The increasing global demand for biopharmaceutical biologics, including vaccines, monoclonal antibodies, enzymes, cytokines, hormones and growth factors, is driven by aging populations, rising cancer incidences, the persistent threat of pandemics such as COVID-19 and endemic infectious diseases such as Tuberculosis and Malaria. While the global biologics market is projected to surpass $1 trillion by 2034, current centralized manufacturing models rely heavily on resource-intensive mammalian systems that pose significant economic and logistical barriers, particularly for the Global South. This review evaluates the imperative for adopting sustainable biomanufacturing pathways to enhance global health security and sovereignty. We critically assess diverse production platforms, ranging from traditional microbial and mammalian cell lines to emerging green systems such as transgenic plants, algae, and cell-free synthesis, against the Triple Bottom Line framework: environmental stewardship, economic viability, and social responsibility. The analysis highlights that while mammalian cells remain the industry standard for complex post-translational modifications (PTMs), plant-based and cell-free platforms offer scalability, reduced carbon footprints, and the potential for decentralized production. Furthermore, the integration of artificial intelligence (AI), digital twins, and single-use technologies is identified as a catalyst for optimizing yield and facilitating net-zero emissions targets. For the Global South, these approaches offer opportunities to overcome resource limitations through localized, low-input platforms. We conclude that transitioning toward resilient, localized, and eco-friendly biomanufacturing is essential to mitigate supply chain vulnerabilities, ensure equitable access to life-saving therapeutics, and safeguard populations against future biological threats.



