A new medical device’s or product’s pathway from concept to cure to commercialization is fraught with pitfalls, setbacks and usually significant financial investment. T3 Labs prides itself in delivering value-based excellence in what we consider phase 2 of this process, preclinical testing.
We are often asked by prospective sponsors for in vivo preclinical studies that are premature. Is the technology successful on bench tests or in vitro? Has a pilot study been performed to verify basic functionality and initial biological response before a GLP study for regulatory submissions? Are there design refinements that could be implemented? We have saved our sponsors thousands dollars by addressing those issues early and implementing improvements, so that when you are ready for preclinical testing, you have the greatest opportunity to make the most of that investment in compliance with regulatory requirements.
Once it’s “go time,” how do you design an efficient in vivo preclinical testing study? What are the top requirements that give the greatest chances for success?
Establishment of study goals
Generally speaking, there are three types of preclinical studies and associated goals needed to advance the product lifecycle.
- Proof of concept. Is there a predicate, or is it a novel technology? Regardless, once the technology has proven itself via bench or in vitro testing, a preclinical proof of concept study should come first to identify the most optimal animal model, demonstrate trouble-free use, and basic functionality.
- Feasibility. Having proven the concept in vivo, the next step before engaging in a GLP (Good Laboratory Practice, 21CFR Part 58) study is a small scale non-GLP pilot study intended to further validate the proof of concept, to show benefits of latest refinements, reveal potential risks, and establish reproducible workflow and solid means of data collection.
- Safety & efficacy. Based on the regulatory requirements, proving the device’s safety and efficacy in a clinically relevant model of human disease along with the GLP reports required by the FDA concludes an efficient preclinical study design and cycle.
Understanding the study process
Our sponsors’ journey begins with our business development team comprised of professionals with significant scientific experience and a passion for their areas of expertise, that will help you develop your preclinical program – including the optimal model. Selecting the right, clinically relevant in vivo model is an essential component to the study’s efficiency and quality. If a large animal model is needed, are there any species specific sizing, anatomical or physiological variables? Is one or the other significantly more clinically relevant / required for regulatory FDA review? What are the required endpoints, sample size and target anatomy? These are questions that the team will answer together based on many years of preclinical experience, more than over 60 GLP studies archived and 35 products granted regulatory approval. Refinement of the study design with wisely selected endpoints will always lead to quality data. For maximum efficiency, multiple separate studies may have to be initiated to provide clear cut data and stay on top of submission timelines.
Quotes, confidentiality agreements and contracts defining the scope of work and protecting precious intellectual property result from this initial interaction.
The scope or statement of work we expect from our sponsor usually includes
- Species and quantity (if known)
- Deliverables (Type of services, need for final reports, need for histology, etc.)
- Any speciality supplies
The next step is the development of the preclinical study protocol and securing IACUC approvals. The study director or PI will work closely with the sponsor to develop the study protocol that includes the species and quantity along with a rationale for selection, study design, objectives, names of the test and control articles, steps for using the test article, in-life observation requirements, endpoints and data retention.
The execution of the study begins, followed by the delivery of data and reports, QAU and an audit with reconciliations. In a GLP scenario, these data are the backbone of regulatory requirements needed to advance a device or product into the third stage of development.
Identification, engagement and commitment of key players
There are approximately seven roles needed to engage in an efficient preclinical testing study.
- Sponsor. The medical product developer. By formal regulatory definition, a sponsor means a person who initiates and supports by provision of financial or other resources, a non clinical laboratory study and submits the study in support of an application for a research or marketing permit. These range from large, publicly traded companies, for e.g St. Jude Medical, to startups like Matrix Surgical or Cormatrix to individual innovators like Dr. Hunter Moyer and Vivid LED Technologies.
- Study director / Principal Investigator / Program Manager. These are the scientists with proven capabilities of successfully coordinating and leading preclinical studies in a range of products, often with significant experience in at least one or two therapeutic areas such as cardiovascular, orthopedics, GI, drugs and biologics, etc. Per regulatory definition, the study director has overall responsibility for the technical conduct of the study, as well as for the interpretation, analysis, documentation and reporting of results, and represents the single point of study control. The Principal Investigator plays a similar role, for a contributing scientist report or a non-GLP study.
- Quality Assurance. Trained professionals that independently monitor the execution of a preclinical GLP study and assure compliance with the protocol and test facility SOPs. By definition, the quality assurance unit is responsible for monitoring the study to assure test facility management that the facilities, equipment, personnel, methods, practices, records and controls are in conformance with regulations.
- Operator/Test device Evaluator. Can be an in-house veterinarian, a physician or a third-party with experience performing the type of procedure required in the appropriate animal model. While a physician is typically the subject matter expert, in many cases, working side by side with a veterinarian who is familiar with the anatomy is advisable.
- Veterinarian/ Veterinary Personnel. The overall health of the animals and the ability to extract quality data should be of paramount importance. The veterinarian and/or veterinary personnel should demonstrate successful expertise, evaluate the health of and care for the animals in accordance with acceptable veterinary medical practice and ensure adherence to USDA, AAALAC and animal welfare guidelines.
- Clinical expert / key opinion leader. When possible, engage these highly recognized physicians or industry leaders at any stage of preclinical testing for instant feedback and expert advice – guaranteed to speed up product development and approval pathway.
- Contributing scientists. Multiple members either from the sponsor’s team, the preclinical CRO’s team, other facility or lab staff and/or independent subject matter experts (engineers, chemists, imaging, histopathology, clinical pathology experts, imaging etc.) will all be needed to successfully and efficiently complete the preclinical study. The study director will gather theses individual reports and summarize findings in the final preclinical study report.
Setting realistic expectations in data acquisition
We have executed GLP studies to completion in as few as eight days. To be clear, that is the exception, not the rule. We have also executed years-long translational studies in the interest of determining very late responses to new devices versus the current standard of care.
Medical product developers should anticipate the following ranges, even in highly efficient preclinical studies, depending on predicate products, truly novel solutions and the type of regulatory approval required.
- Contracting: Zero to 8 weeks. This is highly dependent upon the complexity of the scope of work and negotiations between the sponsor and test facility.
- Sponsor facility audit including program and protocol development: 1-4 weeks.
- IACUC approval: 10 business days.
- Supplies and equipment acquisition: 1-4 weeks.
- Study execution: Dependent on the length of the study.
- Contributing reports: 2-16 weeks, depending on the contributing scientist.
- Final report: 2-8 weeks.
If you are a medical product developer large or small or a physician innovator or engineer with a ‘back of the napkin idea’ and are seeking to maximize your investment in preclinical testing and/or bioskills training, contact us via email at email@example.com or call (404) 894-5227.