Outsourcing Guide

The Dispos-a-vent product developed by Oliver-Tolas Healthcare Packaging consists of a Tyvek flap for breathability and a foil pouch to ensure moisture and oxygen barrier properties.

Combination products that blend drugs, devices and/or biologic products continue to excite investors, motivate engineers and challenge regulators. The technical issues raised by 

these products extend to their packaging. In this article, George Mankel, Product Leader, Films, at Perfecseal, and Jane Severin, Director of Technology at Oliver-Tolas Healthcare Packaging, share their thoughts on some of the packaging predicaments that manufacturers of combination products should bear in mind.

The fundamentals of medical packaging—protecting the device and ensuring an aseptic presentation—continue to apply when developing packaging for combination products, says Mankel. “But the packaging designer also must find a way to maintain the safety and effectiveness of the drug or biologic,” he adds.

When you’re designing for a device, mechanical protection against a breach of the sterile barrier is paramount, adds Severin. “With a drug, you’re looking for chemical protection and stability. You will need high-barrier materials to protect a drug over its intended shelf life,” she explains. That shelf life, incidentally, can present a conundrum when it comes to convergent technologies. “The drug will probably have a longer lifespan than the device, so you’re dealing with the obsolescence of one component of a product that is quicker than the other.”

Sterilisation factors

Both companies have developed packaging technologies that optimise sterilisation for combination products.

Perfecseal has designed a single pouch that supports EtO sterilisation while providing oxygen, moisture and light barrier properties during storage. A premade Tyvek/polyethylene/Tyvek insert is sealed inside a foil pouch, creating two separate pockets, explains Mankel. “One pocket holds the drug eluting stent, in this specific application, and the other contains the scavenging agent that mops up residual oxygen and moisture after the pouch has been gas flushed with nitrogen.”

For its part, Oliver-Tolas developed the Dispos-a-vent pouch to satisfy a similar need. The pouch combines a Tyvek area for breathability with a foil pouch that acts as a moisture and oxygen barrier. “Following the EtO sterilisation process, a seal is formed enclosing the device in the film or foil part of the pouch,” says Severin. The porous section is removed and discarded, and you’re left with a completely nonporous high-barrier system.”

Drug stability and its in-pack shelf life should also be factored into any packaging and sterilisation decisions. Foil-based packaging is recommended by Mankel, because it has the dual advantage of shutting out light and gas. “Other considerations are extractables and leachables that might migrate into the drug or biologic, and up-take of the direct-contact packaging materials.”

Testing requirements

“Packaging materials have to satisfy the requirements of ISO 11607 Part 1: cytotoxicity testing, accelerated and 

real-time aging studies and so forth,” says Mankel. “If these materials are made into a pouch, the process must be validated in accordance with ISO 11607 Part 2,” he says, noting that this involves rigorous stability testing.

Generally speaking, an unused medical device will not lose its effectiveness over time. Obviously, the same cannot be said of drugs. The purpose of stability testing, Mankel explains, is to provide evidence on how the quality of a drug substance or drug product will vary with time under the influence of a variety of environmental factors, such as temperature, humidity and light. The process should also lead to the establishment of a retest period for the drug substance or the determination of a shelf life for the drug product and recommended storage conditions.

A successful combination product is greater than the sum of its parts, says Mankel. The packaging needs to meet that challenge, as well.