In recent years there has been an increasing tendency for more and more pharmaceutical companies to outsource their production to a reliable business partner, as well as companies who seek support in taking their product from early development to commercial manufacturing and throughout the product lifecycle.

The market for outsourcing solid dose services to trusted CDMOs has faced multiple challenges in recent times — one of which has been the high weightage, high product costs and recognized underperformance of established common types of blister packaging.

Polypropylene (PP) monoblisters, which are actively in use by some CDMOs, offer a reliable solution that has the potential to transform the efficiency of a key component to the process of pharmaceutical development. Indeed, the technical problems once associated with producing PP-monoblisters can be successfully overcome if contractors are prepared to take the necessary initiatives. As a result, PP-monoblisters are now an asset that more CDMOs should invest in and utilize to the maximum benefit of their pharmaceutical clients.

The Clear Commercial Benefits
There are at present a wide range of packaging presentations and formats on offer within the CDMO market. PP blister packs have many advantages over older aluminum and PVC blisters, and yet these traditional, inefficient products remain all too prevalent in the industry. This is despite the fact that PP-monoblisters are consistently proven to be better than their aluminum and PVC blister rivals. Essentially, PP-monoblisters are lower in weight, incur significantly less production costs and offer markedly higher performance. At the same time, they are credited with having less of an environmental impact during their use in the relevant stages of the production process. Indeed, we will expand on this “kinder to the environment” factor shortly.

In terms of structure, PP-monoblisters will often consist of two plastic films with different properties, such as Purelay Lid and Etimex Purelay Pharm. The ‘Pharm’ film is a PP thermoforming film similar to the PVC or PvdC (polyvinylidene chloride) coated PVC films used in an aluminum/PVC blister. The difference is that the PP push-through lidding film seals the blister, serving precisely the same purpose as the aluminum. Two prominent examples of where PVC/aluminum blisters have been replaced by PP-monoblisters are the cases of Reliv and Alvedon, two paracetamol products widely used in Sweden.

Unlike aluminum/PVC types, PP-monoblisters do not curve during late-stage production, making it easier to slot them into cartons or other packets. This is primarily due to the fact that they are made of a single material, and do not suffer from differential expansion between the aluminum and PVC.

The thermoforming and sealing films each have their own advantages. PP thermoforming films are more cost-effective than PVC films coated with PVdC sealant wrap, while being much cheaper than mono-PVC. They require fewer raw materials to produce the same amount of extruded film, owing to better water vapor transmission rates. For example, 1 kg of PVC/PVdC produces 2.5 [m.sup.2] of film while the Purelay Pharm yield is 3.5 [m.sup.2], giving 40% more film for the same price per square meter. However, PVC films coated with PVdC have the same or better barrier properties than PP and can be produced in ordinary thermoforming stations, such as those for PVC.

PP thermoforming films are better than PVC in other respects as well. They are less dense, much lighter, more transparent, and their stiffness is better suited to pushing tablets from packaging. In addition, PP thermoforming films produced by heating and quenching the polypropylene possess excellent thermoforming behavior and barrier properties. This is because the film absorbs heat evenly along its length and there is more heat on the outside than there is on the inside of the material. The resulting material has an even crystalline structure and finer crystals in the middle of the film than those found on the outside. Moreover, The PP sealing film is also comparable to or better than aluminum. It is compatible with all standard blister pack printing processes and it is just as easy to push tablets through, as is the case with ordinary aluminum foil.

Despite the many advantages, there are still fewer PP-monoblisters in active use in the pharma development market than there are PVC/aluminum blister packs. Primarily, this is because PP-monoblisters were traditionally more difficult to produce than PVC/aluminum. One reason was older packaging machines, which required manual compensation for PP shrinkage during processing. Newer machines automatically compensate for PP shrinkage, speeding up production. Another reason is that the PP films are temperature sensitive and require being evenly pre-heated before sealing. This means both the speed at which the film is passed through the heating roll and the temperature range used need to be carefully adjusted and maintained. Finally, the PP forming process requires two steps — mechanical and hot air — whereas PVC is formed in a single step using compressed air. Until recently, the extra steps and added complexity of production have prevented PP-monoblisters from replacing aluminum/PVC packs. Now innovative production techniques and improved machinery, together with higher environmental demands from customers, makes this an opportunity for the proactive, forward looking CMDO to stand out in the crowd.

To overcome the challenging barriers that have been outlined, some CDMOs have taken the steps necessary to successfully introduce new PP-monoblisters. Such steps can be broken down and summarized as follows: there needs to be investment in new format parts, and skilled personnel must be trained in the new techniques. In older machines, heating elements are used for the preheating step during the sealing process, and consequently in some of the new machines, these elements should be replaced by NIR techniques. For the forming step, new forming plugs, preheated to achieve good forming, are required. But it must be stressed that even with today’s more advanced machinery, the introduction of a new material, like PP, is challenging and requires high levels of knowledge and acquired experience.

Outsourcing Environmental Effectiveness
One of the associated aims tied to responsible outsourcing is to increase sustainability by improving operational efficiency and saving costs. CDMOs in the newly industrialized countries such as Brazil, China and India currently have a major competitive advantage as a result of low wages (although the wage gap is closing). Concerns often remain however about quality, health, safety and also specific environmental issues. High concentrations of APIs in the effluent from wastewater treatment plants serving manufacturers in India as well as China have highlighted these potential problems. This reinforces the need for pharma companies to take much greater care in their selection criteria for contractors. At present, most pharmaceutical outsourcing remains with CDMOs contracted in the developed world.

Minimizing Environmental Impact
Pharmaceuticals are deliberately manufactured to be biologically active, creating a risk to plants and animals should they be discharged into the environment. Because of this, it is imperative that the drug, packaging and process is considered from all environmental perspectives. The systematic approaches taken by some CDMOs to their manufacturing services can help to minimize future risks.

Sustainability should not be seen as an add-on, but as a route to prosperity for today’s CDMO. Indeed, those that succeed will be the ones that actually offer innovative services, highly efficient and reliable processes and quality commercial outputs. Consequently, key elements within the pharma industry, together with prominent academics and healthcare consumers (the ultimate end-users), are now displaying a strong appetite for minimizing the impact that pharmaceutical products, including blister packaging technology, have on the environment. For example, Professor Benoit Roig of Ecole des Hautes Etudes en Santé Publique (EHESP) in France, has co-ordinated multiple European projects focused specifically on an analysis of pharmaceutical compounds in the environment (FP6 and FP7), including KNAPPE, between 2006 and 2008, and currently PHARMAS. In recognition, he was awarded our company’s 2011 annual award for best environmental performance or environmental innovation by the pharma industry or academia focused on the field.

An Environmentally Innovative CMDO Service
After making the decision to invest in packaging machinery that had the capability to pack in PP-blisters, we initiated an internal lifecycle analysis in 2001 to study the environmental effects that arise from the production of one package of paracetamol painkiller¹. The lifecycle includes the extraction of raw material and packaging material, the production of pharmaceutical granulate and finally the production of the product. Transportation between these steps was also included in the remit. The study revealed environmental effects that were compared to different environmental threats like the greenhouse effect, acidification and other current concerns.

A stark conclusion drawn from the analysis is that there is clearly a substantial difference between the old blister packaging products and the new PP-monoblister offering. One major reason for this is caused by the changes in the packaging of the product, the exchange from aluminum/PVC blister pack to blister pack made of polypropylene. That change means less use of energy resources but also that the packaging can be recycled to a greater extent than before. This is due to the blister pack material being a monomaterial (not containing more than one single type of material). With PP blisters the global warming effect is reduced by as much as 86% in comparison with the conventional Al/PVC blisters.

Environmental Marketplace Issues
There has been much positive feedback throughout the market on more sustainable packaging alternatives such as polypropylene (PP) blister packaging. During recent years, awareness across the pharma industry of the strong case for finding solutions that result in lower environmental impacts has increased significantly. Moreover, consumers have now come to expect this in the technologies employed to manufacture and package drugs. Indeed, a recent study³ shows that as much as 50% of consumers in Sweden are willing to pay 10% more for an environmentally friendly product, including the specific purchase of drugs that cater for their healthcare needs.

We prepared an analysis that compared PP-monoblisters with PVC across 14 different properties and this is best summarized in Figure 1.

There is a tremendous opportunity for the CDMO industry to improve and radically transform the efficiency and performance of the packaging phase. To do so, providers need to invest in the steps necessary to successfully install and properly utilize pp-monoblister technology, a technique and format proven to provide the benefits of low weightage, lower production costs while recognized for generating significantly higher performance than traditional blister packaging methods. Moreover, pp-monoblisters can make a strong contribution to improving the environmental impact of the packaging process to pharmaceutical development.  Indeed, forward looking CDMOs that plan ahead for the future have a golden opportunity to apply packaging innovation and consequently to offer the market and the community better services. 

References

1. KTH Industriellt miljöskydd, Modig, Å. (2002) Livscykelanalys av läkemedel – En miljöbedömning av värktabletten Reliv
2. NIEL packaging. A healthy future-Taylor. D, 2009, Pharmaceuticals in a Sustainable Society, Apoteket AB, Mistapharma, Stockholm Country Council.
3. SIFO Research International, Callius,P., (2007). Den nya miljökonsumenten, Miljö-Sverige

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Mia Ströman is SHE coordinator at Recipharm. She can be reached at mia.stroman@recipharm.com.