Regulatory Focus™ > News Articles > Lack of ISO Interoperability for Syringes Leads Concerned FDA to Issue New Draft Guidance

Lack of ISO Interoperability for Syringes Leads Concerned FDA to Issue New Draft Guidance

Posted 03 April 2013 | By Alexander Gaffney, RAC

A new guidance document posted by the US Food and Drug Administration (FDA) on the use of glass syringes to deliver pharmaceutical and biological products looks to build upon an existing international standard with the intent to reduce the number of adverse events associated with syringes and the devices used to connect them.


A glass syringe is one component of an injection device, which when fully equipped often includes a needle, needleless luer connectors, adapters and/or transfer units-collectively known as connective devices. FDA's guidance observes that the devices are "a critical aspect of patient care," and are often used for intravenous (IV) line luer connections, needleless luer locks, adapters and transfer units, and not just injections.

Such devices are cleared or approved by FDA under a wide range of pathways, including humanitarian device exemptions (HDEs), postmarket applications (PMAs), 510(k) premarket notification. For devices that include a drug product, they can also be approved through the new drug approval (NDA), abbreviated new drug approval (ANDA), and biologics license approval (BLA) pathways.

Those devices have in recent years been subject to the International Standards Organization's (ISO) Standard 11040-4, which was deemed suitable for ensuring that a glass syringe is suitable to be connected to a connecting device.

But FDA's thinking on the matter has changed since 2010 in response, it says, to reports of adverse events and product quality concerns related to connectivity problems. Of particular concern is the potential for the devices to break, clog or otherwise malfunction, particularly with pre-filled syringes.

This was most evident with syringes pre-filled with adenosine, used to correct cardiovascular abnormalities in patients with rapid or irregular heartbeats. Being unable to use adenosine in such a situation could lead to a delay in the administration of a treatment, thereby harming the patient.

Subtle Interoperability Problems

"Accordingly, FDA has determined that, for glass syringes, demonstrating conformity to the ISO 11040-4 standard alone does not ensure that the glass syringe can be properly connected to connecting devices," it explained in a Federal Register posting.

The problem, FDA explained, is that regulators thought that ISO 594-2, another syringe standard, would be interoperable with 11040-4.

"However, the glass syringe standard, ISO 11040-4, has certain undefined key dimensions," FDA said. "For example, the standard lacks dimensions for the glass syringe nozzle internal diameter, thickness of nozzle wall, and barrel neck curvature. In contrast, the standard for the connecting devices, ISO 594-2, has specified dimensions in these areas."

In other words, they're interoperable for the most part, but it's not guaranteed, making it possible that a syringe meeting the 11040-4 standard might not connect with a device meeting the 594-2 standard.

Moving out of ISOlation

So what else is needed? Supplemental testing information, FDA said.

Even if a device meets the 11040-4 standard, FDA said companies need to ensure that devices meeting the 594-2 standard can connect with the device. To accomplish this, companies need to provide information on at least five areas:

  1. syringe inner and outer diameter
  2. height of the nozzle for a glass barrel syringe intended to connect to a luer lock fitting
  3. thickness of nozzle wall
  4. barrel neck curvature
  5. dimensions to accommodate luer locks with a center pin piercing element

"FDA recommends that sponsors submit data to demonstrate that their glass syringe has connectivity (interoperability) to connecting devices to ensure proper delivery of the drug or biological product," it explains in the guidance.

Some companies may need to redesign their products using different types of needles, a different design for the syringe or connectors.

Other performance data, including what needs to be included in submissions for approval or clearance, are explained in depth in the draft guidance. FDA said it advises that sponsors have early discussions with the agency if they are considering developing a glass syringe or injector covered under the document.

Comments on the draft guidance are due by 2 July 2013.

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