Dr. Kathleen Jacobs, global regulatory affairs director, Rousselot, highlights the importance of choosing the right biomaterial from the beginning.
Rousselot
In medical devices, drug delivery systems and regenerative medicine, material selection often begins with familiar criteria: biocompatibility, degradation profile, mechanical performance, and processability. Gelatin and collagen consistently perform well against those benchmarks, which explains their enduring role across haemostatic products, injectable formulations, tissue-engineering scaffolds and cell-culture platforms.
Yet many development programmes encounter the same obstacle late in the process. A material that satisfies functional requirements fails when evaluated through the lens of immunogenic risk, clinical safety or regulatory acceptance. The limiting factor is not the polymer itself. It is the endotoxin burden carried within it.
The question is not whether gelatin or collagen is suitable, the question is whether the gelatin or collagen has been manufactured, purified and documented to a standard that makes it suitable for the intended application.
Performance is only one part of the specification
Gelatin, derived through the partial hydrolysis of collagen, occupies a unique position among biomaterials. Its biological origin, established clinical history and adaptable physicochemical properties allow it to serve functions that synthetic alternatives often struggle to replicate.
Type A and Type B gelatins offer different isoelectric points and processing characteristics. Hydrolysed grades provide stabilisation without gel formation. Crosslinking and chemical modification enable control over degradation kinetics, mechanical strength and release behaviour.
These characteristics underpin applications including:
- Haemostatic sponges, powders and flowables
- Vaccine and injectable drug formulations
- Implantable membranes and wound-healing matrices
- Stem-cell culture systems
- Organoid and organ-on-chip platforms
- 3D bioprinting bioinks
- Tissue-engineering scaffolds
For developers, the attraction is one biomaterial platform that is adaptable and performs effectively across many different therapeutic and device categories.
Endotoxin is the specification that determines access
Endotoxins remain one of the most persistent but underrepresented challenges associated with naturally derived biomaterials. As lipopolysaccharides originating from Gram-negative bacterial membranes, they are highly immunogenic, heat-stable and difficult to eliminate once introduced into a manufacturing process.
The biological consequences are well established. Endotoxins activate TLR4-mediated inflammatory pathways and stimulate the release of pro-inflammatory cytokines. Even low levels can alter cellular behaviour, distort experimental outcomes and compromise clinical performance. At higher exposures, endotoxins are associated with severe inflammatory responses and septic shock.
Even very low levels can provoke significant immune responses, and regulators have set strict limits. For medical devices, the FDA caps endotoxins at 2.15 EU per device, (0.06 EU/ml) for devices contacting the central nervous system via cerebrospinal fluid, and at 20 EU per device (0.5 EU/ml) for peripheral devices reached by the cardiovascular and lymphatic systems.
The problem: traditionally manufactured gelatin and collagen can carry endotoxin levels more than a hundred times those limits. And for developers this can make endotoxin load a gating specification.
A biomaterial can be mechanically suitable, biologically compatible and commercially attractive, yet remain inappropriate for clinical use because its endotoxin profile sits outside acceptable limits.
Sterility and purity are not interchangeable
A persistent misconception within biomaterials development is that terminal sterilisation can compensate for insufficient upstream contamination control. Evidence demonstrates otherwise.
Autoclaving effectively addresses microbial contamination, but endotoxins are notably resistant to heat treatment. Studies comparing standard commercial gelatin with purified low-endotoxin grades show that autoclaving reduces molecular weight and gel strength, while also failing to reduce endotoxin levels to the same extent achieved through dedicated purification. The result is an undesirable trade-off: diminished material performance without adequate removal of the underlying immunogenic contaminant.
This distinction matters particularly in advanced applications where physical characteristics directly influence product function. In bioprinting, scaffold fabrication and controlled drug delivery, changes in molecular architecture translate into measurable changes in performance.
The quality conversation needs to begin upstream
The most effective endotoxin-control strategy is not post-processing. It is process design. Validated purification technologies now allow manufacturers to produce gelatin and hydrolysed collagen grades with endotoxin levels below 10 EU/g, verified batch-by-batch. Importantly, these purification approaches can be applied across Type A, Type B, gelling and non-gelling grades without sacrificing the properties that make the materials valuable.
For developers operating in regulated sectors, however, low endotoxin is only part of the equation. Documentation increasingly carries the same weight as technical performance.
Regulatory scrutiny extends beyond the material itself to encompass sourcing, manufacturing controls, traceability and risk management throughout the supply chain. Procurement teams, quality functions and notified bodies all require evidence that the material's characteristics are not simply claimed but demonstrated and controlled.
Documentation has become a performance characteristic
As regenerative medicine, combination products and advanced therapeutic platforms move toward commercialisation, developers increasingly require biomaterials that arrive with a complete regulatory package rather than a certificate of analysis alone.
That expectation is particularly relevant for animal-derived materials such as gelatin and collagen.
Documented traceability to the farm level provides visibility across the entire sourcing chain. Compliance with EU MDR 2017/745 aligns material selection with the regulatory framework governing medical devices within Europe. Conformity with ISO 22442-2:2020 and ISO 22442-3:2007 demonstrates structured control of animal tissues and management of transmissible-agent risk. Alignment with IPEC-PQG GMP 2017 provides additional assurance around manufacturing quality and pharmaceutical-grade production practices. This documentation serves a practical purpose and reduces qualification burden, simplifies technical-file preparation and supports more efficient interactions with regulators, notified bodies and customers.
Choosing the right biomaterial means choosing the right manufacturing standard
The growing sophistication of medical devices and regenerative therapies has increased expectations of the materials that support them. Performance remains essential, but when evaluating a biomaterial, the function and what that will demand of the manufacturing controls, purification strategy and documentation also need to be considered.
Low-endotoxin specification, validated purification, comprehensive traceability and demonstrated compliance will collectively define whether a biomaterial can move confidently from development into clinical and commercial reality.