Common Costs
These are some of the most common cost types you should consider when planning your preclinical study to give yourself the best chance of getting to market as efficiently as possible while focusing on what matters most — obtaining clearance from regulatory bodies.
1. Protocol Writing
Preclinical studies (non-GLP and GLP) require a detailed protocol that is reviewed and approved by the Institutional Animal Care and Use Committee (IACUC). Study directors and principal investigators (PIs) spend a considerable amount of time writing these protocols, which dictate the conduct of the study and eventual data-based results and reports. While preclinical study protocols share some commonality, they are customized for every product and every study. Preclinical protocol writers bear responsibility for the difficult task of translating a small study synopsis into a detailed protocol. Despite the presence of predicates, protocols, or estimates from other CROs or consultants, protocols are typically written in accordance with the standard operating procedures from the CRO you engage to execute the study. Those standard operating procedures may vary considerably.
2. Animal/Model Acquisition
A good preclinical CRO will purchase models from a purpose-bred USDA-approved vendor designed as “Class A” or “Class B.” A healthy model from a trusted vendor is key to the success of a preclinical study. Therefore, it is the best investment you can make. Acquisition costs for your models include quarantine of the animal(s), vaccinations, USDA health records, transportation, and initial health inspections. Costs vary based on the number of models and the number of shipments needed. For example, if you decide to do a study with three models now and three models six months later, you will incur two separate transportation costs.
3. Procedural Costs
The procedural costs take into consideration the length of the procedure and the requisite staff, facilities, equipment, and supplies needed to perform the procedures based on the scope of work.
Breaking these day further, costs increase as the more “bells and whistles” are added to the procedure. For example, an open chest bypass surgery requires an exhaustive amount of supplies and specialized staff including: anesthesia, bypass supplies, perfusionists, surgeons, and other skilled staff compared to a quick interventional study that may only require a sheath, catheter, and fluoroscope.
Planning these studies is no different than a patient undergoing a surgical procedure at a hospital because the same exact supplies in the same exact setting are being used for the execution of these procedures in a sterile fashion.
LABOR
Highly skilled labor is another important component of the procedure cost. Whether you are bringing your own surgeon or the preclinical CRO is providing the surgeon, you must pay for their expertise. If there is a study director, PI, veterinary technicians, or veterinarians involved, those considerations or requirements can also impact cost.
EQUIPMENT
Depending on your procedure, you may require a wide array of equipment including catheter laboratory, ultrasounds, and endoscopes. The equipment requirements are the same as they would be in a human surgical procedure. The CRO shoulders the burden that ensures these pieces of equipment are in compliance with the federal code of regulations as well as the maintenance and calibration records to ensure GLP compliance.
PROCEDURES
Oftentimes there are several procedures for a single preclinical study. For example, after an initial procedure (such as an implantation), there may be a follow-up procedure like a simple imaging study. The number of added procedures increases the overall cost. You will also want to consider whether or not these need to be done in a sedated or anesthetized model because that impacts the amount of supplies and number of personnel involved.
Keep in mind that procedures must be conducted in consideration of animal welfare regulations. There is no compromising on the supplies, equipment, and personnel needed to ensure animal welfare.
PER DIEMS
These are daily charges per model per day paid during the survival period. Per diems include: standard observations, husbandry and standard medications, food, and water. The longer your study is, the higher the per diem total cost. If, for whatever reason, your study stalls or you have the animals waiting between procedures, you must pay the per diems for those days.
4. Observation/Tests/Follow Ups
The procedural portion of a preclinical study does not end with an implantation. Post-implantation care is required. Depending on the objectives of the study, there can be a significant amount of data collected during the survival period. Keep in mind, the type of data collected during the survival period may be influenced by the expectations of a regulatory body. Some of the common costs during a survival period are as follows:
- Subjective, Objective Assessment Plan (SOAP) examinations are conducted by qualified veterinarian or veterinary technician. A quality CRO will always recommend these and include them in a GLP preclinical study. These observations may include neurological exams, body assessments, and gait assessments. The frequency and length of these exams influences cost.
- Clinical pathology like blood or urine tests drive cost as well. A good preclinical study, especially GLP, includes baseline pre-op, post-op, follow up, and terminal blood work. The number of tests conducted and where anatomically will also influence costs. For example, a CBC test is much cheaper than a biomarker analysis.
- Follow up needs such as sensor reading, cage-side ultrasounds, or other tests add time and personnel, which can increase costs as well.
5. Supplies
Supplies includes everything from medication to sutures. There are some standard medications “baked in” like pain medication or antibiotics, however, just like in clinical cases, there may be specific medication needs. For example, your study may require Aspirin and Plavix — a special anticoagulant drug. Of, if there is an adverse event that requires additional mediations, that can impact cost.
Sometimes there are many supplies needed for the initial procedure as well. Many supplies are considered standard, while others are considered specialty such as stents, catheters, special guide wires, etc.
You will also want to consider predicate devices. Are you expecting the vendor to obtain the predicate device? Predicates aren’t always easy to acquire and special vendor agreements can get expensive very quickly.
6. Reporting
A high-quality, comprehensive report requires expertise and time. While some investigators may simply want data for the publications coming out of their lab, often a full report from an independent lab is better for regulatory submission. When required, a reputable preclinical CRO will deliver a comprehensive preclinical final report. This is where it becomes abundantly clear that you get what you pay for.
- Do you want a comprehensive report that does not generate any questions from a regulatory body?
- Do you want just a transfer of data and tables that will require additional processing before it would be ready for publication or submission?
Our final reports for GLP studies include the incorporation of veterinary reports, necropsy reports, histopathology reports, pathology reports, and any other contributing scientist reports, A 1,000-page report will cost more than a 200-page report, however its value lies in the need and appreciation that regulatory reviewers place in a comprehensive, easily reviewable report that’s completed by an independent and experienced team. Our relationships with regulatory bodies helps guide how we assemble these reports.
7. Third-Party Vendors
The culmination of a preclinical study is often histopathology or toxicology. Is the CRO you hired doing that work themselves or are they outsourcing it to third-party vendors? A good CRO will either have the ability to complete this in-house, or recommend a high-quality third-party vendor that will meet your needs.
8. GLP Charges
For a GLP study, most CROs add a GLP surcharge. This charge exists for good reasons. It helps to cover the vast amount of regulatory and compliance work that mostly takes place behind the scenes. This includes quality control personnel who audit all study data in real time, from the implant procedure to the explant procedure and everything in between. The surcharge also includes data verification, archiving and equipment maintenance and calibration, creating and maintaining SOPs, as well as creating and maintaining training records. Quality assurance team members spend countless hours auditing data. The GLP fee ensures this is conducted.
9. Look Out for Hidden Costs
We are often presented with preclinical study estimates from competitive CROs that appear to be far less than what we quote. Don’t be misled by a low-ball preclinical study estimate! When we examine the details between quotes, we often find that it’s not an apples to apples comparison. For example: overages in the operating room. If you budgeted for a three-hour procedure and it runs five hours, are you seeing those costs in the estimate? If you have added personnel, does the estimate include associated charges for supplies? An estimate should be all encompassing and very close to the total final cost when all invoices for services, supplies, etc., are ultimately reconciled and billed.
It is not realistic to expect to have a preclinical estimate fit a predefined, finite dollar amount. Be sure to do your homework by getting estimates from multiple CROs so that you can budget properly.