Packaging Validation for Medical Devices

For medical devices that have to be provided sterile, packaging validation plays an extremely important role.

The validation of the packaging processes might involve different players, not only the manufacturer, but also the health care facilities and sterilisation subcontractors. The ISO 11607, for which we already discussed within QualityMedDev – explicitly calls for validation of all type of packaging. The present article deals with the following packaging processes:

• pouch, reel, or bag sealing
• sterilization sheets folding and wrapping
• filling, and closing of reusable sterilization containers

Likewise, packaging processes not dealt with here must also be validated as per ISO 11607-2.

In this post, we will go through the main requirements associated with packaging validation, taking into consideration three main different regulations: 

• ISO 11607-1:2019 — Packaging for terminally sterilized medical devices — Part 1: Requirements for materials, sterile barrier systems, and packaging systems
• ISO 11607-2:2019 — Packaging for terminally sterilized medical devices — Part 2: Validation requirements for forming, sealing, and assembly processes
• European GMP guideline.

Aspects of Packaging, Packaging Materials, and Closures

When performing the activity of packaging validation, different aspects shall be taken in consideration, such as:

• the functions of packaging;
• the selection of packaging material;
• the testing of the material selected;
• filling, and assembling;
• sterilization;
• storage, and stability.

The materials that can be used for medical device packaging could be of different types, and they are summarised in the table below.

Packaging validation has surely a critical role for the safety of patients and ensuring an appropriate sterile barrier will reduce the number of infections that happen due to lost barrier, or bad aseptic presentation. In fact, the primary package is a minimum package that prevents ingress of microorganisms and allows aseptic presentation at the point of use. Only intact packaging can serve as a sterile barrier.

ISO 11607 – 2 states that there needs to be a documented validation program in all healthcare facilities where medical devices are packed and sterilized. The validation has as well the goal to prove that the sealer makes a proper seal and that the sealed package can serve as a sterile barrie and that packaging perfectly works in the environment it is supposed to be used.

Responsibilities of the Manufacturer for Packaging Validation Material conformance.

The manufacturer has multiple responsibilities related to packaging validation. First of all only virgin medical-grade materials can be used. No recycled paper, or recycled plastics. The printing process shall be safe (outside of packing area), including the inks that are used to include specific contents on the packaging.

Huge importance for packaging validation standpoint is a clean environment; in this context a quality systems in place as per ISO 13485, ISO 9001, ISO 14001, ISO 22000, could further help the organization. Moreover the manufacturer shall own a declaration of conformity and studies for material compatibility, microbial properties, double pouching validation, etc.

Finally, packaging validation is directly linked with the sterilization method used. Validation of the sterilisation shall be performed and IFU and technical specifications shall be prepared accordingly.

ISO Standards related to Packaging Validation

Different standards provide official guidelines on the activities related to packaging validation. Excluding the ISO 11607-1 and 2 that we have already mentioned earlier, we have

• EN 868 (parts 2 10) related to packaging for terminally sterilised medical devices
• ISO 11140 – 1 : Sterilization of health care products — Chemical indicators — Part 1: General requirements

The Process for Packaging Validation

In principle, a documented process must be available for validation. The general strategy for packaging validation could be the standard IQ/OQ/PQ process. This process comprises:

Drafting a Validation Plan

The validation plan should contain, at least, the following details:

• Responsibilities and Competences
• Description of the packaging process
• Description of the materials /equipment
• Description of the sterilization processes
• Qualification steps (IQ, OQ, and PQ)

Installation Qualification (IQ)

The technical equipment should be properly installed, and users trained. In general, the packing processes involving sterilization sheets as well as reusable sterilization containers are purely manual processes, which is why proof of IQ is based on documentation of training of staff. It is recommended that the corresponding checklists be used to conduct installation qualification (IQ). 

Operational Qualification

In principle, a distinction must be made here between automated, and manual processes and the OQ phases varies a lot based on the subject type of packaging under validation. In general, the typical approach is to take in consideration the worst case process parameters and ensure adequate functionality of the packaging even using this worst case scenario.

Performance Qualification

During performance qualification, proof must be provided after sterilization that the process is under control, and produces optimally sealed, or closed sterile barrier systems.

Validation Report

The validation procedures and results must be documented in a summary report. The checklists, protocols, and any photographic documentation used to serve as evidence and must be enclosed in an annex to the report. The report must contain, at least, the following information:

• Validation plan
• Evidence of implementation of the validation plan (IQ, OQ, and PQ checklists completed as per Annex)
• Evaluation of the results
• Photographic documentation for manual packing processes
• Details, and explanation of any deviations from validation plan
• Formal approval of validation
• Process control, and monitoring
• Process changes, and revalidation

Approval of the Validation Documentation

Validation should be formally approved, and fully documented, by the authorized person appointed by the operator. If all validation results are not accepted, this must be documented, including an assessment of any remaining risks.

Process Control and Monitoring

The established routine tests used during the validation should be documented in the standard operating procedure. This is intended as a means of ensuring that changes in the packaging process are detected on time before they compromise the sterile barrier systems, and the requirements are no longer met. These include;

• Visual inspection
• Peelability 
• Seal integrity test
• Seal integrity indicator
• Tensile strength of seal seam
• Stepwise opening of packaging (in the case of sterilization sheets, or reusable sterilization containers).

Intervals (e.g., daily, weekly, monthly, yearly), and acceptance values must be defined for the routine tests needed, including the action to be taken if a test result is not satisfactory. The routine test results must be documented. This procedure must be set out in the quality management system.

Process Changes and Revalidation

Processes must be revalidated:

• Unscheduled revalidation,
  • in the event of changes to materials, processes, including changes to equipment, or occurring during sterilization (revalidation)
• Scheduled revalidation,
  • at regular intervals, i.e., in general after one year if no changes were made to materials, sealing process, or sterilization (performance requalification).
  • Provides evidence that the packaging process continues to be within the limits defined at the time of initial validation (IQ, OQ, and PQ). That no changes were made to materials, processes, or sterilization compared to the previous validation must be confirmed in the revalidation report. If changes are made to materials, processes, or sterilization, how such changes will affect the packaging process results must be elucidated. Based on the documented results, an individual revalidation plan must be drafted. 

Conclusions

In conclusion, we have been through the main requirements associated with the Packaging validations, and related topics. Specifically, we went through the requirements associated with ISO 11607-1, 11607-2, and GMP.

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