Modernizing Generic and Biosimilar Formulation
As the generic and biosimilar market enters a period of growth, developers are moving away from costly empirical testing and leveraging advanced technologies to overcome technical hurdles to formulation.
Generic and biosimilar drugs are vitally important for healthcare systems around the world and are increasingly in demand from patients thanks to their affordability when compared with the branded originators. While generic and biosimilar drugs comprise the largest proportion of drugs sold across the world, they only constitute a fractional share of the market value and provide significant cost savings for healthcare systems and patients (1–3).
In the U.S., it has been reported that for 2024, generics and biosimilars afforded healthcare systems and patients savings of USD 467 billion (1). European and UK figures demonstrate similar benefits with estimates of savings in the region of EUR 100 billion (USD 117.5 billion) per year in Europe thanks to the introduction of generics (2), and GBP 1.2 billion (USD 1.62 billion) over a period of three years in the UK (3).
Given these obvious cost efficiencies, the rising pressure to continually lower healthcare expenses, and the looming expiration of major branded medications, the generic and biosimilar market is experiencing significant growth, and industry stakeholders are embracing these alternatives more readily (4). However, the complexity of developing these high-quality alternatives often involves overcoming significant technical and regulatory hurdles.
A Technological Evolution
It is well-known that the drug development process is complex, multifaceted, risky, and time- and cost-intensive. While developers traditionally relied upon empirical testing and trial-and-error approaches to gather relevant data to progress candidates, modern drug development has evolved to incorporate more predictive and efficient methods (5,6).
Advanced in silico predictive modeling and simulation tools — such as physiologically based pharmacokinetic (PBPK) modeling and specialized dissolution simulation software— are proving to be particularly beneficial for generics and biosimilars. These advanced, computational tools are now being used to simulate the release profiles of reference listed drugs (RLDs) before physical prototypes are even manufactured. Using simulated and real-world data to guide decision making during the formulation process, these tools allow formulators to understand how variations in critical material attributes (CMAs) and critical process parameters (CPPs) will affect in vivo performance (5,6).
Additionally, by integrating artificial intelligence (AI) and machine learning (ML) into formulation development, it is possible for companies to substantially compress timelines and reduce the reliance on empirical and trial-and-error testing. For example, rather than iterating through dozens of physical formulations, scientists can now use digital twins of both the drug product and the human gastrointestinal tract to narrow the prospective candidates down to a few high-probability ones. Recent evidence suggests that these predictive approaches can reduce the time-to-market by several years and significantly decrease the risk of failed bioequivalence (BE) studies, which historically have been the most expensive bottlenecks in generic development (7,8).
Barriers facing Complex Generics
While the generic and biosimilar pharmaceuticals sector is projected to experience growth, it must also be noted that the growth will not be evenly distributed across the market but mainly concentrated on complex generics and biosimilars — the cost-effective versions of complex drugs, such as long-acting injectables (LAIs), inhalables, and ophthalmic suspensions (9). However, despite recent progresses made into improving efficiencies of generics development, the area of complex generics and biosimilars still faces a plethora of technical barriers (10).
Unlike simple small-molecule generics, the microstructure of the formulation of these complex products is imperative as it is directly related to the drug’s therapeutic effect. For example, in LAIs, to achieve the desired longevity of release, the particle size distribution and porosity of the polymer matrix are critical; whereas, for inhalables, formulators must be precise when it comes to the drug–device combination as any slight difference in the plume geometry or fine particle fraction can impact the deposition pattern in the lung. Therefore, to ensure the microstructure of the generic or biosimilar product matches the RLD, developers need orthogonal bioanalytical testing and advanced manufacturing controls (10).
Fortunately, technological innovations, such as the aforementioned in silico models, are helping companies to overcome the challenges associated with complex generics and biosimilars through providing simulated drug delivery systems and improved predictions of various characteristics (10). Furthermore, regulatory bodies are adapting to help facilitate approvals and improve the level of understanding of these more complex products (11).
Managing Regulatory Divergence
Even though there is continual progress on collaborative efforts between regulatory authorities, academia, and industry, a lack of harmonization between each region is still problematic. For instance, while regulators’ priorities are inevitably safety and efficacy, varying requirements for bioequivalence studies or stability data from region to region, some of which lack scientific justifications, create barriers to development of generic and biosimilar products and limits patient access worldwide (12).
As a result of this regulatory divergence, companies are often forced to adopt strategies that avoid potential duplication of work or reduce complexities as much as possible. However, these types of strategies tend to favour the regions where greater profits may be achieved, which can mean that other regions in dire need of more cost-effective medicines get neglected (12).
To help improve regulatory harmonization across jurisdictions, several international initiatives are already underway, including the Prequalification of Medicines Programme (PQP), developed by the World Health Organization to ensure the quality of essential medicines and facilitate access to affordable generics (12). The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use has also expanded its guidance to cover generics and biosimilars and various work-sharing initiatives have reduced duplication of effort and enabled multi-region approvals for some products (12). Furthermore, the ongoing reform of EU pharmaceutical legislation in 2026 aims to harmonize some of these processes, but currently, separate strategies and additional studies remain a reality for global players (13).
References
AAM. Generic and Biosimilar Medicines Save $467 Billion in 2024. Press Release, Sept. 3, 2025.
Troein, P.; Newton, M.; Travaglio, M.; Stoddart, K. Beneath the Surface: Unravelling the True Value of Generic Medicines. IQVIA White Paper, April 2024.
NHS England. NHS Saves £1.2 Billion on Medicines Over Three Years. News Release, July 1, 2022.
Cognitive. Generic and Biosimilar Pharmaceuticals Market Analysis 2026. Market Research Report, March 2026.
Konagurthu, S.; Ranathunga, D.T.S.; Buchanan, S.; Mehta, N.M.; Reynolds, T. The Predictive Edge: Modeling and Simulation in Drug Product Development. Adv. Drug Deliv. Rev., 2026, 230, 115784.
Chougule, M.; Kollipara, S.; Saha, P.; Ahmed, T. Role of Physiologically Based Modeling and Simulations in Clinical Pharmacokinetic Study Waivers for Orally Administered Drug Products. JOJ Case Stud. 2024, 14 (5), 555899.
Emili, L.; Rizk, M.A. In Silico Technologies: Leading the Future of Drug Development Breakthroughs. DIA Global, Global Forum, Oct. 2024.
DrugPatentWatch. How Technology is Redrawing the Map for Generic Drug Development: AI/ML, Continuous Manufacturing, IP Valuation, and the Competitive Dynamics Shaping the ANDA Landscape Through 2030. Blog Post, March 19, 2026.
DrugPatentWatch. The Global Generic Drug Market: Trends, Opportunities, and Challenges. Blog Post, Feb. 22, 2026.
Sreedevi, A.; Raj, E.A.; Sreedhar, D.; Ligade, V.S. Exploring the Challenges Faced by Generic Version of Complex Drugs: A Scoping Review. Syst. Rev. 2025, 14, 183.
DrugPatentWatch. Complex Generic Products: Development Challenges and Strategic Solutions for Emerging Markets. Blog Post, Nov. 13, 2025.
Rodriguez, A.; Miller, R.; Krishnan, V.; Polli, J.; Schwenderman, A. Importance of Single Global Development of Generic and Biosimilar Medicines for Patient Access. International Generic and Biosimilar Medicines Association, Final Report, October 2025.
EMA. Reform of the EU pharmaceutical legislation. Official Update, Jan. 15, 2026.
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