April 13, 2026 — Merck's Keytruda (pembrolizumab) is the world's best-selling pharmaceutical product, generating $29.48 billion in 2024 revenue and approved across more than 40 cancer indications. With key patents expiring in the EU in June 2028 and at least 14 biosimilar candidates now in clinical development globally, the race to manufacture pembrolizumab at commercial scale is creating one of the largest demand signals the bioprocessing supply chain has ever seen.
Unlike the Humira biosimilar wave — which involved a relatively straightforward adalimumab molecule — pembrolizumab is a humanized IgG4 monoclonal antibody requiring complex CHO cell culture, stringent glycosylation control, and extensive comparability testing. For API suppliers, cell line developers, and contract testing organizations, the Keytruda cliff represents both a massive commercial opportunity and a technical benchmark that will define the next generation of biosimilar manufacturing.
The geography and timing of pembrolizumab patent expiries create a staggered market entry pattern that suppliers should map carefully.
In the European Union, core composition patents expire in June 2028 — the earliest major-market opening. Formycon AG, one of the most advanced developers, has already announced positive primary endpoint data from its pivotal Dahlia pharmacokinetic study for FYB206 and is preparing regulatory submissions. The company has partnered with Zydus Lifesciences for Indian market commercialization and with Lotus Pharmaceutical for Asia-Pacific distribution.
In the United States, the situation is more complex. While certain key patents extend through 2036, multiple biosimilar developers are positioning for earlier entry through design-around strategies and patent challenges. At least 14 biosimilar candidates are in clinical stages globally, with Formycon, Alvotech (partnered with Dr. Reddy's), Biocon Biologics, Bio-Thera Solutions, and NeuClone (partnered with Serum Institute of India) among the most active.
In emerging markets, biosimilar entry is already beginning. Bioéticos has claimed to have launched the first pembrolizumab biosimilar in select markets, and PlantForm is collaborating with Brazil's Bio-Manguinhos to develop a biosimilar using plant-based manufacturing technology — a novel approach that could reduce upstream bioprocessing costs.
The supply chain implications of the Keytruda cliff differ fundamentally from the adalimumab biosimilar wave of 2023. Pembrolizumab is a humanized monoclonal antibody produced in CHO cells, and its manufacturing requires several specialized capabilities that are not universally available.
Cell line development. Each biosimilar developer requires a proprietary high-producing CHO cell line expressing a pembrolizumab antibody with matching glycosylation profiles. Cell line development contract research organizations — particularly those with expertise in clone selection, stability testing, and cell banking — are already seeing increased demand as 14+ programs advance toward commercial readiness.
Upstream bioprocessing. Large-scale monoclonal antibody production requires single-use or stainless-steel bioreactor systems, chromatography resins (particularly Protein A), depth filtration systems, and cell culture media. With multiple pembrolizumab biosimilar programs simultaneously scaling up, aggregate demand for these consumables will increase significantly.
Analytical comparability. Regulatory agencies require extensive biosimilarity demonstrations — including physicochemical characterization, biological activity assays, and immunogenicity assessment. Contract testing laboratories with capabilities in glycan analysis, surface plasmon resonance (SPR), peptide mapping, and forced degradation studies are positioned to capture substantial demand.
A recent partnership illustrates how the biosimilar supply chain is organizing itself. In March 2026, Samsung Bioepis signed a global license, development, and commercialization agreement with Sandoz for up to five next-generation biosimilar candidates, beginning with SB36 (a vedolizumab biosimilar referencing Takeda's Entyvio, which generated approximately $5.6 billion in 2024 revenue).
Under the agreement, Samsung Bioepis — which operates one of the world's largest biologics manufacturing facilities in Incheon, South Korea — will handle development, regulatory registration, manufacturing, and supply. Sandoz will manage commercialization across global markets excluding China, Hong Kong, Taiwan, Macau, and South Korea.
For suppliers, this model demonstrates the growing role of dedicated biologics CDMOs as the manufacturing backbone of the biosimilar industry. Samsung Bioepis's Incheon campus, with over 360,000 liters of bioreactor capacity, is designed to serve multiple biosimilar programs simultaneously — creating concentrated, recurring demand for upstream and downstream bioprocessing consumables.
As the pembrolizumab biosimilar wave builds toward the 2028 EU patent cliff, suppliers across the biologics value chain should consider several strategic actions:
1. Secure capacity for mid-tier developers. Cell line, analytical, and process development relationships established during clinical-stage development often translate into commercial supply contracts. Companies serving mid-tier developers — particularly those in India, China, and South America — offer the highest risk-adjusted return.
2. Invest in glycosylation analytics. Pembrolizumab's efficacy depends heavily on its glycosylation profile. Laboratories that can demonstrate rapid, high-resolution glycan analysis with ICH Q5E-compliant comparability data will be in premium demand.
3. Build relationships with emerging-market developers. PlantForm's plant-based manufacturing platform and Bio-Manguinhos's Brazilian government-backed program represent unconventional but potentially high-volume biosimilar supply chains.
4. Monitor the compounding enforcement landscape. The FDA has been actively enforcing against compounding pharmacies using imported APIs. This regulatory tightening drives demand toward approved biosimilars and their associated supply chains.
Keytruda's patent cliff is the single largest biologics market opening in pharmaceutical history. At $29.5 billion in annual revenue, it dwarfs the Opdivo cliff ($10B+), the Eylea cliff ($9B+), and even the Humira wave ($21B at peak). The bioprocessing infrastructure, analytical capabilities, and supply chain relationships built around pembrolizumab biosimilars will set the template for the broader wave of biologic patent expirations unfolding through 2030.
For API suppliers, bioprocessing equipment manufacturers, and contract testing organizations, the message is clear: the Keytruda cliff is not a future event to watch — it is a present-tense commercial opportunity to prepare for now. The 2028 EU patent date is the first major inflection point, and the manufacturing buildout required to meet it has already begun.
