If the pharmaceutical workplace model were a shapely wedge of clay ready to be retooled, contract organizations might be the hands that create its next form. How will science professionals cope with the transition of their roles and the transfer of technology to these core components of a decentralized model?
The answer is the focus of an upcoming SLAS2012 session that will launch the SLAS Technology Transfer and CRO/CMO Project Management Special Interest Group (SIG). Contract research organizations (CRO) and contract manufacturing organizations (CMO), some of which were once in-house departments within big pharmaceutical companies, can optimize lab work either by performing time-consuming, foundational tasks, or tackling complicated projects that may not be as cost efficient for their client-sponsors to conduct. The model for this work has been around for 40 or 50 years, according to SLAS member, SLAS2012 presenter and SLAS Technology Transfer SIG Chair Liming Shi, M.A., M.Sc., former senior scientist in Bioanalytical Chemistry of Amylin Pharmaceuticals, Inc. in San Diego, CA.
"I remember Lancaster Laboratories originally conducted chemical testing for agriculture. Later on the company evolved into pharmaceuticals and recently into the biopharmaceutical industry," he notes. He adds that the trend picked up momentum for a couple of reasons, primarily because of the length of time required in the biopharmaceutical process. "It's really challenging. It takes more than $1 billion and an average of 15 years to develop a drug," he explains. The second reason lies within recent statistics that show the success rate in this process is approximately 14 percent.
The financial incentive to outsource projects is high. When outsourcing is successful, the sponsor companies can increase testing capacity, expand resources, add reproducibility and robustness, accelerate clinical timelines, and meet business continuity requirements. On the down side, difficulties in technology transfer can increase the timeline and expense.
The end result is a restructuring of the profession. Some professionals find themselves working for a virtual biotech after years of working for a corporation and are now focusing on a narrower range of objectives related to a larger project. Many professionals, regardless of the size of the company in which they work, find their scientific jobs are morphing into managerial roles that oversee the work of an outside contract organization.
"The people's mindset has to be adjusted," asserts Shi. "In the current environment, you have to be very specialized. You have to attain thorough knowledge in that area. Furthermore, you will have to be multitalented as well. You will have to know quality, compliance, technology, statistics and the transfer to be developed. You have to focus on your competency, but you also have to have broad knowledge. That is the requirement for outsourcing or off-shoring trends."
Shi's fellow SLAS2012 panelist, Melissa Rosness, M.B.A., agrees that a broad knowledge base is important, and adds: "Everyone needs supply chain knowledge in today's environment. I have seen an increased number of small and virtual companies spring up – the employees are from large pharmaceutical companies and their backgrounds are scientific," she explains. Rosness, a senior director in Biologics & Business Processes for Althea Technologies, Inc., a contract organization located in San Diego, CA, says that a scientific knowledge base needs to be paired with business management skills. To avoid the set up costs of labs and equipment, these virtual companies can outsource contract development, testing, and manufacturing work and simply troubleshoot and transfer processes based on their previous experience, but only if the players have enough business background to successfully manage the process.
"You have to leverage existing space or partner with companies that offer expertise so you don't have to build or hire someone to do the actual experiments," comments Raymond Price, Ph.D., M.B.A., the third panelist in the SLAS2012 Technology Transfer presentation. Price, director of business development for San Diego-based contract organization GenScript, continues: "The goal of the CRO/CMO is not to replace the client's workforce, but to reinforce it. When companies downsize or reduce their workforce, it disrupts relationships and creates a paralysis in decision making."
Frequently the contract organization can help clients decide what work is better outsourced to free up in-house staff time. "Rather than spending a month or two cloning out a gene and putting it in a vector to grow in bacteria, we can deliver that material to them so they can begin novel experiments right away," Price explains. "Another aspect is taking on a project that is difficult to do internally. Perhaps the client company has already tried it and finds that they need to test a lot of parameters at once – such as constructs or incubation times – and they don't have the resources to do that. Outsourcing this type of project makes a division look great and efficient. That is one of the biggest benefits."
The accountability for projects still lies with the client, so the selection of contract organizations should proceed with care. Shi warns that there can be big differences between providers. He mentions an incident in July 2011 in which the Food and Drug Administration (FDA) alerted the pharmaceutical industry that clinical trials conducted by one CRO between April 2005 and June 2010 needed reevaluation. "Since the CRO did the pharmacokinetics (PK) studies for many sponsor companies between 2005 and 2010, there was a huge impact for some FDA submissions," Shi comments.
Companies wanting to outsource should first evaluate the history and reputation of the contract organization under consideration, says Price. Review references and discuss the complexity of the project and the science being pursued.
Next, consider the accessibility of the people managing the project. "What kind of capacity does the contract organization have? The scope of work that can be done by a 10-person versus a 1,000-person facility can be enormous. Maybe at first this doesn't matter, but if you seek to expand in the future, it is something to consider," Price comments. "Anticipate the future of the relationship and know what the company is capable of doing beyond the immediate project you want to outsource."
Resist the urge to be locked into cost, he continues. The price tag on the project, while important, is secondary to the quality of the materials provided and the turnaround time the contract organization has to offer. "Whether you need to make 100 genes or 1,000 genes, you need to know if you can still get those in two to three weeks time to make the project deadline. Match up what the company can do with your current and future priorities," Price advises.
Image courtesy of Melissa Rosness, for Althea Technologies, Inc.
Risk and benefit are both associated with technology transfer, which includes, among other aspects, establishing bio-analytical methods, process development, and manufacturing to support biologics. The first step usually is for the sponsor company to transfer bioanalytical methods in order to qualify its contract organization to perform the analytical procedure, according to Shi.
Successful transfer requires a lot of people skills, he explains. "It's a lot of communication management of technology styles – you have to predict where to control and plan. There are a lot of things jeopardized here. You need people who have expertise in different specialized areas – technical, project management, statistical, business development, laboratory standards compliance. They all have their special knowledge they combine together to handle the whole project."
Rosness believes the greatest challenge in establishing the sponsor-contractor relationship is the alignment of the project scope and project expectations during the up-front contract proposal process. "More time can be spent developing the contract proposal than anywhere else in the contracting process," she explains. "The client clearly has to define the scope of work details and what they will provide in terms of documentation, data, batch records, standard operating procedures (SOPs), etc. The more clearly they can define that up front in the proposal process, the more streamlined the actual execution is going to be. It helps the contract organization get a head start on the process." Moving too rapidly through the technology transfer can create errors, Shi states. Finding candidates, conducting screening, establishing a promising candidate pool, nominating leads and moving into a second-development stage requires expertise and thorough research. "The method has to be developed rock solid scientifically before it can be transferred. The sponsor company should make certain that the method is truly representative of what is supposed to be performed," Shi explains.
Rosness agrees. "Challenges occur when sponsor companies attempt to transfer assays that have not been fully developed. If an assay is going to need some development work, that could change the scope of the project," she comments. It also could end the project before it begins if the sponsor company is dealing with a CMO that can't do analytical development. Even for CMOs that can do such work, the timeline of the project will need to be extended so that analytical development can be completed before the process development and manufacturing activities begin.
Another important aspect is for the sponsor company to establish a subject matter expert (SME). "The CMO can assign an SME on their side as well so that those two technical people who really have the knowledge base can freely interact and exchange information," Rosness says. "Regular project team meetings also are important. The more that they meet and share information as it becomes available, the more streamlined and seamless the process is in tech transfer. There will always be bumps in the road. You have to be prepared, tackle challenges head on and work constructively."
Price recommends that client companies conduct thorough due diligence that covers the hard questions before the work begins. This should include what deliverables are, how the material will be used (i.e., avoid using buffers that are toxic to the cells, etc.), timelines, and how to address problems as they arise. "IP ownership is something to establish up front and make certain expectations are clear as to where the IP will fall out," he says, explaining that some contract organizations create more of a hybrid. "Those companies partner with the client companies to provide services at cost in exchange for equity or downstream royalties."
Compliance is another issue to resolve – particularly when selecting off-shore options. Because compliance requirements vary from country to country, Shi explains that companies must have at least a CMO or have their own manufacturing facility in Asia to market products there. "You have to have your license approved there by a local regulatory board," he explains. "These countries have many well educated, hard working young people and the labor costs are comparatively inexpensive."
Shi asserts that the CRO/CMO needs to focus on compliance and quality control procedures regardless of their location, and the CRO/CMO needs to be certain they can repeat the analytical method and to be certain they can scale up the procedure for process as well. The CRO/CMO also needs to make certain that hardware and software throughout the process are compliant and align with products used by the sponsor company. Technology improvements, particularly in telecommunications, and the rapid progress of data transfer via secured software options such as SharePoint have greatly enhanced the process, according to Shi.
He calls this the early-stage story because off-shore CRO options are already taking the spotlight. In recent years, China and India's emerging markets have grown at such rates that not only are projects outsourced, but research and development also are sent off-shore. "I can predict that this momentum is growing. China now conducts almost all varieties of clinical testing."
Because every project is unique, it would be difficult to consider every aspect of technology transfer. However, the SLAS Technology Transfer and CRO/CMO Project Management SIG will be there to meet the individual needs of professionals caught up in the process. The inaugural meeting will be held at SLAS2012 and unfold in three separate presentations that will culminate in a panel discussion to be held from 11:30 a.m. – 1:00 p.m. on Wednesday, Feb. 8, 2012.
"The purpose of this session is to provide a platform for industry colleagues, especially in the technology transfer arena," says Shi, whose professional experience includes many years of national and international technology transfers with contract organizations. "SIG members can share unique experiences or case studies. It doesn't matter if it was a failure or a success story; everyone will benefit from it. We can hold discussions, exchange useful information, work on industry standards, and even possibly produce a white paper. Everyone has their unique experience. That's the beauty of this kind of group."
The SIG has a unique opportunity to show SLAS professionals the upside of the CRO/CMO trend. "There is both pro and con," Shi says. "The glass is half empty, but when you look, you see there is water still there. With the current economy, it is a necessity to consider all options."
January 23, 2012