Richard Bhella is Global Product Manager, Single-Use Storage and Delivery Technologies at ATMI Lifesciences.

Richard Bhella

Richard Bhella. Global Product Manager for Single-Use Storage and Delivery Technologies at ATMI.The growing uptake of single-use sterile packaging in pharmaceutical production processes mirrors the broader trend towards single-use across every sector of the pharmaceutical industry. The primary drivers for this trend continue to be cost control, speed and flexibility. The value of single-use is so compelling that this trend is sure to continue at a rapid pace into the foreseeable future; ATMI and other manufacturers are backing this continued growth by investing heavily in new manufacturing capacity and leading-edge technologies.

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. 

The 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. 

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.

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.

Articles

The growing uptake of single-use sterile packaging in pharmaceutical production processes mirrors the broader trend towards single-use across every sector of the pharmaceutical industry.

Developing Sterile Packaging For Aseptic Environments

Life science industry users of single‑use devices have legitimate questions about the potential for leachables to impact the quality of their pharmaceutical products. Extractables data using model solvents can be a useful indicator of leachables risk, but until now users have struggled to make like‑for‑like comparisons between the various single‑use technologies they are considering. In some cases, cautious users may even choose to stick to what they know rather than open what can seem to be a Pandora’s Box of new extractables questions. The Bio‑Process Systems Alliance (BPSA) guides do a great job of clearing the fog and demystifying the myths surrounding the extractables and leachables debate, establishing which testing is most valuable and which testing is less so. This has obvious benefits, not only for users, but also for suppliers; more uniform customer expectations will allow us to invest in the right validation data package and avoid expending development resources on generating data that is of little or no value to customers.

 Richard Bhella. Global Product Manager, Single-Use Storage and Delivery Technologies at ATMI Lifesciences.

Challenges of developing the right materials

The trend towards ever cleaner and purer contact materials is driving single‑use manufacturers to adopt tighter cleanroom standards and more carefully controlled polymer resins. At ATMI we are extruding our own polymer films and manufacturing our single‑use products entirely under ISO Class 5/Class 100 cleanroom conditions rather than the less exacting ISO Class 7/Class 10000 conditions that are still the industry norm. All new ATMI films are manufactured using medical grade resins that are free of animal‑derived components, a trend that has accelerated rapidly in the last couple of years. In addition to the obvious regulatory compliance advantages of these newer medical grade resins, they also typically have much more stringent change controls in place. Furthermore, as there are relatively few such resins on the market, there is greater likelihood that films from different vendors will, in fact, be using the same contact material, which has advantages in validation. 

Pharmaceutical contact materials for single‑use processes are under the microscope now more than ever before. In fact, when our customers are planning to implement a new single‑use technology, the biggest hurdle they face is probably materials validation — raw materials need to be more traceable, the supply chain needs to be entirely free of animal‑derived components and change control needs to be more rigorous. What was considered acceptable just a few years ago would not pass muster today. Indeed, more and more users are looking back at material selection decisions made in the past and asking serious questions about whether their legacy single‑use technologies may need to be revisited. In such circumstances, the importance of validation cost containment becomes ever more apparent.

If we can offer new technology made from a material that the client has already validated for contact with their product, the validation hurdle can be eased dramatically. If the client already has a mixing bag film validated for contact with their drug product, for example, then validating the same film for storage applications should take much less effort than if the client was to use a new film. This is the cornerstone of our recent initiative; one film for every application from liquid and powder storage, to mixing to cell culture and fermentation. 

Today, every end‑user must still use their own knowledge and intuition to decide on what tests are required for materials used for single‑use systems. I would love to see end‑users and single‑use suppliers reach a strong and clear consensus on materials compatibility testing. We are not quite there yet, but the BPSA guides are a critical step in the right direction. I look forward to a not‑too‑distant future when contact material harmonisation will allow users to pick the technology that works best for them without worrying about materials compatibility at all. Given the similarities of contact materials in the market today, that day may be closer than we think. 

Life science industry users of single?use devices have legitimate questions about the potential for leachables to impact the quality of their pharmaceutical products.