electronic supplementary material

1  Methods

1.1  Goal and scope

The system boundaries for the +PLUSPAK™ and glass bottle are shown in Fig. S1.

1.2  Life cycle inventory analysis

Bottle materials supply chain

The +PLUSPAK bottle consists of a pharmaceutical-grade polypropylene vial, rubber stopper, and polypropylene cap; the glass bottle consists of a glass vial, rubber stopper, and a crimp seal made of aluminum and polypropylene (Fig. S2 and Table S1). +PLUSPAK contains only virgin materials. The glass bottle contains 10-30% glass cullet (with 20% recycle content assumed as default for this analysis), all from internal rework at the manufacturer thus ensuring full manufacturer control over the composition. The bottle components (vials, caps, and either rubber stoppers or crimp seals) are manufactured by supply chain vendors in several countries. In the main analysis, all the electricity usage is assumed to be European since most of the components are manufactured in Europe. A sensitivity analysis considers the effect of bottle component manufacturing in China or the U.S.

The bottle components are then transported via a combination of truck and freight ship to three GE Healthcare facilities for assembly and filling: Cork, Ireland; Shanghai, China; and Oslo, Norway (the Norway facility currently only assembles glass bottles).

The burdens associated with the production of the scrap, rejected bottles, broken or frozen bottles, and bottles to be recycled at end of life are included in the study, but their refurbishment is ignored in the main comparative analysis as they are sent to an external recycler for reprocessing and the recycled materials used by another manufacturer. An alternate scenario is also considered in which recycling impacts are allocated using a market-based approach (as described in the end-of-life section of this paper).

Assembly and filling

The glass vial bodies are depyrogenated (heat treated) prior to filling, whereas the +PLUSPAK vials do not require this process step (although for ease of manufacturing the +PLUSPAK vials do pass through the depyrogenation equipment but with the heat turned down to a minimum setting). The bottles are then filled with contrast media, closed and sealed. Autoclaving is used as a final sterilization process for both bottle types. Following a quality check, the bottles are labeled and packaged. The glass bottles are packaged in a double-walled corrugated board box that includes dividers for additional protection; the +PLUSPAK bottles are packaged in single-walled corrugated board boxes without dividers.

Transport and use

The bottles are distributed to different global markets including but not limited to the U.S., Europe, China, India, and Korea where they are used and disposed of. The transport is via air freight, transoceanic freight, and road. A detailed model was created based on the countries to which the product is shipped from each manufacturing facility, the amounts shipped from each facility, and the transportation modes used. Air and transoceanic freight distances were calculated for each transport leg. Domestic distribution distances via road transport within China were based on a rounded average of 1000 km.

The shelf-life of contrast media is the same in both bottle types and both are stored at the same temperature. Before administering the contrast media, the bottles are typically placed in an incubator to bring the contrast media to body temperature prior to injection. Slightly more energy is needed for the glass bottle as it is heavier and has a higher specific heat capacity. The study also accounts for the contrast media itself, including the additional contrast media needed due to breakage and freezing of some bottles caused by cold weather during transport.

Cut-off criteria

Cut-off criteria are often used in LCA practice for the selection of processes or flows to be included in the system boundary. The processes or flows below these cut-offs or thresholds are excluded from the study. Several criteria are used in LCA practice to decide which inputs are to be considered, including mass, energy, and environmental relevance. In this study, every effort is made to include all the flows associated with the processes. During the interpretation phase, processes or flows with less than 1% contribution to the total environmental impact – as calculated by the ReCiPe (H) impact assessment method (Goedkoop et al. 2009) – are considered negligible and excluded from further study.

Excluded data

Typically in an LCA, some aspects are excluded due to redundancy or statistical insignificance. In this study, the following aspects are excluded: (1) assembly and filling process that are the same for both +PLUSPAK and glass bottles; (2) shrink wrap used to wrap multiple shipping containers (same for both); (3) pallets used to move shrink wrapped boxes (same for both); (4) infrastructure of GE Healthcare manufacturing facility (same for both); and (5) human activities such as driving to and from work.

Assumptions

The following assumptions are made: (1) the reference flows using a functional unit of 96 mL are one 100 mL bottle, two 50 mL bottles, one-half of a 200 mL bottle, and one-fifth of a 500 mL bottle; residual contrast media left in the bottles after all doses are delivered is assumed to be thrown away; (2) GE Healthcare makes all bottle sizes except the 500 mL glass bottle. The weights of secondary packaging and shipping container for the 500 mL glass bottle are extrapolated based on the data for other glass bottle sizes. Distribution transport distances are assumed to be the same as the 200 mL bottle.

2  Results and discussion

Life cycle impact assessment

Table S2 shows the life cycle midpoint impacts for the comparison of the 100 mL polymer and glass bottles.

End-of-life

The study results using the cut-off allocation method indicate that +PLUSPAK is environmentally favorable compared to the glass bottle regardless of the end-of-life disposal method used for either bottle type (Table 4). Recycling is generally the least impactful disposal option for both +PLUSPAK and glass, and pre-shred, autoclave and incineration is generally the most impactful disposal option for both bottle types.

The results are also evaluated using the market-based approach, in which the level of material utilization in the market for the recycled materials determines how the environmental burdens and benefits of recycling are calculated and distributed between the production systems. The current demand for recycled polypropylene is high and the market is considered to be fully utilized (Block 2011; Resource Recycling 2012). The recycling of the +PLUSPAK bottle is therefore modeled by crediting the system for the displaced virgin polypropylene. In the case of the glass bottles, the current recycling rate in Europe is estimated at 68% (CEE Packaging 2012; FEVE - The European Container Glass Federation 2012). The model therefore includes a credit for displacing 68% virgin glass, and the remaining 32% is assumed to be sent to municipal incineration (there is no energy recovery from glass).

Incineration of polypropylene and rubber using the market-based approach is modeled by crediting the system for the recovered heat and electricity (ecoinvent Centre 2010). The incineration of the glass vial or the aluminum crimp seal does not include any credit as there is no energy recovery.

The market-based results (Table 4) indicate that +PLUSPAK is environmentally favorable compared to the glass bottle regardless of the end-of-life disposal method used for either bottle type. Recycling is generally the least impactful disposal option for both +PLUSPAK and glass. Recycling of the bottles can be particularly beneficial if there is a high demand for post-consumer polypropylene and glass. Pre-shred, autoclave and incineration is generally the most impactful disposal method for glass, whereas municipal treatment is generally the most-impactful disposal method for +PLUSPAK using the market-based approach.

Fig. S3 shows the sensitivity of the model results to end-of-life disposal method for both the cut-off and market-based allocation approaches. This comparison looks at the worst-case disposal treatments for +PLUSPAK (pre-shred, autoclave and incineration for cut-off approach; municipal treatment for market-based approach) with the best-case treatment for glass bottle (recycling for both cut-off and market-based approaches). The results of this worst-best case comparison indicate that +PLUSPAK has lower life cycle impacts compared to the glass bottle in all impact categories regardless of disposal method or allocation approach.

Sensitivity analyses

Bottle size: The study compares different bottle sizes on a functionally equivalent “per dose” basis – two 50 mL bottles, one 100 mL bottle, half of a 200 mL bottle, and one fifth of a 500 mL bottle. The +PLUSPAK bottle outperforms the glass bottle for each bottle size (Fig. S4). The 500 mL bottle has the lowest impacts per dose and the 50 mL bottle has the highest impacts per dose for both bottle types. This can be attributed to the need for less bottle material and packaging (per dose) for the larger bottle sizes.

Secondary packaging configuration: +PLUSPAK and glass bottles are packaged in various configurations depending on the GE Healthcare facility they are shipped from and the markets they are shipped to (Table S3). For both bottle types, multi-pack packaging configurations are considerably less impactful than single-pack configurations since less packaging materials are required per functional dose (Table 3). When multi-pack secondary packaging configurations are used, +PLUSPAK exhibits lower environmental impacts compared to the glass bottle in all impact categories considered. The differences are less clear when single-pack secondary packaging configurations are used (due to the much higher proportion of secondary packaging materials per functional dose).

Manufacturing electricity grid mix: The European electricity grid is used as default in the main analysis since most of the bottle components are manufactured in Europe. Sensitivity analyses are conducted with the Chinese and U.S. grids for the glass bottle and with the Chinese grid for +PLUSPAK (only manufactured in Europe and China). The Chinese grid results in slightly higher impacts for most of the impact categories for both bottle types (Table S4). +PLUSPAK still exhibits lower impacts in all impact categories regardless of manufacturing electricity grid mix.

Glass bottle recycled content: The glass bottle contains about 10-30% cullet, which is less than the average borosilicate glass. Although increasing the cullet beyond 10-30% is not within the material specification for this product, a more typical 60% cullet content would reduce the energy required during the glass manufacturing process, resulting in up to 20% reduction in the impact of the glass bottle (Table S4). The comparison is still found to be favorable for +PLUSPAK.

+PLUSPAK scrap rate: The glass bottle manufacturing process has a higher scrap rate than +PLUSPAK bottle manufacturing based on data provided by bottle suppliers. Sensitivity to this parameter is evaluated by comparing both bottle types using the highest reported scrap rate for the glass bottle (Table S4). +PLUSPAK has lower environmental impacts compared to the glass bottle even with the higher scrap rate.

Mode of distribution transport: Sensitivity to air freight is examined by replacing all of the air transport with ocean freight for both bottle types. This change can reduce impacts by up to 30% for +PLUSPAK and up to 20% for the glass bottle, but +PLUSPAK is still favorable compared to glass (Table S4).

Contrast media: Several different contrast media are used with +PLUSPAK and glass bottles for both X-ray and MRI procedures. The type of contrast media has negligible impact on the study results, and the results for MRI application (results not shown) are proportionally the same as for X-ray.

Choice of impact assessment method: Sensitivity of the comparison is tested by using the IMPACT 2002+ method. The results are favorable for +PLUSPAK in all but the carcinogens category, primarily due to aromatic hydrocarbons in the industry average polypropylene data set. To further test this finding, the comparison is conducted again using the USEtox method. The USEtox results do not coincide with the IMPACT 2002+ results, but instead are in agreement with the findings of the ReCiPe method. It should be noted that the IMPACT 2002+ method is older than either ReCiPe or USEtox and that newer versions of the method use the USEtox chararacterization factors for toxicity.

Limitations

Note that a comparative life cycle assessment should not be the sole basis used to determine environmental superiority or equivalence, as additional information may be necessary to overcome some of the inherent limitations in the life cycle impact assessment. Even if a study has been critically reviewed, the impact assessment results are relative expressions and do not predict impacts on category endpoints, threshold exceedance, or risks. It is further recognized that there are other tools available for environmental assessment such as risk assessment, environmental impact assessment, and others. Life cycle assessment was chosen as the best environmental tool to cover the goal and scope of this product comparison. The ability of LCA to consider the entire life cycle of a product makes it an attractive tool for the comparative assessment of potential environmental impacts.

References

Block DG (2011) Recycled Resin Prices Still Rising in First Quarter. Available from http://www.ptonline.com/articles/recycled-resin-prices-still-rising-in-first-quarter. Accessed May 1 2012

CEE Packaging (2012) No improvement in glass recycling. Available from http://ceepackaging.com/2012/05/02/no-improvement-in-glass-recycling/. Accessed May 1 2012

ecoinvent Centre (2010), ecoinvent data v2.2. ecoinvent reports No. 1-25, Swiss Centre for Life Cycle Inventories, Dübendorf, available from: http://www.ecoinvent.org

FEVE - The European Container Glass Federation (2012) Good practices in collection and closed-loop glass recycling in Europe. Available from http://www.feve.org/images/stories/pdf2012/goodpractices-collection-closed-loop%20glass%20recycling%20in%20europe%20-%20report.pdf. Accessed May 1 2012

Goedkoop M, Heijungs R, Huijbregts M, De Schryver A, Struijs J, van Zelm R, (2009) ReCiPe 2008: A life cycle impact assessment method which comprises harmonised category indicators at the midpoint and the endpoint level, VROM–Ruimte en Milieu, Ministerie van Volkshuisvesting, Ruimtelijke Ordening en Milieubeheer. Available from http://www.lcia-recipe.net.

Resource Recycling (2012) PetroChem Wire: Recycled polypropylene prices rise in March. Available from http://resource-recycling.com/node/2629. Accessed May 1 2012

Table S1 Component materials and weights of +PLUSPAK and glass bottles

+PLUSPAK
Bottle component / Bottle size / Weight (grams) / Material / Comment
Vial / 50 mL / 11.9 / Polypropylene
100 mL / 16.3
200 mL / 26.1
500 mL / 44.1
Cap / - / 4.8 / Polypropylene / Same for all sizes
Stopper / - / 3.7 / Synthetic rubber / Same for all sizes
Glass bottle
Bottle component / Bottle size / Weight (grams) / Material / Comment
Vial / 50 mL / 55 / Type 1 glass
(10-30% cullet)
100 mL / 95
200 mL / 170
500 mL / 290
Crimp seal / - / 3 / 52% Aluminum;
48% Polypropylene / Same for all sizes
Stopper / - / 7 / Synthetic rubbers / Same for all sizes

Source = GE Healthcare and suppliers
Type 1 glass is a borosilicate glass commonly used in pharmaceutical products