In sporting contests, such as the Stanley Cup Finals or the FIFA World Cup, teamwork can make the difference between the thrill of victory and the agony of defeat. Similarly, in biopharmaceutical development, teamwork between clients and contact research organizations (CROs) can lead to successful outcomes or costly mistakes.
Rapid technological progress, increased regulatory complexity, and continuing globalization are driving many biotechnology and pharmaceutical companies to outsource to CROs. Knowing the critical aspects for successful partnering from the get-go will help ensure a win-win situation for both. GEN spoke with industry leaders who offered some game-day advice on the ways CROs and their clients can work together most efficiently and economically.
Knowing when to engage a CRO
There are many reasons for considering outsourcing opportunities with CROs, says Elisha Talley-Roithner, senior vice president of dev ops and portfolio management at PPD, a global, full-service CRO that offers end-to-end Phase I–IV solutions with therapeutic expertise that spans large drug disease markets as well as growing areas of R&D innovation.
Talley-Roithner begins by citing the importance of finances. “Utilizing a CRO can reduce the monetary impact of staffing, real estate, and equipment because the CRO owns those aspects of the business function,” she maintains. “But just as important, outsourcing is a valuable option when internal capabilities, capacity, and expertise don’t match the specific needs of the project, particularly if a specific short-term or unique situation presents itself.
“At times, there’s the need to augment staff when broader coverage is required, such as to have feet on the ground in geographies where a company doesn’t have employees or to provide core functions the pharma does not have in-house. At the same time, the internal expertise already may be available in-house, but that expertise might be better used with other high-priority projects that would benefit from the institutional knowledge and experience of company employees. And, while in-house staff routinely bring many great new ideas to the table, more minds equal more ideas equal more potential opportunities for innovation.”
According to Talley-Roithner, another key consideration is alignment. “The CRO needs to understand the client’s business drivers and how its work contributes to those drivers,” she points out. “That includes alignment relating to mutually defining roles and responsibilities accurately, to prevent efforts from being duplicated and to ensure that the right ratio of staffing and oversight exists.
“Alignment also is important in the areas of language, definitions, and terminology, as well as a common understanding of the scope of a project and agreement on how to handle out-of-scope items, which are inevitable. And while it’s a more abstract aspect, common cultural alignment is important. A clash in culture could be the difference between success and failure.”
Beyond alignment, other aspects are also critical for success. She posits, “Trust, reliability, and a shared vision all come to mind when considering critical success factors. It’s also important that there’s a champion of the relationship with each organization. Those people are responsible for steering everyone clear of an ‘us vs. them’ perspective and for helping their respective teams appropriately address and respond to problems.”
A final consideration is governance. “The governance structure,” Talley-Roithner emphasizes, “needs to be fit for purpose and customized for the partnership—robust, but not overengineered.”
Recognizing that all CROs are not alike
Keeping up with the regulatory and operational aspects of gene therapies is a complex process, particularly during the clinical development phase. To ensure that the process is well managed, biopharmaceutical companies may want to engage with a full-service CRO prior to any clinical application or submission, suggests Pete Robinson, PhD, vice president of medical and scientific strategy at Syneos Health.
The company provides beginning-to-end services from preclinical support and early clinical development, through clinical stages and into launch and commercialization. Syneos also actively supports all sizes of companies developing cell and gene therapies.
“The CRO team can bring later-stage thinking into the process earlier to enhance the clinical development plan for the product,” Robinson says. This encouraging suggestion comes some additional advice: CROs may differ in quality and services.
“All CROs are not alike,” Robinson elaborates. “They vary significantly in size, scope, and capabilities. There are small, niche CROs that work deeply in certain therapeutic or technical areas, and there are large, full-service CROs that can provide end-to-end support along the product lifecycle. It is important to look for a CRO partner with the expertise you need, the depth of support that the sponsor may not have or want to create internally, the geographical reach, and the right culture to work well with the product development teams.”
Don’t just opt for the lowest price, Robinson warns: “Settling on a CRO based on price from a proposal that is flawed can create significant delays for the sponsor companies and incur significant cost increases as well.”
Besides demanding sound proposals, sponsor companies should insist on a CRO that can field a strong team. “[The CRO should] provide a team that fits and works well with the sponsor’s staff and has its own internal support in the form of oversight and systems/processes to be effective,” Robinson explains. “This is especially true when working in newer technologies like gene therapies where the landscape for development is evolving and knowledge needs to be continually updated and shared for effective delivery.”
Robinson offers a few other pointers for navigating efficiently: “Working effectively and economically isn’t rocket science—or gene therapy science for that matter! It boils down to good communication, expectations, role definition, and a well-defined scope. Even in a rapidly advancing area such as gene therapy, these basics of management combined with the right therapeutic, scientific, and regulatory expertise will drive success.”
Ultimately, it is the quality of the relationship that helps ensure success for both parties. Robinson reflects, “In my experience, teams that have open discussion, strong management support, and clear roles/expectations deliver best, and this usually keeps costs down as well. In the case of gene therapies, which bring a ‘perfect storm’ of complexity, regulatory fluidity, and rapid technologic evolution, it’s no surprise that well-vetted and supported teams successfully deliver.”
Avoiding common mistakes
When sponsors select a CRO, they should avoid making common mistakes. For example, sponsors should not underestimate the importance of finding the “best fit,” even if it’s not the least costly option. “Good CROs work very closely with sponsors, building relationships based on trust,” says Nuala Murphy, PhD, president of clinical research services at ICON, a full-service, global CRO.
“CROs come in all shapes and sizes—from small CROs that specialize in preclinical work, to large, full-service CROs like ICON, which can take treatments from Phase I right through to Phase III and beyond,” she continues. “It’s important to ensure that a CRO has experience in the relevant clinical area and indication, and that the investigators understand the required patient population and have access to the right regions.”
“It would be a mistake to choose a CRO based purely on cost,” Murphy insists. “If a trial fails, it can add years to the development timeline and actually increase costs.”
Another mistake is neglecting patient recruitment, which is often the biggest challenge in drug development. “Getting that right is key, as is ensuring a CRO has the expertise to select the right trial sites,” Murphy points out. “We launched ICON’s Accellacare site network to ensure we could offer sponsors effective recruitment solutions.”
Yet another pitfall is missing the opportunity to “do it right the first time.” According to Murphy, starting well may require establishing well-designed trial protocols with clear endpoints. “It is important to maintain clear lines of communication throughout the trial process, at all levels of the organizations,” she adds. “This allows any challenges to be flagged early and solved quickly, minimizing any disruption to the trial timeline.
“Again, getting to know your partner and building trust are essential for success in the relationship. Many of our sponsors are long-term clients, and we understand their company culture, giving us a clear advantage when it comes to collaboration. We also apply cutting-edge innovations such as decentralized trials and remote monitoring to make drug development faster, safer, and less expensive.”
ICON recently assisted in a vaccine trial for Pfizer/BioNTech. “This trial,” Murphy recalls, “was one of the largest and fastest randomized control trials ever conducted.”
The importance of customer service
To improve the efficiency of drug development, biotechnology and pharmaceutical companies must overcome daunting barriers, warns Steve Yang, PhD, co-CEO of WuXi AppTec, a company that offers a range of services, including development and manufacturing services, to companies that provide small-molecule drugs, cell and gene therapies, and other medical products.
“[Barriers include] high investment requirements, a high risk of failure, and a lengthy development cycle,” Yang elaborates. “These barriers not only impose a high cost for companies, but also negatively impact patients by delaying their access to therapeutics and medicines that would help them manage their health conditions and live better.”
Yang reports that WuXi AppTec’s customer service approach emphasizes the curation of customized products to meet the unique needs of individual customers. He states, “By providing services in our partners’ markets, WuXi AppTec’s localized yet globally enabled platforms offer flexibility, reliability, and consistency to our customers. We are proud of our strong reputation for delivering high-quality and tailored solutions for our partners, and providing them with innovative and cutting-edge solutions that drive R&D efficiencies and generate synergies with our existing discovery, preclinical, clinical, and manufacturing pipelines.”
Yang emphasizes that sponsors should benefit from a collaborative environment when working with a CRO. “Fostering innovation and collaboration across the industry and around the world is critical to the future of the pharmaceutical and biotechnology industries,” he declares. “Our company is committed to strengthening the capabilities and capacities of our platform so we can continue to bring important advances in health and medicine and enable our customers to find a treatment for every disease and discover every needed drug.”
Working together long term
CROs differ from each other in myriad ways. Consequently, choosing the right CRO means that sponsors must weigh multiple factors. Important factors are response time, technical support capabilities, and project management capabilities. Perhaps the most important factor of all is the ability to sustain a long-term relationship.
Advice on these factors is forthcoming from Kay Chuang, head of RSBU marketing, GenScript, a company that maintains a broad portfolio of services to support over 300,000 researchers from more than 160 countries. The company’s services include gene synthesis, mutant library generation, peptide synthesis, recombinant antibody and protein production, virus and cell line generation, and antibody discovery services.
According to Chuang, it is important to determine a CRO’s response time because some CROs may take days or even weeks to respond to a request. “Most of GenScript’s customers,” she asserts, “hear back from our account managers within the same day. The project’s turnaround time and guarantees are also important. You may find different turnaround times for the same request from different CROs.”
With respect to technical support, Chuang notes that some CROs can provide valuable suggestions on project design. For example, CROs can design expression systems, perform codon optimization and library design, and even help identify potential design errors in the constructs.
Chuang observes that CROs vary in the ability to facilitate project management. “Some CROs provide routine updates or have an online status bar to track a project’s progress,” she says, “whereas other CROs may disappear until you follow up on the status.” Project management, Chuang adds, involves other considerations, such as the need to initiate confidentiality agreements ahead of time.
“Reviewing legally binding contract agreements can be a lengthy process,” she warns. “For critical materials or key partnerships, make sure you audit the manufacturing site and meet with the scientists and program managers who will be working on your projects.”
The most important factor for mutual success, Chuang emphasizes, is establishing long-term relationships: “CROs usually provide higher priority and flexibility to key customers they have partnered with for extended periods. GenScript often assigns the same team to support key clients to facilitate communication and to ensure quality and consistency.”
Whether in sports or business, great teamwork pays off. As Henry Ford reflected, “Coming together is a beginning, staying together is a process, and working together is success.”