The content of the next few sentences may be disturbing to read. My hope is that by the end of this article, you will be ready to channel your disgust into action. I am writing this article in mid-April. Over the past two days, I have learned from multiple independent sources of the accidental death of a monkey at a preclinical facility in the U.S. I contacted the CRO and its communications department has confirmed this incident. Apparently, a live monkey was accidentally sent through a cagewash machine at the facility.

This is the third incident of accidental deaths of monkeys in the U.S. preclinical CRO site within the last 18 months. One of these previous incidents also occurred at the same facility while the other occurred elsewhere. The other incidents are well known in the industry and don’t require elaboration here other than the fact that they help to comprise a deplorable trend. Again, we will hear the same words about commitment to animal welfare, employee training, and oversight. In my opinion, past remediation steps have been ineffective. As these incidents have shown, there is a difference between talk and results. I know: It was an accident. I will be the first to say that accidents do happen in preclinical operations but we now have more than 30 accidental monkey deaths in the industry within the last 18 months. All but one of these deaths occurred at a single facility. There are others in the CRO industry who are reading this article and starting to squirm in their chairs because they know that a similar accident could happen in their own facilities. Everyone in CRO management must understand that this same type of accident can happen at any preclinical facility anytime. I think we lean too much on the word “accident,” as if to suggest that these situations can’t be controlled. The word we should be using is “unacceptable”; that is the position we should take.

What are the root causes of these accidents? Clearly, it was human error. But were there other contributing factors? Did rapid industry expansion create excessive employee workloads that compromised quality? Did layoffs leave key functions understaffed or impact employee morale to the point that there was a loss of focus? Has staff been hired with appropriate qualifications or have these operational issues been the result of low-cost staffing strategies? While these are legitimate questions that are worthy of discussion, the bottom line is that precious laboratory animals have needlessly died. Despite all of the rhetoric, there is nothing to prevent this from happening again and again anywhere in the industry. It needs to stop and it needs to stop now. It is time for action.

In the past few weeks, I have had the opportunity to meet the senior management personnel from several preclinical CROs who have told me that they are avid readers of my articles. That’s good, because the message I have is for CRO management, CRO employees, and CRO customers and consultants.

Preclinical CROs in the U.S. are governed by the FDA’s Good Laboratory Practice (GLP) regulations. The care and well-being of laboratory animals is governed by the Animal Welfare Act which is enforced by the USDA. Together these regulations guide the conduct of preclinical research. Did you know that it is possible to conduct preclinical research where the operational quality is poor (e.g., monkeys are accidentally killed) yet the research is still compliant with these regulations? Based on recent history, these regulations are not enough to assure operational quality. Accordingly, I call on the preclinical CRO industry, customers, and consultants to seek and insist on higher industry standards. Let me be clear, I am not seeking more federal regulations. What I want and what I believe everyone affiliated with the preclinical CRO industry should demand is a set of performance standards that become the new model for how preclinical research is conducted. Perhaps we should call these “BLPs” or “Best Laboratory Practices.” Here are performance standards that I think should be established immediately:

Eliminate accidental deaths in cagewash machines

Every CRO should establish detailed written procedures for how animal cages should be cleaned in a way so that animals do not inadvertently go through and die in a cagewash machine. The new expectation should be that ALL cages will be double-checked by two separate individuals before any cage is washed. This activity should be documented and subject to review by the CRO’s Quality Assurance Unit. If establishing this performance standard opens this process to FDA and USDA scrutiny, that is fine with me. Clearly, this process is crying out for more oversight. Compliance with this standard should be the basis for continuing employment for employees and management, whether an accidental death occurs or not. By the way, if you are in CRO management and you don’t agree with this proposal, send me an E-mail at [email protected]. I would love to understand how you would justify not doing everything possible to eliminate accidental deaths of this kind in your facility.

Revamp animal welfare training

Every employee should go through a robust animal welfare training program. Many CROs have these programs in pace. If they were effective, I wouldn’t be writing this column. The new expectation is that animal welfare training requires more than employees’ signatures documenting that they sat in a conference room – and possibly slept through – a lecture on animal welfare. All CRO management and research oriented employees should be required to participate in the facility’s animal environmental enrichment program at least one day each year. For CRO management, if you want to be an effective leader then you need to experience what it takes to care for these animals. As for the rest of the staff, mistakes are less likely to occur if the organizational expectation for animal care is practiced rather than preached.

Establish failsafe (i.e., human-proof) procedures for animal room environmental conditions

Effective procedures should be established to assure that facility environmental conditions are controlled, checked, and double checked. Processes should be reviewed to make sure that there is no possibility that animal welfare can be compromised by human error. The new expectation is that there is no possible way that an environmental excursion can go undetected and not addressed in a timely manner.

Establish failsafe (human-proof) procedures food and water availability and animal welfare observations

Effective procedures should be established to assure and verify that animals have ample access to food and water. Automated watering systems need to be checked daily. The connections of the water line to the cage and/or water bottles need to be checked at least daily. The new expectation is that all animals will be observed multiple times each day whether they are actively involved in research activities or not.

Establish minimum training times for new employees

CROs will establish minimum timeframes for training before new employees are permitted to work with animals and before they are permitted to work alone. While many CROs have some type of guidance in this area, the pressure to bring new capacity on-line has forced less experienced staff into “production mode” faster and faster. These individuals are not adequately trained and the likelihood for operational mistakes increases dramatically. Management needs to rethink the benefit of rushing inexperienced staff into revenue generating activities versus the loss of revenue and reputation due to mistakes made by these individuals.

Establish minimum time-in-job requirements

I keep hearing that the workforce today isn’t satisfied to stay in technical roles but would rather use these jobs as a stepping stone to higher paying positions. Tough! There are millions of unemployed people that would do anything to get the salary and benefits of today’s CRO technical workforce. Perhaps recruiting efforts should be adjusted accordingly. CRO management needs to establish the expectation to all new and existing employees that there are minimum time-in-job requirements. I am all in favor of career development once an individual has provided a substantial contribution to the company. Employee turnover and transition leads to operational inconsistency and inexperience. This is prime breeding ground for operational errors. The last I checked, it was the CRO management that were supposed to be running the company.

Reassess the effectiveness of existing management teams

Re-evaluate the performance of each person in CRO management from the site general manager to frontline supervisors. Does management arrogance so deflate morale that the staff is worried about everything except critical responsibilities? Are frontline supervisors covering for ineffective personnel because they don’t want to look bad? Is asking for help regarded as a sign of weakness? Is there competition among various departments in your organization? If you can answer “yes” to any of these questions, you have an operational problem. If you are in senior management in a CRO, would someone proactively tell you if anything is wrong in the organization? If your answer is “yes,” are you sure? If this has happened, were you receptive to the feedback or did you “shoot the messenger”? If your answer was “no,” why wouldn’t someone proactively approach you? The problem in this business is that not all scientists make the best managers and the best managers don’t always understand preclinical operations even though they think they do. While it may be challenging to establish this initiative as a performance standard in the industry, in my opinion this area is the root cause of most operational issues. If you are a customer or consultant and have management concerns at a CRO, address these concerns with senior CRO management. You will be doing them a favor.

Commit to issuing a press release should an accidental death occur in a non-rodent species

I know, CRO management teams are rolling their eyes at this suggestion because this could hurt their business. And they’re darn right it will! You see, this performance standard will measure your level of commitment to eliminate accidental deaths. Consider the following:

• Even if you think that the news of an accidental death can be kept quiet, the news will leak from your organization and spread among the industry, leaving potential clients wondering what you were trying to hide. That will be their perception. In the U.S., you need to report the incident to the USDA and it will eventually become available through the Freedom of Information Act, so not sharing this information proactively could end up looking deceptive.
• If your CRO is publicly traded, consider that a press release may avoid the appearance that your company was trying to keep bad news from potential investors and/or protect your stock price. For long-term success, it would be best to focus on leading your company and not trying to manage Wall Street.
• Perhaps most importantly, if you are willing to take a stand and issue a press release in the event of an accidental death in future, I can virtually guarantee that you will eliminate this concern, because your staff will align behind you and embrace your commitment. Knowing that the news of accidental deaths will be shared publicly will provide extra motivation to eliminate this possibility in your company. That’s called leadership. If you are not willing to adopt this performance standard, that could suggest to your staff (and the readers of this article) that you may not be committed to preventing – or, worse yet, you may not believe that you can prevent – accidental deaths in your operations. In my opinion, if the fear of looking bad is the driving force behind how you conduct your business, that fear will paralyze your employees, accidents will occur, and your business will look bad.

If you are in CRO management and are still reading this article, you must be thinking that my proposals above are going to cost you time and money. You are absolutely correct, so let me give you a few tips: hand out a few less baseball tickets to clients; scale back on your use of the company plane; cut back on those client dinners where absolutely zero business is transacted; send fewer people to national meetings; and, instead of laying off the staff that could be preventing accidental deaths, rethink your marketing budget. No one really buys the hype. Customers place work based on performance and I am sure they would give up a few treats to save the lives of research animals. Even, if you aren’t swayed by moral obligations, when you consider the revenue that can be lost and the damage that can be done to your company’s reputation due to an accidental death, is there any amount of money that is too much to eliminate the potential for this problem? If you really want to be considered a leader in this industry, I have given you the opportunity to start acting like one. All preclinical CROs should jump at the chance to embrace the performance standards above.

If you are preclinical CRO customer or an industry consultant, I ask that you embrace these performance standards as well. The next time you visit a CRO or are requesting a bid for a study, ask them about their processes to prevent accidental deaths. Compare their answers to the list of performance standards above. The only way the industry is going to change is if customers raise their expectations. If you aren’t swayed by moral obligations, consider that the next time this happens, it could be an animal on your study and your company’s name could be affiliated with the horrible incident as media reports it over and over again. If you determine that a CRO has not embraced these performance standards, consider taking your business to one that will.

In closing, I have one final question for everyone who is reading this article: If these performance standards will eliminate unacceptable animal deaths, why wouldn’t you embrace them? Each of you can make a difference by exerting your influence and expecting more. It is time for action.

Steve Snyder is a consultant with more than 25 years of experience in preclinical toxicology as an outsourcing customer and provider.