Instructions for Use (IFU) – Low-Leachables & Extractables-Control Workflows

This IFU applies to professional additive manufacturing workflows in which low residual-species release, low extractables, low leachables or high-purity performance is an important functional or safety objective.

Important: a low-leachables outcome is not an intrinsic or universal property of a resin alone. It depends on the complete material–printer–process–post-processing–use system, including formulation version, polymer conversion, geometry, extraction medium, extraction conditions, drying, post-curing, downstream processing and final use environment.

This IFU does not establish that a material or printed part is biocompatible, medical-device compliant, free of extractables or suitable for a regulated application. Final acceptance criteria must be defined and validated by the user or legal manufacturer for the intended use.

This document should be used together with the 3Dresyns® Instructions for Use (IFU) Hub, the relevant technology-specific IFU and, for medical or dental workflows, the IFU for Biocompatible Photopolymer Resin Systems.

Purpose and scope

The purpose of this IFU is to provide a structured approach for designing and validating workflows intended to minimize the release of mobile residual species from printed photopolymer parts.

These principles may be relevant to medical, dental, laboratory, microfluidic, analytical, high-purity, fluid-contact and other applications in which the chemical species released from a printed part may affect safety, analytical performance, fluid purity or functional behavior.

Governing principle

Residual species, extractables and leachables

Photopolymer networks may contain unreacted or partially reacted species, additives, photo accelerant fragments, light blockers, reaction by-products, cleaning-fluid residues or other process-related substances. Their mobility depends on molecular size, polarity, polymer network structure, degree of conversion, temperature and the medium contacting the printed part.

• Residual species are substances remaining in or on the printed polymer after manufacturing and post-processing.
• Extractables are substances that can be released under defined laboratory extraction conditions.
• Leachables are substances released under actual or simulated conditions of use.

For medical-device chemical characterization, ISO 10993-18 distinguishes laboratory-estimated extractables from substances measured under clinical use conditions as leachables.

Manufacturing purification is not analytical extraction

Start with maximum achievable polymer conversion

Low-leachables processing should begin with a printing and post-curing strategy capable of achieving the highest practical and validated degree of polymer conversion without damaging the part or compromising its required properties.

• Use calibrated printer output and controlled exposure conditions.
• Use the resin version and processing parameters associated with the intended workflow.
• Account for light attenuation in colored, opaque, thick or highly filled prints.
• Use thermal or combined light/thermal post-curing where required by the specific material system.
• Do not assume that surface hardness or apparent dryness confirms complete conversion through the bulk of the part.

Primary removal of uncured resin

Before advanced extraction or purification, remove uncured surface resin and resin trapped in holes, channels, recesses, supports and internal features using the cleaning procedure specified for the material system.

The initial washing stage and the subsequent low-leachables extraction stage serve different purposes. Initial washing primarily removes uncured resin and surface contamination. Advanced extraction is intended to remove mobile species remaining within or on the polymer after the initial cleaning step.

Selection of the extraction medium

The extraction medium must be selected according to both its ability to remove relevant mobile species and its compatibility with the cured polymer.

Selection should consider:

• polarity and solvation capability relative to the species of concern,
• compatibility with the printed polymer and any fillers, pigments or functional additives,
• potential for swelling, softening, cracking, stress relaxation, whitening, discoloration or dimensional change,
• ability to penetrate the relevant geometry and internal channels,
• ease of subsequent removal and drying,
• purity of the extraction medium and risk of introducing new contaminants,
• relevance to the final service environment.

Purified water may be appropriate for selected aqueous-contact systems. Organic solvents or specialized cleaning fluids may be appropriate for other systems only where compatibility has been demonstrated. The best medium for initial resin removal is not necessarily the best medium for final purification or conditioning.

Why fresh extraction medium matters

Extraction is driven by mass transfer from the printed polymer into the surrounding medium. As the medium becomes loaded with extracted species, the concentration gradient can decrease and further removal may become less efficient.

For demanding low-leachables workflows, prolonged immersion in a single static bath should therefore not be assumed to provide the same purification efficiency as controlled extraction using fresh or renewed medium.

Repeated fresh-medium extraction

A practical strategy is to use sequential extraction stages with fresh medium. The number of stages, residence time and medium volume must be determined experimentally for the material, geometry and intended application.

A representative workflow may be:

initial cleaning → fresh extraction stage 1 → fresh extraction stage 2 → additional fresh stages as required → controlled drying → subsequent validated processing

The sequence is illustrative only and does not define universal processing conditions.

Continuously renewed or continuous-flow extraction

For higher-throughput or high-purity workflows, a validated system may continuously supply fresh extraction medium while removing loaded medium from the extraction chamber. This can help maintain the driving force for diffusion and reduce accumulation of extracted species around the print.

Relevant system variables include:

• fresh-medium flow rate,
• extraction chamber volume,
• part loading and exposed surface area,
• temperature,
• agitation or fluid velocity,
• residence time,
• filtration or purification strategy where recirculation is used,
• materials of construction of pumps, tubing, seals and vessels,
• cross-contamination control between batches.

Important: simple recirculation of the same extraction liquid is not equivalent to continuous extraction with fresh medium. If the recirculated medium is not renewed or effectively purified, extracted species may accumulate and reduce the concentration gradient.

Agitation, flow and ultrasound

Agitation, controlled fluid flow or ultrasound may improve transport from the print surface and assist removal from difficult geometries. These methods must be validated because aggressive mechanical or ultrasonic conditions can damage fragile features, accelerate solvent attack or alter dimensional accuracy.

Temperature-assisted extraction

Increasing temperature can increase diffusion and mass-transfer rates, but it can also increase polymer swelling, relaxation, chemical attack or deformation. Temperature-assisted extraction should therefore be used only within a validated material-specific processing window.

The selected temperature must not be assumed safe merely because it is below the nominal thermal transition temperature of the polymer. Solvent exposure can change the effective mechanical and dimensional response of the printed network.

Intended-contact medium and final conditioning

Where technically appropriate, a final extraction or conditioning stage using the actual intended-contact medium, or a scientifically representative medium, should be considered after the main purification sequence.

Examples may include purified water for parts intended for aqueous service or another validated medium representative of the real contact environment.

This approach can be useful for removing species that are preferentially mobile in the service medium and for assessing whether the part remains dimensionally and functionally stable after conditioning.

Important: final conditioning in an intended-contact medium is a manufacturing or process-development step. It does not replace application-specific leachables testing or biological evaluation where these are required.

Geometry and diffusion path length

Extraction efficiency depends strongly on part geometry. Thin open structures are generally easier to purify than thick sections, closed cavities or parts containing long internal channels.

• Design drainage and access paths where possible.
• Avoid trapping cleaning or extraction fluids in closed regions.
• Consider the longest diffusion path from the bulk polymer to the extraction medium.
• Validate representative worst-case geometries rather than only simple test coupons.
• For microfluidic channels, verify complete flushing and removal of retained cleaning or extraction medium.

Sequence of extraction and post-curing

The order of washing, extraction, drying and post-curing can influence the final residual-species profile. Increased polymer conversion can reduce the amount of unreacted material, while network densification can also change the mobility and diffusion of remaining species.

Do not assume that one universal sequence is optimal for every formulation. The sequence must be established for the specific material and application through controlled comparison of final chemical, mechanical and dimensional performance.

Drying and removal of retained extraction medium

After extraction, the printed part must be dried sufficiently to remove retained water, solvent or cleaning fluid where required by the intended workflow.

Incomplete drying can introduce a new source of extractables, interfere with subsequent post-curing, alter dimensions or affect analytical results. Drying conditions must be compatible with the printed polymer and geometry.

Determining the extraction endpoint

There is no universal number of baths, extraction time or solvent volume that guarantees a low-leachables outcome for all photopolymer systems.

The extraction endpoint should be defined using application-relevant acceptance criteria. Depending on the workflow, process development may compare successive extraction stages or use targeted or non-targeted chemical analysis to determine whether further extraction provides a meaningful reduction in released species.

Any analytical endpoint must be linked to the intended use, material version, geometry, extraction medium and validated manufacturing process.

Monomer Free and reduced-residual systems

Monomer Free (MF) or other reduced-residual formulation strategies can reduce selected reactive species at the formulation level and may support low-leachables process development. However, the absence of conventional monomers does not imply the absence of extractables, leachables, additives, reaction by-products or process-related residues.

MF and other high-purity systems must therefore still be processed, extracted and validated according to the intended application.

Laboratory exhaustive extraction and Soxhlet-type approaches

Soxhlet-type extraction and other exhaustive or accelerated laboratory extraction approaches may be useful during research, chemical characterization or process development when their relevance and material compatibility are understood.

They should not be treated as universal production post-processing methods for 3D printed photopolymer parts. Soxhlet extraction typically exposes a solid repeatedly to hot condensed solvent, which can create conditions substantially more aggressive than the intended manufacturing or service environment.

US EPA Method 3540C is an established Soxhlet extraction method for extracting nonvolatile and semivolatile organic compounds from solid matrices such as soils, sludges and wastes. It is not a medical-device photopolymer processing standard and should not be presented as such.

If a Soxhlet-type or other exhaustive extraction method is considered for printed photopolymers, solvent compatibility, extraction temperature, duration, dimensional stability, mechanical performance and chemical changes to the polymer must be independently validated.

Chemical characterization and biological evaluation

For medical-device applications, chemical characterization should be designed within the applicable biological-evaluation and risk-management framework.

• ISO 10993-18:2020 provides the framework for chemical characterization of medical-device materials, including estimation of extractables under laboratory extraction conditions and measurement of leachables under clinical use conditions.
• ISO 10993-12:2021, together with its applicable amendments, addresses sample preparation and preparation of extracts for biological evaluation; chemical-characterization extractions are addressed by ISO 10993-18.

Compliance with a standard cannot be inferred from following this IFU. The legal manufacturer or responsible organization must define the applicable standards, extraction conditions, analytical methods, toxicological evaluation and acceptance criteria for the final device or application.

Contamination control

Low-leachables processing requires control of contaminants introduced after printing as well as species originating from the resin itself.

• Use extraction vessels, tubing, seals, filters and handling tools compatible with the selected medium.
• Avoid cross-contamination between resin families or between qualified and non-qualified workflows.
• Control particulate contamination and residues from gloves, wipes, detergents and processing equipment.
• Use water, solvents and cleaning fluids of suitable and controlled quality for the intended process.
• Maintain documented cleaning and replacement schedules for extraction equipment.

Downstream processing and change control

Finishing, coating, bonding, sterilization, packaging, accelerated aging, storage and service exposure can change the chemical species released from a printed part.

Changes to resin version, printer, exposure settings, geometry, cleaning chemistry, extraction medium, extraction equipment, extraction temperature, drying, post-curing or downstream processing must be assessed through the user's change-control and validation process.

Recommended workflow-development logic

1. Select the resin system and version appropriate for the intended application.
2. Establish validated printing and maximum-achievable conversion conditions.
3. Remove uncured surface resin using the specified initial cleaning workflow.
4. Select an extraction medium based on removal efficiency and polymer compatibility.
5. Compare static extraction with repeated fresh-medium or continuously renewed extraction where appropriate.
6. Optimize temperature, agitation, flow and extraction duration without damaging the print.
7. Define drying and post-curing sequence.
8. Consider final conditioning in the intended-contact or representative medium where relevant.
9. Establish an analytical or application-specific extraction endpoint.
10. Validate representative worst-case geometries and final-use conditions.
11. Lock the qualified workflow under documented process and change control.

Responsibilities of the user

• Users are responsible for selecting suitable materials, extraction media, equipment and processing conditions.
• Users must validate solvent and temperature compatibility with the printed polymer.
• Users must establish application-specific chemical, mechanical, dimensional and biological acceptance criteria where relevant.
• For regulated applications, conformity assessment, biological evaluation and final device compliance remain the responsibility of the legal manufacturer.

Related 3Dresyns® documentation

• Instructions for Use (IFU) Hub
• IFU for Biocompatible Photopolymer Resin Systems
• Extractables and leachables in photopolymer 3D printing
• Medical & Biocompatible 3D Printing Framework
• Technical documentation

External technical references

• ISO 10993-18:2020 – Biological evaluation of medical devices – Part 18: Chemical characterization of medical device materials within a risk management process
• ISO 10993-12:2021 – Biological evaluation of medical devices – Part 12: Sample preparation and reference materials
• US EPA SW-846 Method 3540C – Soxhlet Extraction