Synthetic sutures date back to ancient Egypt, when surgeons used plant fibers, hair, tendons, and wool to close patients’ wounds.¹ The first synthetic absorbable suture was made from polyvinyl alcohol in 1931.² There were several other suture-related milestones in the following decades, but the segment took a giant leap forward when U.S. regulators approved an absorbable stent for coronary artery disease in 2016. 

Today, absorbable medical devices are being commercialized at an increasing pace, in everything from cosmetic enhancements to life-saving cardiovascular interventions. While these devices play critical roles in modern medicine, the very feature that makes them so appealing—i.e., their ability to break down and be absorbed—also presents unique challenges for manufacturers. Understanding the complexities of material degradation, biocompatibility, and regulatory requirements is crucial to ensuring safety and efficacy. 

Absorbable Medical Device Characteristics and Applications

As stated in ISO/TS 37137-1:2021 (Biological evaluation of absorbable medical devices, Part 1: General requirements), “absorbable implants are intentionally designed to degrade and therefore release degradation products into the patient, a feature making these products fundamentally different from other medical devices that are not intended to be absorbed by the patient’s body.” Consequently, standard extraction approaches, chemical characterization, and biocompatibility evaluations may all be impacted by the nature of these products, and adjustments to these approaches are often necessary. 

A comprehensive biological evaluation for an absorbable medical device relies heavily on understanding the material and its degradation products. Knowing a device’s chemical profile allows manufacturers to predict and mitigate risks associated with the release of potentially harmful compounds. The data gathered during chemical characterization, which can be accomplished by chemical analyses per ISO 10993-18:2020, by standards specific to degradation (SO 10993-9:2019, ISO 10993-13:2010; ISO 10993-14:2001; ISO 10993-15:2019), or material evaluations, followed by a toxicological risk assessment (TRA) in accordance with ISO 10993-17:2023, can often support the evaluation of many biological endpoints described in international regulatory standards. 

Some of the most common applications for absorbable devices include:

• Dermal fillers, used in cosmetic surgery to enhance facial features, fill wrinkles, or add volume to specific areas. 

• Orthopedic bone screws, used to secure bone fragments and provide temporary support as a bone heals.

• Adhesion barriers, used in abdominal or pelvic surgeries to prevent internal tissues and organs from sticking together during healing. 

• Bone void fillers, which promote bone regeneration in orthopedic and dental surgeries.

• Bioresorbable stents, which provide mechanical support, gradually absorbing to allow natural healing

• Absorbable surgical clips, sutures, and staples, which close wounds or incisions and hold tissues together during surgery.

• Hemostatic sponges, used to promote blood clotting and control bleeding during surgery. 

• Vascular scaffolds, which support blood vessels during procedures like angioplasty. 

• Absorbable surgical mesh, used in hernia repair and other reconstructive surgeries to temporarily support weakened tissue. 

• Advanced wound care treatments, used specifically for burns or chronic wounds.

While these devices reduce patient discomfort, minimize the need for follow-up surgeries, and improve the overall healing process, using them requires careful consideration of material choice, degradation profiles, and biocompatibility.

Regulatory Drivers 

The regulatory landscape for absorbable medical devices leans heavily on ISO 10993-1:2018, ISO/TS 37137-1:2021, and U.S. regulatory guidance to provide a structured framework for evaluating biological safety. A detailed breakdown of these standards and their relevance to absorbable medical devices follows.

U.S. Regulatory Guidance on ISO 10993

American regulators have adopted much of ISO 10993 in their regulatory frameworks for medical devices, with additional considerations tailored to U.S.-specific requirements. The 2023 guidance on using ISO 10993 provides further clarification, particularly for absorbable materials, including those that polymerize in situ.

Absorbable devices often require more complex testing protocols due to the evolving nature of their interaction with the body. Key aspects of these devices’ regulatory guidance include:

• Emphasizing a comprehensive biocompatibility evaluation framework that mirrors ISO 10993, focusing on endpoints tailored to device type and contact duration.

• Complete chemical characterization is essential for absorbable materials or those that polymerize in situ to identify potential extractables and leachables, degradation products, and residuals that might be introduced during manufacturing. 

• The TRA is crucial in determining which biocompatibility tests are needed. For example, if chemical characterization does not identify constituents present at levels of toxicological concern, it may reduce or refine the need for extensive in-vivo testing.

ISO 10993-1:2018

This standard is the cornerstone of biocompatibility evaluation for all medical devices, including absorbable products. It outlines a framework for developing a biocompatibility evaluation, focusing on managing risk throughout the device’s lifecycle. The central premise is the biological evaluation must align with device type, materials used, and duration and nature of body contact body.

For absorbable medical devices, ISO 10993-1 highlights the importance of understanding how the body will interact with the material as it degrades. Before beginning any type of biological testing or chemical characterization, the manufacturer must understand the potential degradation mechanisms. This information, which could be gathered from in vivo studies, in vitro predictions, or literature reviews, will inform the test plan for both chemical and biological evaluation. 

Manufacturers must evaluate potential risks by considering all possible exposure routes, and the impact of degradation products over time. This biological evaluation is part of an overall safety program, including mechanical performance testing, chemical characterization, and TRA.

ISO/TS 37137-1:2021

This specific technical specification builds upon the principles of ISO 10993-1:2018 but tailors them to the unique challenges posed by absorbable medical devices. The standard specifies the general requirements for evaluating absorbable devices as part of a biological risk assessment. It focuses on the risks associated with degradation products, ensuring the materials, as they break down, cause no adverse biological effects. Two critical parts of this evaluation include:

• Degradation profile assessment: Understanding how fast and completely the device absorbs and what byproducts are produced during degradation. 

• Long-term safety considerations: Absorbable devices remain in the body until degradation, so the material’s short- and long-term local and systemic effects must be considered. 

ISO/TS 37137:2021 highlights many of the unique challenges to working with absorbable devices within a standard ISO 10993-1:2018 framework (e.g., osmolality or pH challenges with extractions), and provides thoughtful stepwise approaches to addressing these issues. 

Despite ISO/TS 37137-1:2021 and ISO 10993-1:2018 working harmoniously to keep absorbable medical devices safe, U.S. regulators only partially recognize the latter standard. As such, all relevant standards and U.S. guidance documents should be considered when developing a test plan for an absorbable device. 

The Challenge in Assessing Toxicological Risk

A TRA evaluates the potential risks associated with a device’s materials and their interaction with the body. The TRA focuses on understanding three primary factors: 1) the chemicals extracted from the device during its use or degradation; 2) the concentration or quantity of chemicals present; and 3) how much/how long patients will be exposed to each chemical. 

However, assessing potential exposure can be particularly challenging because exposure assumptions often default to worst-case scenarios. This approach—while conservative and safety-forward—can lead to overestimating risk. For example, chemical characterization per ISO 10993-18:2020 testing typically involves a range of solvent polarities that may not be clinically relevant, as these solvents might not accurately represent the environment in which the device will degrade in vivo. Also, tests are often conducted under elevated time and temperature conditions to accelerate the extraction process, which may not reflect the actual exposure profile a patient would experience during normal use.

Another limitation of these tests is the lack of release kinetics data, meaning that assumptions are made regarding daily exposure to the extracted or dissolved chemicals. This is problematic because these tests are not designed to mimic in vivo absorption and degradation over time, making it difficult to understand how the device behaves in real-world conditions. 

It is important to conduct chemical characterization and a TRA on absorbable devices. But due to TRA limitations, manufacturers should also plan to conduct in vivo testing in accordance with ISO 10993-6:2016 and -11:2017. The in vivo testing is imperative to capture the local effects during the absorption process and characterize the test material. Also, incorporating systemic toxicity (ISO 10993-11:2017) based on the absorption profile could help mitigate concerns identified in the toxicological risk assessment based on chemical characterization studies that are either exhaustive extractions or complete dissolution—neither of which adequately captures the product’s gradual absorption.

Advice for Manufacturers

There is no one-size-fits-all approach to biocompatibility testing, as different materials interact with the body differently. Depending on their chemical composition, for example, polymers may degrade through hydrolysis, oxidation, or enzymatic reactions. 

Absorbable metals, conversely, can undergo corrosive degradation, which may cause hydrogen gas pockets that could potentially compromise the device’s mechanical integrity over time.

Other materials, including cyanoacrylates, may release formaldehyde during curing and gradually through hydrolysis, adding another layer of complexity to safety assessments.

Given these varying mechanisms, a thorough understanding of how a material degrades is essential before beginning a biocompatibility test program. Different approaches offer different insights into the degradation profile and biocompatibility risks, helping to tailor testing programs to the specific material and application.

U.S. regulators also recommend that device manufacturers schedule pre-submission meetings before beginning their testing programs. These meetings provide an opportunity to receive feedback on the need for, or approach to, key testing protocols, including chemical characterization, TRA, and implantation studies. 

It is also worth noting that pre-submission feedback may differ depending on whether the device includes novel components versus materials already approved for use. In addition, the meeting clarifies patient exposure to the device—whether in its polymerized or uncured state—and any related safety concerns. This early dialogue can streamline the regulatory approval process and help manufacturers align with current regulatory expectations.

The Bottom Line

Absorbable medical devices represent a significant leap forward in medical technology, offering solutions that reduce patient discomfort and eliminate the need for follow-up procedures. But their nature presents complex challenges for manufacturers. Thorough biological evaluations—including chemical characterization, TRAs, and biocompatibility testing—proactive communication with regulators and collaboration with experienced lab partners can help mitigate concerns and streamline regulatory submissions.

References

¹ tinyurl.com/mpo241141

² tinyurl.com/mpo241142

Dr. Kimberly Ehman has over 20 years of toxicology and medical device experience. As director of Regulatory Toxicology, she offers expertise in toxicological risk assessments for medical devices, food and beverage products, and electronic nicotine delivery systems. Dr. Ehman previously worked as a toxicologist for RTI International, Toxicology Regulatory Services, and Altria Client Services. In her current position, Dr. Ehman provides technical and regulatory support for biocompatibility test programs and conducts quantitative toxicological risk assessments to support product safety and risk management decisions.

Molly Haan navigates the complexities of regulatory inquiries, creating and managing intricate study designs, tracking regulatory trends, and delivering high-level technical guidance, particularly in extractable/leachable testing. She earned a bachelor’s degree in microbiology from North Dakota State University, a master’s degree in biological sciences from the University of Minnesota, and a master’s degree in business from Walden University.