Process Reliability through Qualification and Validation

Today’s packaging machines are built to help operators achieve process reliability; qualification packages simplify procedures



By Ed Wood, Director, and Wil Caraballo, Technical Sales Advisor
Medical-Consumer-Industrial Division, Multivac Inc. (Kansas City, MO)



Multivac thermoform-fill-seal systems like the R535 (pictured) are available with ISO 11607 compliant validation packages for medical applications.

Sterile medical products require the highest degree of packaging reliability. Achieving such reliability involves validation of the packaging process and its result, as well as preparation of extensive documentation that complies with relevant regulations. All critical details of the packaging process must be monitored and recorded, and the process must be qualified. Careful calibration of the central measuring devices is critical to the overall success of the packaging system.

Comprehensive process monitoring

Guaranteeing the reproducibility of the packaging process requires capturing and recording the most important parameters. These are primarily the relevant process values for sealing: sealing pressure, temperature, and duration. These three parameters are subject to precise monitoring. The operator can adjust the values within the maximum preset permitted deviation. If this tolerance is exceeded, the faulty cycles are automatically expelled. If the error occurs in a series, the machine will stop, which means that no faulty packages will be allowed to reach the final customer.

For example, on a Multivac thermoform-fill-seal machine, the temperature in the forming station is continuously monitored. In addition, the leak resistance of the formed packaging molds can automatically be checked in the forming station itself or using a separate testing station, often referred to as “pinhole detection.” This pinhole-detection monitoring is conducted using pressure or vacuum on the basis that the pressure or the vacuum may not change over a preset time period. If it does change, the automatic insertion of the product into the defective formed pocket is prevented, and the cycle is automatically expelled.

Sealing pressure is a critical factor for a stable and clean seal. To guarantee reproducibility of this parameter, it is monitored precisely by means of an additional pressure transducer in the sealing die. The sealing time is initially calibrated; during the operation, the internal clock of the machine control system serves as a reference. The sealing temperature can be measured in the sealing die in a precise and reproducible manner with calibrated thermocouples or resistance temperature detectors (RDTs).

There can be additional inspections such as a check for empty packages by means of a vision inspection system. Here, too, there can be an automatic expulsion of faulty cycles. In addition, there are continuous checks for potentially protruding products using swinging gates. These are on the same level as the package and cause the machine to stop if they are lifted. This prevents problems in the sealing die before they occur.

Validation in compliance with ISO EN 11607:2006

Qualification and validation are decisive components of process reliability. Qualification refers to the process of demonstrating that the system is capable of fulfilling the specified requirements. Validation is establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product that meets its predetermined specifications and quality attributes. For terminally sterilized medical devices, the authoritative standard is created by ISO EN 11607:20061. The regulation presumes a quality management system and risk analysis in advance, and the operator of the system is responsible for the proof.

All test and protocol steps as specified in ISO EN 11607:2006 for validation and qualification are the responsibility of the medical device manufacturer. To an increasing degree, machine suppliers like Multivac directly support medical device manufacturers in validations. “Validation packages” are often provided by suppliers in order to qualify the packaging process according to ISO EN 11607:2006. Such packages contain documentation of all functions and potential risks together with the proof of process suitability. Risk analysis is employed so that possible risks are systematically identified and evaluated in connection with the machine. In addition, these services can be defined:

Design qualification

  • Project-specific validation plan.
  • Duty book or functional specification.
  • Hardware design specification.
  • Software design specification.

Installation qualification

  • Inspection of the equipment.
  • Establishing documented evidence that the equipment is installed in compliance with the technical specifications.

Operational qualification

  • Test of the product-relevant components and component groups.
  • Test of the machine-specific software modules.
  • Error test protocols.
  • Documented verification that equipment is capable of repeated operation within anticipated operating ranges.

Process Qualification

  • Establishing documented evidence that machine operating characteristics and the product conform to the defined limits set out in the specifications.

The Need for calibration

Calibration is the determination of systematic deviations in measurements. Certain measuring and regulating procedures are examined for deviations in measurements according to the requirements of the device manufacturer. Then the deviations can be compensated for by setting up an offset. The calibration applies to temperature, pressure, and vacuum sensors. The results are recorded in a calibration protocol of the initial calibration. The same protocol also describes the procedure for a recalibration. The operator receives a template for recalibration on a CD, which provides the required material to repeat the calibration regularly. However, recalibration is complex. It is advised that the machine manufacturer support calibration.



1. ISO EN 11607:2006, “Packaging For Terminally Sterilized Medical Devices (2006-04-07), Part 1: Requirements for Materials, Sterile Barrier Systems, and Packaging Systems; Part 2: Validation Requirements for Forming, Sealing, and Assembly Processes.”



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