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ISO 28824:2016 — Medical devices — Infusion sets
Requirements and test methods for sterile single-use infusion sets for liquid pharmaceutical preparations
ISO 28824:2016 specifies requirements and test methods for sterile, single-use infusion sets intended for the administration of liquid pharmaceutical preparations to patients. This standard covers the complete fluid pathway from the container (IV bag or bottle) to the vascular access device, including drip chambers, tubing, flow control devices, injection ports, and connectors.
1. Infusion Set System Architecture and Component Requirements
ISO 28824 defines the minimum requirements for each component of an infusion set and for the assembled system as a whole. The standard covers continuous and gravity-fed infusion sets used in hospital and home-care settings, including basic administration sets, transfusion sets, and metered-volume chambers for paediatric use. Each infusion set comprises several functional elements: the spike (piercing the container closure), the drip chamber (enabling visual flow monitoring and air elimination), the tubing (flexible PVC or non-PVC material), the flow regulator (roller clamp or precision orifice), the injection port (for secondary medication or bolus administration), and the terminal connector (luer-lock or luer-slip for attaching to the vascular access device).
The standard specifies dimensional, mechanical, and functional requirements for each element. For the drip chamber, the drop formation rate at the reference flow of 20 drops/mL must be within ±5 % of the manufacturer’s declared value — this is critical for the accuracy of gravity-fed infusion where the caregiver counts drops to estimate the infusion rate. For the tubing, the internal diameter tolerance must be within ±0.1 mm, and the flow resistance (measured as pressure drop at a specified flow rate) must be consistent within ±10 % across the production batch to ensure predictable flow rate when used with infusion pumps. For the flow regulator, the standard specifies that the flow rate must be adjustable from zero to the maximum rated flow, and that the flow must remain stable within ±25 % of the set value over a 12-hour continuous infusion period.
| Component | Requirement | Test Method | Acceptance Criterion |
|---|---|---|---|
| Spike | Penetration force, connection stability | Force measurement, pull-off test | Penetration ≤ 25 N, retention ≥ 15 N |
| Drip chamber | Drop size accuracy, air elimination | Drop counting vs. gravimetric, bubble point | ±5 % of declared drops/mL |
| Tubing | Dimensions, flow resistance, kink resistance | Micrometer, pressure drop, flow reduction at 90° bend | ID tolerance ±0.1 mm, flow resistance CV < 10 %, kink flow > 50 % |
| Flow regulator | Adjustability, stability over 12 h | Flow rate measurement at multiple settings | ±25 % of set flow over 12 h |
| Injection port | Seal integrity after multiple punctures | Pressure test after 20 punctures with 22G needle | No leakage at 50 kPa |
| Terminal connector | ISO 594 compliance, connection force | Luer lock/slip gauge test | Per ISO 594 (now ISO 80369 series) |
A frequently overlooked design detail is the drip chamber inlet nozzle geometry. The nozzle determines the drop size, which directly affects the drops-per-millilitre calibration. A 10 % variation in nozzle diameter translates to approximately a 20 % variation in drop volume (since drop volume scales with approximately the square of nozzle diameter). Mould tool wear over the production run can cause a gradual increase in nozzle diameter, affecting drop-count-based infusion rate accuracy. Implement statistical process control with measurement at every Nth moulding cycle.
2. Flow Performance, Occlusion Alarms, and Back-Pressure Effects
ISO 28824 addresses the flow performance of infusion sets under various operating conditions, including when used with infusion pumps and under back-pressure from patient venous pressure, height differentials, or downstream occlusion. For infusion pump-compatible sets (often labelled as “non-PVC, DEHP-free” for modern applications), the standard specifies that the tubing must withstand the pump-induced compression forces without permanent deformation or wall sticking that could occlude the fluid path. The tubing must be tested with the specific pump model(s) declared compatible by the manufacturer — this testing must demonstrate flow accuracy within ±5 % at the programmed rate across the pump’s full flow range.
Occlusion detection is another critical aspect. Many infusion pumps detect downstream occlusions by monitoring the pressure rise in the tubing between the pump and the patient. ISO 28824 requires that the tubing be sufficiently rigid to transmit the pressure wave to the pump’s sensor, but not so rigid as to create a patient safety hazard from excess force on the vascular access site. The standard specifies a minimum burst pressure of 200 kPa for the tubing and all connections, ensuring that the set can withstand the maximum pressure generated by an infusion pump in the event of a distal occlusion without rupturing or leaking.
When selecting tubing material, consider that PVC remains the most widely used material for infusion sets due to its excellent balance of flexibility, clarity, and kink resistance. However, DEHP (di-2-ethylhexyl phthalate) plasticiser has come under regulatory scrutiny in recent years for IV administration. For non-DEHP alternatives, the leading options are: PVC plasticised with DINCH (1,2-cyclohexane dicarboxylic acid diisononyl ester), polyurethane, and polyolefin elastomers. Each alternative material has different flow resistance characteristics, kink recovery properties, and compatibility with infusion pump mechanisms — always verify pump compatibility with alternative materials before designation.
| Performance Parameter | Test Condition | Requirement | Clinical Relevance |
|---|---|---|---|
| Flow resistance | 100 mL/h water, 20 °C | ≤ 10 kPa typical per metre | Pump start-up time, gravity flow rate |
| Burst pressure (tubing) | Hydrostatic pressure ramp | ≥ 200 kPa | Safety under pump occlusion alarm |
| Pump compatibility | Specific pump models | Flow accuracy ±5 % | Reliable drug delivery |
| Kink resistance | 90° bend with 5 mm radius | Flow reduction ≤ 50 % | Prevent unplanned occlusion |
| Leakage under back-pressure | 50 kPa for 30 s | No leakage at connections | Patient safety, infection prevention |
| Particulate matter | Per pharmacopoeia | ≤ 25 particles/mL ≥ 10 μm | Reduce embolic risk |
3. Sterility Assurance and Biological Safety
ISO 28824 requires that infusion sets be supplied sterile with a sterility assurance level (SAL) of 10⁻⁶. The standard specifies that the sterile barrier system must comply with ISO 11607-1 and be validated per ISO 11607-2. Ethylene oxide (EO) sterilisation is the most common method for infusion sets due to their long, narrow lumens and heat-sensitive materials. The standard requires that EO residuals be controlled to the limits specified in ISO 10993-7 (maximum 250 μg/g for EO and 50 μg/g for ethylene chlorohydrin), and that the aeration time be validated to ensure residuals are below these limits at the time of clinical use.
Biological safety requirements follow the ISO 10993 series. Infusion set materials are classified as blood-contacting devices (external communicating, path of blood — per ISO 10993-1 categorisation), requiring: cytotoxicity (ISO 10993-5), sensitisation (ISO 10993-10), irritation (ISO 10993-23), acute systemic toxicity (ISO 10993-11), haemolysis (ISO 10993-4), and material-mediated pyrogenicity testing. The standard also requires that the infusion set be non-pyrogenic, with the bacterial endotoxin limit set at ≤ 0.5 EU/mL for paediatric infusion sets and ≤ 2.0 EU/mL for adult sets as per pharmacopoeial requirements.
A critical and often underestimated safety consideration is the potential for leachables from the infusion set materials to enter the patient’s bloodstream — particularly during prolonged infusions (≥ 24 hours) or with lipid-based formulations that can act as extractants. DEHP leaching from PVC sets is dose-dependent: the leached amount increases with infusion duration, lipid content of the infusate, and temperature. For neonatal and paediatric intensive care, where patients are most vulnerable to the potential effects of DEHP exposure, many regulatory authorities now recommend DEHP-free infusion sets. Always review the latest regulatory guidance in your target market.
Frequently Asked Questions
Q1: What is the relationship between ISO 28824 and ISO 8536?
ISO 8536 is the International Standard series for infusion equipment for medical use. Part 4 of ISO 8536 specifically covers infusion sets for single use, gravity feed. ISO 28824:2016 was developed to harmonise and supersede the various national and regional standards for infusion sets, incorporating additional requirements for safety, biocompatibility, and pump compatibility not fully covered by ISO 8536-4.
Q2: Are non-PVC infusion sets covered by ISO 28824?
Yes. While PVC with DEHP plasticiser has been the traditional material, the standard is material-neutral. Non-PVC alternatives (polyurethane, polyolefin blends, PVC with non-DEHP plasticisers) are fully covered. However, manufacturers must demonstrate that the alternative material meets or exceeds all requirements of the standard, including flow resistance, kink resistance, pump compatibility, and biocompatibility — the same requirements as for PVC-based sets.
Q3: How is the “drops per millilitre” calibration verified?
The standard specifies a gravimetric calibration method: 200 drops are counted under controlled temperature (20 °C ± 1 °C) using deionised water. The total mass is divided by 200 and converted to volume using water density. The resulting volume per drop is used to calculate the drops/mL value. The calibration must be verified at three flow rates covering the usable range of the set.
Q4: What is the maximum length of infusion set tubing?
The standard does not specify a maximum length explicitly — length is a design parameter determined by the intended clinical use. However, practical considerations limit typical lengths to 1.0–2.5 metres. Longer sets increase flow resistance (approximately proportional to length), increase the volume of the fluid path (priming volume), and can affect the accuracy of infusion pump flow rate control. Every metre of additional tubing adds approximately 1–3 mL of priming volume (depending on internal diameter) and increases the compliance of the system, which can affect occlusion alarm response time.
