Advances in the production and downstream processing of antibodies

Sales of monoclonal antibody (mAbs) therapies exceeded $ 40 billion in 2010 and are expected to reach $ 70 billion by 2015. The majority of the approved antibodies are targeting cancer and autoimmune diseases with the top 5 grossing antibodies populating these two areas. In addition over 100 monoclonal antibodies are in Phase II and III of clinical development and numerous others are in various pre-clinical and safety studies. Commercial production of monoclonal antibodies is one of the few biotechnology manufacturing areas that has undergone significant improvements and standardization over the last ten years. Platform technologies have been established based on the structural similarities of these molecules and the regulatory requirements. These improvements include better cell lines, advent of high-performing media free of animal-derived components, and advances in bioreactor and purification processes. In this chapter we will examine the progress made in antibody production as well as discuss the future of manufacturing for these molecules, including the emergence of single use technologies.     

Global Economic Burden of Norovirus Gastroenteritis

BackgroundDespite accounting for approximately one fifth of all acute gastroenteritis illnesses, norovirus has received comparatively less attention than other infectious pathogens. With several candidate vaccines under development, characterizing the global economic burden of norovirus could help funders, policy makers, public health officials, and product developers determine how much attention and resources to allocate to advancing these technologies to prevent and control norovirus.MethodsWe developed a computational simulation model to estimate the economic burden of norovirus in every country/area (233 total) stratified by WHO region and globally, from the health system and societal perspectives. We considered direct costs of illness (e.g., clinic visits and hospitalization) and productivity losses.ResultsGlobally, norovirus resulted in a total of $4.2 billion (95% UI: $3.2–5.7 billion) in direct health system costs and $60.3 billion (95% UI: $44.4–83.4 billion) in societal costs per year. Disease amongst children <5 years cost society $39.8 billion, compared to $20.4 billion for all other age groups combined. Costs per norovirus illness varied by both region and age and was highest among adults ≥55 years. Productivity losses represented 84–99% of total costs varying by region. While low and middle income countries and high income countries had similar disease incidence (10,148 vs. 9,935 illness per 100,000 persons), high income countries generated 62% of global health system costs. In sensitivity analysis, the probability of hospitalization had the largest impact on health system cost estimates ($2.8 billion globally, assuming no hospitalization costs), while the probability of missing productive days had the largest impact on societal cost estimates ($35.9 billion globally, with a 25% probability of missing productive days).ConclusionsThe total economic burden is greatest in young children but the highest cost per illness is among older age groups in some regions. These large costs overwhelmingly are from productivity losses resulting from acute illness. Low, middle, and high income countries all have a considerable economic burden, suggesting that norovirus gastroenteritis is a truly global economic problem. Our findings can help identify which age group(s) and/or geographic regions may benefit the most from interventions.     

The role of therapeutic antibodies in drug discovery

The last 5 years have seen a major upturn in the fortune of therapeutic monoclonal antibodies (mAbs), with nine mAbs approved for clinical use during this period and more than 70 now in clinical trials beyond phase II. Sales are expected to reach $4 billion per annum worldwide in 2002 and $15 billion by 2010. This success can be related to the engineering of mouse mAbs into mouse/human chimaeric antibodies or humanized antibodies, which have had a major effect on immunogenicity, effector function and half-life. The issue of repeated antibody dosing at high levels with limited toxicity was essential for successful clinical applications. Emerging technologies (phage display, human antibody-engineered mice) have created a vast range of novel, antibody-based therapeutics, which specifically target clinical biomarkers of disease. Modified recombinant antibodies have been designed to be more cytotoxic (toxin delivery), to enhance effector functions (bivalent mAbs) and to be fused with enzymes for prodrug therapy and cancer treatment. Antibody fragments have also been engineered to retain specificity and have increased the penetrability of solid tumours (single-chain variable fragments). Radiolabelling of antibodies has now been shown to be effective for cancer imaging and targeting. This article focuses on developments in the design and clinical use of recombinant antibodies for cancer therapy.     

Process economics of industrial monoclonal antibody manufacture

Pressures for cost-effective manufacture of antibodies are growing given their high doses and increasing market potential that have resulted in significant increases in total site capacities of up to 200,000 L. This paper focuses on the process economic issues associated with manufacturing antibodies and reviews the cost studies published in the literature; many of the issues highlighted are not only specific to antibodies but also apply to recombinant proteins. Data collated at UCL suggest current benchmark investment costs of $660-$1580/ft2 ($7130-$17,000/m2) and $1765-$4220/L for antibody manufacturing facilities with total site capacities in the range of 20,000-200,000 L; the limitations of the data are highlighted. The complications with deriving benchmark cost of goods per gram (COG/g) values are discussed, stressing the importance of stating the annual production rate and either titre or fermentation capacity with the cost so as to allow comparisons. The uses and limitations of the methods for cost analysis and the available software tools for process economics are presented. Specific examples found in the literature of process economic studies related to antibody manufacture for different expression systems are reviewed. The key economic drivers are identified; factors such as fermentation titre and overall yield are critical determinants of economic success. Future trends in antibody manufacture that are driven by economic pressures are discussed, such as the use of alternative expression systems (e.g. transgenics, E. coli and yeast), disposables, and improvements to downstream technology. The hidden costs and the challenges in each case are highlighted.     

The challenge of enzyme cost in the production of lignocellulosic biofuels

With the aim of understanding the contribution of enzymes to the cost of lignocellulosic biofuels, we constructed a techno-economic model for the production of fungal cellulases. We found that the cost of producing enzymes was much higher than that commonly assumed in the literature. For example, the cost contribution of enzymes to ethanol produced by the conversion of corn stover was found to be $0.68/gal if the sugars in the biomass could be converted at maximum theoretical yields, and $1.47/gal if the yields were based on saccharification and fermentation yields that have been previously reported in the scientific literature. We performed a sensitivity analysis to study the effect of feedstock prices and fermentation times on the cost contribution of enzymes to ethanol price. We conclude that a significant effort is still required to lower the contribution of enzymes to biofuel production costs.     

EB66 cell line,a duck embryonic stem cell-derived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity

Monoclonal antibodies (mAbs) represent the fastest growing class of therapeutic proteins. The increasing demand for mAb manufacturing and the associated high production costs call for the pharmaceutical industry to improve its current production processes or develop more efficient alternative production platforms. The experimental control of IgG fucosylation to enhance antibody dependent cell cytotoxicity (ADCC) activity constitutes one of the promising strategies to improve the efficacy of monoclonal antibodies and to potentially reduce the therapeutic cost. We report here that the EB66 cell line derived from duck embryonic stem cells can be efficiently genetically engineered to produce mAbs at yields beyond a 1 g/L, as suspension cells grown in serum-free culture media. EB66 cells display additional attractive grown characteristics such as a very short population doubling time of 12 to 14 hours, a capacity to reach very high cell density (> 30 million cells/mL) and a unique metabolic profile resulting in low ammonium and lactate accumulation and low glutamine consumption, even at high cell densities. Furthermore, mAbs produced on EB66 cells display a naturally reduced fucose content resulting in strongly enhanced ADCC activity. The EB66 cells have therefore the potential to evolve as a novel cellular platform for the production of high potency therapeutic antibodies.     

Health Disparities from Economic Burden of Diabetes in Middle-income Countries: Evidence from México

The rapid growth of diabetes in middle-income countries is generating disparities in global health. In this context we conducted a study to quantify the health disparities from the economic burden of diabetes in México. Evaluative research based on a longitudinal design, using cost methodology by instrumentation. For the estimation of epidemiological changes during the 2010–2012 period, several probabilistic models were developed using the Box-Jenkins technique. The financial requirements were obtained from expected case management costs by disease and the application of an econometric adjustment factor to control the effects of inflation. Comparing the economic impact in 2010 versus 2012 (p<0.05), there was a 33% increase in financial requirements. The total amount for diabetes in 2011 (US dollars) was $7.7 billion. It includes $3.4 billion in direct costs and $4.3 in indirect costs. The total direct costs were $.4 billion to the Ministry of Health (SSA), serving the uninsured population; $1.2 to the institutions serving the insured population (Mexican Institute for Social Security–IMSS-, and Institute for Social Security and Services for State Workers-ISSSTE-); $1.8 to users; and $.1 to Private Health Insurance (PHI). If the risk factors and the different health care models remain as they currently are in the analyzed institutions, health disparities in terms of financial implications will have the greatest impact on users’ pockets. In middle-income countries, health disparities generated by the economic burden of diabetes is one of the main reasons for catastrophic health expenditure. Health disparities generated by the economic burden of diabetes suggests the need to design and review the current organization of health systems and the relevance of moving from biomedical models and curative health care to preventive and socio-medical models to meet expected challenges from diseases like diabetes in middle-income countries.     

Costs associated with gunshot wounds in Canada in 1991.

OBJECTIVE: To estimate the costs (in 1993 dollars) associated with gunshot wounds in Canada in 1991. DESIGN: Cost analysis using separate estimates of gunshot incidence rates and costs per incident for victims who died, those who survived and were admitted to hospital and those who survived and were treated and released from emergency departments. Estimates were based on costs for medical care, mental health care, public services (i.e., police investigation), productivity losses, funeral expenses, and individual and family pain, suffering and lost quality of life. SETTING: Canada. OUTCOME MEASURES: Costs per case, costs by type of incident (e.g., assault, suicide or unintentional shooting) and costs per capita. RESULTS: The total estimated cost associated with gunshot wounds was $6.6 billion. Of this, approximately $63 million was spent on medical and mental health care and $10 million on public services. Productivity losses exceeded $1.5 billion. The remaining cost represented the value attributed to pain, suffering and lost quality of life. Suicides and attempted suicides accounted for the bulk of the costs ($4.7 billion); homicides and assaults were the next most costly ($1.1 billion). The cost per survivor admitted to hospital was approximately $300,000; this amount included just over $29,000 for medical and mental health care. CONCLUSION: Costs associated with gunshot wounds were $235 per capita in Canada in 1991, as compared with $595 in the United States in 1992. The differences in these costs may be due to differences in gun availability in the two countries. This suggests that increased gun control may reduce Canada''s costs, especially those related to suicide.     

The Economic impact of ME/CFS: Individual and societal costs

Background

ME/CFS is characterized by debilitating fatigue in addition to other physical and cognitive symptoms. It is estimated to affect over 800,000 adults in the U.S. ME/CFS often results in diminished functionality and increased economic impact. The economic impact of an illness is generally divided into two categories: direct and indirect costs. Despite high prevalence rates and the disabling nature of the illness, few studies have examined the costs of ME/CFS at the individual and societal level. In fact, of the four studies examining the economic impact of ME/ME/CFS only two used a U. S. sample. The current study used community and tertiary samples to examine the direct costs of ME/CFS.

Methods

Using archival data, Study 1 examined the direct cost of ME/CFS in a community-based sample in Chicago. Study 2 estimated the direct cost of ME/CFS in a tertiary sample in Chicago. Both Study1 and Study 2 assessed direct costs using office visit costs, medical test costs, and medication costs.

Results

For Study 1, the annual direct total cost per ME/CFS patient was estimated to be $2,342, with the total annual direct cost of ME/CFS to society being approximately $2 billion. In Study 2, the annual direct was estimated to be $8,675 per ME/CFS patient, with the total annual direct cost of ME/CFS to society being approximately $7 billion.

Conclusion

Using ME/CFS prevalence data of 0.42 and indirect costs estimates from Reynolds et al. (2004), the direct and indirect cost of ME/CFS to society was estimated to be $18,677,912,000 for the community sample and $23,972,300,000 for the tertiary sample. These findings indicate that whether or not individuals are recruited from a community or tertiary sample, ME/CFS imposes substantial economic costs.

     

Industrialization of mAb production technology: The bioprocessing industry at a crossroads

Manufacturing processes for therapeutic monoclonal antibodies (mAbs) have evolved tremendously since the first licensed mAb product (OKT3) in 1986. The rapid growth in product demand for mAbs triggered parallel efforts to increase production capacity through construction of large bulk manufacturing plants as well as improvements in cell culture processes to raise product titers. This combination has led to an excess of manufacturing capacity, and together with improvements in conventional purification technologies, promises nearly unlimited production capacity in the foreseeable future. The increase in titers has also led to a marked reduction in production costs, which could then become a relatively small fraction of sales price for future products which are sold at prices at or near current levels. The reduction of capacity and cost pressures for current state-of-the-art bulk production processes may shift the focus of process development efforts and have important implications for both plant design and product development strategies for both biopharmaceutical and contract manufacturing companies.     

Industrialization of mAb production technology The bioprocessing industry at a crossroads

Manufacturing processes for therapeutic monoclonal antibodies (mAbs) have evolved tremendously since the first licensed mAb product in 1986. The rapid growth in product demand for mAbs triggered parallel efforts to increase production capacity through construction of large bulk manufacturing plants as well as improvements in cell culture processes to raise product titers. This combination has led to an excess of manufacturing capacity, and together with improvements in conventional purification technologies, promises nearly unlimited production capacity in the foreseeable future. The increase in titers has also led to a marked reduction in production costs, which could then become a relatively small fraction of sales price for future products which are sold at prices at or near current levels. The reduction of capacity and cost pressures for current state-of-the-art bulk production processes may shift the focus of process development efforts and have important implications for both plant design and product development strategies for both biopharmaceutical and contract manufacturing companies.Key words: bioprocessing, cell culture, purification, economics, capacity, manufacturing, production, facility, biopharmaceutical     

Transgenic rice endosperm as a bioreactor for molecular pharming

Plants provide a promising expression platform for producing recombinant proteins with several advantages in terms of high expression level, lower production cost, scalability, and safety and environment-friendly. Molecular pharming has been recognized as an emerging industry with strategic importance that could play an important role in economic development and healthcare in China. Here, this review represents the significant advances using transgenic rice endosperm as bioreactor to produce various therapeutic recombinant proteins in transgenic rice endosperm and large-scale production of OsrHSA, and discusses the challenges to develop molecular pharming as an emerging industry with strategic importance in China.     

Chemical and morphological characterization of sugarcane bagasse submitted to a delignification process for enhanced enzymatic digestibility

Background

While advantages of biofuel have been widely reported, studies also highlight the challenges in large scale production of biofuel. Cost of ethanol and process energy use in cellulosic ethanol plants are dependent on technologies used for conversion of feedstock. Process modeling can aid in identifying techno-economic bottlenecks in a production process. A comprehensive techno-economic analysis was performed for conversion of cellulosic feedstock to ethanol using some of the common pretreatment technologies: dilute acid, dilute alkali, hot water and steam explosion. Detailed process models incorporating feedstock handling, pretreatment, simultaneous saccharification and co-fermentation, ethanol recovery and downstream processing were developed using SuperPro Designer. Tall Fescue (Festuca arundinacea Schreb) was used as a model feedstock.

Results

Projected ethanol yields were 252.62, 255.80, 255.27 and 230.23 L/dry metric ton biomass for conversion process using dilute acid, dilute alkali, hot water and steam explosion pretreatment technologies respectively. Price of feedstock and cellulose enzymes were assumed as $50/metric ton and 0.517/kg broth (10% protein in broth, 600 FPU/g protein) respectively. Capital cost of ethanol plants processing 250,000 metric tons of feedstock/year was $1.92, $1.73, $1.72 and $1.70/L ethanol for process using dilute acid, dilute alkali, hot water and steam explosion pretreatment respectively. Ethanol production cost of $0.83, $0.88, $0.81 and $0.85/L ethanol was estimated for production process using dilute acid, dilute alkali, hot water and steam explosion pretreatment respectively. Water use in the production process using dilute acid, dilute alkali, hot water and steam explosion pretreatment was estimated 5.96, 6.07, 5.84 and 4.36 kg/L ethanol respectively.

Conclusions

Ethanol price and energy use were highly dependent on process conditions used in the ethanol production plant. Potential for significant ethanol cost reductions exist in increasing pentose fermentation efficiency and reducing biomass and enzyme costs. The results demonstrated the importance of addressing the tradeoffs in capital costs, pretreatment and downstream processing technologies.     

EB66 cell line,a duck embryonic stem cell-derived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity

Monoclonal antibodies (mAbs) represent the fastest growing class of therapeutic proteins. The increasing demand for mAb manufacturing and the associated high production costs call for the pharmaceutical industry to improve its current production processes or develop more efficient alternative production platforms. The experimental control of IgG fucosylation to enhance antibody dependent cell cytotoxicity (ADCC) activity constitutes one of the promising strategies to improve the efficacy of monoclonal antibodies and to potentially reduce the therapeutic cost. We report here that the EB66 cell line derived from duck embryonic stem cells can be efficiently genetically engineered to produce mAbs at yields beyond a 1 g/L, as suspension cells grown in serum-free culture media. EB66 cells display additional attractive growth characteristics such as a very short population doubling time of 12–14 h, a capacity to reach very high cell density (>30 million cells/mL) and a unique metabolic profile resulting in low ammonium and lactate accumulation and low glutamine consumption, even at high cell densities. Furthermore, mAbs produced on EB66 cells display a naturally reduced fucose content resulting in strongly enhanced ADCC activity. The EB66 cells have therefore the potential to evolve as a novel cellular platform for the production of high potency therapeutic antibodies.Key words: duck, embryonic stem cells, monoclonal antibody, fucose, ADCC     

Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore

Background

Dengue illness causes 50–100 million infections worldwide and threatens 2.5 billion people in the tropical and subtropical regions. Little is known about the disease burden and economic impact of dengue in higher resourced countries or the cost-effectiveness of potential dengue vaccines in such settings.

Methods and Findings

We estimate the direct and indirect costs of dengue from hospitalized and ambulatory cases in Singapore. We consider inter alia the impacts of dengue on the economy using the human-capital and the friction cost methods. Disease burden was estimated using disability-adjusted life years (DALYs) and the cost-effectiveness of a potential vaccine program was evaluated. The average economic impact of dengue illness in Singapore from 2000 to 2009 in constant 2010 US$ ranged between $0.85 billion and $1.15 billion, of which control costs constitute 42%–59%. Using empirically derived disability weights, we estimated an annual average disease burden of 9–14 DALYs per 100 000 habitants, making it comparable to diseases such as hepatitis B or syphilis. The proportion of symptomatic dengue cases detected by the national surveillance system was estimated to be low, and to decrease with age. Under population projections by the United Nations, the price per dose threshold for which vaccines stop being more cost-effective than the current vector control program ranged from $50 for mass vaccination requiring 3 doses and only conferring 10 years of immunity to $300 for vaccination requiring 2 doses and conferring lifetime immunity. The thresholds for these vaccine programs to not be cost-effective for Singapore were $100 and $500 per dose respectively.

Conclusions

Dengue illness presents a serious economic and disease burden in Singapore. Dengue vaccines are expected to be cost-effective if reasonably low prices are adopted and will help to reduce the economic and disease burden of dengue in Singapore substantially.     

Recombinant plant-derived pharmaceutical proteins: current technical and economic bottlenecks

Molecular pharming is a cost-effective platform for the production of recombinant proteins in plants. Although the biopharmaceutical industry still relies on a small number of standardized fermentation-based technologies for the production of recombinant proteins there is now a greater awareness of the advantages of molecular pharming particularly in niche markets. Here we discuss some of the technical, economic and regulatory barriers that constrain the clinical development and commercialization of plant-derived pharmaceutical proteins. We also discuss strategies to increase productivity and product quality/homogeneity. The advantages of whole plants should be welcomed by the industry because this will help to reduce the cost of goods and therefore expand the biopharmaceutical market into untapped sectors.     

An Analysis of Costs and Health Co-Benefits for a U.S. Power Plant Carbon Standard

Reducing carbon dioxide (CO₂) emissions from power plants can have important “co-benefits” for public health by reducing emissions of air pollutants. Here, we examine the costs and health co-benefits, in monetary terms, for a policy that resembles the U.S. Environmental Protection Agency’s Clean Power Plan. We then examine the spatial distribution of the co-benefits and costs, and the implications of a range of cost assumptions in the implementation year of 2020. Nationwide, the total health co-benefits were $29 billion 2010 USD (95% CI: $2.3 to $68 billion), and net co-benefits under our central cost case were $12 billion (95% CI: -$15 billion to $51 billion). Net co-benefits for this case in the implementation year were positive in 10 of the 14 regions studied. The results for our central case suggest that all but one region should experience positive net benefits within 5 years after implementation.     

Trends in capacity utilization for therapeutic monoclonal antibody production

The administration of high doses of therapeutic antibodies requires large-scale, efficient, cost effective manufacturing processes. An understanding of how the industry is using its available production capacity is important for production planning, and facility expansion analysis. Inaccurate production planning for therapeutic antibodies can have serious financial ramifications. In the recent 5th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, 434 qualified respondents from 39 countries were asked to indicate, among other manufacturing issues, their current trends and future predictions with respect to the production capacity utilization of monoclonal antibodies in mammalian cell culture systems. While overall production of monoclonals has expanded dramatically since 2003, the average capacity utilization for mammalian cell culture systems, has decreased each year since 2003. Biomanufacturers aggressively attempt to avoid unanticipated high production demands that can create a capacity crunch. We summarize trends associated with capacity utilization and capacity constraints which indicate that biopharmaceutical manufacturers are doing a better job planning for capacity. The results have been a smoothing of capacity use shifts and an improved ability to forecast capacity and outsourcing needs. Despite these data, today, the instability and financial constraints caused by the current global economic crisis are likely to create unforeseen shifts in our capacity utilization and capacity expansion trends. These shifts will need to be measured in subsequent studies.Key words: capacity, production, monoclonal antibody, survey, biopharmaceutical, manufacturing, constraints, facilityBuilding new capacity and improving existing systems to meet the demand for new monoclonal antibody (mAb) therapeutics, whether through in-house manufacturing or out-sourced contract manufacturing, has long-term cost implications for biotechnology firms. Bringing new capacity on line requires accurate market knowledge, lead-time, large capital expenditures and careful planning, and understanding trends in capacity utilization for the manufacture of mAbs can be critical to the planning process.For the first three quarters of the twentieth century, the traditional and most efficient way of producing antibodies was to immunize a large vertebrate, bleed the animal and, from the serum, collect the polyclonal protein. Because of their hardy binding specificity, the value of immunoglobulins, especially as a potential therapeutic tool, was evident from the time of their discovery because scientists envisioned them as probes and transporters of therapeutic tools. Limitations of using polyclonals were also evident from early on. Therapeutic antibodies needed to be delivered in very high concentration, and polyclonals, a heterogeneous group of molecules, directed against many different epitopes of an antigenic source, could only be extracted from serum in tiny quantities.A solution to at least some of the problems seemed to appear in 1984 when Kohler and Milstein¹ described a novel method for producing antibodies from an immortalized cell line capable of continually producing a virtually unlimited amount of a single antibody, directed at a single epitope. The medical and scientific communities realized that this hybridoma technology could produce sufficient quantities of antibodies for therapy, and in 1986, the first mAb for human use (Orthoclone OKT3—Ortho Pharmaceuticals) was approved for the prevention of kidney transplant rejection.As hybridoma technology evolved, it was clear that there were obstacles to overcome. The first mAbs were murine, but therapeutic candidates needed to be less immunogenic in order to avoid transplantation incompatibility. So chimeric antibodies and humanized mAbs (part murine, part human), and fully human mab production technologies were developed. The OKT3 approval was followed by a wave of mostly anti-cancer mAbs through the 1990''s, and since then, these proteins have become a dominant component of the biopharmaceutical market, representing approximately 20% of all biologic products, with combined revenues of over $20 billion in 2006.²Administration of high doses of therapeutic antibodies requires large-scale, efficient, cost effective manufacturing processes. Over the past few years, improvements have been made in cell line generation, expression vectors, transfection technology and large-scale cell culture production, allowing biotech firms to successfully move candidates through the pipeline. Today''s technologies are enabling five times the concentration of antibody produced by technologies just 5 years ago.³ Biotechnology drugs, including mAbs, now make up more than one-quarter of the FDA filings for approval, and over 40% of preclinical trials are now large molecule candidates, and as a result, planning for biologics manufacturing will continue to require strategic approaches to avoid potentially disruptive production bottlenecks. The long lead-time required to successfully launch a mAb requires pre-planning for capacity. This planning demands a new level of partnership between manufacturers and suppliers to develop novel technologies that will keep pace with industry''s need for capacity.     

Economic Assessment of Greenhouse Gas Emissions Reduction by Vehicle Lightweighting Using Aluminum and High‐Strength Steel

The life cycle greenhouse gas (GHG) reduction benefits of vehicle lightweighting (LW) were evaluated in a companion article. This article provides an economic assessment of vehicle LW with aluminum and high‐strength steel. Relevant cost information taken from the literature is synthesized, compiled, and formed into estimates of GHG reduction costs through LW. GHG emissions associated with vehicle LW scenarios between 6% and 23% are analyzed alongside vehicle life cycle costs to achieve these LW levels. We use this information to estimate the cost to remove GHG emissions per metric ton by LW, and we further calculate the difference between added manufacturing cost and fuel cost savings from LW. The results show greater GHG savings derived from greater LW and added manufacturing costs as expected. The associated production costs are, however, disproportionately higher than the fuel cost savings associated with higher LW options. A sensitivity analysis of different vehicle classes confirms that vehicle LW is more cost‐effective for larger vehicles. Also, the cost of GHG emissions reductions through lightweighting is compared with alternative GHG emissions reduction technologies for passenger vehicles, such as diesel, hybrid, and plug‐in hybrid electric powertrains. The results find intensive LW to be a competitive and complementary approach relative to the technological alternatives within the automotive industry but more costly than GHG mitigation strategies available to other industries.