Continuous manufacturing (CM) is changing how medicines are produced. For most of its history, the pharmaceutical industry has used batch manufacturing, where raw materials are added, processed, and removed in separate steps. In continuous manufacturing, materials move steadily through a connected system, and production and quality checks happen at the same time.
Industries like petrochemicals and chemicals adopted continuous methods many years ago. Pharma has only started using them in the last decade, encouraged by regulators and advances in technology. ¹ This shift can make medicine production faster, more flexible, and better for the environment. However, it also brings regulatory and technical challenges that companies need to solve.
This article looks at the main benefits of continuous manufacturing, the difficulties it presents, and real-world case studies that show its impact on the future of pharmaceuticals.
What Is Continuous Manufacturing?
In a batch process, manufacturing occurs in isolated steps: mixing ingredients, granulating, drying, and compressing them into tablets. Each step often occurs in separate equipment, and material sits in inventory between stages while samples are sent to quality labs. Continuous manufacturing links these operations into a single flow. Material is added at one end of the line, processing parameters are tightly controlled, and the finished product emerges at the other end with real‑time monitoring and control. Process analytical technology (PAT) and automated feedback enable real‑time adjustments. Because CM relies on a constant flow, it requires sophisticated equipment integration, advanced sensors and software, and high levels of process understanding. The International Council for Harmonisation (ICH) formalized definitions and regulatory expectations through its Q13 guideline in 2022, providing a harmonized framework for the continuous manufacturing of drug substances and drug products.²
Benefits of Continuous Manufacturing
Improved Efficiency and Productivity
Continuous processes eliminate downtime between batches, allowing higher throughput. A case study from Gill’s Process Control notes that CM allows uninterrupted operations, increasing drug output and reducing waste.³ By optimizing process parameters, manufacturers can run equipment continuously and minimize cleaning or changeover time. A comprehensive review of continuous manufacturing for recombinant proteins reported a three‑ to five‑fold increase in volumetric productivity and up to a 70 % reduction in equipment footprint, leading to facility cost reductions of 30–50 % compared with batch processes. These gains arise from intensified reactions, shorter residence times, and better utilization of equipment.
Enhanced Product Quality and Consistency
Real‑time monitoring and control offer significant quality advantages. Continuous lines use inline sensors to track critical attributes, allowing operators to adjust parameters before a product drifts out of specification. Gill’s case notes that CM improves product quality by reducing variability and minimizing human error because automated systems require fewer manual interventions. The review by Niazi et al. explains that continuous processing of recombinant proteins leads to more consistent material because the process is at steady state. When combined with PAT and digital controls, continuous manufacturing allows real‑time release testing, meaning products can be released to market more quickly without waiting for extensive lab analyses.
Cost Savings and Faster Time to Market
While continuous manufacturing requires significant upfront investment, it can substantially lower long-term operational costs. The process uses equipment more efficiently, which reduces labor, energy use, and raw material waste. It also minimizes storage and inventory expenses by eliminating the need for large intermediate holding tanks.
Another key advantage is speed. Continuous systems shorten production cycles, allowing companies to scale up from development to commercial manufacturing much faster. For example, Janssen’s HIV drug Prezista is a well-documented case. After adopting continuous manufacturing, the company reduced its testing-to-release time from 30 days to just 10. This not only cut costs but also enabled patients to receive life-saving medications sooner.⁴
Sustainability and Environmental Benefits
Continuous manufacturing supports greener pharmaceutical production by reducing energy consumption and improving resource efficiency. Because systems run at a steady state, equipment does not need to be repeatedly heated and cooled, which saves energy. Optimized reactions also generate less waste, and solvents and reagents are used more sparingly.
Studies further show the environmental and economic advantages. Continuous bioprocessing has been linked to 30–50% reductions in facility costs, along with lower energy use, while still maintaining product quality . These sustainability benefits align with increasing regulatory and societal expectations for more environmentally responsible manufacturing.
Flexibility, Scalability, and Supply‑Chain Resilience
Continuous manufacturing lines can be adjusted rapidly to meet shifting market demands. Unlike batch facilities, which are locked into fixed production volumes, CM can run longer or shorter without major equipment changes. Scholarly reviews indicate that continuous systems support linear scale-up, meaning process parameters validated at smaller scales can be applied to commercial production, simplifying technology transfer and reducing risk.
Another major benefit is supply-chain resilience. Because CM reduces dependency on large bulk intermediate storage, it shortens lead times and mitigates vulnerabilities in warehousing and distribution. This flexibility is particularly valuable during crises when rapid production of essential medicines is critical.⁵
Challenges and Barriers
Despite its advantages, continuous manufacturing faces significant hurdles that limit widespread adoption.
● High Costs and Investment Risks: Moving from batch to continuous production needs major spending on new equipment, sensors, and facility upgrades. Many companies view the high upfront cost as the biggest obstacle and want clear proof of return on investment before committing.
● Regulatory Uncertainty: Regulators support continuous manufacturing, but companies remain unsure about requirements for validation, documentation, and approvals. This lack of clarity creates hesitation. Early discussions with regulatory agencies can help reduce these concerns.
● Skills and Training Gaps: Running continuous systems requires expertise in automation, analytics, and process control. Many companies report a shortage of skilled staff. Training programs and partnerships with universities are needed to build the right workforce.
● Process Complexity and Reliability: Continuous lines bring together multiple steps in a single flow. Any disruption can affect the whole process. Strong process design, monitoring, and control are essential to maintain stability and ensure consistent product quality.
Regulatory Framework and Industry Trends
Regulators worldwide are supporting the shift to continuous manufacturing. The ICH Q13 guideline, finalized in 2022, sets a harmonized global framework for both small-molecule and biologic drug products. In the United States, the FDA’s Emerging Technology Program encourages companies to engage early, offering guidance on development and submissions. The European Medicines Agency (EMA) has approved several continuous production lines, while Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) has also adopted pathways for advanced manufacturing. Together, these efforts reduce uncertainty and create a supportive regulatory environment.
Industry adoption is also gaining momentum. Recent analyses report that leading manufacturers in North America, Europe, and the Asia Pacific are combining perfusion upstream with continuous downstream steps to achieve end-to-end bioproduction. Investment in new facilities is growing; for example, Eli Lilly built a $40 million continuous active ingredient plant in Ireland, and several generic drug makers are exploring continuous lines for high-volume medicines.
Case Studies
1. Janssen’s Prezista (Darunavir)
In 2016, the U.S. FDA approved Janssen’s switch from batch to continuous production for its HIV drug Prezista (darunavir), marking the first time the agency allowed such a change. Janssen collaborated with Rutgers University to develop the continuous process. The switch reduced testing-to-release time from 30 days to 10 days, demonstrating how real-time monitoring accelerates quality assurance. FDA Deputy Director Lawrence Yu called this a “significant step” and urged other companies to follow suit.⁶ The case illustrates regulatory openness and the operational benefits of continuous manufacturing.
2. Continuous Granulation with ConsiGma®
A major pharmaceutical company examined GEA’s ConsiGma® platform for continuous wet granulation, aiming to improve efficiency and reduce costs. In the feasibility study, the team selected a formulation from its batch granulation portfolio and used a design of experiment approach to evaluate time, quality, cost, and agility. By running long trials with online monitoring, the team confirmed process stability and robustness. Continuous granulation eliminated scale-up steps because the same equipment design can be used from the lab to production scale. Faster development cycles, improved process control, and reduced waste led to cost savings, including smaller equipment footprints and lower energy consumption.⁷ This case demonstrates that continuous granulation can deliver both quality and economic benefits.
3. Transitioning Metoprolol Succinate Extended-Release Tablets
Researchers from the U.S. FDA and Rutgers University investigated switching from batch high-shear granulation to continuous twin-screw granulation for metoprolol succinate extended-release tablets. The study used a central composite design to correlate batch parameters (impeller speed, granulation time, and binder feed rate) with continuous parameters and to identify critical granulation characteristics. Adjusting processing parameters allowed the continuous process to achieve dissolution profiles equivalent to the batch product (f2 > 50). The authors concluded that using performance-based granulation characteristics can facilitate switching from batch to continuous manufacturing.⁸ This case highlights the technical work required to translate established formulations to continuous processes while maintaining quality.
Future Outlook
Continuous manufacturing is set to grow as drug makers look to cut costs and boost efficiency when patents expire. Reviews show it can lower facility costs by 30–50% and raise productivity three to five times. Regulatory support, including ICH Q13 and the FDA’s Emerging Technology Program, is helping adoption.
Challenges remain, mainly high upfront costs, skill gaps, and process complexity. Hybrid systems, pilot projects, and investment in workforce training can ease these barriers. Wider use of digital tools like advanced controls and predictive analytics will also be key.
Summary
Continuous manufacturing can streamline drug production by improving efficiency, quality, and speed while cutting costs. Studies report up to 70% smaller equipment footprints, three to five times higher productivity, and 30–50% lower facility costs. With regulatory backing and growing industry interest, CM is positioned to become a standard in pharma, enabling more agile and resilient supply chains.
FAQs
Q1. What is continuous manufacturing?
It is a process where raw materials are fed into a line continuously and finished products come out steadily, with quality checked in real time. Batch manufacturing works in separate lots, with testing done after processing.
Q2. What are the benefits?
Continuous manufacturing improves efficiency, reduces downtime and costs, enhances quality through real-time monitoring, speeds up approvals, and is more sustainable.
Q3. What are the main challenges?
High upfront costs, regulatory uncertainty, and a shortage of skilled staff are the biggest barriers. Strong process control and advanced analytics are also needed.
Q4. Are there real-world examples?
Yes. The FDA approved Janssen’s switch to continuous production for the HIV drug Prezista, cutting release time from 30 to 10 days. Other successful cases include continuous granulation platforms for tablets.
Q5. How do regulators view it?
ICH Q13 offers global guidance for continuous manufacturing. Agencies like the FDA and EMA have dedicated programs and have already approved several continuous lines.
References
1. Niazi SK. Continuous Manufacturing of Recombinant Drugs: Comprehensive Analysis of Cost Reduction Strategies, Regulatory Pathways, and Global Implementation. Pharmaceuticals. 2025;18(8):1157-1157. doi:https://doi.org/10.3390/ph18081157
2. Process analytical technology in continuous manufacturing of a commercial pharmaceutical product. International Journal of Pharmaceutics. 2018;538(1-2):167-178. doi:https://doi.org/10.1016/j.ijpharm.2018.01.003
3. Clarke M. Gill’s Process Control, Inc. Gill’s Process Control, Inc. Published April 2, 2025. Accessed September 25, 2025. https://www.gillsprocess.com/blog-1/2025/4/2/benefits-of-continuous-manufacturing-in-pharma
4. Wahlich J. Review: Continuous Manufacturing of Small Molecule Solid Oral Dosage Forms. Pharmaceutics. 2021;13(8):1311. doi:https://doi.org/10.3390/pharmaceutics13081311
5. Srai JS, Badman C, Krumme M, Futran M, Johnston C. Future Supply Chains Enabled by Continuous Processing—Opportunities Challenges May 20–21 2014 Continuous Manufacturing Symposium. Journal of Pharmaceutical Sciences. 2015;104(3):840-849. doi:https://doi.org/10.1002/jps.24343
6. Gray N. In first, FDA approves Janssen’s switch to continuous manufacturing for HIV drug. BioPharma Dive. Published April 14, 2016. https://www.biopharmadive.com/news/in-first-fda-approves-janssens-switch-to-continuous-manufacturing-for-hiv/417460/
7. Continuous Granulation: A Case Study. Gea.com. Published 2025. https://www.gea.com/en/customer-cases/continuous-granulation/
8. Lalith Kotamarthy, Feng X, Alaadin Alayoubi, et al. Switching from batch to continuous granulation: A case study of metoprolol succinate ER tablets. International Journal of Pharmaceutics. 2022;617:121598-121598. doi:https://doi.org/10.1016/j.ijpharm.2022.121598
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