drug costs,” he says. “Candidates will have a field day with headlines like the 5,000 percent mark-up of Daraprim. This is concerning because, based on my experience, I have a very good sense of both the up-front and sustainable costs to produce biologics, and it just cannot be done inexpensively without sacrificing quality.” Desai agrees that sticker shock as well as the cost of new breakthrough and lifesaving therapies (e.g. $1,000/pill announcement for Harvoni) will continue to fuel these conversations. “Pressure will increase to contain drug costs, and rhetoric on biopharmaceutical pricing will increase in the run-up to the upcoming U.S. presidential election.”
It is no secret that some drugs do come with a high price tag. However, when you look at the recent report from the Tufts Center for the Study of Drug Development citing the current cost of bringing a drug to market at $2.6 billion, the solution becomes clearer: Lower the cost of making the drug, and you can lower the final price tag. So while the presidential candidates continue to battle into the primaries, pharma can only continue to look at ways to reduce R&D costs, just as Desai says Merck will be doing in the next year.
Dr. Gargi Maheshwari and Dr. Graham Tulloch contributed to Dr. Desai’s input for this article.
Will Today’s Biopharma Trends Impact The Rising Immunotherapy Market?
According to a recent market research report, nearly 50 percent of today’s oncology drug market is made up of cancer immunotherapy drugs. More importantly, though, is the fact that this market is expected to nearly double in value ($41 billion to $80 billion) in the next five years. Marc Better, VP of product sciences at Kite Pharma, a biopharma company focused on developing immunotherapy products, discussed with me some of the opportunities and challenges in this electrifying market.
"Moving forward, we are likely to see new, perhaps disruptive, technologies for gene transfer."
Q: What biopharmaceutical trends are you most excited about?
A: We are seeing a trend now toward automated solutions for the handling of liquids that can, at least in theory, be integrated into commercial manufacturing operations. Concurrently, we are seeing new solutions for managing the entire process flow, thereby allowing real-time management of the manufacturing process. In addition to new equipment that is being developed for industrial use, systems for real-time tracking of the product during the manufacturing process are being developed by a variety of suppliers.
Q: Are there any trends you think will be problematic for the growth of the cell therapy market in 2016?
A: As the excitement in this area has grown, we have seen a tremendous increase in the number of new entities (academic, biotech, and pharma) working in this space. This has resulted in increased demand on CMOs that support this industry. CMOs of cell therapy products, as well as other contract vendors that support this industry, may be stretched to meet this growing demand, which could eventually outstrip the current available capacity.
Q: How are you preparing to face these trends?
A: We see investment in process automation as a valuable option to bring important new products to patients who need them in a cost-effective and efficient manner. To help bring our products through clinical development, we are also investing in both clinical and commercial manufacturing organizations. Kite has built a clinical manufacturing facility near its headquarters in Santa Monica, CA. Once this facility is fully qualified, we will have capacity to produce more than 300 autologous T-cell products per year for clinical trials. In addition, Kite is building a commercial manufacturing facility in El Segundo, CA, for KTE-C19, our anti-CD19 CAR T-cell product for lymphoma and leukemia. We expect to complete construction by early next year and be ready to support commercial launch of KTE-C19 by 2017.
Q: What advancements in cell therapy need to happen in order to see continued growth?
A: In the immunotherapy space, we are looking forward to new technologies to bring new genes into cells as well as target-specific cellular proteins to either increase cell therapy effectiveness or overcome inhibitory signals. Currently, there is a variety of means to introduce new genes into cells using either viral vectors or nonviral mediated gene transfer. Moving forward, we are likely to see new, perhaps disruptive, technologies for gene transfer. We are also likely to see considerable advances in technologies for gene editing that may allow gene therapy products to provide enhanced functions in vivo. Together, these technologies should allow rapid production of cell therapy products that are both more effective and more specific than what is possible with the technology available today.