As regulatory pressure keeps rising, affecting every aspect of the drug manufacturing process, quality is an ongoing quest for pharma companies
Add to this the increasing number of complex drug molecules, and it’s abundantly clear why packaging materials have recently been placed in the spotlight. Although pharmaceutical companies continuously develop and market new treatments, the main packaging material — borosilicate glass — has basically remained unchanged for more than a century. Are there better alternatives? For an industry focused on high level research, this is an important question to ask.
It was precisely this issue that brought the industry together in Washington DC, USA, at the beginning of the year to attend PDA’s first glass quality conference since 2013. Here, experts presented and discussed progress and developments in material technology and handling.
First, to put the question into perspective, it’s worth taking a look at the actual material: using glass is a century old pharma tradition. Its purest form — silicon dioxide or quartz — occurs frequently in the continental crust and is very stable and inert. These properties make it an attractive material in which to package drugs.
Yet, from a manufacturing standpoint, there are disadvantages: high temperatures are required to make the material viscous — and forming remains a challenge. To assist the melt and influence the final product properties, boron oxide (among other compounds) is added (hence the name, borosilicate glass). Boron is a network former and becomes fully integrated into the glass structure.
However, it can evaporate if the forming process is not properly adjusted. Yet, as borosilicate glass has been used within the pharmaceutical industry for more than a century and is used for approximately 40 billion containers of injectable drugs per annum, the behaviour of the material during the converting process and, even more importantly, with respect to the drugs it’s supposed to store, is well researched.
Meanwhile, packaging vendors have made progress on critical glass forming parameters, resulting in containers with improved and more durable inner surfaces. LDP Vials (Ompi), Vialex (Nipro), Gx Armor (Gerresheimer) and, last but not least, Schott Vials Delamination Controlled are prominent examples.
Nevertheless, alternative materials have recently sparked considerable interest in the industry. It therefore made sense for the Washington delegates to discuss aluminosilicate glass as a possible alternative. There’s a clue in the name: more aluminium instead of boron is introduced into the glass matrix to increase its processability. Just like borosilicate glass, this glass type has a longstanding history.
Today, it’s mainly used for electronic devices. To make a smartphone display glass suitable to package complex biomolecules, intense treatment is necessary. As a matter of fact, a study showed that without this treatment, aluminosilicate glass shows a roughly 60% higher amount of extractables than borosilicate glass.1 Once processed, it can certainly be used as an alternative for niche applications; yet, incoming inspection would have to be done to avoid any confusion with untreated containers.
To fully understand the borosilicate versus aluminosilicate question, we need to go beyond the extractables and leachables (E&Ls) profile and take glass breakage and particles into account — two major factors that may determine whether aluminosilicate glass can be positioned as a “universal solution.”
The generation of free glass particulates mainly occurs as a result of scuffing: on older production lines, glass containers rub against each other and the ensuing friction causes particulates to come off. Currently presented aluminosilicate solutions have made significant progress in this field. One example in particular showed a reduction of 92%.2 Yet, this advantage was achieved independently of the glass chemistry, and can be attributed to a coating of the outer surface.
Breakage resistance can also be enhanced using chemical treatments, such as an ion exchange process that has been a standard practice in the industry for decades. Again, this process is independent of glass type.
But how much toughness is right for pharmaceutical filling processes? One revelation might come as something of a surprise: developing ever stronger and possibly unbreakable glass is, in fact, not particularly helpful. The reason behind it is simple: when a force is applied, something has to give. Ergo, if the glass doesn’t break, eventually the filling machine will.
A presentation by Novo Nordisk illustrated that glass strength is determined by flaw properties, and breakage results when a tensile stress is applied to a weakened glass surface.3 The glass acquires flaws, such as scratches or chips, throughout its lifecycle, mainly during transportation or production. This, by definition, means that strictly eliminating glass-to-glass contact to maintain a flawless surface will secure the naturally high breakage resistance of glass and protect the machinery at the same time.
All in all, it’s safe to say that using toughened glass will not preclude pharmaceutical companies from optimising their lines. Quite the contrary, it means that line optimisation is even more important when using toughened glass. Moreover, toughened (aluminosilicate) glass may be very stable against side compression … but can still break on impact. As such, FDA’s general advice to do precise root cause analyses is more than understandable.
Offering new insight, Smart Skin Technologies, a Canadian company, is able to measure the movement, forces and stress applied to pharmaceutical containers during the production or filling process. Vial clones with a sensitive outer skin are sent through the production line to identify pressure points and critical areas.
About 200 sensors constantly transmit information to a Microsoft Surface tablet with the company’s Quantifeel software regarding how the vials move through the line, how they spin, tilt or experience pressure or shock. After 6–10 rounds, the manufacturer is able to identify any stress patterns and implement corrective action. According to a corresponding study by Roche and Genentech regarding this approach, small adjustments — such as optimising the synchronisation between moving parts — can significantly reduce breakage.4
The beverage industry has been using the system for years to reduce scuffing and optimise lines. Roche in Switzerland approached Smart Skin Technologies in 2015 to adapt its system for parenteral filling. Today, the system works with vials, syringes and cartridges.
Is that the end of the story? Not quite! The PDA conference also comprised a session on the latest improvements to borosilicate glass containers. Surface treatments and coatings open the door to new application fields, and significant progress has been made in improving overall glass container quality. Interest in quartz as the purest material to package drugs remains high, and companies such as Momentive Performance Materials keep working on improving the converting process to offer fused quartz vials.
Other vendors are just as innovative and are combining silicon dioxide with standard packaging materials. Here, polymer vials or borosilicate vials with an inner quartz coating are offered by companies such as SiO2 Medical Products and Schott Pharmaceutical Systems, respectively. The latter has recently doubled its production capacity for coated vials, which demonstrates how well the approach is being received by the pharmaceutical industry. Or, as one conference delegate put it: “Borosilicate glass is standing stronger than ever.”