GMP #12: Optimizing Pharmaceutical Good Manufacturing Processes

Authored By: Michael Sassano & Antonio Guedelha 


Michael Sassano

Founder, Chairman & CEO Somai Pharmaceuticals -Investor, Cannabis, GMP, Pharmaceutical &Herbal Medicine



Antonio Guedelha



Manufacturing process optimization aims to increase productivity, decrease operational costs, and make the manufacturing process more robust via a more stable, controlled analysis with fewer errors. We will concentrate on step-by-step improvements using the Plan, Do, Check, and Act (PDSA) methodology.

Manufacturing process optimization includes but is not limited to machinery improvements, assessing manufacturing process variables, process control, quality monitoring, and maintenance planning. Manufacturing process optimization aims to produce the maximum output with the highest quality and the lowest amount of resources, such as energy, consumables, time and personnel. Automation is often the result of these analyses because it reduces time and human error.


Unique Considerations in Pharmaceutical GMP

In pharmaceutical GMP, all the changes you may wish to implement in the manufacturing process must demonstrate they do not compromise the quality of the product. Quality checks imply additional tests, reports, validation, and stability studies. Manufacturing process optimization requires risk analyses to show that the facility can implement cost-related changes without affecting quality.

Process Analytical Technology (PAT) is defined by the United States Food and Drug Administration (FDA) as a mechanism to design, analyze, and control pharmaceutical manufacturing processes through the measurement of critical process parameters (CPP), which affect critical quality attributes (CQA).


There are several methodologies for manufacturing process optimization:


“Kaizen” is a Japanese word and means continuous improvement by eliminating waste and creating value. It’s a methodology of improvement is based one fundamental question each step: “What should be the ideal for each single operation or process?” Implementing the PDCA with this question involves your entire staff, from the operator to top management. It uses tools to drive results.

Overall Equipment Effectiveness (OEE)

Manufacturing productivity measurement is done mainly by OEE. This process identifies the percentage of time that is genuinely productive. For example, an OEE of 100% means that you achieve a 100% quality rating, 100% of performance by way of time savings, and 100% availability, meaning no manufacturing stops. These ratings will allow you to identify where you have faults or inefficiencies to improve.

Lean Manufacturing

Lean manufacturing is a way to produce more with fewer resources, less equipment, fewer steps, less time, less human effort, and less space with a final goal of coming closer to providing customers exactly what they want.

There are five main principles of lean manufacturing: 
  1. Value, which is what the customer is willing to pay for the product or services
  2. Map Of Value Stream, which focuses on analyzing materials and other resources necessary to produce a product or service to remove waste, get improvements and remove all the components the costumer doesn’t value
  3. Create Flow by improving internal and external lead times and smoothing out the manufacturing process to avoid delays
  4. Pull System, which is guided by the customer purchase orders or actual demand
  5. Perfection, which one must constantly pursue as defined by the Kaizen methodology.

Six Sigma

Six Sigma is a methodology developed by Motorola that uses data analysis and statistics to reduce errors or defects. Six Sigma refers to the six standard deviations between average and acceptable limits using the DMAIC methodology:

  • Define the problem
  • Measure Key aspects
  • Analyze
  • Improve the process
  • Control

Total Quality Management (TQM)

TQM aims to increase customer loyalty by delivering products and services consistently  that keep the customer happy and coming back. Total Quality Management requires continuous and consistent feedback from employees and customers to determine how the company can improve its services and products.

TQM has eight principles:  

  1. Customer focus
  2. Total employee involvement
  3. Process-centric
  4. Integrated system
  5. Strategic and systematic approach
  6. Continual improvement
  7. Fact-based decision making
  8. Communication

Standard tools used in TQM methodologies:

  • Poka-yoke is another Japanese word that means “mistake-proofing.” It is a mechanism that helps an operator avoid mistakes and defects by preventing, correcting and/or drawing attention to human errors as they occur.
  • Gemba is Japanese for “the real place” and focuses on where the real work is happening. The Gemba involves a walk in the place where work is done and uses three crucial elements: Go and see, ask why and respect people.
  • Value Stream Mapping (VSM) is a technique developed by manufacturing companies like Toyota in the ’90s. VSM is a visual way to document, analyze and improve the flow of information or materials to produce a product or a service. The goal is to remove waste and make complex processes more efficient.
  • Kanban means “Card” or “Signalization” in Japanese and uses cards to indicate the flow advance of materials in the manufacturing process. Kanban uses precision to  control the manufacturing process and facilities to find problems.
  • Five Whys is a practice of asking “why” repeatedly when encountering a problem to get the root cause. It’s a simple technique with notable results.
  • Fishbone Diagram (also known as the Ishikawa Diagram) The Fishbone diagram is used to show potential causes of an occurrence. It can help to find the possible reasons or errors behind the production of non-conforming products.
  • Key Performance Indicator (KPI) KPIs are indicators of the performance of management and manufacturing processes. KPIs are often used when setting management and quality assurance standards.
  • IoT (Internet of Things) Industry 4.0 tools will allow machine data connectivity, and with IoT, you can access every detail of the manufacturing process in real-time. Gathering this information and using machine learning can improve your manufacturing process.
  • Root Causes and Inefficiencies Identification is a way to address defective products, equipment failures, machine downtime, materials fault, missing materials when needed, and other factors which can help identify and determine the root causes of errors in real-time.
  • Zero-Error utilizes automated manufacturing analytics software combined with machine learning to anticipate failures in real-time, so you may take actions towards achieving zero-error or determine the improvements to be made.


All this comes to PAT, with FDA recommendation, as a GMP methodology for manufacturing process optimization. The key is constantly analyzing your processes and procedures to ensure you maintain the highest quality while minimizing costly errors and waste. Making efficient processes will increase your profits, improve customer relations, and show that your facility is a long-term manufacturer of the highest quality pharmaceutical products.

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