Process Analytical Technology

Implementation

Incorporating the ESP™ is a low risk process. This innovative blend uniformity monitoring system is designed for easy, logical, step-by-step implementation into your organization:

  1. Evaluation – working offline to ensure effusivity is an appropriate proxy
  2. Monitoring – retrofitting a blender and evaluating results
  3. Controlling – using online effusivity results to actively vary blend times

At each phase of the process, there are steps to validate the procedures and ensure compliance with current quality measures and standards. The result of implementation is increased blending knowledge and improved uniformity of formulations.

3 Phases of Implementation

Evaluate

In an offline mode, evaluate effusivity of formulation components with a single sensor ESP™system

Determine:

  • Effusivity of ingredients
  • Effusivity of thieved samples
  • Correlation to existing QA

Establish that effusivity varies in the major excipients

Output: Sensitivity analysis

Owner: Formulation – new, Tech Ops – existing

Gate: Locate a key formulation with effusivity

Monitor

Retrofit a blender with sensors (ESP™) and monitor the results for X months

Determine:

  • Effusivity endpoints
  • Blend characteristics
  • Correlation to CU

Monitor results on a retrofitted blender to determine end point based on two criteria:

  • Minimal relative standard deviation between multiple sensor responses
  • Expected average effusivity of the final blended product

Output: Process recommendations, Improved blending knowledge

Owner: Manufacturing

Gate: Correlate effusivity with other quality measures

Control

Use effusivity as a control method by changing standard operating procedures from time-based to variable control to increase final product uniformity

Determine:

  • SPC charts
  • Seasonal and lot trends
  • Correlation to incoming ingredients

Monitor results on a retrofitted blender to determine end point based on two criteria:

Output: Improved vendor specs, Consistent uniformity

Owner: Manufacturing

Increased Blending Knowledge

The ESP™ pharmaceutical blend uniformity monitoring system unlocks a wealth of new information about your formulations – and vastly improves your blending knowledge. This new insight into your process allows refinements within Standard Operating Procedures (SOP) or variations to SOP to optimize uniformity.

The following scenarios demonstrate how the real time information provided by the ESP™ can be applied to maximize product quality:

Case 1

Formulation: Unknown

Process: Optimized

Case 1 represents a situation where the blend is stopped at the point it reaches uniformity, but it is unknown what might happen to this blend if conditions change.

Case 2

Formulation: Stable

Process: Stable

In Case 2, variability in optimal blend time would not influence product quality. A window of acceptable times is possible compared to Case 3 where any variation can move the operation away from ideal.

Case 3

Formulation: Sensitive

Process: Overblended

Case 3 represents a clearly overblended situation. By understanding the problem, changes can be made to adjust the system so that the blend time corresponds to the stop time.

Solution Options

Within the SOP:

  • Turn off intensifier bar
  • Decrease speed of bar
  • Decrease RPM
  • Change blender size
  • Change blender type
  • Change batch size and fill%
Based on information provided by the ESP™, adjustments can be made within the Standard Operating Procedure (SOP) to effectively slow the blending process. As represented in the graph above, this stretches the “funnel” and ensures uniformity - the point of lowest standard deviation between readings of the 8 sensors - is optimized at the conclusion of the fixed blend time.

Change in SOP:

  • Decrease blend time
Maximum uniformity of the formulation is easily obtained if changes to the SOP are undertaken. In this example, decreasing the blend time to the point of lowest standard deviation between readings of the 8 sensors will achieve the desired result.

Retrofitting Blenders with the ESP™ System

A key benefit of the ESP™ system is that it can be retrofitted to existing equipment – eliminating the need for significant capital cost expenditures. To permit maximum flexibility, the sensors can be retrofitted into the walls or covers as appropriate, depending on the blender size and type. Once installed, the stainless steel sensors are flush with the inside surface of the blender, and can be easily removed for maintenance and cleaning.

  

The stainless steel sensors of the ESP™ can be retrofitted to existing V-blenders and bin blending equipment – on the covers or side walls. The flush mounted sensors are designed to be simple to clean and maintain.

For information on pharmaceutical equipment manufactures, visit the following companies:

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Note: samples are disposed of 2 weeks after release of test results unless client notified C-Therm of their desire to have the samples returned (client's expense). Any hazardous materials that cannot be disposed of in municipal waste will be returned to client for disposal (client's expense).