Today's LIMS allow research institutions to monitor and manage a broad array of biomedical research processes end-to-end and remotely. But how do they accommodate the ongoing flood of discoveries in areas such as genetics, the -omics, regenerative medicine and behavior, ongoing adjustments to workflows and protocols, tens of thousands of animals, and the evolution of legislative, welfare quality, and ethics directives?
To find out first hand, I spoke with Dr. Sara Capdevila Larripa DVM, MSc, the Assistant Director of the AAALAC-accredited Animal Facility at the Barcelona Biomedical Research Park (PRBB) in Catalonia, in the northeast of Spain.
Managing the Life Story of One Hundred Thousand Animals
PRBB is one of the largest biomedical research hubs in southern Europe and acclaimed as the area's leader in biomedical translational research.
Fourteen hundred people from 55 countries work there in one of seven Centers. The campus is 50,000 square meters, or nearly 540,000 square feet, located near the sea where natural beauty eclipses the bustle of what is arguably Spain's most stylish city.
The Animal Facility is a Core PRBB Service. As such it houses 50,000 rodents, 50,000 zebrafish, and 400 frogs used by 80-90 research groups. Research groups own their animals, so the LIMS is a platform for management of the animal facility and also a set of subsystems managing each Centre's animal data. The diversity of work at the Park's Centers suggests the breadth and depth required of the Animal Facility LIMS, encompassing everything from organogenesis to finding treatments for neurodegenerative diseases.
Typically 400 users are connecting to animal workflow data at any one time. Each animal's profile will include for example age, strain, matings, and any litters the animal has borne, room where the animal is and the IACUC procedure related to each one. The LIMS allows researchers to export data to EXCEL and to integrate LIMS reports into the research group's software. However individuals may not modify the LIMS by uploading individual research group's data to the central system database; the animal facility staff update it daily.
The Animal and Facilities Management System
When PRBB decided to choose an animal and facilities management system in 2006, they had several special considerations. For one thing, PRBB is five different research institutions in one building. Additionally, they had to find a system that worked for both new and experienced users and would aid them with regulations, reporting, workflows and protocols, ethics committee approvals and more.
They chose a software vendor that worked with them to design the software to meet the facility’s unique needs. To that end, they formed a design team that was made up of software analysts and engineers on the vendor side and experienced facility supervisors, technicians, facility directors, and veterinarians from PRBB. The team met regularly throughout the development process, and the vendor even created screen shots of the software on a regular basis for supervisors and technicians to review.
This resulted in a software that met the individual needs of the facility, that allows for complete traceability for each animal.
Supervisors and Technicians are Analysts and Facilitators
Experienced PRBB supervisors and technicians serve as the LIMS analysts for the vendors programmers and describe adjustments to fit with PRBB needs as they arise.
“Every year new utilities have been added to the LIMS,” Sara told me. “Supervisors know the LIMS inside out. They know the subsystem goals and the strategy to achieve each goal. They foster collaboration, communication, and understanding. Theirs is a work of continuing improvement. They are the LIMS facilitators.”
“Patience, attention to detail and systematic testing,” Mireia Juan, a senior PRBB Animal Facility supervisor says, “help us stay in control of what is happening to every animal, respond to requests from researchers within 48 hours and catch glitches in the system before they become problems.” Mireia has been working with research animals for 15 years. She deals with researcher requests, manages several technicians, monitors the LIMS and serves as the communication link between PRBB and the software vendor.
“It is part of my job to describe the functionality for a new application or workflow change, to commuicate the need to the vendor and to review new functionality live but before we upload it. And when there is a glitch, I can invite the software vendor to my computer to view the problem and start the fix.”
“We have had relatively few glitches,” Sara says. “This is in part because our own supervisors know from daily work what the research community needs. We have senior supervisors who undertake special training and are responsible for two others who are less experienced in informatics. All our veterinarians, supervisors, technicians, and caretakers learn and understand the technology's capabilities, and how to adjust the system to meet evolving research needs.”
Managing Changing Requirements
Facility technicians update the information and the system daily and advise animal owner-researchers of changes such as receipt of new animals, new matings, new litters, or a sacrifice.
There are formal and informal updates of the software. There is a formal update every six months when needed and at last once a year. Every update is coordinated with agreement from all affected personnel. This ensures that the benefits of updating do not produce unexpected interruptions. Someone from PRBB speaks or meets, at least every fortnight though often more, with the vendors client account manager.
Along the way supervisors and technicians are in close ongoing communication with animal facility directors about changes needed. Requests for new utilities are decided at the time of annual budgeting.
The LIMS Platform: A Contribution to the 3Rs
“One of the 3Rs—refinement—is implemented with the use of modular LIMS in the managing of an animal facility,” Sara told me. “Accurate information and communication and shortened workflows at the animal facility facilitates a proper and accurate usage of the animals for research purposes.”
Here is an overview of the PRBB LIMS modules:
- The IACUC Module
This module stores information about approved protocols and specifies records to be kept for each procedure that include anesthesia, suffering, and end point. Violations to IACUC regulations are handled privately by the Animal Welfare Officer and the animal owner, and most problems are handled with dispatch, though all violations are recorded in the IACUC module. Veterinarians can access reported violations.
- The Animal Welfare Module
This module houses information about welfare problems caretakers detect. They enter details of the problem and the system sends an email to a veterinarian requesting examination. After observation and examination, the veterinarian sends the proposal on how to solve each animal issue via the system to the animal’s owner, who confirms how to manage the situation, and action is taken immediately. This system allows that any sickness or welfare issue can be solved very quickly. The Welfare Module is linked to every research group in the research park.
- Mouse Strain Module
This module holds data on 900 strains that includes, for each strain, breeding, characteristics, tics/stereotypies, and developmental/behavioral history.
- Import/Export Module
This module manages and details the movement of animals internationally. The researcher (animal owner) only documents details of an animal's import or export, and animal facility and administration of the institution work together through the LIMS to make that shipment possible. It also includes health monitoring reporting at sending and at receiving. Once the animals have been sent or received, the researched receives an e-mail from the system. So they are always informed. There is a chain of events for every movement of any animal imported to, exported from or moved within the lab. To import ten mice from Breeder A with arrival in two weeks, someone asks for a quotation, waits for quotes, records quotes, requests expense approval, and orders the animals. Breeder A warrants the animal's provenance, health status, and observation at time of shipment. When the animal arrives a medical check is done. The entire history of the animal's movement including details of both visual inspections and physical, medical examinations are managed in a system flowchart. There is no room for error. If someone skips a step, the system will flag that slip-up.
Every step with an animal—surgery, anesthesia, and necropsy, among the dozens of others—takes place within the animal facility’s lab. The Scheduling module handles reservations for room and equipment so any researcher in the institution knows that when he comes to the animal facility he will have the equipment ready for his work.
- Aquatics Module
This module differs slightly from the rodent module in that animals are not identified individually; we identify the individuals by their tank bar codes.
No Mobile Devices?
It is of note that PRBB's animal facility LIMS does not accommodate electronic lab notebooks or input from tablets, iPads or smartphones. Gonzalo Fernández Miranda, a Research Associate at the Institute for Research in Biomedicine (IRB Barcelona) who works in molecular medicine in a group concerned with translational control of cell cycle and differentiation, says this is not surprising and is probably a good thing for now.
“In my day-to-day work I use different LIMS to manage laboratory basic reactives (plasmids, antibodies, cell lines) and animal models such as mice that are housed at PRBB. The PRBB animal facility LIMS is a fine example of how LIMS should evolve. This platform is regularly updated with suggestions from users and managers. It is an indispensable tool.
“Some people wonder why there is no provision for the use of mobile devices, but it seems reasonable to me. After all, it is not known whether and if so how the strong signals generated by Wi-Fi in such a large facility will affect the animals. Without that knowledge—and I have not seen any research in that arena—we dare not risk compromising the research data. At some point someone will investigate and then we will know if it is safe to use Wi-Fi in an animal facility."
The author offers warm thanks to Sara Capdevila Larripa for her time, patience, and help painting a rich picture of the PRBB LIMS. This article originally appeared in ALN Magazine. Helen Kelly is Contributing Editor, International. She may be reached at [email protected]