The Challenge

A Pharmaceutical Manufacturer in Indiana requested help from Performance Validation (PV) with the commissioning and qualification of a continuous manufacturing process train. The process train was the first commercial continuous manufacturing suite for the company. The continuous manufacturing process closely mimicked a process train in the development area.


The Continuous Manufacturing process is an equipment train located within a dedicated suite. For products amenable to a direct compression process, the system is designed to continuously and accurately meter raw materials to attain a specified target unit formula, uniformly blend these materials, and compress the blend into finished tablet cores without isolation, interruption, or manual intervention. This is achieved through a vertical arrangement of loss-in-weight feeders, a horizontal high-shear paddle-style mixer, and a conventional tablet press which are integrated via a distributed control system. Tablet quality is assured through real-time evaluation of feeder, mixer, and tablet press performance in combination with periodic sampling and analysis of produced tablets in an automated tablet tester equipped to evaluate tablet weight, thickness, and hardness (where tablet shape permits). Additional process analytical technology instruments and real-time process models are present in the system.

The Solution

Performance Validation (PV) provided validation engineering resources to aid in the development and execution of the testing for this equipment, and to provide a lifecycle approach for documentation, including requirements, specifications, system and component criticality assessments, and summary using the company policies and procedures, to successfully release the equipment:

  • User Requirements and Design Specifications: collaborated with internal process engineering prior to testing to establish critical process parameter ranges and critical user requirements to achieve optimal performance of the equipment.
  • Failure Modes and Effects Analysis (FMEA): Ran FMEA meetings for Process train equipment. Meetings included client subject matter experts from areas such as Process Engineering and Automation.
  • Equipment Acceptance: interfaced with the vendor to complete factory turnover of the computer communication system software package prior site acceptance.
  • Commissioning: developed, executed and compiled Commissioning Packages, which contained Receipt Verification, System Installation Verification, and Functional Testing.
  • Qualification: developed and executed the qualification testing for critical process parameter ranges successfully through release for GMP use.
  • Used protocols that were utilized to qualify development equipment to streamline the document develop process and provide cost savings for the customer.
  • Project Management: provided active leadership and communication throughout the duration of the project, helping the project team to identify and avoid potential bottlenecks.

The Results

The Continuous Manufacturing process was qualified and released on time per project schedule. This enabled the company to use the equipment for commercial manufacturing.

The Benefits

The company successfully transitioned a batch manufacturing process to a continuous manufacturing process.  This resulted in an increased performance and product yield from the facility and associated manufacturing equipment.  This improved performance led the company to replicate this process at two other manufacturing sites. As identified by ISPE in the Facility of the Future Award the manufacturer was recognized for the progressive mass balance control scheme anchored by advanced automation and PAT technology, key to insuring consistent control, low process variability, and high quality assurance.

Have a question about Performance Validation? Please schedule a call with one of our subject matter experts.

Brad Henry
Vice President, Indiana Division Director
Performance Validation

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