The Right Test, Not More Tests: Rethinking Biocompatibility Strategy

OEMs in the medical device industry understand that different devices require different biological safety evaluations. A skin-contact wearable is not assessed like an implant, and a catheter is not evaluated like a surgical drape.

Yet many OEM teams struggle with a deceptively simple question: How do we determine the right evaluation strategy?

Historically, biological safety evaluation resembled a testing checkbox exercise. You matched the device categories, ran listed tests, and submitted results. Modern standards changed that model. Today, biocompatibility evaluation is a risk-management process requiring simultaneous understanding of the device, end-user, materials, and clinical context. Testing should occur when existing evidence is insufficient to assess the biological hazards presented by a device and its intended patient use.

Misunderstanding this shift is why OEMs frequently over-test, under-test, or test at the wrong time.

Regulatory guidance and standards include tables that categorize devices based on contact nature and outline biological endpoints required for evaluation. The table tells you what to think about, not what to automatically test.

The tables provided by FDA Guidance on the Use of ISO 10993-1:2018 and ISO 10993-1:2025 are useful starting points to identify which biological effects must be evaluated. The biological effects identified by the FDA and ISO 10993-1 are mandatory; however, they also explicitly acknowledge additional risks may exist depending on material novelty, patient population, and exposure route. For example, a neonatal intravascular device made from a common polymer may require more evaluation than an adult skin-contact device made from the same material.

The table didn’t change; the risk did.

Once key biological effects of concern are identified, the next step is to evaluate whether existing evidence is sufficient and whether data generation via testing is needed. Biological safety evaluation follows the following sequence.

Understand the device and how it interacts with the body. Does it touch skin, blood, internal tissue, mucosa? Is it an implant? How long does the device contact the patient?

Identify what biological risks exist. Could the device cause irritation, toxicity, sensitization or implantation effects?

Evaluate existing evidence to decide whether testing is needed, and which specific test makes sense.

Once testing begins, complexity can increase quickly. Patient-contacting devices require evaluation of cytotoxicity, irritation and sensitization, at a minimum.

Take irritation as an example of testing complexities. A device placed on top of intact skin requires skin irritation testing. A device that contacts mucosal eye tissue needs ocular irritation testing. A device that contacts vaginal mucosal tissue requires vaginal irritation testing. A device that contacts internal tissue requires intracutaneous irritation testing.

Same endpoint, completely different studies. Treating biocompatibility as a standard test panel can create delays and regulatory questions. One of the fastest ways to derail a development timeline is to start testing before internal strategy is clear.

What do we already know about the device? Assess the device, intended use, manufacturing process, and materials. Determine type and duration of body contact. Gather information based on intended use to identify data gaps or biological hazards.

What type of testing do I need? Following risk assessment, select appropriate tests based on the device’s contact with the body. When uncertain, consult biocompatibility experts or seek FDA feedback through a pre-submission including the Biological Evaluation Plan (BEP).

Where can I test my devices? To start, identify high-quality testing laboratories (GLP and ISO 17025 accredited). Be prepared to discuss your device, including the contact nature, with the testing laboratory.

Biocompatibility strategy is driven by how the device interacts with the body, who uses it, what it’s made of, and how. To build a defensible biological evaluation plan, you must evaluate five characteristics of the device.

The invasiveness of your device is directly correlated with the invasiveness of your biocompatibility evaluation. The deeper or longer a device interacts with the body, especially blood circulation, the more extensive the biological evaluation required.

Exactly how components interact with fluids and tissues, including indirect pathways, must be clearly understood. A catheter manifold may not physically touch the patient, but if fluid flows through it into the bloodstream, it becomes an indirect blood-contact component. That distinction dramatically changes testing requirements. It is best to work cross-functionally across clinical, engineering, regulatory and biocompatibility teams to create alignment on intended use.

You must define how, where, and in whom the device will be used before testing decisions can be made. If the intended use is unclear, you are not ready to test. Every downstream decision depends on how the device will be used clinically. 

Some populations, including infants, pregnant patients, and immuno-compromised individuals require additional biological safety considerations.

All materials and residues down to the chemical level must be identified and assessed; gaps may require chemical characterization, degradation or other testing as applicable.

In the context of ISO 10993-1 and FDA’s Biocompatibility Guidance on the Use of ISO 10993-1, a material is considered novel when there is no legally marketed device with the same material, processing, contact type, and duration, meaning there is no established history of safe clinical use in the intended application.

Novel materials require more extensive biological evaluation, like deeper chemical characterization, broader toxicological assessment, and careful consideration of degradation products or particulates. Historically, many materials now considered “standard” implant metals and alloys were once novel and only became lower-risk choices after decades of preclinical testing, clinical experience, and the development of detailed material standards.

Importantly, even a familiar material can become novel. FDA and ISO emphasize that the same material can present very different biological risks.

A material can become novel when it lacks a predicate with equivalent use, exposure route changes, contact duration changes, or patient populations change.

Silicone breast implants were widely used for years, but the introduction of certain textured surface designs created a new pattern of tissue interaction and was later linked to a rare lymphoma. Same base material category, new surface feature, completely different risk profile.

Biocompatibility timelines are influenced primarily by the duration and type of studies required, rather than by device complexity alone. Chemical characterization, short-duration in vitro or ex vivo assays, and basic acute studies are generally quicker, whereas sensitization, long-term systemic toxicity, implantation, and complex hemocompatibility programs tend to have the longest timelines. A well-designed ISO 10993-18 chemical characterization program can reduce the need for certain long-duration in vivo studies.

The length of biocompatibility testing depends on the device’s contact duration and the specific studies required. For implants, the timeline is driven by the longest systemic toxicity or implantation study. Sensitization testing is needed even for non-implanted devices, which is usually around three months from sample receipt to final report. Most devices will need about six months end-to-end; however, CRO queues, test article issues, and repeat testing can easily push timelines longer. 

Perfect test conditions are difficult to achieve, so it’s better to plan conservatively for a testing timeline. It’s important to plan upfront, invest in strong chemical characterization, and set realistic expectations internally to avoid major delays.

OEM companies often make common mistakes when it comes to determining the right biocompatibility approach for their medical device. Testing takes time. Estimate timelines conservatively.

You can’t design the right testing strategy if you don’t know exactly what the device will be made from or how it will be produced. Even small changes, like coatings and processing aids, can change biological risk.

Running tests before design freeze can result in testing a device that won’t be marketed. You can miss regulatory timelines if you test too late and discover required studies take several months.

Using FDA and ISO tables as a shopping list can cause either massive over-testing (do everything the table says) or critical under-testing (skipping things not called out line-by-line). Both can lead to unexpected outcomes or regulatory delays.

It’s best to start your biological evaluation plan at the beginning of your device development, even if you know the plan will change. Become familiar with the critical development milestones and regulatory decision points needed before you can begin testing. It may be necessary to conduct an initial “screening” set of testing followed by full testing once the design is frozen.

Plan early and decide on materials sooner to avoid costly rework and delays.

Not all labs provide the same value. If internal expertise is limited, choose a testing partner that also offers meaningful consulting. And evaluate them on more than turnaround time and price.

Look for labs that provide credentials, such as GLP compliance and ISO 17025 accreditation; realistic turnaround times; clear communication and an understanding of target markets; coordinated scheduling across studies; early identification of potential failures or retesting risks; willingness to challenge assumptions; and post-submission regulatory support.

The best lab partners help to avoid unnecessary studies by helping ensure the right tests are selected from the start.

Biological safety (biocompatibility) is about performing a scientifically sound evaluation to determine the safety profiles of any patient-contacting medical device. Biocompatibility is required for every patient-contacting device, and the level of evaluation must match its intended use.

If you’re unsure if you need help or are unsure where to start, begin with the FDA biocompatibility guidance, which covers the core concepts and is free online [search “FDA biocompatibility guidance”]. Understanding ISO 10993-1 is critical.

Testing is the evidence-generation tool when other evidence is insufficient. When OEMs shift from “Which tests do we need?” to “What risks must we understand?” the strategy becomes clear. As a result, timelines, costs, and regulatory interactions can improve dramatically.

Biocompatibility is a safety story, and regulators expect the evidence to support every chapter. Remember that most biocompatibility experts enjoy talking about this topic. If you’re stuck, find an expert you trust; a short conversation early on can save time, money, and frustration later.

MORE FROM THIS AUTHOR: The Hidden Cost of Unplanned Biocompatibility Testing

Katie Brinkman leads development and strategic positioning of Hohenstein Medical’s medical device biocompatibility program, with a focus on chemical characterization, ISO 18562 gas pathway testing, and ethical, non-animal assays. Brinkman has over 15 years of experience in biological sciences, authoring numerous biocompatibility and toxicological risk assessment reports supporting global regulatory submissions. Brinkman earned a bachelor of science degree in biology from Mississippi University for Women, is an active member of the Society of Toxicology and the Regulatory Affairs Professionals Society. She’s also certified as a Biological Safety Specialist by NAMSA.