What is Continuous Manufacturing? A Guide for Pharmaceutical Manufacturers

For decades, pharmaceutical firms have manufactured their products in batches. In batch manufacturing, a “batch” is a specific quantity of a drug produced through a multi-step process.

While batch production is a tested manufacturing method, the motion between steps can be slow and inefficient.

To streamline production, manufacturers have begun to apply continuous manufacturing technologies to the pharmaceutical production process.

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If batch production involves the sequential processing and testing of material across multiple discrete stages (and potentially facilities), continuous manufacturing combines the full manufacturing stream into a single, fully integrated flow. This “continuous” production eliminates built-in production gaps and can shorten manufacturing times from months to days.

While adoption of continuous manufacturing has been slow, the FDA supports increased implementation of continuous manufacturing technologies. Continuous manufacturing seems poised to play a major role in the coming years, as the number of continuous production facilities under review has quadrupled in the last half-decade.

In this post, we’ll look at the ins and outs of continuous manufacturing. We’ll cover the definition, history, benefits, and challenges of continuous production for pharmaceutical manufacturers.

The widespread support for continuous manufacturing comes from inefficiencies that naturally result from batch processes.

Let’s look at a few.

Long Hold Times

Batch manufacturing occurs across multiple stages. Between each stage, materials are sent to a quality lab for testing. The bulk of the work-in-progress is stored until quality is confirmed, and then materials are moved to the next stage. These “hold times” add up, and contribute to lengthy manufacturing cycles.

Supply Chain Complications

At times, this involves shipment to a new facility. If there are any supply chain disruptions or if specified holding conditions aren’t met, material can degrade and compromise a batch. Supply chain disruptions — especially multinational pharmaceutical supply chains — have led to an increase in drug recalls in recent years.

Low Utilization

Because batches move sequentially, each step must be fully complete before the next can begin. If the full manufacturing stream contains 6 or 7 steps, the waiting times can add up. This can lead to low utilization levels and complicated process scheduling.

Batch production is the industry standard and the inefficiencies are well known. As are the advantages (low set-up costs, easier adjustments, deep industry expertise, and best-practices). Nevertheless, enduring problems with production times, human error, and supply chain contingencies have made continuous processes an appealing alternative to regulators and manufacturers alike.

Continuous manufacturing is a method for manufacturing pharmaceutical products from end-to-end on a single, uninterrupted production line.

Where batch manufacturing requires transporting, testing, and re-feeding materials from one process to the next, continuous processes execute all testing, feeding, and processing inline. Sophisticated process analytical technologies ensure quality in-process.

History of Continuous Production

Though new to pharmaceutical manufacturing, continuous manufacturing isn’t new.

In fact, continuous processes have been the norm in some industries for nearly a century. Continuous production has a long history in iron production, where facilities can run uninterrupted for years. It’s also the norm in the petrochemical industry, as well as some food and beverage processes.

Here are examples of continuous manufacturing industries and products:

• Oil Refining
• Metal smelting
• Paper
• Pastes
• Some foods and beverages, like peanut butter

The turn to continuous manufacturing in the pharmaceutical industry has gained momentum over the last decade. Manufacturing technology matured enough to accommodate the complex manufacturing techniques used in pharmaceutical production. Sensors and analytical technology matured enough to bring quality control in-line. And the regulatory and economic environment encouraged manufacturers to pursue innovation. The FDA quickly recognized the potential of continuous manufacturing to improve quality, meet demand, and improve service to patients, and they’ve consistently voiced their support.

In 2015, Vertex Pharmaceuticals became the first firm to secure FDA approval for a drug manufactured on a continuous line. In the next three years, Janssen, Eli Lilly, and Pfizer each received approval for continuously manufactured products.

Here's a side-by-side comparison to make the distinction clear:

Inline definition
Continuous manufacturing = uninterrupted drug production with real-time monitoring and control across processing steps.

In practice, the biggest leap isn’t just technical, it’s cultural. Batch manufacturing gives teams more manual control. Continuous systems rely on automation, sensors, and digital oversight, which means organizations must trust their data and shift how they validate processes.

Continuous manufacturing helps firms eliminate hold times, utilize the full capacity of their manufacturing lines, and bring quality testing inline.

Continuous manufacturing can also help manufacturers react more quickly to changes in demand. A continuous line can process higher and lower quantities of a drug as needed, it allows manufacturers to respond more rapidly to changing markets.

It also enables recipes not possible using traditional batch methods.

In short, the benefits of continuous manufacturing are:

• Improved utilization
• Flexible batch sizes
• Simplified scaling
• Greater control over critical process parameters
• Less energy consumption
• Better adherence to schedules

Continuous manufacturing processes have their fair share of challenges.

Manual Changeovers

For one, changeovers on continuous manufacturing lines are complicated and can take over a week to perform. Continuous manufacturing systems have thousands of parts that need to be cleaned, changed out, and verified. Changeovers are a highly manual process (one made easier by digital SOPs), and they can be time-consuming for even skilled operators.

As one expert put it:

“Whether frequent changeovers can be performed efficiently to enable short duration runs and small batches is still an open question. While the desired goal is to be able to changeover in less than a day, current lines can take a week or more for changeover due to the extensive time for disassembling, cleaning, and reassembling.”

Difficult Training

Operating continuous manufacturing equipment requires extensive training. The complexity of the equipment and the risk of mistakes means that everyone involved needs sufficient exposure and understanding of the system to ensure proper usage.

Complex Economics

While there are clear manufacturing benefits to continuous manufacturing systems, the economics of the pharmaceutical industry has presented a challenge. Between expenditures for new equipment, abandoning existing capacity, and projections for lifetime profitability of a given therapy, manufacturers are always concerned with the returns on any investment in continuous manufacturing technology.

Switching to continuous manufacturing depends less on the machines themselves and more on the systems wrapped around them. Four areas stand out:

Process Analytical Technology (PAT)
PAT gives you visibility during production instead of after the fact. Tools measure flow, temperature, pH, and particle size in real time. With that data, operators can correct drift before it becomes a deviation and stay within regulatory limits without halting the line.

Digital Twins and Simulation
A digital twin is a working model of the process. Teams can test new setups, predict responses, and stress the system virtually before touching live equipment. It shortens design validation and reduces the risk when scaling or adjusting a qualified process.

MES and No-Code Platforms
Conventional MES often slows continuous setups because of rigid workflows and long IT cycles. Tulip’s no-code system changes that. Engineers, QA, and supervisors can build and adjust apps themselves—whether it’s batch records, PAT integration, or procedural enforcement—without waiting on customization projects.

Real-Time Monitoring and Industrial IoT
Sensors and edge devices collect data from across the line. Dashboards make that information usable on the floor, so issues can be addressed before they escalate. The same infrastructure supports predictive maintenance, traceability, and process improvement, all of which matter when every minute of uptime counts.

Moving into continuous manufacturing isn’t about tearing down everything you’ve built. The plants that succeed start small, prove it works, and expand at a steady pace.

Step 1: Feasibility and Pilot Runs
Start with a clear-eyed feasibility check. Pick a product or step you know inside and out, that runs at volume, and that fits a continuous setup. Some examples of common starting points are blending, granulation, or coating.

Run a pilot with real materials and proper instrumentation. Use it to:

• Shake out process control logic

• Tie in PAT tools for live monitoring

• Build a digital twin to pressure test scenarios before you change the line
  

The aim is simple: show that continuous flow works reliably without creating new quality headaches.

Step 2: Validation and Regulatory Alignment
Pilot results only get you so far. The harder part is proving it to regulators. Many teams stall here and not for technical reasons, but because of uncertainty about what FDA or EMA will accept.

That picture is improving. Both agencies now publish detailed guidance for continuous setups, including real-time release testing and model-based control. To get through this step, make sure you:

• Engage regulators early and explain your plan

• Use PAT data to back up process stability

• Validate both the line and the supporting software, especially MES
  

Step 3: Scale-Up and MES Integration
Once a continuous line is validated, expansion is less about equipment and more about how systems connect. You’ll need to coordinate material movement, enforce SOPs digitally, record batches electronically, and support real-time decisions.

This is where a flexible MES pays off. A no-code approach lets engineers, QA, and supervisors standardize operations across lines without waiting on long IT projects. Many plants start by digitizing a single operation, then extend across the site.

Practical tip: Bring IT and QA in from the beginning. If they’re looped in late, you’ll lose time untangling compliance and integration issues that could’ve been avoided.

Continuous manufacturing is no longer an experiment, it’s moving into day-to-day use. The next questions are about how to make it smarter, more adaptable, and easier to scale globally. Five directions are already taking shape.

AI-Driven Process Control
Continuous lines throw off more data than any team can track manually. The shift now is toward systems that learn from that data and adjust on the fly.

These systems can:

• Spot process deviations before they show up in product quality

• Correct drift automatically within validated ranges

• Strengthen real-time release testing
  

Pilot projects are underway in oral solids and biologics, and as regulators get more comfortable with model-based control, you can expect broader adoption.

Hybrid Models (Batch + Continuous)
Most plants won’t move fully overnight. Hybrid setups let teams modernize where it makes sense without reworking an entire facility.

Practical examples:

• Continuous granulation with batch compression

• Batch formulation followed by continuous coating
  

The hard part is coordination. Data and controls must bridge both modes, and that takes flexible digital systems. No-code MES platforms are proving useful for connecting the pieces without dragging out integration projects.

Digital Twins
Digital twins are moving from design tools into real-time operations. They give teams a way to test process changes, control strategies, and parameter shifts without touching production equipment.

In practice, they’re helping:

• Build and refine control strategies

• Predict how CQAs respond to changes

• Speed up validation and continuous process verification
  

Coupled with PAT and edge analytics, digital twins give a clearer picture of how processes behave under real-world conditions.

Edge Analytics
Cloud systems can’t always react fast enough for a continuous line. Edge analytics brings the decision-making closer to the equipment.

This makes it possible to:

• Detect and flag anomalies in milliseconds

• Keep processes running even if the network drops

• Filter and route IoT and PAT data more intelligently

It’s a practical step toward resilient, autonomous operations.

Modular Facilities
Facility design is also changing. Modular plants built from skidded units can be deployed quickly, replicated globally, and reconfigured as needs shift.

They offer:

• Faster startup for new products

• Easier transfer of processes between sites

• Consistent operations across regions

When combined with digital twins, IoT, and a composable MES, modular facilities become adaptable building blocks, fit for the pace of modern pharma.

Even if adoption rates are low, the benefits of continuous manufacturing for the pharmaceutical industry are clear. As advanced manufacturing becomes the norm in life sciences manufacturing, expect to see broader adoption of continuous production.