Background

in response to NHS England’s National Patient Safety Alert – Transition to NRFit™ connectors for intrathecal and epidural procedures, and delivery of regional blocks issued in January 2024, aseptic units are being asked to provide all intrathecal and epidural injections in NRFit syringes from 31^st January 2025.

There is little published data for aseptically prepared medicines stored in NRFit syringes. The NHS Pharmaceutical Aseptic Services Group (PASG)  has previously issued guidance to the NHS regarding the Pharmaceutical Testing Requirements for Neuraxial Syringes and Syringe Caps and there has been some work to assess NRFit syringes manufactured by GBUK and BBraun. The guidance and advice notes from these studies are available via the Pharmaceutical Aseptic Services Group website.

Aseptic units may therefore need to extrapolate stability data between luer lock and NRFit container/closure systems, considering two main factors:

• physicochemical stability
• syringe container/closure integrity

Physicochemical Factors

Physicochemical factors to consider include:

• potential interactions between the drug and the syringe’s lubricants and rubber components
• differing materials allowing greater gas permeability
• the effect of extractables and leachables on extended storage

MHRA guidance on assigning shelf lives

The MHRA has issued guidance to specials manufacturers for determining expiry dates of products based on the following principles:

• product expiries to be based on scientific rationale, including test data
• test data may be obtained from literature searches, provided the literature is relevant to the product formulation and the container/closure system proposed
• expert opinion on product shelf life must be supported with documented rationale and test data, if available
• the assigned shelf life must include a margin of safety from the stability data available

Extrapolation between luer lock and NRFit

If the luer lock and NRFit syringes differ only in the nozzle design, and

• are made by the same manufacturer
• use the same materials of construction
• are made using the same manufacturing processes

there is unlikely to be any significant difference relating to physicochemical stability of the products prepared in the two container/closure systems, so physicochemical stability data can be extrapolated.

Where there are differences in materials of construction, or different syringe manufacturers are being used, an impact assessment is required before extrapolating data.

When extrapolating data, apply a conservative shelf life to ensure there is a margin of safety.

Potential differences between syringes

Syringe construction may differ in the following areas:

• the composition of the plastics used for the barrel & plunger
• the constituents of the rubber grommet & lubricant
• the vulcanising agent used in the grommet
• the method of sterilisation (ethylene oxide, gamma irradiation)
• overall syringe dimensions

SPS has compared brands of luer lock syringes commonly used in the NHS with the available NRFit syringes, summarised in this table.

The data shows that within each of the BBraun and BD syringe ranges, there are no differences in material of construction or method of manufacture between their luer lock and NRFit designs This means that physicochemical stability can be extrapolated from:

• BD Hypodermic and Plastipak Luer-Lok syringes to BD NRFit syringes
• BBraun Omnifix luer lock Syringes to BBraun Omnifix NRFit Syringes

Syringe Container/Closure Integrity

Integrity testing data is valid only for the specific syringe and closure tested, therefore data on syringe integrity cannot be extrapolated from luer lock syringes to NRFit syringes.

Syringe integrity testing must be performed on the NRFit syringe closure combination and the NRFit syringes must be included in ongoing media validation studies.

The NHS QA Committee has issued guidance for the microbiological and physical integrity testing of syringes: Microbiological Protocol for the Integrity Testing of Syringes.

In all circumstances NHS guidance for maximum syringe fill volumes (no more than 85%) must be followed. Refer to PASG website (log in required) for details.