Steve Snyder10.10.07
Those of you who read this column each month know that I believe that the three key components to conducting preclinical toxicology studies are facility space, the ready availability of appropriate laboratory animals, and an experienced staff. If a preclinical research component has significant operational issues in any of these areas, the probability of a successful outcome for a study can decrease dramatically. In the September issue of Contract Pharma ("In Recognition"), I highlighted just a few of the key roles that are critical to the conduct of preclinical studies. One critical role that I did not address in that article but is no less important to any research operation is that of the facilities manager.
I recently had the opportunity to interview Terry Receveur who is the Director of Production for Taconic Farms, Inc. Terry has more than 22 years of direct laboratory animal facility management experience that includes opportunities in not-for-profit, academic, pharmaceutical, and animal supply organizations. His education includes a BS in Animal Science, an MBA in Finance, an AALAS (American Association of Laboratory Animal Science) certification, and a Six Sigma Green Belt. Since Terry is a recognized industry expert in facility management, I thought you might benefit from his behind-the-scenes perspective.
Steve Snyder: What is AAALAC accreditation and why is it important for preclinical research facilities?
Terry Receveur: Often referred to as AAALAC accreditation, the term is an acronym for the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC Int.). "AAALAC Int. is a private, nonprofit organization that promotes the humane treatment of animals in science through voluntary accreditation and assessment programs. More than 700 institutions around the world have earned AAALAC International accreditation, demonstrating their commitment to responsible animal care and use. They include universities, hospitals, government agencies, pharmaceutical and biotechnology companies, and other types of research organizations. AAALAC has been working to promote animal well-being and enhance life sciences research and education since 1965".1
AAALAC Int. accreditation is important to preclinical research because it provides a consistent quality standard for organizations to measure against. When researchers or regulatory agencies review data generated in facilities that are AAALAC Int. accredited, they have a high comfort level that the research was conducted in a manner that controlled many of the unwanted environmental variables. Additionally, any Contract Research Organization (CRO) that conducts research in an AAALAC Int. accredited facility will have a competitive advantage over those that do not. It is also important to note that many government contracts specifically require, in their Request For Proposal (RFP), AAALAC Int. accreditation.
SS: I routinely advise clients that one way that they can assess operational performance is to assess the appearance (i.e., cleanliness) of a preclinical research facility. What are the items that you look at to assess the effectiveness of facility management?
TR: A good sanitation program is imperative to a quality preclinical research facility and operation. A quick assessment involves two phases: 1) visual; and 2) record keeping.
Visual -- A quick visual inspection of the less apparent areas; such as cage washer pits, tunnel washer screens, chemical pits, animal room waste trenches, animal and/or procedure room sinks, procedure room cabinets and drawers, and carcass/waste chill rooms are all a good place to gauge institutional commitment to sanitation.
Record Keeping -- As in any quality AAALAC Int. accredited facility, there will be a very good documentation trail of all sanitation practices. The basic Good Laboratory Practices (GLP) rule, "If it isn't documented, it didn't happen," holds true in a sanitation program as well. Ask for sanitation records of some of the more obscure areas mentioned above and the extent and availability of such records can be a great indicator of overall effectiveness of the facility management.
SS: In previous articles, I have contended that a growing workload is beginning to overwhelm the workforce, particularly in preclinical operations, where there are initiatives to diminish overall headcount or remain headcount neutral. From a facility management perspective, what are the signs that suggest that a preclinical operation is overburdened?
TR: When funds become tight and resources limited, sanitation is one of the first things to suffer. Some quick indicators are procedure support areas, corridors, and storage rooms. Most institutions recognize that the animal room will be under the most scrutiny and will generally keep up with the sanitation requirements. A quick look at the general condition of a procedure support room can be very telling. A good AAALAC Int. accredited facility will have sanitation logs for all phases of the operation. The lack of a well documented sanitation program in the support areas can be an indication of other issues.
SS: What are some of the current trends in facility management?
TR: Preclinical research facilities are feeling the societal pressure of high drug prices and every effort to reduce overall cost of operation is at the forefront. Many facilities are turning to outsourcing as a way to reduced fixed costs. Some of the more routine tasks, traditionally limited to internal staff, are now being performed by contract labor. General facility housekeeping services, cage wash operations, and in some instances basic animal husbandry are now being performed by an outsourced partner.
Automation is another trend being pursued in order to reduce costs. We all know that Full Time Equivalents (FTEs) are one of the most expensive components of operations and any initiative that can reduce labor cost is worth looking at. There are some pretty exciting automation initiatives going on that could change the way we do business. New cage wash robots, automated bottle filling systems, bedding dispensers, cage transport robots, and rotary racks are all worth looking into.
Disposables are another trend being considered and piloted. There are some new caging systems on the market now that really make you look at the cost of processing caging. Disposable watering bags are becoming a very cost effective alternative to the ergonomically intense process of bottle washing and filling. Disposable isolation gowns and lab coats are now the standard. The low cost of these items makes it financially illogical to incur the costs of processing reusable items.
SS: Some sponsors will outsource their preclinical development work while they may have internal resources (facility space, laboratory animals, and/or research staff) that may be underutilized. Can you explain the costs involved in maintaining underutilized research capabilities?
TR: The cost of maintaining an underutilized facility can be very high depending on the age and level of depreciation of the building. Certain fixed costs are incurred regardless of whether the building is fully occupied or not. Facility rent/mortgage, depreciation, insurance, real estate taxes, etc. are all expenses incurred based on total square feet of the building. It varies very little whether the space is occupied or not. Electricity, gas, water, and general maintenance costs will still be accrued in unused areas as well. If a facility is not kept up by running equipment, performing general housekeeping, and keeping up with the preventative maintenance program (filters, belts, lubrication, etc.), it can be a very daunting and expensive task to restart operations. We all know of the pains of having underutilized staff. It can be a managerial nightmare when staff have free time on their hands. They may be constantly worried about their job security and can be very disruptive to others who are busy. Staff like to be kept busy.
SS: Given the increasing demand for preclinical outsourcing, what are your thoughts on the future of preclinical research facilities at Pharma and Biopharma companies? Do you see these companies building new preclinical facilities or do you believe that this work will continue to be outsourced?
TR: We are at a crossroads for determining what will happen in the future. I define preclinical outsourcing in two realms: 1) traditional toxicology profiling; and 2) discovery research. CROs have a long and successful history of providing toxicology support and I don't see this diminishing. This component of CRO work is very standardized and companies have proven successful procedures. As mentioned in one of your previous articles, the level of resources available to meet the demand of Pharma or Biopharma is a concern. Quality will definitely diminish in an understaffed operation. The second component, discovery research outsourcing, is in its infancy and CROs do not yet have a strong process for accommodating the highly flexible requirements. If CROs can deliver quality data to its discovery customers then the market will explode. If they continue to struggle with understanding the needs of discovery research, Pharma and Biopharma will resource internally.
SS: What are your views on preclinical research outsourcing in China and India? From a facilities perspective, what challenges do you see?
TR: The biggest challenge I see is mostly cultural. Animals in China and India often are not held in the same high regard as they are in Western cultures. The media has led us to believe that China has struggled with human rights, so it may be very difficult to commit the appropriate level of resources to provide the level of animal care that the Western countries expect. China and India do not yet have the intense level of oversight for animal welfare as do Western countries. Additionally, some of the basic needs for appropriate animal care are frequently not intuitively considered. For example, it has been reported that there is a facility in China that would provide animal drinking water from a collection cistern of rain runoff water from the roof. The overall control of environmental variables is a big challenge for facilities in China or India.
In China, facilities are built in a very different way than we are used to in the U.S. Chinese firms will often build a shell building and then retrofit to the needs of the tenant. This creates huge logistical issues for a specialized animal research facility. Retrofitting for waste trenches, floor drains, cage washer and chemical pits, automated water systems, etc. is very difficult and costly.
One of the biggest hurdles in outsourcing to China or India will be overcoming the stigma that companies are doing so in order to avoid the stringent animal welfare requirements of the U.S. This challenge will need to be overcome by the U.S. regulatory agencies and the general population.
SS: You have already discussed AAALAC accreditation. What are the regulations that govern preclinical research facilities?
TR: The use of animals in research is highly regulated. It begins with the Animal Welfare Act (AWA), which sets forth standards for the care and treatment of laboratory animals, including housing, feeding, cleanliness, ventilation and veterinary care (currently, AWA regulations do not cover rats and mice bred specifically for research). All facilities using laboratory animals covered under the AWA must register with and be inspected by the United States Department of Agriculture's enforcement arm, the Animal and Plant Health Inspection Service (APHIS). It is the responsibility of APHIS -- through random, unannounced inspections -- to ensure that institutions are complying with all USDA regulations. The Animal Welfare Act also requires that each institution establish an Institutional Animal Care and Use Committee (IACUC), which is responsible for evaluating the total animal care program, as well as for scrutinizing all proposed animal experiments. The committee must include at least one person who is unaffiliated with the institution and one veterinarian. Researchers proposing a procedure must explain to the committee in writing the number of animals they plan to use, why a certain species is necessary, and what steps will be taken to prevent unnecessary suffering. The committee has the power to reject any research proposal and stop ongoing projects if it believes USDA standards are not being met. Any institutions receiving grants from the U.S. Public Health Service (PHS) must adhere to its animal welfare assurance Policy. Under the terms of the Policy, not only must institutions adhere to the AWA, they also must follow the detailed recommendations on animal care and treatment that are contained in a book called the Guide for the Care and Use of Laboratory Animals (Guide). The Guide is published by the Institute of Laboratory Animal Resources. The PHS policy covers all animals, including rats and mice. The Health Research Extension Act of 1985 (Public Law 99-158) provides the legislative mandate for the PHS Policy. The Office of Laboratory Animal Welfare, or OLAW (formerly the OPRR Division of Animal Welfare) implements the PHS Policy.2
In this interview, we learned that there is much more that goes on in a laboratory animal research operation than what is evident even to those who utilize the facility. Effective facility management is essential for any research operation. There are some in research management who regard this role as the most critical in a research operation. This is encouraging, as it suggests a realization that there is more to a research facility than bricks and mortar. Like many other roles in preclinical research, facility management is one of those infrastructure jobs that get the most attention when something goes wrong. I have noted in the past that people conduct research, not facilities. Based on what we learned above, it follows then that it is one thing to build a research facility but quite another to effectively operate it according to regulatory, scientific and operational standards.
References
AAALAC International website: http://www.aaalac.org/accreditation/rules.cfm#definitions
Foundation for Biomedical Research website: http://www.fbresearch.org/education/laws.htm
I recently had the opportunity to interview Terry Receveur who is the Director of Production for Taconic Farms, Inc. Terry has more than 22 years of direct laboratory animal facility management experience that includes opportunities in not-for-profit, academic, pharmaceutical, and animal supply organizations. His education includes a BS in Animal Science, an MBA in Finance, an AALAS (American Association of Laboratory Animal Science) certification, and a Six Sigma Green Belt. Since Terry is a recognized industry expert in facility management, I thought you might benefit from his behind-the-scenes perspective.
Steve Snyder: What is AAALAC accreditation and why is it important for preclinical research facilities?
Terry Receveur: Often referred to as AAALAC accreditation, the term is an acronym for the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC Int.). "AAALAC Int. is a private, nonprofit organization that promotes the humane treatment of animals in science through voluntary accreditation and assessment programs. More than 700 institutions around the world have earned AAALAC International accreditation, demonstrating their commitment to responsible animal care and use. They include universities, hospitals, government agencies, pharmaceutical and biotechnology companies, and other types of research organizations. AAALAC has been working to promote animal well-being and enhance life sciences research and education since 1965".1
AAALAC Int. accreditation is important to preclinical research because it provides a consistent quality standard for organizations to measure against. When researchers or regulatory agencies review data generated in facilities that are AAALAC Int. accredited, they have a high comfort level that the research was conducted in a manner that controlled many of the unwanted environmental variables. Additionally, any Contract Research Organization (CRO) that conducts research in an AAALAC Int. accredited facility will have a competitive advantage over those that do not. It is also important to note that many government contracts specifically require, in their Request For Proposal (RFP), AAALAC Int. accreditation.
SS: I routinely advise clients that one way that they can assess operational performance is to assess the appearance (i.e., cleanliness) of a preclinical research facility. What are the items that you look at to assess the effectiveness of facility management?
TR: A good sanitation program is imperative to a quality preclinical research facility and operation. A quick assessment involves two phases: 1) visual; and 2) record keeping.
Visual -- A quick visual inspection of the less apparent areas; such as cage washer pits, tunnel washer screens, chemical pits, animal room waste trenches, animal and/or procedure room sinks, procedure room cabinets and drawers, and carcass/waste chill rooms are all a good place to gauge institutional commitment to sanitation.
Record Keeping -- As in any quality AAALAC Int. accredited facility, there will be a very good documentation trail of all sanitation practices. The basic Good Laboratory Practices (GLP) rule, "If it isn't documented, it didn't happen," holds true in a sanitation program as well. Ask for sanitation records of some of the more obscure areas mentioned above and the extent and availability of such records can be a great indicator of overall effectiveness of the facility management.
SS: In previous articles, I have contended that a growing workload is beginning to overwhelm the workforce, particularly in preclinical operations, where there are initiatives to diminish overall headcount or remain headcount neutral. From a facility management perspective, what are the signs that suggest that a preclinical operation is overburdened?
TR: When funds become tight and resources limited, sanitation is one of the first things to suffer. Some quick indicators are procedure support areas, corridors, and storage rooms. Most institutions recognize that the animal room will be under the most scrutiny and will generally keep up with the sanitation requirements. A quick look at the general condition of a procedure support room can be very telling. A good AAALAC Int. accredited facility will have sanitation logs for all phases of the operation. The lack of a well documented sanitation program in the support areas can be an indication of other issues.
SS: What are some of the current trends in facility management?
TR: Preclinical research facilities are feeling the societal pressure of high drug prices and every effort to reduce overall cost of operation is at the forefront. Many facilities are turning to outsourcing as a way to reduced fixed costs. Some of the more routine tasks, traditionally limited to internal staff, are now being performed by contract labor. General facility housekeeping services, cage wash operations, and in some instances basic animal husbandry are now being performed by an outsourced partner.
Automation is another trend being pursued in order to reduce costs. We all know that Full Time Equivalents (FTEs) are one of the most expensive components of operations and any initiative that can reduce labor cost is worth looking at. There are some pretty exciting automation initiatives going on that could change the way we do business. New cage wash robots, automated bottle filling systems, bedding dispensers, cage transport robots, and rotary racks are all worth looking into.
Disposables are another trend being considered and piloted. There are some new caging systems on the market now that really make you look at the cost of processing caging. Disposable watering bags are becoming a very cost effective alternative to the ergonomically intense process of bottle washing and filling. Disposable isolation gowns and lab coats are now the standard. The low cost of these items makes it financially illogical to incur the costs of processing reusable items.
SS: Some sponsors will outsource their preclinical development work while they may have internal resources (facility space, laboratory animals, and/or research staff) that may be underutilized. Can you explain the costs involved in maintaining underutilized research capabilities?
TR: The cost of maintaining an underutilized facility can be very high depending on the age and level of depreciation of the building. Certain fixed costs are incurred regardless of whether the building is fully occupied or not. Facility rent/mortgage, depreciation, insurance, real estate taxes, etc. are all expenses incurred based on total square feet of the building. It varies very little whether the space is occupied or not. Electricity, gas, water, and general maintenance costs will still be accrued in unused areas as well. If a facility is not kept up by running equipment, performing general housekeeping, and keeping up with the preventative maintenance program (filters, belts, lubrication, etc.), it can be a very daunting and expensive task to restart operations. We all know of the pains of having underutilized staff. It can be a managerial nightmare when staff have free time on their hands. They may be constantly worried about their job security and can be very disruptive to others who are busy. Staff like to be kept busy.
SS: Given the increasing demand for preclinical outsourcing, what are your thoughts on the future of preclinical research facilities at Pharma and Biopharma companies? Do you see these companies building new preclinical facilities or do you believe that this work will continue to be outsourced?
TR: We are at a crossroads for determining what will happen in the future. I define preclinical outsourcing in two realms: 1) traditional toxicology profiling; and 2) discovery research. CROs have a long and successful history of providing toxicology support and I don't see this diminishing. This component of CRO work is very standardized and companies have proven successful procedures. As mentioned in one of your previous articles, the level of resources available to meet the demand of Pharma or Biopharma is a concern. Quality will definitely diminish in an understaffed operation. The second component, discovery research outsourcing, is in its infancy and CROs do not yet have a strong process for accommodating the highly flexible requirements. If CROs can deliver quality data to its discovery customers then the market will explode. If they continue to struggle with understanding the needs of discovery research, Pharma and Biopharma will resource internally.
SS: What are your views on preclinical research outsourcing in China and India? From a facilities perspective, what challenges do you see?
TR: The biggest challenge I see is mostly cultural. Animals in China and India often are not held in the same high regard as they are in Western cultures. The media has led us to believe that China has struggled with human rights, so it may be very difficult to commit the appropriate level of resources to provide the level of animal care that the Western countries expect. China and India do not yet have the intense level of oversight for animal welfare as do Western countries. Additionally, some of the basic needs for appropriate animal care are frequently not intuitively considered. For example, it has been reported that there is a facility in China that would provide animal drinking water from a collection cistern of rain runoff water from the roof. The overall control of environmental variables is a big challenge for facilities in China or India.
In China, facilities are built in a very different way than we are used to in the U.S. Chinese firms will often build a shell building and then retrofit to the needs of the tenant. This creates huge logistical issues for a specialized animal research facility. Retrofitting for waste trenches, floor drains, cage washer and chemical pits, automated water systems, etc. is very difficult and costly.
One of the biggest hurdles in outsourcing to China or India will be overcoming the stigma that companies are doing so in order to avoid the stringent animal welfare requirements of the U.S. This challenge will need to be overcome by the U.S. regulatory agencies and the general population.
SS: You have already discussed AAALAC accreditation. What are the regulations that govern preclinical research facilities?
TR: The use of animals in research is highly regulated. It begins with the Animal Welfare Act (AWA), which sets forth standards for the care and treatment of laboratory animals, including housing, feeding, cleanliness, ventilation and veterinary care (currently, AWA regulations do not cover rats and mice bred specifically for research). All facilities using laboratory animals covered under the AWA must register with and be inspected by the United States Department of Agriculture's enforcement arm, the Animal and Plant Health Inspection Service (APHIS). It is the responsibility of APHIS -- through random, unannounced inspections -- to ensure that institutions are complying with all USDA regulations. The Animal Welfare Act also requires that each institution establish an Institutional Animal Care and Use Committee (IACUC), which is responsible for evaluating the total animal care program, as well as for scrutinizing all proposed animal experiments. The committee must include at least one person who is unaffiliated with the institution and one veterinarian. Researchers proposing a procedure must explain to the committee in writing the number of animals they plan to use, why a certain species is necessary, and what steps will be taken to prevent unnecessary suffering. The committee has the power to reject any research proposal and stop ongoing projects if it believes USDA standards are not being met. Any institutions receiving grants from the U.S. Public Health Service (PHS) must adhere to its animal welfare assurance Policy. Under the terms of the Policy, not only must institutions adhere to the AWA, they also must follow the detailed recommendations on animal care and treatment that are contained in a book called the Guide for the Care and Use of Laboratory Animals (Guide). The Guide is published by the Institute of Laboratory Animal Resources. The PHS policy covers all animals, including rats and mice. The Health Research Extension Act of 1985 (Public Law 99-158) provides the legislative mandate for the PHS Policy. The Office of Laboratory Animal Welfare, or OLAW (formerly the OPRR Division of Animal Welfare) implements the PHS Policy.2
In this interview, we learned that there is much more that goes on in a laboratory animal research operation than what is evident even to those who utilize the facility. Effective facility management is essential for any research operation. There are some in research management who regard this role as the most critical in a research operation. This is encouraging, as it suggests a realization that there is more to a research facility than bricks and mortar. Like many other roles in preclinical research, facility management is one of those infrastructure jobs that get the most attention when something goes wrong. I have noted in the past that people conduct research, not facilities. Based on what we learned above, it follows then that it is one thing to build a research facility but quite another to effectively operate it according to regulatory, scientific and operational standards.
References