ICH Q13: Everyone Talks About Continuous Manufacturing. Almost Nobody Talks About the Batch.

When people first hear the term continuous manufacturing, they often assume that batches disappear.

After all, if material is continuously entering a process and product is continuously leaving it, what exactly constitutes a batch?

Surprisingly, one of the most important messages in ICH Q13 is that continuous manufacturing does not eliminate the need for batches.

In fact, defining a batch remains one of the foundational requirements of a continuous manufacturing control strategy.

Why Batches Still Matter

Many of the quality systems used throughout the pharmaceutical industry depend on batches.

Batches provide the foundation for:

Without a clearly defined batch, it becomes difficult to determine what product was affected by a process issue, what product should be released, and what product may need to be recalled.

This creates a challenge for continuous manufacturing because the manufacturing process itself may never truly stop.

Defining a Batch in Continuous Manufacturing

In traditional batch manufacturing, batch boundaries are often obvious. A batch begins when manufacturing starts and ends when manufacturing stops.

Continuous manufacturing requires a different approach.

ICH Q13 recognizes several approaches for defining batches, including:

Regardless of the approach selected, manufacturers must establish clear and scientifically justified batch boundaries.

The objective is not simply administrative. Batch definitions serve as the basis for traceability and product disposition decisions throughout the product lifecycle.

The Importance of Traceability

One of the reasons batch definition becomes so important in continuous manufacturing is that material is constantly moving through the process.

If a disturbance occurs like an equipment malfunction, or unexpected process variation, the manufacturer must determine exactly which material was affected.

This is where concepts such as Residence Time Distribution (RTD) become critical.

RTD helps manufacturers understand how material moves and mixes throughout a process. By understanding the relationship between process conditions and product location, manufacturers can identify which material experienced a disturbance and which material remained unaffected.

Rather than rejecting an entire production campaign, manufacturers may be able to take targeted action on only the affected material segment.

Continuous Manufacturing Does Not Eliminate Quality Principles

One of the themes that appears repeatedly throughout the ICH Quality guideline series is that quality principles rarely change.

The application changes.

Continuous manufacturing may introduce new technologies, new monitoring approaches, and new control strategies, but the underlying quality expectations remain largely the same.

Manufacturers still need:

ICH Q13 does not replace these concepts. Instead, it provides a framework for applying them within a manufacturing process that operates continuously rather than in discrete batches.

Final Thoughts

The most interesting aspect of ICH Q13 is not the technology itself.

It is the way the guideline forces us to rethink familiar quality concepts in a new manufacturing environment.

Perhaps no concept illustrates this better than the batch.

Even in a process designed to run continuously, batches remain essential because quality systems, release decisions, investigations, and recalls all depend on them.

Continuous manufacturing changes how batches are defined.

It does not eliminate the need for them.

Audits and Self-Improvement: Lesson’s From Peter Drucker on Quality in Combination Products, Medical Devices, Pharmaceuticals and Life

In this episode of Let’s ComBinate, we dive into the fascinating world of audits—a cornerstone activity for ensuring quality, compliance, and continuous improvement across industries. Whether you’re managing combination products, medical devices, or pharmaceuticals, audits are critical for assessing systems objectively and identifying opportunities for growth.

As the year draws to a close, I reflect on my own tradition of reading Managing Oneself by Peter Drucker. This essay, deceptively simple in format, offers profound insights into self-improvement, values, and performance—concepts that align remarkably well with the purpose of audits.

What Makes Audits So Valuable?

Audits are systematic, independent, and documented processes for obtaining and evaluating evidence against predefined criteria. For industries like combination products, they ensure compliance with overlapping regulatory frameworks, such as 21 CFR Part 4, which integrates drug, device, and biologic CGMPs. These audits help organizations maintain harmony in their quality systems, bridging complex regulations like:

By ensuring compliance with these regulations/standards, audits provide a clear-eyed view of processes and help organizations uphold patient safety and trust.

Types of Audits in the Quality Landscape

  1. First-Party Audits (Internal Audits):
    These are proactive evaluations within an organization to ensure the quality management system (QMS) is functioning effectively. For example, under ISO 13485, internal audits act as in-house checkups to catch and resolve issues early.
  2. Second-Party Audits (Supplier or Contractor Audits):
    External evaluations of partners like contract manufacturers or test labs. This is especially crucial in the combination product space, where gaps in supplier compliance can lead to regulatory scrutiny.
  3. Third-Party Audits (Certification or Regulatory Audits):
    Conducted by independent bodies or regulatory agencies like the FDA, EMA, or MHRA, these high-stakes audits can result in certifications or findings like Form 483 observations.

Each type serves a unique purpose, from internal preparation to external validation.

Audits vs. Inspections

While audits and inspections are related, they differ in focus and execution.

Think of audits as annual reviews and inspections as spot checks—both essential for maintaining quality and compliance.

Combination Products and Regulatory Complexity

For combination products, audits must address the unique integration of drug, device, and biologic regulations. The FDA’s guidance on combination product inspections emphasizes the need for robust systems that harmonize requirements from different CGMP frameworks. This complexity highlights the importance of a well-structured audit program to ensure regulatory readiness and product integrity.

Self-Audits and Personal Growth

Interestingly, the principles of audits extend beyond organizations. In Managing Oneself, Drucker emphasizes self-reflection as a tool for improvement. Questions like What are my strengths? How do I learn? What are my values? mirror the audit process of assessing and improving systems.

Just as audits help companies thrive, self-audits foster personal growth. As Drucker says, “Acting on this knowledge is the key to performance.”

Key Takeaways for Quality Professionals

Audits may feel daunting, but they’re among the most effective tools for growth, both professionally and personally. As we wrap up the year, I encourage you to reflect, audit yourself, and embrace the opportunity to improve—whether through Managing Oneself or your next QMS review.

Happy New Year, and remember: Together, we can simplify by combinating!

Did you enjoy this episode? Subscribe to Let’s ComBinate and leave us a five-star review. Here’s to a successful year of audits, harmony, and quality in 2025!

Should You Study Bioengineering in 2025? Insights from a Decade in Pharma and Medical Devices

Choosing a college major is one of the most significant decisions you’ll make in shaping your future career. For many, bioengineering stands out as a promising path, blending cutting-edge innovation with the potential to make a meaningful impact on people’s lives. But is it the right choice for you?

In this blog post, based on the latest episode of my podcast, Let’s ComBinate, I share insights from over a decade of experience in the pharmaceutical and medical device industries. We’ll explore not only whether bioengineering is the right path but also how to approach it if you decide to pursue this challenging yet rewarding field.

Bioengineering vs. Biomedical Engineering: Does It Matter?

One of the first questions prospective students often ask is: What’s the difference between bioengineering (BioE) and biomedical engineering (BME)?

Here’s the gist:

Bioengineering is a broad field, encompassing everything from medical devices to agriculture, environmental applications, and even food production.

Biomedical Engineering is more specialized, focusing on healthcare and medical devices, often diving into subfields like tissue engineering or neural engineering.

From an industry perspective, these distinctions are minor. In my career, spanning both medical devices and pharma, I’ve seen BioE and BME graduates work on similar projects in similar roles. So, don’t get too hung up on the terminology—focus on the university and program that best suits your goals.

Why Bioengineering? My Journey

I started my academic journey at the University of Illinois at Chicago (UIC), initially majoring in chemical engineering with plans to go to medical school. However, after realizing medicine wasn’t my calling, I transitioned to bioengineering—a choice that has shaped my career in profound ways.

Bioengineering’s interdisciplinary nature made it the perfect fit for my interests. It allowed me to explore innovations in medicine without the need for a stethoscope. My experiences have taken me from designing drug delivery systems to contributing to regulatory frameworks for combination products.

What I’ve learned is this: your success in bioengineering (or any field) depends less on the major itself and more on how you approach your studies and career development.

The Pros of Studying Bioengineering

1.Diverse Career Opportunities

Bioengineering opens doors to a wide range of fields, including biotech, healthcare, pharma, academia, and even tech. You can work on software, hardware, product development, or testing.

2.High Demand

With the global population aging and healthcare innovation accelerating, bioengineers are in high demand. The U.S. Bureau of Labor Statistics projects a 7% job growth for bioengineers from 2023 to 2033, outpacing many other professions.

3.Strong Earning Potential

The median salary for bioengineers is over $100,000 annually, making it a financially rewarding field.

4.Global Applicability

Unlike some engineering fields that are localized, bioengineering has a global reach, with opportunities to work in multinational organizations.

 

The Challenges of Bioengineering

1.Academic Rigor

Bioengineering programs are demanding. Expect to juggle math, biology, physics, and programming.

2.Ambiguous Career Paths

Unlike civil or mechanical engineering, bioengineering doesn’t always have a clear trajectory. You’ll need to carve out your path by seeking internships, certifications, or advanced degrees.

3.Highly Regulated Industry

Working in medical devices or pharma means navigating strict regulatory environments. While this ensures safety and efficacy, it can slow down innovation and project timelines.

 

How to Study Bioengineering in 2025

Whether you’re a high school student considering bioengineering or an early college student thinking of switching majors, here’s my advice:

1.Focus on Skill Development

Beyond excelling in coursework, master practical tools like MATLAB, SolidWorks, and LabVIEW. Familiarize yourself with programming languages like Python.

2.Build Your Network

•Connect with upperclassmen who can guide you toward internships and job opportunities.

•Leverage platforms like LinkedIn to reach out to professionals and learn about their day-to-day work.

3.Learn Stats and Data Analysis

Understanding statistics is crucial in bioengineering, whether you’re analyzing experimental data or designing experiments.

4.Set Clear Goals

Establish short-term goals, like learning a new skill, and long-term ones, like landing a specific internship. Staying focused in today’s distracting world is key to success.

 

Final Thoughts

Bioengineering is a dynamic and rapidly evolving field with immense potential. But your success in it depends more on your mindset, the skills you cultivate, and the experiences you seek out than on the major itself.

If you’re passionate about innovation, comfortable navigating ambiguity, and eager to work on problems at the intersection of engineering and biology, bioengineering could be the perfect fit.

For more insights, practical advice, and industry stories, check out the full podcast episode. And if you have questions, feel free to reach out—I’m always happy to help aspiring engineers chart their course.

Happy 2025!

Subscribe to Let’s Combinate for more conversations on engineering, pharma, and innovation.

 

U.S. Bureau of Labor Statistics Occupational Outlook Handbook for Bioengineerings and Biomedical engineers : https://www.bls.gov/ooh/architecture-and-engineering/biomedical-engineers.htm

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