Continuous Manufacturing vs. Batch Manufacturing: The Real Choice Logic in the Pharmaceutical Intermediate Stage

In the pharmaceutical industry, continuous manufacturing is often seen as the future trend, especially with the policy advocacy of the FDA and EMA, leading more and more innovative drug companies and large pharmaceutical companies to discuss continuous manufacturing routes.

However, in the pharmaceutical intermediate stage, a frequently overlooked practical question is: Is continuous manufacturing truly more suitable for intermediates than traditional batch manufacturing?

From practical project experience, the answer is not a simple “yes” or “no.”

In the intermediate stage, the choice of production mode is essentially a trade-off between risk management, process maturity, supply chain stability, and compliance pathways.

Why Can’t the “Intermediate Stage” Simply Replicate the Continuous Manufacturing Logic of APIs or Finished Drugs?

In the API or formulation stage, the advantages of continuous manufacturing are very clear:

• Highly fixed product structure and route;
• Clear process window with low change frequency;
• Long-term stable commercialization after scale-up.

However, intermediates are the opposite, possessing several essential characteristics:

• The synthetic route is still evolving and may be adjusted with API optimization;
• Impurity profiles are highly correlated with raw material sources;
• Batch size varies significantly with project stages;
• More frequent changes in raw materials, regulations, and customer strategies.

Therefore, in the intermediate stage, “flexibility” is often more important than “maximum efficiency.”

Core Advantages of Batch Manufacturing in the Intermediate Stage

Although continuous technology has received considerable attention, batch manufacturing remains the mainstream choice for most intermediate projects. This is not due to technological backwardness, but rather because it better aligns with the actual risk structure.

1️⃣ More responsive to process adjustments and route changes

• Easier to handle route fine-tuning
• Lower costs for raw material replacement and condition optimization
• No need for overall systemic restructuring

This is particularly crucial in early- or mid-stage intermediate projects.

2️⃣ Higher tolerance for raw material and supply chain fluctuations

• Acceptable fluctuations in raw material specifications
• Easier to introduce alternative suppliers
• Naturally compatible with a “dual supply system”

This directly relates to whether projects will stall due to non-technical reasons.

3️⃣ More mature compliance pathways and higher audit comprehension

• Clear GMP batch record logic
• More traditional audit focus
• More controllable registration and customer review risks

For intermediate companies primarily engaged in exports and CDMO collaborations, this is a real advantage.

The Real Challenges of Continuous Manufacturing in the Intermediate Stage

Continuous manufacturing is not unsuitable for intermediates, but its application conditions are extremely stringent.

In our project evaluations, continuous intermediate production often faces the following practical challenges:

⚠ High coupling between process scale-up and stability

• Any fluctuation in raw material quality is amplified
• Impurities, once formed, are difficult to eliminate in a timely manner
• Downtime costs are far higher than batch production.

⚠ More “idealistic” raw material quality requirements

• Extremely high requirements for the consistency of key raw materials
• Signaling between dual suppliers becomes significantly more difficult
• Upstream risks are amplified, not reduced.

⚠ Compliance and auditing experience is not yet widespread

• Different understandings among auditors
• Change assessment logic is more complex
• Higher requirements for data integrity and real-time monitoring

This is why continuous production in the intermediate field remains largely a “pilot project” rather than a widespread rollout.

What Kind of Intermediates are Truly Suitable for Continuous Production?

Based on practical experience, continuous production is only truly meaningful when the following conditions are met simultaneously:

• Synthetic routes have been locked in for ≥ 2–3 years
• Raw materials are highly standardized and have stable supply
• Impurity pathways are clearly defined and can be monitored in real time
• The goal is long-term, high-volume, single-use
• Customers and regulators have fully accepted the continuous production model

These intermediates are often close to API precursor levels, rather than early-stage or multi-purpose intermediates.

An Overlooked Conclusion: Production Models Themselves as “Risk Management Tools”

In the intermediate stage, the choice of production model is not essentially a technological race, but rather a matter of:

• Whether the project can continue to advance in an uncertain environment
• Whether it has the ability to respond quickly to changes
• Whether it can maintain a balance between quality, compliance, and cost

From this perspective:

• Batch production = Higher system resilience
• Continuous production = Higher efficiency ceiling, but lower tolerance for error

Conclusion: Continuous Production is not an “Upgraded Version,” but Rather an “Optimal Solution under Specific Conditions”

For pharmaceutical intermediates:

Batch production remains the most robust, replicable, and supply chain-resilient mainstream choice.

Continuous production is not a wrong direction, but rather needs to be used with the right intermediates, the right stage, and the right supply chain structure.

Truly mature manufacturing strategies are not about blindly chasing trends, but about rational judgments based on project risks, compliance paths, and long-term business goals.

If you are developing or optimizing intermediates for API programs,
contact us to discuss your route, supply requirements, and manufacturing strategy. → sunqian0123@gmail.com
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