Subcutaneous Implantation Biocompatibility Testing (ISO 10993-6)

1. Biological Effect: In Vivo Tests
2. Turnaround time: to be individually determined (after approval from Local Ethics Committee)
3. Sample Requirements:

ISO

to be individually determined;

4. Animal Quantity: 6 rats
5. Duration of implantation: to be individually determined

 

ISO 10993-6

The purpose of the study is to evaluate the medical device for local effects on living tissue when implanted subcutaneously in rats. The bioreactivity of a test item is determined through microscopic and macroscopic through a comparison of the tissue response caused by the medical device as compared to an appropriate control material. The area of the tissue surrounding the center position of each implant will be processed and a histopathologist will process the implanted sites for histopathological evaluation.

What Is Subcutaneous Implantation Testing?

Subcutaneous implantation testing is an ISO 10993-6 biocompatibility study that evaluates how soft tissue beneath the skin reacts to a medical device material. In practice, this means a small piece of the material is placed under the skin of an animal model. The surrounding tissue is monitored for signs of irritation, inflammation, fibrosis, or other changes.

Why subcutaneous tissue? It’s accessible, well-vascularized, and quick to respond. The layer just under the skin makes it easier to observe and compare tissue reactions. That is why regulators often require it as an early signal of compatibility. 

Think of it as a “first look” at how the body might respond before moving on to more complex systems like muscle or bone.

Subcutaneous testing is often paired with muscle implantation studies to compare how different tissues respond. Muscle provides a higher-stress, mechanically active environment, while subcutaneous tissue offers a clearer view of local inflammation and healing. 

Together, the two studies help build a more complete picture of material safety.

Key Regulatory Standards & Guidance

ISO 10993-6:2016 overview

The backbone of subcutaneous implantation testing is ISO 10993-6:2016, the international standard for evaluating local effects after implantation. 

It explains how tissues should be examined (both macroscopically and microscopically) and sets clear expectations for study design. Regulators across markets look to this document as the baseline when reviewing device safety.

FDA/MDR alignment

Passing one regulator’s bar doesn’t guarantee approval everywhere else. 

The U.S. Food and Drug Administration expects subcutaneous data as part of a broader biological evaluation, and the same applies under the European MDR framework. 

Meeting both expectations often depends on aligning biocompatibility strategy with FDA and MDR requirements, ensuring that a single dataset can support submissions in multiple regions without repeat testing.

How Long Does Subcutaneous Implantation Testing Take?

Subcutaneous implantation studies usually last 4 weeks for sub-chronic designs or 13 weeks for chronic designs. These durations come from ISO 10993-6 and are long enough to capture key tissue reactions.

Here’s what those timelines mean:

• 4 weeks – captures short-term responses like acute inflammation and early healing.
• 13 weeks – shows delayed outcomes such as fibrosis, capsule formation, or chronic irritation.

It’s important to note that this timeline isn’t about how long an implant would last in a patient. In testing, “duration” refers only to how long the sample stays under the skin before tissue is collected and analyzed.

Study planning also shapes how quickly results are delivered. With the right preparation, overall schedules can be shortened without losing data quality. This approach is reflected in fast-tracking the Biological Evaluation Plan, where efficient study design helps keep projects on track for regulatory approval.

What Outcomes Are Measured in Subcutaneous Implantation?

Typical outcomes include inflammation, fibrosis, necrosis, edema, and pigmentation changes. These reactions give regulators and manufacturers a clear view of how tissue responds to a device material over time.

• Inflammation – early immune response, seen as redness, swelling, or clusters of immune cells under the microscope.
• Fibrosis – scar-like tissue that forms when the body walls off the implant instead of integrating with it.
• Necrosis – areas of dead tissue, often indicating poor compatibility.
• Edema – fluid accumulation in surrounding tissue, a sign of irritation.
• Pigmentation – changes in skin or tissue color around the implant.

These findings are recorded at two levels:

• Gross observation – visible inspection of the tissue at removal.
• Histology – microscopic analysis of slides, sometimes paired with capsule thickness scoring.

Together, these outcomes feed directly into the Biological Evaluation Plan (BEP), where they determine whether additional testing is required before moving forward.

When Is Subcutaneous Implantation Required?

Subcutaneous implantation testing is required when materials or devices are expected to contact soft tissue, during the preclinical stage of development, or when existing devices undergo modifications.

Manufacturers typically include this study when evaluating new polymers, coatings, or drug-eluting materials. It also becomes necessary when a familiar device changes in a way that could alter tissue response—for example, a new surface finish or added coating. 

Regulators expect updated data to confirm that these changes don’t create unexpected risks.

Requirements don’t end at first approval. The lifecycle approach to biocompatibility shows why subcutaneous testing may be needed again after design updates or when devices are re-evaluated post-market.

How Much Does Subcutaneous Implantation Testing Cost?

There’s no single price for subcutaneous implantation studies. The cost depends on study design and project scope.

Several factors influence the budget:

• Study duration – short 4-week studies require fewer resources than 13-week chronic designs.
• Animal count – more animals or more implant sites increase complexity.
• Histology workload – the number of slides and level of detail directly affect cost.
• Ethical approvals – timelines and local requirements can change project length and cost.
• Extra analyses – imaging, capsule thickness scoring, or biomechanical tests add to the scope.

Cost drivers are similar to those seen in bone implantation testing, though scaled for soft tissue work.

Request a custom quote from NABI to get an exact estimate for your study.

Why Choose NABI for Subcutaneous Implantation Testing?

Choosing a lab for subcutaneous implantation means trusting that the results will stand up to regulatory review. NABI is built around that responsibility.

• Trusted accreditations – All studies are performed under ISO 10993, GLP principles, and ISO 17025 accreditation, ensuring data integrity across markets.
• Ethics first – Local ethics committee approvals are secured before every study, and animal welfare is integrated into protocol design.
• Efficient timelines – Projects are typically completed within 12–21 weeks, with custom designs available for specific device needs.
• Clear deliverables – Clients receive full reports with histopathology images, gross observations, and regulator-ready interpretations.

This approach is part of broader compliance, tied closely to biocompatibility regulations and key insights for device development.

FAQs about Subcutaneous Implantation Biocompatibility Testing

What animals are typically used for subcutaneous implantation?

Studies are usually performed in rats, where implants are placed under the skin to evaluate tissue response.

Which regulators accept ISO 10993-6 data?

Data generated under ISO 10993-6:2016 is accepted by the FDA, European authorities under MDR, and most international agencies that recognize ISO standards.

How are tissue responses evaluated?

Responses are assessed through gross observation at the implant site and microscopic histology, with capsule thickness or scoring used to compare test and control materials.

How many animals or samples are needed?

The number varies by design, but protocols typically involve multiple implant sites per animal to reduce overall animal use while still meeting regulatory requirements.

Can the study timeline be shortened?

Shortening is possible if ethical approvals and samples are ready before the start. However, chronic studies (13 weeks) must run their full length to meet regulatory requirements.

What is the difference between subcutaneous and deeper implantations?

Subcutaneous implantation focuses on soft tissue response just under the skin, while muscle or bone implantation evaluates how materials perform in mechanically active or load-bearing tissues.

Get a Custom Quote for Subcutaneous Implantation Testing

Every device has its own requirements, and so does every study. That’s why NABI provides custom quotes rather than flat pricing. By tailoring the design, timeline, and reporting to your device, we ensure your results are regulator-ready.

Request a Quote

For direct inquiries:

Email: contact@nabi.bio
Phone: +1 (407) 278-6815