Life Cycle Assessment Analysis of Pharma Production Facility Part 3

Environmental Footprints of a Flexible Pharmaceutical Production Facility:  A Life Cycle Assessment Analysis Part 3

This article was published in the September/October 2016 edition of Pharmaceutical Engineering^® Magazine. Missed the beginning of this three part series?  Catch up now:

• Life Cycle Assessment Analysis of Pharma Production Facility
• Life Cycle Assessment Analysis of Pharma Production Facility Part 2

Operational Phase

The analysis of the operational phase becomes essential to understand the environmental performance of the facility. In particular, it is necessary to examine the relationship between the three basic types of systems that define the operational phase as described previously (see Table B from Part 2). These are process, building, and utility systems. The comparison of three different facility configurations each with a different production output allows determining the relative impact between the different systems. The three bioreactor configurations analyzed are 2 × 1,000 L, 2 × 2,000 L, and 4 × 2,000 L. The number of batches per production bioreactor per year and the facility lifetime are the same across all configurations. Accordingly, the production doubles between configurations: for 4 × 2,000 L, the amount of mAbs produced is twice that of 2 × 2,000 L, or four times the amount of 2 × 1,000 L in the same time frame. Figure 3 shows the breakdown of the impact for the operational phase for the three facility configurations. It can clearly be seen that with an increase in the production output, the carbon footprint grows significantly. By doubling the production output, the carbon footprint increases by approximately 25% and 60%.

Process system’s impact grows at a very high pace every time the capacity doubles, between 40% and 100%. The result comes to indicate that the 2,000-L configuration is more efficient than the 1,000-L. Utilities system impact also increases but at a slower pace, between 38% and 55%. However, the increase of the production output has a limited influence on the environmental impact of the building systems, with a relative growth of 20% between a low and high output configuration. This is true even if a slightly larger facility were considered to accommodate four production bioreactors instead of two. The increased production output also shows that the overall shares of the process systems rise from 44% to more than 60%. At the same time, the contribution of the building system decreases from 47% to just less than 30%. Utility systems remain almost constant at around 10%. These results point out that the building and process systems are the main contributors to the overall environmental impact. They also indicate that to mitigate the environmental burden of a manufacturing facility, more than just efficient design of HVAC systems is important. Also, the impact generated by process systems, particularly at high production outputs, needs to be considered and optimized. These results also demonstrate the relevance of the functional units when different values or studies are compared. For instance, on a per-batch basis, the 1,000-L batch size shows a lower or similar environmental efficiency with 32 tons of CO₂ per batch, compared to 31 or 39 tons of CO₂ per batch for a 2,000-L scale. However, on a per-product basis, the 1,000-L batch with 11 kg of CO₂ per gram of product is higher than the 5 – 7 kg of CO₂ per gram of product for the 2,000-L batch. However, the authors’ recommendation would be to compare results based on per gram of product basis when different scenarios or studies are compared. This seems to be more plausible, taking into account that the total impact is more logical to depend on the total product output (i.e., total mass of product) than on the number of batches per year, when this can have a different size and, consequently, different mass and energy demands or relative impact. 

Economy of Scale

The environmental impact caused by process systems was further examined to determine if it can be reduced at a larger process scale, as indicated in the previous analysis. For that, the process impacts of three configurations were compared:

• 2 × 500 L, 24 batches per bioreactor per year
• 2 × 1,000 L, 12 batches per bioreactor per year
• 2 × 2,000 L, 6 batches per bioreactor per year

The three cases have the same production output over their lifetime (i.e., 72 kg of mAbs per year). The calculated values are 7, 5, and 3 kg of CO₂ per gram of product for the 500-L, 1,000-L, and 2,000-L configurations, respectively. The results show that bigger-process scales lead to considerable environmental savings. These savings do not necessarily originate from a reduced process demand (e.g., electric power consumption, etc.), but rather from the amount of used consumables and their size. The amount of plastic waste from consumables, excluding packaging, generated for a 500-L, 1,000-L, and 2,000-L batch are 357, 478, and 660 kg, respectively. Therefore, the relative amount of waste per kilogram of product is clearly reduced by increasing the batch size: 238, 159, and 110 kg plastic waste per kilogram of product. At larger process scale, the number and volume of the single-use bags are used more efficiently, resulting in a reduced overall demand for consumables.

Process Systems by Unit Operation

The process systems carbon footprint breakdown by unit operation, following the process sequence, is shown in Figure 4. The impact per unit operation is further divided to identify the main impact causes. These include consumables (e.g., plastic bags) and operating materials (e.g., raw materials) supply chain, electric power consumption, waste treatment of consumables, and packaging waste. Supply chains hereby include the manufacturing, gamma irradiation at a different location if required and all transportation routes to the facility site.

It is important to note that just four unit operations—the production bioreactors, clarification, initial capture, and intermediate chromatography steps—are responsible for 69% of the environmental burden of the process systems in the operational phase. None of the remaining unit operations represents more than 7%. This impact distribution over the process flow corresponds to the unit operations with the largest size or volume. The handling of larger process volumes demands a larger size or number (i.e., total mass) of consumables, such as bags, tubing, connectors, or filter cartridges. This is confirmed by looking at the total process systems breakdown per impact sources. The consumables supply chain is, by far, the major part of the environmental impact for each unit operation. In total, it is responsible for 81% of the impacts of the process systems that occur during the operational phase of the facility. Considering that:

• 94% of the overall impacts of a manufacturing facility happen in the operational phase,
• 50% of those impacts are related to the process systems for a medium/average production output, and
• 81% of those impacts can be traced back to the consumables supply chain,

It can be reckoned that 38% of the total environmental impact of a facility, over its entire lifetime, is related to the consumables supply chain alone.

Process Systems by Impact Sources

Process systems’ operational footprint was further analyzed to identify key impact sources. This time, the supply chain impacts were split into manufacturing and transportation. Thereby, consumables manufacturing also includes packaging manufacturing and gamma irradiation of consumables. All waste treatment is broken down in waste incineration, without heat recovery and landfilling. Electric power consumption covers just the electricity necessary to run the process equipment, whereas transport considers all transports that occur (e.g., from the manufacturing site of consumables or operating materials to the biopharmaceutical facility or from the facility to the waste treatment location). Figure 5 shows the impact breakdown following this approach. Although consumables are basically a mix of different kinds of plastics, their manufacturing, including packaging and further treatment, has just a limited effect on the overall process systems’ carbon footprint, with a share of 14%.

An important focus on the discussion around consumables has always been on their disposal, in particular considering that usually 478 and 660 kg of plastic waste, excluding packaging, are generated per a 1,000-L and 2,000-L batch, respectively. In this regard, the results show that the impacts related to their waste treatment only play a limited role (9%), even if it is comparable to their manufacturing impact (14%). Nevertheless, the impact of consumables is very significant in relationship to their transportation. With a share of approximately 67%, the transportation impact clearly dominates the carbon footprint in the operational phase of the process systems. The reason for this is largely rooted in the huge transportation distances from the consumables manufacturing plant to the biopharmaceutical manufacturing site, which are located on different continents. Therefore, the consumables are often transported by plane over more than 12,000 km (7,456 miles). In contrast, the transportation impact for operating materials is much lower, due to the possibility to source operating materials regionally and with alternative modes of transportation. It can be concluded that the location of the facility relative to the consumables manufacturing site plays a key role on the overall environmental impact of the facility. It also points out the challenging task of reducing the impact by optimizing the supply chain or the transportation system. Moreover, it demonstrates the need to understand the worldwide environmental impact of the facility more fully instead of focusing on the local impact around the facility site.

Conclusions

Full modeling allows a holistic understanding of the environmental impact of a biopharmaceutical facility across its entire life cycle. This should allow us to define where to focus the effort if we intend to be more sustainable. On the one hand, it confirms that the biggest impact occurs during the operational phase of the facility and all sustainability efforts should focus on this phase more effectively. On the other hand, it reveals that the largest impact (31%) of the operational phase relates to transportation and has little to do with the actual production process. As a consequence, it limits any sustainability improvement done at the site and challenges the supply chain or the facility location. Finally, it demonstrates that the efforts on HVAC optimization will have a larger contribution than, for instance, looking at alternative waste treatments of consumables, where a large part of the discussion is focused. By: Johannes Tvrdinić and David Estapé, PhD