Lean Thinking For Pharma — Flow Without Facility Upheaval

By Irwin Hirsh, Q-Specialists AB

Lean manufacturing literature — like Ed Byrne’s The Lean Turnaround or Daniel Markovitz’s Building the Fit Organization — offers powerful concepts that inspire continuous improvement. But in pharma, these ideas can feel disconnected from the realities of GMP.

Take “one-piece flow.” In a GMP-regulated setting, implementing it physically often triggers:

• requalification and revalidation of equipment,
• disruption of validated workflows, and
• downtime with significant commercial consequences.

Flow cells are at the heart of Lean manufacturing. They’re the efficient nucleus of physical activity where all value-adding steps occur in one place. In bioprocessing, compliance demands that we isolate certain steps — such as those before and after virus filtration — making focus on physical flow cells a fallacy.

So how do we capture the value of Lean without compromising compliance or incurring excessive risk?

This article explores Lean practices as enablers of operational excellence within the context of GMP environments. Instead of starting with equipment rearrangement, we begin with flow — that is, the flow of knowledge, people, and decisions.

Rather than mimicking a physical cell, we might:

• Align QA, QC, and operations into cross-functional product teams.
• Bring data closer to decision points using at-line and inline measurements.
• Enable faster, even preventive, deviation handling through better visibility and digital workflows.

In this light, one-piece flow is no longer about layout — it’s about enabling continuous, cross-functional insight and action.

These ideas build on my 2024 article series on knowledge management in pharmaceutical development, which emphasized:

• Mapping processes to expose and eliminate non-value-added steps.
• Using standard work to ensure reproducibility and reduce error.
• Digitizing knowledge selectively based on its value, context, and use.

Principles For Successful Implementation

Understanding the principles and their purpose

Many pharma sites abandon Lean initiatives too early — not because Lean doesn’t work, but because its implementation is misunderstood. Too often, Lean is approached as a one-size-fits-all toolkit, focused solely on speeding up production or reducing waste.

While those benefits are desirable — and achievable — they are not the purpose.

Successful Lean implementation in GMP-regulated environments requires adaptation:

• to the culture of the site,
• to the constraints of compliance, and
• most importantly, to the strategic goals of the organization.

Leaders must understand that the change they are driving itself is the goal. A Lean transformation is not about installing tools — it's about building an organization capable of consistently acting on what matters most.

When Lean tools are applied in service of strategic clarity — rather than imposed as stand-alone fixes — they become powerful levers for transformation.

A GMP lens for Lean

To reimagine Lean for pharma, I suggest we first shift the focus from moving product faster to enabling smarter, faster decision-making. That means:

• accelerating the flow of information,
• enabling timely QA collaboration, and
• reducing decision latency as aggressively as physical cycle time.

When teams have clear priorities, real-time insight, and aligned processes, they can move with both speed and compliance. That is Lean in its most strategic and sustainable form.

From tools to thinking

When in improvement mode, it's not enough to copy and apply Lean tools (random acts of kaizen). Instead, we must first understand the operations well enough to know whether a classic Lean intervention is even needed and, if so, how it aligns with the business objective: improved throughput, stability, margins, and cash flow.

The biggest risk is not “Lean won’t work here” — it’s misdiagnosing the problem and applying tools without understanding the real business constraint let alone those of the GMPs.

Operational excellence is not about applying Lean — it’s about applying Lean thinking.

The following pharma-based tables were constructed to illustrate how thinking can be structured for the application of common Lean tools into operations.  

Table 1. Prerequisite Operational Understanding Before Changes

Thought Question:
“Do we really need this practice, or are we solving the wrong problem?”

Classic Lean Practice	What To Understand About Operations First	How This Can Support The OpEx Strategy
One-piece flow/Flow cell	Are delays due to handoffs or lack of ownership? Do QA, QC, and Ops align on batch priorities? Are people organized by product or function?	Ensures teams form around flow, not silos — accelerates batch movement and decision speed
Just-in-time (JIT)	Do we know the lead time for each raw material and component? Receipt to release for use into (SAP) system? Is material availability a constraint on production? What drives stockouts or excess?	Avoids unnecessarily tying up cash and ensures materials don’t delay critical batches
Line balancing (Takt-time)	Is demand stable or erratic? Where is the real constraint? Is it people, equipment, or QA? Are any steps consistently backlogged or starved?	Helps identify true bottlenecks and align staffing, cross-training, or planning to increase throughput
Pull system (Kanban)	Are there repeatable signals to trigger the next step? Do we run out of materials, tools, or documents at the point of use? Are delays predictable?	Introduces discipline in preparation, reduces firefighting, and improves flow predictability
Quick changeover (SMED)	How much of changeover time is productive? Are we waiting for paperwork or QA delay cleaning? Are campaigns too short?	Targets wasted time during non-value-adding setups; protects uptime during transitions. Puts focus on critical parameters and their control
Visual management	Are people waiting on information to act? Are priorities clearly visible to all (QA, planners, ops)? Are escalations timely?	Accelerates decision-making and aligns daily actions to turnaround goals like faster release and throughput
Empowered teams (Andon)	Can front-line teams solve 80% of their own issues? Is QA or management required for every minor decision? Are bottlenecks human or policy-driven?	Builds capability and speed into the organization; reduces small delays that aggregate into major lost time; and increases engagement
5S	Is time lost finding tools, documents, or cleaning materials? Are errors due to clutter, mislabeling, or inconsistency? Is space underutilized?	Improves repeatability, reduces deviation triggers, and stabilizes the workplace for consistent output, safety, and less frustration “looking”
Improvement events (Kaizen)	Do we know the real root cause of the problem? Have we mapped the information and decision flow — not just the physical steps? Is it safe to change?	Focuses limited improvement energy on areas with clear business impact Puts improvement into the hands of the true experts, those who regularly perform the process
Load levelling (Heijunka)	Are spikes in demand or internal pressure causing chaos? Are campaigns driven by external constraints or just legacy thinking? Is planning reactive?	Enables smoother production planning, protects resources, and reduces firefighting cycles that can cause stress and errors/deviations/injury

 

Table 2. Implementing Lean in Regulated GMP Environments

Thought Question:
“How do we adapt the standard thinking for application in GMP?”

Classic Lean Practice	Why It’s Challenging In GMP	Reimagined Approach / Mitigation
One-piece flow in a flow cell	Equipment relocation prompts requalification, revalidation, facility modification.	Create virtual flow cells using product or modality-aligned product teams (Ops, QA, QA Ops, QC) to streamline
Just-in-time inventory (JIT)	GMP requires quarantine, release testing, vendor qualification, which means long lead times.	Implement just-in-time with risk-based logic — set strategic inventory buffers for high-risk or high-value items, segment suppliers by reliability, and prioritize stock based on customer impact (e.g., high-volume, essential medicines, or frequent stockouts).
Takt-time line balancing	Biopharma processes often have biological variability and long batch processes.	Apply takt principles to information and support processes, like QA review and deviation closure by measuring how reliably and quickly critical information is delivered. Track lead time, process time, and percentage of complete and accurate handoffs to identify and reduce delays.
Pull systems (Kanban)	Raw materials require release testing and often cannot be pulled on demand.	Use kanban to manage the readiness of key support items — such as line clearance kits, changeover tools, and pre-approved documentation — so they’re always available before they’re needed.
Quick changeovers (SMED)	Line clearance, cleaning validation, and QA checks add fixed time to every changeover.	Focus SMED on internal preparation — reduce waiting for paperwork, pre-stage documentation, align QA in advance.
Visual management at the line	GMP data is often hidden in batch records, not available in real time.	Develop QA-approved digital visual boards for WIP, release status, deviation age, and document cycle times.
Empowered teams/Andon	GMP culture often limits operator autonomy; escalation is bureaucratic.	Define preapproved escalation pathways and empower teams with real-time decision criteria and triage logic.
5S workplace organization	Changes to workspace or labeling require controlled documentation.	Implement 5S via SOP-compliant visual aids and controlled cleaning/labeling protocols to align with site master plan.
Improvement events (Kaizen)	Changes to validated processes may require formal change control and QA review.	Focus events on information flow, role clarity, or non-product impacting processes (e.g., scheduling, meetings).
Load levelling (Heijunka)	Pharma batch sizes are dictated by campaign plans, stability studies, or validation schedules.	Apply level loading to support functions (QA, QC, documentation review, sampling).

 

Closing Thoughts — And More Tables

In many organizations, operational excellence teams are disconnected from strategic planning, while strategy-setters may struggle to translate business goals into actionable initiatives. The following tables are designed to bridge that gap using common financial metrics:

• For OpEx teams, it provides clarity on where to focus Lean efforts for maximum strategic impact.
• For leadership, it offers a framework to define and communicate improvement initiatives that are clearly aligned with measurable business objectives.

There are three groupings of metrics:

Liquidity And Flexibility

This group of metrics focuses on a site’s ability to generate and manage cash efficiently. Lean improvements in this area help reduce unnecessary capital tied up in materials, streamline the movement of goods and decisions, and increase responsiveness to both internal and external changes, without compromising GMP compliance.

These metrics are especially critical during turnarounds or rapid growth phases, where financial agility matters most.

Asset And Resource Efficiency

These metrics reflect how well a site uses its people, equipment, and capital investments to create value. Low efficiency often signals underutilized assets, bloated inventory, or overreliance on reactive fixes.

Lean supports better asset performance by increasing flow, reducing downtime, and helping teams do more with what they already have before investing in more.

Operational Profitability

This group highlights the cost-effectiveness and reliability of day-to-day operations. From gross margin to first-time-right, these metrics track how consistently value flows through the system without waste, error, or delay.

Lean strengthens profitability by embedding control at the source, reducing variation, and enabling smooth, right-first-time execution across cross-functional teams.

Liquidity And Flexibility

Metric	Definition	Why It Matters	Lean Opportunity	Lean Goals For Impact
Working Capital	Current assets – current liabilities	Indicates liquidity and efficiency. High working capital can signal cash trapped in excess inventory.	Free up cash by improving inventory flow and reducing delays in production and release.	Implement pull-based replenishment systems. Standardize line clearance and changeover procedures. Use tiered visual management to highlight aging inventory.
Free Cash Flow	Cash from operations after capital expenditures.	Indicates how much cash is available for growth, debt reduction, or weathering volatility.	Lean can lower costs and reduce cash tied up in operations without adding risk.	Standardize critical operations to reduce waste and rework. Apply pull-based systems to prevent overproduction. Shorten QA cycle times to reduce capital tied up in finished goods.
Cash Conversion Cycle (CCC)	(Days inventory) + (days sales outstanding) – (days payables outstanding)	Measures how quickly investments are turned into cash. Shorter cycles improve liquidity.	Reduce batch delays, material buildup, and invoicing inefficiencies.	Improve inventory turns via better material flow. Accelerate QA batch release processes. Streamline order-to-cash cycle through right-first-time production.

 

Asset And Resource Efficiency

Metric	Definition	Why It Matters	Lean Opportunity	Lean Goals For Impact
Inventory Turns	COGS/average inventory	Higher turns signal efficient inventory use and reduce cash tied up in stock.	Reduce inventory buffers by improving process flow and demand alignment.	Use pull-based planning and demand-aligned production. Apply 5S and visual controls to manage inventory staging. Increase process reliability to reduce safety stock needs.
Return on Assets (ROA)	Net income/total assets	Reflects how effectively assets are being used to generate income.	Increase throughput and reduce asset idleness by improving flow and coordination.	Improve scheduling and reduce changeover time. Enable smaller batch sizes to increase asset flexibility. Use visual controls to prevent underutilization.
Return on Invested Capital (ROIC)	Net operating profit after tax/invested capital	Indicates how effectively capital investments are being turned into profits.	Maximize asset use and ensure investment aligns with real constraints.	Maximize throughput before adding capacity. Link A3 problem-solving to capital justification. Eliminate hidden costs through standardization and waste reduction.

 

Operational Profitability

Metric	Definition	Why It Matters	Lean Opportunity	Lean Goals For Impact
Gross Margin %	(Revenue – COGS)/revenue	Indicates how efficiently revenue is converted into profit before overhead.	Improve yield and reduce rework to raise profitability.	Standardize work and improve operator training. Use deviation tracking to reduce recurring waste. Align batch sizes to demand and optimize changeovers.
Operating Margin %	Operating profit/revenue	Measures how efficiently the organization turns revenue into operating profit, accounting for all operating expenses including QA and support.	Improve support process efficiency and reduce overhead burden by streamlining cross-functional coordination and removing waste.	Value stream map support processes like QA review and planning. Introduce tiered escalation and decision-making to reduce delays. Eliminate redundant review steps and documentation loops. Apply A3 thinking to identify and resolve recurring support inefficiencies.
Conversion Cost per Unit	(Total manufacturing cost – material cost) / units produced	Highlights cost to convert materials into finished product; helps pinpoint inefficiencies in labor, equipment, and QA activities.	Lower conversion cost by improving equipment uptime, scheduling consistency, and streamlining quality-related tasks.	Apply SMED to reduce setup/changeover times. Use performance boards to track idle labor and delays. Standardize low-value documentation and testing steps. Balance workloads across shifts and teams.
First-Time-Right (FTR)/Right-First-Time (RFT)	Percentage of batches that pass through the process without rework, deviations, or repeated QA reviews.	Directly reflects quality, consistency, and alignment; high FTR reduces cost, improves speed, and increases trust in operations.	Improve process understanding, reduce variability, and strengthen documentation and training.	Standardize critical process parameters. Improve batch record and work instruction clarity. Use structured problem-solving for root cause analysis. Enhance operator competency through targeted training.

 

Glossary Of Terms

Lean Term	Simplified Definition for GMP Manufacturing
One-piece flow	Work moves one unit at a time through each step without waiting in batches. Often associated with work cells where movement of a piece is optimized and often one worker can move with the piece from station to station/machine to machine within the cell due to cross-training. Having each stage of the operation so close also makes problems obvious quickly.
Just-in-time	Making or moving only what is needed, when it’s needed, according to customer demand, to reduce waste. Requires good control across the value chain from raw materials through to delivery. It lets you know if you can predict demand and if you have good relations with your suppliers.
Takt-time	The pace needed to complete each task to meet customer demand. Too fast, and you waste resources and bloat inventories. Too slow, and you fail to meet delivery expectations.
Kanban	A visual system to signal when materials or tasks need to be started or restocked. This has recently become a methodology for avoiding backlogs in workflows, especially within Agile.
SMED	Stands for “single-minute exchange of die,” however, it now represents the development of approaches that make equipment changeovers faster and more consistent.
Andon	A way for staff to signal problems quickly so support arrives without delay. It can also simply be moving feedback closer to those who need it so that they can adjust their actions and decisions, ideally in real time, rather than later when it has almost no business impact.
Lean	A business management system that focuses on creating products, improving operations and developing people to deliver customer value and business prosperity, while consuming the fewest possible resources.
5S	A method to organize and maintain clean, safe, and efficient workspaces. Each S represents a step in the process of creating this workspace: sort, set in order, shine, standardize, sustain.
A3	A one-page (A3 size) format for clearly describing problems and solutions. It contains the current and future state. Creating the A3 brings clarity to the way forward. Once completed, the A3 becomes a simple visual communication tool.
Heijunka	A way to level out work so that teams are not overloaded or waiting. For example: restructure the weekly schedule so campaign prep, production, and release steps are evenly distributed across the week. Align QA, QC, and cleaning support activities to match this new rhythm.

 

About The Author:

Irwin Hirsh has nearly 30 years of pharma experience with a background in CMC encompassing discovery, development, manufacturing, quality systems, QRM, and process validation. In 2008, Irwin joined Novo Nordisk, focusing on quality roles and spearheading initiatives related to QRM and life cycle approaches to validation. Subsequently, he transitioned to the Merck (DE) Healthcare division, where he held director roles within the biosimilars and biopharma business units. In 2018, he became a consultant concentrating on enhancing business efficiency and effectiveness. His primary focus involves building process-oriented systems within CMC and quality departments along with implementing digital tools for knowledge management and sharing