Hiring a Contract Research Organization can expedite the drug development process.
Companies of all sizes use contract research organizations (CROs) to support their drug discovery and research and development (R&D) programs. Companies first embraced the concept of outsourcing elements for running clinical trials. Today, this outsourcing concept has moved up the value chain from clinical trials to target discovery and validation.
Today, it is possible to outsource all aspects of drug discovery and development, which has led to the creation of “virtual pharma” companies in the last few years.
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Figure 1: CRO Functions (Source: SRI International)
A CRO is a for-profit, nonprofit, academic, or other organization that performs a wide range of research-related functions and services for a “sponsor,” which can be a pharmaceutical, biotechnology or drug delivery company, or a government entity. CROs can serve a variety of functions as listed in Figure 1.
Originally, CRO stood for “clinical research organization,” which came into vogue in the 1980s and evolved through the 1990s. At that time, various government entities were outsourcing functions related to drug R&D under grants and contracts to contractors.
Although earlier CROs generally entered the scene in Phase 3, late in the clinical development process, over time they started to offer services earlier in the process. As capabilities expanded to non-clinical development activities, the name “clinical research organization” evolved into “contract research organization.”
CROs eventually became involved with drug discovery with the advent of combinatorial chemistry in the mid-to-late 1990s. It was then that pharmaceutical companies entered sizeable collaborations with specialized chemistry companies to feed the demand for large compound libraries in support of high-throughput screening.
The history of the CRO has not always been rosy. In 1976, the US Food and Drug Administration (FDA) found that a major CRO, Industrial Bio-Test (IBT), committed significant scientific fraud, had unsuitable documentation, and demonstrated gross incompetence in many studies. The result of FDA’s findings was the promulgation of the Good Laboratory Practice (GLP) regulations in 1978. IBT had to repeat and resubmit hundreds of studies performed for large pharmaceutical clients to the FDA.
Other CROs have come and gone over the years. In the 1980s, many universities attempted to conduct GLP work, an incongruous match from the typical academic research mindset. After many FDA citations, most universities have exited the GLP and GMP arenas and now focus exclusively on basic research.
The role of CROs
A sponsor may outsource certain R&D functions to gain expertise in specialized knowledge in technology, for a particular therapeutic area, for clinical trials, or for regulatory affairs in a particular country or territory. A key goal of CROs is to provide flex capacity or complementary capabilities for a sponsor’s in-house operations. A sponsor can take advantage of the CRO to avoid or convert certain fixed costs—such as those for maintaining specialized personnel with specific expertise, as well as facility expenses—into variable costs. CROs can also provide expertise for specific needs. Thus, CROs can add momentum to a sponsor’s R&D process, ultimately decreasing development time as well as minimizing the effect on the sponsor’s bottom line.
CROs are specialized, but function independently of the sponsor. Most companies hire CRO partners to perform a selection of duties that are most effective and efficient for the sponsor to outsource. An in-house project manager or management team supervises the CRO. Pharmaceutical companies are more likely to outsource clinical activities and collaborate on specialized technologies or for capabilities they lack. Biotech companies tend to specialize in a particular stage of the development process (e.g., drug discovery and non-clinical development or clinical development in specialized pharmaceuticals) and outsource the other activities to CROs. With a full repertoire of R&D activities now available through CROs, ”virtual biotech” —where a management team will outsource the entire drug discovery and development process to multiple CROs—has arisen.
Finding the Right CRO
When a sponsor decides it is ready to outsource to a CRO, finding the right fit takes diligence. Thorough background research can help ensure that the relationship will be mutually beneficial. Regardless of specialty, sponsors should examine a CRO’s experience, stability, product-specific knowledge, relationships with regulatory agencies, and connections with other CROs.
Experience, including the extent of experience is paramount. A CRO should have a breadth of experience in multiple sectors including commercial, government, and academic. Review the organization’s experience in taking drugs through the various phases of development.
Stability is important, particularly when regulated (GLP and GMP) work is involved. When Oread, Inc., a major preclinical CRO, filed for bankruptcy in 2001, sponsors had no idea where their study records were or the status of archived tissues. Losing the supporting data for a GMP drug substance or product, or working with a CRO that lacks the ability to provide GLP records for an FDA audit, is a serious deficiency that can stop a drug program dead in its tracks. Less-established CROs might offer a price savings, but sponsors must weigh potential savings against the risk of being unable to support future FDA filings.
The CRO must have a strong knowledge base in pertinent areas. This understanding is important when compiling documents together for filing; when setting up and running trials; when creating efficacy models for qualifying a compound to move forward; and when analyzing, interpreting and providing data feedback. A preclinical CRO with extensive expertise developing CNS drugs might not be of much value to an organization with an anti-infective drug program.
A strong relationship with regulatory agencies is critical. When evaluating various CROs, sponsors must explore past and present working relationships with the CRO’s client base and collaborators (government and commercial agencies) looking for positive relationships, a clean bill of health, strong success records, and solid problem-solving abilities. To be thorough, sponsors should look at the CRO’s FDA Form 483s over the previous five years. Most labs will have 483 findings, but the severity of the findings is important. FDA Warning Letters can be found on the FDA Web site (https://www.fda.gov/foi/warning.htm). A first-rate CRO will have no Warning Letters and will have addressed all 483 findings. It should conduct all research in full compliance with GLP and GMP guidelines.
Solid connections with other CROs in subsequent development stages or companies the sponsor is working with is less critical, but it remains an important factor to consider. While many sponsoring organizations are savvy and manage such relationships themselves, a high-quality CRO can manage and facilitate connections when needed.
Selecting a CRO
Working with a CRO can bring significant value to a sponsor when the partnership is robust. While background research on the CRO is necessary, it is equally important that the sponsor take a detailed look at its own needs, creating a plan for leadership, identifying a project manager or project management team and having a plan for open communication.
The sponsor should outline its needs before selecting a CRO. Once it selects a CRO, the sponsor can further define the project in detail with input from the CRO. Through this process, the sponsor can set appropriate milestones, establish deadlines and construct reporting structures. Most established CROs have effective reporting systems already in place, so choosing an experienced CRO can make this process run smoothly.
CROs cannot provide overall program leadership, and sponsors should not expect them to provide this. By drawing clear lines, sponsors can ensure that CROs will give completely objective advice.
The sponsor must maintain an active project management role, particularly for project areas that might have ambiguous outcomes. Open lines of communication can prevent errors that cost time and money. A clear feedback loop is imperative, especially at critical moments in the process.
Finally, the sponsor should treat the CRO partner as it would any close business associate—fairly and as an equal. High-quality CROs genuinely work in the sponsor’s best interests. While they want to see the product succeed to gain repeat business, the CRO’s staff takes significant pride in bringing life-saving therapeutics to the public. Listening to the CRO’s advice and working in partnership with them will lead to the best program design for supporting discovery and development needs.
About the Author
Nathan Collins is Executive Director, Drug Discovery in the Biosciences Division of SRI International. He manages drug discovery and business development for the Biosciences Division.
This article was published in Drug Discovery & Development magazine: Vol. 10, No. 11, November, 2007, pp. 42-46.
Filed Under: Drug Discovery