If you’re new to the process of preclinical medical device testing, you may not be clear on exactly how APS helps you through this testing phase.
In fact, you may need an introduction to the entire testing process, given the past and future growth of the medical testing services market. The global market is expected to grow at a CAGR of 11.5% in each of the next five years to reach a 2025 size of $13.4 billion, according to a report published by Intrado. The preclinical phase of testing is expected to hold the greatest share of that market into the indefinite future.
Contributing to that growth will be significantly increased spending by product developers, a trend in more outsourcing and boosted demand for novel in-vitro testing that can replace more traditional animal testing methods, according to the report. Other factors will include stringent regulatory standards pertaining to user safety, increased demand for quality products and a significant consolidation in the CRO space.
If you’re ready to be a part of the tsunami of new medical devices in development and are ready to begin next steps toward regulatory approval, here’s a description of the next steps you can take with American Preclinical Services (APS).
Step one: Consultation
Many clients from a larger companies stacked with regulatory specialists on staff would already have a preclinical development plan mapped out by the time they walk in the door at APS. Because they’re looking to APS to supply their services and come well-versed in the complexities of the preclinical testing, the consultation stage is typically swift and minimal for this group.
However, APS sees plenty of clients that are new to the medical device sector, whether they come from small to midsize companies or a virtual startup. Part of the consultation process is helping these clients design a study plan that would get their concept to the regulatory review stage, says Mark Smith, Chief Scientific Officer Emeritus at American Preclinical Services.
A common misconception, Smith says, is a client believes their device is ready for the pivotal GLP preclinical safety study because it shares enough similarities with an already approved device. But it’s still a different device that was tested in a different lab, he says. This means they shouldn’t skip any feasibility and discovery studies the APS team would need to create a foundation for the GLP preclinical study.
APS is willing to sit down and help clients shape a preclinical development plan, so they understand where they are in development, and which steps they need to complete to reach the preclinical stage. Here’s a look at some of these phases:
At this stage, the device or process might undergo biocompatibility studies to show they can be safely used on a living subject. The APS team may also recommend smaller, non-GLP feasibility studies using animal models. These early studies are extremely useful for proving feasibility (which can aid in the client securing additional funding from a board of directors, a venture capital group, or during a fundraising activity for further research). Outcomes from these studies can guide the team when it comes time to design pivotal preclinical GLP safety studies that would be carried out and submitted for regulatory review.
“Your GLP studies need to be done in a way where there are no surprises,” Smith says. “You don’t want to learn anything new in a study that you’re going to submit to the FDA.”
Conducting early studies provides that opportunity to learn.
Preclinical GLP safety study
At this phase, it’s all about preparing and executing a study so you can submit results for regulatory review. The idea is to offer enough evidence that a device or process is safe enough, so development can proceed to the clinical trial phase. The APS team puts together a study protocol and study design. As mentioned, this phase should not include any new information or outcomes, but confirm previous findings from the non-GLP study or studies. This GLP data will then be compiled into a report by APS and data to submitted for regulatory review by the Sponsor.
Regulatory submission and review
After a successful preclinical study, all the documents and reports are submitted to the regulatory agency (such as the Food and Drug Administration) for review to seek approval to move forward with clinical studies.
After you’ve completed the consultation process with APS, your team will know where your device development falls within this continuum, and what your next steps are.
Step two: The contract
Before any level of testing commences, your team will sign a contract with APS. Unlike other preclinical service providers, an APS contract is precise and extremely detailed, Smith says. The goal is to provide clear answers to three fundamental questions:
- What’s it going to cost?
- When will it get done?
- Can we get it sooner?
APS works hard to be as comprehensive in estimating study costs as possible. The APS team works carefully to compile quotes that include and account for everything that could happen during testing. To build this, they’ll draw from their experiences from other studies, disclosing up front what could add cost to the study, Smith says. This lets you plan and be transparent with your investors.
At the same time, the team is cognizant of managing their clients’ expenses. So if a trial gets completed faster than expected, or they discover an opportunity to streamline the process, they will do so and pass along the savings to the client, Smith says.
“We charge only for the work we do,” he says, adding that other testing companies may not take this approach.
The study timeline is another area spelled out in the contract, so the client understands when they can expect project completion. If you have a fixed deadline, Smith says, APS makes a good faith effort to meet that. Expedited timelines can typically be accommodated for an additional cost, but does depend on current workloads. APS will need to charge additional fees to accommodate overtime and shuffled workloads.
The third and final area of the contract is materials. When it comes to providing materials for a pivotal GLP study, it’s critical that the Sponsor provide them exactly as specified in the contract and protocols. Deviations from this could cause an unplanned delay in the start of the project.
Sometimes, things happen to disrupt that, and it may be out of the client’s control. Labeling, product stability and expiration are the top three issues around materials, Smith says. Even though some changes may seem small and inconsequential, they can have a big impact on the study.
As an example, the client may provide materials that have expired, but pushes to use them anyway, Smith says. Expired materials are not eligible to be utilized in a GLP study, so this can also lead to delays while the Sponsor attempts to source unexpired materials.
Another common obstacle to the start of a safety study is if one of the materials arrives with a different label or even an unanticipated name change. Manufacturing processes changes can also be an issue, as it can alter the makeup of the component or material.
Smith advises clients to submit change notices as soon as they become aware of changes in the study materials. Otherwise, they would not match the protocols set out during study design, and APS would have no choice but to delay the start of the study.
Step 3: Research
It’s important to understand that many unknowns can arise in even the best-designed studies, Smith says.
Despite the in-depth preparation and confidence in the outcomes, GLP studies are occasionally unsuccessful. Smith says if it becomes apparent the trial is failing, the APS team shuts down the study quickly. To avoid further loss, the APS team gives the option to convert it to a non-GLP discovery study, and use the data to design a better GLP study. Valuable work can come out of failed studies, he says.
It’s also important to predict and plan for possible animal disruptions as much as possible, because “The animal’s job is to ruin your study,” Smith says dryly. It’s also important to predict and plan for possible animal disruptions as much as possible. For example, you might be testing a device that’s designed for an immobilized patient in an intensive care unit.
“But try that in an animal model, and that’s a whole different story,” Smith says. “No matter how much you restrain within the guidelines, animals sometimes do things to devices that humans won’t do.”
Step 4: Follow-up
Once APS hands over the reports and data (that’s also been successfully reviewed by the study auditor), the client takes it and submits their package for regulatory review. During this stage, the regulatory agency can come back with a set of questions about the data. The APS team will work with the client to resolve those questions.
If the question from the FDA is associated with an error or omission, APS will respond quickly to repair that by answering questions quickly, filling in the data or descriptions, and bringing in additional resources, if needed, Smith says. This is done at no cost.
Sometimes the nature of the question is beyond anyone’s control. For example, one of the FDA reviewers may be a technical expert in a specific area, and want to see more detail, asking questions that weren’t previously asked in prior studies. If gathering that data requires additional research that goes above the scope of the original project, APS would quickly put together a bid for the additional work.
When new questions from regulatory agencies arise, APS uses these experiences to guide future GLP studies, Smith said. APS “continuously improves processes, records, and templates. We don’t want to see those kinds of questions returned more than two to three times. We learn to adjust our processes to align with what the FDA is looking for.”
If the outcome of a study is a close call, a matter of opinion, the client may push forward to seek approval. If a deficiency statement comes back from the FDA, sometimes APS can perform additional evaluations and gather the data needed to address the issues.
The preclinical journey has many complexities and obstacles, which is why it pays to have an experienced team like APS on your side. We’re prepared to help you plan and navigate the journey so you can meet your goals.
Still have questions? Contact us to learn more about how we can help you get your promising new product closer to market.