USP Pens First Standard for Metal PackagingUSP Pens First Standard for Metal Packaging

A new USP draft standard is ready for comments. 〈662〉 Metallic Packaging Systems and Their Materials and Components of Construction is the first global compendial standard for metal packaging.

Desmond Hunt, PhD, USP Senior Principal Scientist, explains, “The standard really is looking to … find the common or baseline standard by which suppliers could [then] be held accountable for; but also drug product manufacturers can start using as a measuring stick of minimum quality attributes that’s necessary for a packaging material component made of metal.”

The new <662> chapter outlines testing procedures and relevant defined acceptance criteria in two areas: Functional Tests and Chemical Analysis (aka Extractables).

• 3.1 Functional Tests specifically covers burst pressure; particulate matter; surface coatings; tube air tightness; tube deformation (guillotine test); and foil pinholes.

While all these tests are important, Hunt specifically points to particulate matter. “When we look at particulate matter in a final drug product, that’s a red flag for the FDA,” Hunt says. “When you start thinking about where this particulate matter comes from, the majority comes from the packaging system — 80%. If you can control particles on a packaging system, you can effectively reduce the particle load of a drug product. So having a specific test for particulate matter for metal packaging is significant.”

Related:New Pharmaceutical Packaging Test Method Earns USP Approval

• 3.2 Chemical Analysis — Extractables involves solvent mediated extractions; and thermal extraction.

“Obviously, you want to understand what extracables, metals, are coming from a metal container,” Hunt says. “Most metal materials are pretty standard. You know the composition, but you may not know how easily something may extract out of the material vs another material, which is quite important.”

Together, the functionality and extractables tests provide a strong baseline for packaging quality. “When you start thinking about the functionality test, obviously, you want the packaging system to be robust [for] the supply chain. So those tests are important,” Hunt says. “But understanding the chemical nature of it as well is just as important.”

According to the draft: “Common metal packaging components include aluminum and its alloys, stainless steel, tin-free steel, and tinplate. Within the pharmaceutical industry, primary metal packaging systems can include aerosols, blister packs, canisters, collapsible tubes, drums, and gas cylinders, and secondary packaging systems such as overwraps and seals.”

There are a few exceptions not covered — “Metallic components that are part of drug delivery systems — such as springs for auto-injectors, metering valves for metered dose inhalers, or staked needles for prefilled syringes — are out of scope. Similarly, aluminum caps (seals) for vials and bottles are also excluded. For medical devices and combination products regulated as medical devices (e.g., delivery devices) and for packaging that is considered a device-constituent part, users should refer to additional device-specific FDA Guidances for Industry. Metal cylinders for medical gasses and metallic manufacturing components — such as filling needles, tanks, and valves — are also out of scope.”

Additionally, USP’s General Chapters — Packaging and Distribution Expert Committee has written a new companion general information chapter 〈1662〉 Materials and Manufacturing Processes for Metallic Packaging Systems. <1662> supports <662> by providing information on the materials of construction, manufacture, and processing of metallic packaging containers used in pharmaceutical packaging/delivery systems for inhalation, nasal, topical, mucosal, and oral dosage forms.

Gaining traction.

USP has been actively revising all its packaging standards since 2010. “We’ve been getting queries since 2010, asking us questions about metal packaging, about what chapters apply,” says Hunt. So there was plenty of stakeholder interest. USP would point people to other chapters that weren’t specific for metal packaging, if the test philosophy was the same.

But when USP did a gap analysis in 2013, it realized no pharmacopeia had a chapter on metals. USP tried to create one in 2017, unsuccessfully. “Sometimes you have to have the right group of experts with the right deal of motivation,” says Hunt.

It was only after conversations in 2020 with the Chinese Pharmacopeia that <662> and <1662> were developed. “Both organizations thought would be a good opportunity to collaborate,” Hunt recalls. “When you have the will of the Chinese Pharmacopeia and USP, something’s going to happen.”

USP released <662> and <1662> draft standards on July 1, 2024; and is accepting comments until September 30, 2024. No date has been set yet for releasing the final standards, but Packaging Digest will monitor the progress and report back.