For my first column of 2012, I decided to go back to the basics and examine some of the commonly held beliefs that impact decision-making in preclinical drug development. Consider the following:
Myth: “No one can do preclinical drug development better than us.”
The roots of this myth trace back to the pharmaceutical industry in the 1980s and ‘90s. At that time, this belief probably made sense. The industry had expansive preclinical facilities that were staffed (maybe even over-staffed) with scientists. Back then; this belief was likely the biggest obstacle for the growth of preclinical CROs. Today, we know that the pharmaceutical industry has gone through considerable changes. In-house preclinical facilities in the pharma industry have been closed, sold, and/or downsized. Thousands of scientists have been laid off during the past 10 years as the industry increasingly embraced preclinical outsourcing as a business strategy. There are still preclinical drug development capabilities within the pharmaceutical industry and some at these facilities may still believe that the quality of their preclinical research is superior to what can be found through outsourcing. In 2012, if we were to compare the overall quality of preclinical research on a single project at a pharmaceutical company with that at a CRO, the claim that the pharma industry research quality is better may be true . . . but maybe it isn’t. It is easy for any organization to excel when it only has to focus on one project, but we now know that survival in the pharmaceutical industry is not only based on the quality of the research but maintaining multiple projects in their drug development pipeline. As the capabilities at preclinical CROs matured, we now see that some of these organizations are able to handle large volumes of work and still achieve equivalent levels of quality. It is also worth considering the larger volumes of work at CROs may result in higher levels of technical proficiency than what can be found in pharma facilities. This reality may be hard to accept but it is probably true at many CROs. Still, some in the pharmaceutical industry are reluctant to embrace preclinical outsourcing because they believe that they have more control of their studies if they are conducted at their own facilities. As long as a Pharma company can afford the overhead to maintain preclinical facilities and staff, there is nothing wrong with this strategy.
The bottom line: With careful evaluation, acceptable preclinical research capabilities can be found in the CRO industry. Pharma and biopharma companies that have limited or no preclinical research operations have shown that drugs can be developed effectively through outsourcing.
Myth: “Pharma companies have better control if they conduct studies at their own facilities rather than outsourcing them to a CRO.”
Pharmaceutical scientists would like to have the ability to walk down the hall in their own facility to be able to check on their preclinical studies. These scientists often know the staff that will be conducting their studies. There is a belief that the level of accountability and reliability is higher when studies are conducted internally and not outsourced. With this myth, familiarity has been equated with an increased sense of control. It is true that there are risks associated with outsourcing. CROs conduct studies for multiple clients and some pharma clients may worry that their studies may not receive individualized attention. Many of the factors that drive pharma scientists to want to conduct their studies at their own facilities are absent when their studies are conducted at a CRO . . . unless the pharma scientists have implemented tactics to mitigate these risks.
The bottom line: No one likes to hear this but preclinical studies are never really “under control.” Each time any individual is in contact with a study or the study data, it is an opportunity for an error to occur, regardless of whether the study is conducted in house or at a CRO. The sense of familiarity gained from conducting an in-house study may, in fact, provide a false sense of security. Having plans to mitigate risk is essential for any preclinical study regardless of the location where the study is conducted. Staff familiarity with the study protocol, effective communication processes, and periodic study monitoring will mitigate risk. Absolute “control” of any preclinical study is something that you strive for but never really attain.
Myth: “Pharma companies can get preclinical studies reported faster if the studies are conducted internally.”
This belief could be valid in some situations. As indicated earlier, any research operation can perform admirably if it can focus their Resources on one or two projects. This belief may also prove to be true if a pharma company outsources work to a CRO that doesn’t have the reputation for on-time reporting. In the late 1990s and several years thereafter, pharma companies would often vacillate between outsourcing and conducting work internally.
Whenever they encountered any issue with a CRO, they would often pull work internally thinking that this would address their concerns (e.g., see the myths above). The problem is that this influx of work often taxed the resources of the in-house preclinical operations, which would lead to a return to outsourcing. Today, some individuals in the pharma industry will tell you that they can get preclinical work done so much faster via outsourcing. Some pharma companies have even established virtual organizations that outsource all preclinical activities. We need to remember that conducting and reporting a preclinical study is the CRO business . . . they do it all of the time.
The bottom line: It shouldn’t make any difference whether a study is conducted at a pharma facility or at a CRO if there is proper planning, as well as well-defined work processes and someone with the appropriate oversight to organize the necessary resources. Some CROs have developed a reputation for reliably meeting reporting deadlines. If the work is to be outsourced, the appropriate due diligence should be conducted to determine if a CRO can meet project milestones.
Myth: “Preclinical outsourcing requires fewer staff resources.”
If a pharma company is using preclinical outsourcing to supplement its internal capabilities, then the reality is that additional staff will be required to oversee outsourcing activities. This is actually a key area where pharma companies increase their outsourcing risks because they have been lulled into thinking that additional staff is not necessary. The misjudgment is often compounded when outsourcing planning and oversight is assigned to the same scientists who are already conducting studies at the pharma’s facilities. These individuals are now torn between maintaining their internal responsibilities and providing information to the CROs for the outsourced studies. In these situations, CROs don’t get information in a timely manner, which increases the risk of operational errors.
The bottom line: Thoughtful preclinical outsourcing can be an effective strategy to help control internal staffing in pharmaceutical research operations. At the same time, effective outsourcing requires dedicated staffing.
Myth: “There is a better chance of outsourcing success at a larger CRO.”
After the slowdown in preclinical outsourcing demand from 2008 through 2010 finally ended, capacity began to fill up at smaller CROs faster than larger CROs. While smaller CROs do have less space to fill, it seems that clients were drawn to the individualized attention and more personalized customer service that is purported to exist at these smaller companies. Larger CROs may have more capabilities and facility space than their smaller counterparts, but this does not necessarily mean that larger CROs excel at all aspects of every service that they provide. Pharma companies with a large number of projects in preclinical development will often spread their outsourced work across a number of CROs. While some selections may be based on the CRO having sufficient facility capacity, the pharma company ultimately has to determine which CRO has the best capabilities and experience to conduct their studies. Facility size means nothing if the CRO can’t deliver. We also have learned over the years that, among the large CROs that have multiple sites, some clients may prefer one site over another based on their outsourcing experiences. While large CROs strive to have harmonized capabilities across their sites, performance can vary from site to site.
The bottom line: Clients will outsource work to those CROs that will afford them the best opportunity for outsourcing success based on the reputation of the CRO, the client’s own due diligence, and their past experiences. Just because the infrastructure of a large CRO may be similar to that of a large pharma company, familiarity should not be the sole determining factor in outsourcing decisions.
Myth: “The more you pay, the higher the quality of an outsourced study.”
While some CROs may want you to believe this, a higher price does not necessarily correlate to higher quality. Go back and read the myth about “control.” Mistakes can occur on an expensive study just as easily as they can occur on an inexpensive study. Suggesting that higher prices equates to higher quality is a tactic that either plays off of the client’s fear of failure and/or is reflective of a CRO’s organizational arrogance. In the latter case, just like our first myth, show me a research operation that believes that it is superior to others and I will show you a research operation that is susceptible to quality issues. It’s called “complacency” and it is the cancer of any preclinical research operation. That being said, a low-cost study is no guarantee of acceptable quality or a successful outsourcing experience. If quoted study costs are so low, the client should wonder if sufficient resources will be available to conduct the study successfully and to provide sufficient oversight. Clients should seek bids from at least three CROs before deciding where to place a study. Because of the uncertainty that can go into a low bid, it is best not to award work to that CRO. Unfortunately, the outsourcing policies of some companies require them to accept the lowest bid, so the potential for increased risk exists before the study ever starts. It is also important to be sure that bids are based on equivalent comparisons. A low bidder may not have priced in a key element of the protocol. A high bidder may have inadvertently overpriced a study. This whole process requires effective interactions with those CROs that are bidding for the studies. Client feedback to the CRO helps it to be more effective with their bidding.
When all is said and done, successful preclinical research is not about competition between research operations and it isn’t about facility size or location. No amount of money can buy a guarantee of success or ensure absolute “control” of a preclinical study. You see, these parameters are part of the myths that are commonly used to assess research operations by those who may not understand preclinical research operations. Conducting a critical assessment of capabilities and staff experience, evaluating study and reporting processes, communicating effectively and in a timely manner, and close monitoring of the study conduct are just some of the keys to successful preclinical research regardless of where it is conducted. In the end, the ultimate goal is risk mitigation, but you can’t mitigate risk if you are managing by myths.
Steve Snyder is a consultant with more than 25 years of experience in preclinical toxicology as an outsourcing customer and provider. He can be contacted at email@example.com.