Cleanliness is always concern number one when it comes to designing and manufacturing sterile packaging. Sterile packaging for product or filling components is typically much closer to the patient than other single-use containers. As such, there is virtually zero tolerance of particles and particularly bioburden, such as hair; one eyelash that makes its way into a vial can cost millions of Euros in lost drug product, recalls and regulatory/legal costs.
Key industry trendsThe critical need for the cleanest possible packaging is driving leaders in this market to manufacture under near-sterile conditions; there is a growing consensus that the use of ISO Class 5 cleanroom conditions is imperative (by comparison, the norm for the rest of the single-use bag industry is only ISO Class 7). Maintaining such stringent conditions while using materials like Tyvek (DuPont) can be a huge challenge, and requires a great deal of manufacturer “know how” and experience.
The use of sterile packaging in pharmaceutical manufacture is incredibly diverse, ranging from breathable bags for steam sterilisation, to covered trays for e-beam sterilisation, to gamma stable packages for irradiation applications.
An interesting trend in recent years has been the growing use of barrier isolator technology. As more processes are performed inside isolators, the cost and challenge of transferring sterile items into them has grown. The industry response has been a wholesale move away from reusable containers in favour of flexible single-use bags mated to isolator “beta ports”. This new technology allows clean, sterile components like stoppers or syringe parts to be shipped to the point of use, sterilised if necessary, and then introduced to the isolator all in the same single-use bag. This capability can deliver a significant process efficiency boost for the end user.
How have materials adapted?
The growing demand for single-use solutions has driven the industry to find new disposable materials and specialty cleaning procedures for those materials.
Perhaps the most interesting material in use today is Tyvek, a non-woven film made by DuPont from high density polyethylene. Its breathability makes it ideal for use in autoclaves for sterilisation of just about anything from stainless equipment to rubber stoppers. Shippable and sterilisable Tyvek-HDPE bags are rapidly displacing traditional stopper washers for delivering clean, sterile stoppers to final fill lines, providing a significant reduction in capital and running costs. These same bags are also replacing paper bags for autoclaving process equipment in biotech plants because they are transparent, much stronger, don’t tear when wet, and are virtually particle-free.
Other innovations revolve around shippability — not all packages can be shipped without a risk of pinhole formation and consequent integrity/sterility breach. Careful material selection in consultation with the package manufacturer is the key to avoiding problems down the road.
Ensuring full sterility
Other than cleanliness and suitability for the chosen sterilisation method, there are a number of practicalities that need to be considered to ensure the final sterile package is suitable for aseptic environments. The use of double-layer packaging of the product allows outer layers to be peeled away as the package is moved from a less clean “gray space” into the aseptic environment. In some cases, the outside of the package may need to be sanitised by bleach or alcohol wipedown, or even by VHP — obviously, the package should withstand this treatment without degradation.
One interesting innovation that we are proud of at ATMI is a feature we developed called Easy Tear; a tearable strip on our packaging that allows the user to tear the bag open instead of cutting it. This apparently minor feature produces substantially fewer particles than cutting a similar bag with scissors, resulting in reduced contamination of product and process for our customers.