Kaye Solutions for Freezers/Fridges

 Wired

• Kaye Validator AVS
• Accessories

 Wireless

• Kaye ValProbe Wireless Process Validation

 Wireless

• Kaye ValProbe® RT (Real time RF)

Application at a Glance

Freezers, Refrigerators, and Cold Rooms: Optimal Storage for Biotechnological and Pharmaceutical Products

Freezers, refrigerators, and so-called cold rooms are essential in the biotechnological and pharmaceutical industries. These specialized storage solutions ensure that sensitive products such as vaccines, medications, and scientific samples are stored at specified temperatures to maintain their integrity and safety.

A central component of the cold-chain process is the adherence to strict regulations for the validation and monitoring of controlled temperature chambers. This ensures that storage conditions always remain within defined limits. Key standards and guidelines include Good Distribution Practice (GDP) and Good Manufacturing Practice (GMP). Additional specific standards, such as ISO 13485 for medical devices and the WHO guidelines for vaccine storage, provide detailed quality control requirements.

The continuous monitoring of temperature is an indispensable part of validating these processes. Sensors and data loggers continually capture storage conditions, and this data is maintained as part of quality documentation. This not only ensures compliance with legal regulations but also guarantees that the products remain in optimal condition.

Kaye offers solutions with the Kaye Validator AVS, Kaye ValProbe real-time data loggers (ValProbe RT), and the wireless measurement system Kaye ValProbe RF, not only for the validation and qualification of these systems. Furthermore, with Kaye LabWatch IoT, a GxP-compliant continuous monitoring system is offered. These advanced monitoring technologies ensure process safety and high operational efficiency, which ultimately enhances the quality and integrity of pharmaceutical products.

For any questions, please contact us directly or reach out to one of our certified dealers in your country.

Kaye Solutions for Freeze Dryer/ Lyophilisator

 Wired

• Kaye Validator AVS
• Accessories

 Wireless

• Kaye ValProbe Freeze Dryer Logger

 Wireless

• Kaye ValProbe Wireless Process Validation

 Wireless

• Kaye ValProbe® RT (Real time RF)

Freeze-Drying in the Pharmaceutical and Biotech Industry

Freeze-drying, also known as lyophilization, is a significant manufacturing process in the pharmaceutical and biotechnology sectors. This procedure is primarily applied to liquid products, transforming them into a stable, solid powder through sublimation. The process offers numerous benefits, notably extended shelf life and enhanced stability of the final product, significantly easing subsequent handling and storage.

Process Workflow

The process can be simplified into the following steps:

1. Freezing:
   Initially, the liquid starting product is cooled to very low temperatures under extreme vacuum. Depending on the product, temperatures of -45°C, -60°C, or even -80°C are fairly common. The rate and temperature of freezing are critical as they can influence the freezing behavior and microstructure of the final product.
2. Primary Drying (Sublimation):
   In this step, the pressure in the freeze-drying chamber is further reduced and heat is applied to directly convert the frozen solvent (mostly water) from the solid to the gaseous phase without passing through the liquid phase. Sublimation requires precisely controlled conditions to ensure high product quality.
3. Secondary Drying (Desorption):
   To remove the remaining water, the temperature is further increased. The goal of this step is to reduce the water content to a minimally acceptable level while preserving the structure and potency of the active substances.

Critical Process Parameters

The following parameters must be monitored and controlled for successful freeze-drying:

• Temperature:
  It influences both the freezing and sublimation rate. A precisely controlled temperature profile ensures the structure of the final product is maintained.
• Pressure:
  The pressure in the drying chamber determines the sublimation conditions. An optimal vacuum level is crucial for efficient drying and achieving high product quality.
• Time:
  The duration of each process phase must be precisely tuned to achieve optimal drying results. Too short or too long drying times can negatively impact product quality.

These critical process parameters must also be documented during Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) as well as during regular annual qualification and validation to ensure compliance with the relevant regulations for this application. Particularly challenging in this context is the measurement of plate temperature. Typically, at least five temperature sensors are used per plate. Consequently, measurements with more than 60 sensors are not uncommon. In addition to plate temperature, a temperature distribution study is also conducted during the sterilization process step. The very high vacuum, wide temperature range, measurements lasting up to 72 hours, and often high number of measurement sensors make freeze-drying an application with demanding requirements for both qualification personnel and the measurement technology used.

The Kaye AVS and ValProbe RT validation systems are ideal for the qualification and validation of freeze-drying/lyophilization equipment. These advanced monitoring technologies ensure process safety and high operational efficiency, ultimately enhancing the quality and integrity of pharmaceutical products.

Kaye Solutions for Steam-in-Place

 Wired

• Kaye Validator AVS
• Accessories

 Wireless

• ValProbe II Wireless Process Validation

 Wireless

• Kaye ValProbe Wireless Process Validation

 Wireless

• Kaye ValProbe® RT (Real time RF)

Steam-in-Place (SIP) Sterilization in the Pharmaceutical Industry

Steam-in-Place (SIP) sterilization is a critical process in the pharmaceutical industry to ensure the sterility of fixed installations such as tanks, pipelines, and bioreactors in aseptic manufacturing. This process uses saturated steam to kill microorganisms and contaminants without requiring the disassembly of the equipment. The same standards and regulations as those applied in steam autoclaves/sterilizers are used here. Applicable norms for moist heat sterilization, such as EN 285 or ISO 17665, are considered.

As a precursor to the SIP process, that is, the sterilization of the equipment, the CIP process (Cleaning-In-Place) is typically performed. Cleaning-in-Place (CIP) describes the on-site cleaning of industrial equipment without disassembling individual components or the entire system. This process cleans complete production facilities, including valves, pumps, pipes, sight glasses, and sensors, through multi-stage cleaning systems and various rinsing cycles with different cleaning solutions. CIP enables an economical and time-efficient cleaning process. While CIP focuses on the removal of product residues and contaminants, it also serves as a necessary precursor to Steam-in-Place (SIP) sterilization. After thorough CIP cleaning, SIP sterilization takes place to kill the remaining microorganisms and ensure the sterility of the equipment. Since SIP guarantees sterility, CIP sets the stage by removing all visible and invisible residues. Together, these processes ensure an aseptic manufacturing environment in accordance with the stringent requirements of pharmaceutical production.

The SIP process itself consists of several phases and must be adapted to the specific equipment. Common procedural patterns include preheating, steam sterilization, and cooling. During the preheating phase, the system is flushed with steam to achieve uniform heating. In the steam sterilization phase, saturated steam is introduced at 121.1°C/ 250°F and a defined pressure over a specified period. This critical step ensures the complete sterilization of the equipment.

Essential to the SIP sterilization process is the continuous monitoring of parameters such as temperature and pressure both during operation and during the annual qualification and validation. This ensures the compliant operation of the equipment according to standards.

After the steam sterilization phase, the system is often cooled by introducing, for example, nitrogen. This process minimizes thermal stress on the materials and prevents potential damage.

Procedures such as Cleaning-In-Place (CIP) and SIP require substantial validation effort, especially for fixed installations. Validation requirements must be considered as early as the system design phase (Design Qualification, DQ) through appropriate validation ports to avoid complications during GxP-compliant commissioning (Installation Qualification, IQ / Operational Qualification, OQ / Performance Qualification, PQ).

The Kaye AVS, ValProbe-RT, and ValProbe RF validation systems are ideal for the qualification and validation of fermenters, bioreactors, tanks, and pipelines in aseptic manufacturing under GMP considerations. These modern monitoring technologies ensure process safety and high operational efficiency, ultimately increasing the quality and integrity of pharmaceutical products.

For more information about our products and solutions, please visit our website. We are pleased to support you with tailored solutions for your specific requirements in the pharmaceutical and biotechnology sectors.