Packaging Validation – A Simple Example

Once upon a time, a company decided to improve their packaging sealing process. They selected equipment with a new technology that would process more products in less time with improved seal characteristics. The equipment was specified and approved.

A qualification project team was formed and prepared a validation project plan that described how the revised processes would be developed and tested, how the equipment would be evaluated, its short term capability assessed, how the entire process would be revalidated, and who will be responsible for testing.

Installation Qualification

Installation Qualification (IQ) protocol and report were prepared and approved. These documents established that the installation conformed to the manufacturer’s recommendations. It included things like:

  • Wiring and Electrical Checks
  • Basic Functionality Tests
  • Confirmation of the Drawing against the Actual Equipment
  • Environmental Conditions
  • Safety and Ergonomic Assessment

After completing the IQ, the qualification project team established a maintenance program, which involved quarterly checks of the motor, the rotary belts, and lubrication of the parts. They also established the calibration program, which involved a semi-annual check of the pressure gauges and temperature indicators against calibration standards. PM and calibration documents were created and routed for approval. After the IQ report was approved, the equipment was then logged into the Change Control program. Now any time a change is being considered for the equipment, it must be formally documented and assessed for its impact on the state of qualification.

Operational Qualification

The operational Qualification (OQ) was planned and documented in an OQ protocol. The qualification project team performed a risk analysis. The equipment was fully tested to ensure it performed as expected. Equipment controls were exercised over their specified operating ranges. The related operating characteristics including heat distribution in sealing zone and time to reach uniform temperature were measured and established. The qualification project team verified that the equipment operated in a stable and safe manner.

The heat-sealing process was developed. A desired seal strength was identified through experiments conducted on the equipment; using representative product to determine what process settings resulted in the desired seal strength. Raw data was recorded on data sheets, and reviewed by independent reviewers to confirm that accepted good documentation practices (GDP) were followed.

Worse case operating conditions, the ranges of process parameters and associated conditions that resulted in acceptable product, were defined. Operating procedures with the new process parameters and operating instructions were prepared and approved.

The qualification project team and the operations staff were trained. The training was documented.

Performance Qualification

A performance qualification (PQ) was written and approved. The key characteristic was seal strength. The acceptance criteria were detailed for all evaluations/testing. Sampling plans based on statistical rationale providing confidence in the results detailed how many samples would be collected and at what times. For heat-seal strength, the plan was to collect two samples every five minutes from the beginning and end of each three hour run.

One of the two samples would be tested. The other would be retained in case the first was spoiled or an investigation was necessary. Process controls were set at midpoint for each of the three PQ runs.

Prior to the execution of the approved PQ protocol, the packaging engineer needed to make a change to one of the PQ tests. An amendment to the PQ protocol was prepared and approved by the same approvers of the PQ protocol before execution.


During the heat-seal strength test, the tester did not follow the required 10 minute ambient exposure time for test sample preparation prior to testing. A deviation report was prepared to document the deviation. It described the deviation and the impact and resolution. Also, some samples from the second run were accidentally dropped on the way to the lab. An exceptional condition / exception report was prepared to document this unexpected incident. It described how they were spoiled and defended statistically that the missing samples would have minimal effect on the conclusions of the qualification results. The deviations and exceptional conditions reports were attached to the PQ report for approval.

PQ Report

The PQ report summarized the validation activities, listed all the deviations and exceptional conditions/exception. All acceptance criteria were met. The PQ report provided a conclusion that the modified process met or exceeded product and process specifications. The approval authority approved the PQ report. There was no need to update the risk analysis document, as there no open issues or new risks at the end of the PQ.

Design validation was not required, the product specification were not changed. It would not be necessary to repeat clinical trials.


  • wafaa

    procss validation packing not cover all type such injection,solution and cream

  • wafaa

    procss validation packing not cover all type such injection,solution and cream

  • Willo

    How was the acceptance criteria for seal strenght developed. Please explain the method used and how the values were obtained. In addition, please let me know how the Heat Seal Process was characterized.

  • Willo

    How was the acceptance criteria for seal strenght developed. Please explain the method used and how the values were obtained. In addition, please let me know how the Heat Seal Process was characterized.

  • ME Walk

    How was the acceptance criteria for seal strenght developed. Please explain the method used and how the values were obtained. In addition, please let me know how the Heat Seal Process was characterized.?


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The Difference Between Qualification and Validation [Video]

There is a general saying within the life sciences:

“We qualify a system and/or equipment and validate a process”

A system and/or equipment must be qualified to operate in a validated process.

For example:

“You qualify an autoclave, whereas you validate a sterilization process”

Manufacturers should identify what validation and qualification work is done. All systems, equipment, processes, procedures should be reviewed and the manufacturer should decide what qualification and validation work needs to be performed.

Direct, Indirect or No Impact

All facility areas, utilities and process equipment must be assessed and classified as direct impact, indirect impact or no impact following an analysis of their impact on the identity, strength, quality, purity or safety of products manufactured at the facility and also the safety of the operators & environment.

Impact on Quality

Each system or item of equipment having direct or indirect impact on the product quality must be validated. The extent of validation or qualification should be determined by performing the risk assessment of that particular system or equipment.

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The Difference Between Prospective, Concurrent and Retrospective Validation

Unless you’re starting a new company you will need to plan on a variety of approaches.

Prospective validation occurs before the system is used in production, concurrent validation occurs simultaneously with production, and retrospective validation occurs after production use has occurred.

In this article we will discuss all three and also discuss the role the master validation plan (MVP) performs for each one.

1. Prospective Validation

Prospective validation is establishing documented evidence, prior to process implementation, that a system performs as is intended, based on pre-planned protocols.

This is the preferred approach.

Production is not started until all validation activities are completed.

The MVP need not go into much detail about this approach since it’s the standard method, however, prospective validation follows a step wise process illustrated here.

The process commences with the development of a Validation Plan and then passes through the DQ, RA, IQ, OQ and PQ phases after which process, computer, analytical and cleaning validations are performed which are followed by a final report.

After which the instrument or equipment will be subject to preventative maintenance and requalification on a routine basis.

Periodic Basis

On a periodic basis all instrumentation and equipment should be reviewed. This review is intended to identify any gaps which may have developed between the time it was last qualified and current requirements.

If any gaps are identified a remediation plan will be developed and the process will start again.


The MVP may need to describe what is done with product produced during prospective validation. Typically, it is either scrapped or marked not for use or sale.

The product may be suitable for additional engineering testing or demonstrations, but appropriate efforts need to be made to ensure this product does not enter the supply chain.

Ideally, all validation is done prospectively; i.e., the system is validated before use. However, there are cases and conditions which may prevent this.

2. Concurrent Validation

Concurrent validation is used to establish documented evidence that a facility and process will perform as they are intended, based on information generated during actual use of the process.

In exceptional circumstances (for example, in a case of immediate and urgent public health need) validation may need to be conducted in parallel with routine production. The MVP needs to define how product is managed throughout the process.

Typically, the product batches are quarantined until they can be demonstrated (QC analysis) to meet specifications.

The Right Decision?

The decision to perform concurrent validation should not be made in a vacuum. All stakeholders including management, Quality Assurance and the government regulatory agencies should all agree that concurrent validation is an acceptable approach for the system under consideration.

As always the principal requirement is patient safety is not compromised. The rationale to conduct concurrent validation should be documented along with the agreement to do so by all the stakeholders. This can be part of the Validation Plan or documented as a deviation.

The Process

The concurrent validation process is identical to that of prospective validation. The process starts with the development of a Validation Plan, followed by the DQ, RA, IQ, OQ and PQ phases after which process, computer, analytical and cleaning validations are performed, ending with a final report.

Again, routine preventative maintenance, requalification and periodic review are performed.

3. Retrospective Validation

Retrospective validation is validating a system that has been operating for some time. There are various schools of thought on how to approach retrospective validation. Some may feel that a full-blown validation is required to assure the system is functioning properly.

Others may feel that since the system has been in use, presumably without issues, validation is not necessary and a memo to file justifying why validation is not necessary may be issued.

Doing a full validation may not be required, since you already have proof that the system functions as required – at least in the situations in which production was conducted. Doing nothing, though, is a risk.

It’s likely that the controls haven’t been challenged so there may be some hidden flaws that haven’t been identified that could lead to non-conforming product, hazardous operating conditions, extended delays, etc.

Historical Data

Historical data can certainly be used to support validation. For example, if there is detailed and statistically-significant evidence that production runs are well controlled you could rationalize and justify not doing full validation.

During retrospective validation, it’s advisable that existing product be quarantined, and production put on hold until validation is complete.

As an exception, producing product as part of the validation exercise would follow concurrent validation. This may not be practical since product may have already been distributed, but caution is advised for the reasons outlined.

General Process

The general process for retrospective validation follows the same process as for prospective and concurrent validation except DQ is seldom performed, as the system has already been in use for some time.

Instead a survey and review of available information is performed. This normally occurs before the validation plan is created.

The MVP should also provide guidance on managing inventory during retrospective validation.

One Major Issue

One potential major problem that can occur with retrospective validation the determination of what action should be taken if an issue is found with the system during retrospective validation?

As with everything else, a risk-based decision is warranted. This could be anything from product recall, to customer notifications, to just documenting the justification of the decision why nothing was done.

Again, the MVP should provide guidance on dealing with situations concerning out of specification conditions revealed during retrospective validation, which should also definitely include involving regulatory support.



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