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Auditing Process Validation & Developing Protocols

In the auditor’s notes, we would expect details on each of the seven parts of the turtle diagram. This might include the following items:

  • ID# of the thermocouple used to verify temperature of the sealer
  • Equipment ID# for the sealer that was validated
  • Name and title of the operator who ran the equipment for the process validation
  • Equipment maintenance work instruction and operating instructions from the DMR
  • References to peel test data analysis for Tyvek pouches sealed with heat sealer
  • Maximum and Minimum validated pressures, temperatures and dwell times for the sealer
  • Accuracy and precision of the temperature sensor integrated into the sealer

Additionally, we would expect the auditor to have follow-up trails where an operator was interviewed—possibly the same person who performed the original process validation. The auditor should be asking what the operator does at start-up to make sure that the seal is good and to learn what the operator does if the seal is not good. Ideally, the operator can provide examples and should be showing the auditor where these instructions can be found in a controlled document.

Another follow-up trail for the auditor is to interview maintenance personnel to verify that required maintenance has been performed. The auditor would also verify that the equipment has not been moved, or has been revalidated if it was moved. The auditor should also be reviewing calibration records for the sealer and the thermocouple used to calibrate the sealer. During the initial interview of the manufacturing engineer, the auditor may have even asked how low or high the temperature can deviate from the work instruction before the sealer will begin producing weak seals. The engineer should be able to identify this information within the operational qualification (OQ) report.

How to develop a validation protocol:

I frequently receive requests to share a process validation protocol template. The template to which I refer everyone can be downloaded for free from the International Medical Device Regulators Forum (IMDRF). The specific document that I recommend was actually created by the Global Harmonization Task Force (GHTF) about ten years ago, and the guidance documents have been maintained by IMDRF since the GHTF was disbanded. Study Group 3 (SG3) was responsible for creating the guidance document (i.e., GHTF/SG3/N99-10:2004):

This is a 36-page document that was updated (i.e., edition 2) in January 2004. The core of the guidance document is 13 pages, and then there are Appendices. Appendix A provides ten pages of statistical methods and tools for process validation. Appendix B provides examples of process validation protocols for the most common process validation in the medical device industry—heat sealer validation. Examples are available in MS Word and PDF formats. Therefore, you can easily edit the Word version and conduct your own heat sealer validation with minimal time required for protocol writing. The example protocols include:

1. A process validation protocol
2. Installation qualification (IQ) results
3. Operational qualification (OQ) results
4. Performance qualification (PQ) results
5. A final report

If you need a validation protocol for a different type of process, you can start with the basic templates provided in the GHTF guidance document. However, three primary areas need to be reviewed, and will probably change. The first area is the equipment used. Heat sealers are simple machines with three operating parameters: 1) pressure, 2) temperature and 3) dwell time. Some sealers have cooling, vacuum and other features, but automated filling equipment would be an example of equipment that is more complex and that has multiple operations that require validation, including heat sealing. Before writing a protocol, all of the elements of the equipment that require maintenance, adjustment, monitoring and control should be identified. Each element needs to be covered in the IQ at a minimum.


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