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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An Alternative View of the ICH Q10 Pharmaceutical Quality System (PQS)

The image below is that depicted by the International Conference of Harmonisation (ICH) Q10, Annex 2, and is supposed to depict a PQS or Pharmaceutical Quality System.

Typically, I really love the ICH. When we have to deal with outdated regulations from different global organizations it becomes a real nightmare trying to keep track of the nuances and the ICH has done a pretty good job of bringing several of the key organizations together and aligning them on how best to organize and meet the expected requirements.

That being said the diagram below and the depiction in Q10 of what a PQS should look like is greatly lacking.

Development Phases

In section 1.8 under the Quality Manual the ICH Q10 guidance states, “The description of the PQS should include: …(c) Identification of the pharmaceutical quality system processes, as well as their sequences, linkages and interdependencies.

Process maps and flow charts can be useful tools to facilitate depicting the pharmaceutical quality system processes in a visual manner”.

I completely agree.

The problem is using the graphical depiction they present in Annex 2 is completely worthless.

Basically they listed some of the PQS elements in a bar and then said they all apply to the entire product lifecycle, which simply isn’t true.

When we are in the development phase of our product lifecycle why would we do that under the change management system, or monitor process performance?


Controlling Change – No Value Add

There is no point in controlling changes for a product that is purposely being changed, nor does it offer any value to monitor the process performance for a process that has yet to be developed.

This isn’t a graphic depiction of the PQS, but rather a graphic of how they depict the lifecycle management (which also has some issues).

The PQS is the quality system and its subsystems and how they interrelate.

While it’s useful to look at how the PQS and product Lifecycle Management overlap and what elements of the PQS system are relevant at each lifecycle stage, it is not the point of the PQS, and even if that’s the end goal it’s not depicted here at all.

This image offers almost no value.

A Better Approach

So, what should this graphic look like?

While this is not a perfect view of a PQS, I would propose that the image below is a much better depiction of how the PQS should be visualized and a good place to start.

At the core of any quality system should be management. This goes back to Deming, who said, “Quality begins with the intent that is fixed by Management”.

Quality has to be rooted in the executive management team.

Define Core Quality Systems

Core quality systems then need to be defined. These are systems that impact all aspects of the business and include a Risk Management Policy, Resource Management, Document Control and CAPA systems.

All of the other subsystems, Deviations, Supplier Management, Equipment Qualifications, Validation, Material Management, etc, etc. all should be risk based or involve risk assessment, they all require resources and training, they call require documents (procedures, policies, records), and the CAPA system of course drives for process improvement regardless of the process.


All subsystems feed back into the main Management module. The subsystems listed, all are interconnected, with the exception of Post Market Systems.

The subsystems are important too, but they are farmed out to different groups and have different levels of importance depending on the stage of the product lifecycle.

Post Market Systems

The one exception is the Post Market Systems. This includes complaint management, product reviews, recall processes and other systems to support marketed products.

These generally do not interact with the other subsystems unless it is through the CAPA system or other management functions, but still utilizes all the systems under the management umbrella.

Alternate View

The PQS presented here, isn’t intended to be perfect, but I thought it was worth presenting an alternate view to the one presented by the ICH.

The ICH concept is a good one, and the ideas are fairly well laid out in the ICH, but the graphical representation of the PQS leaves a lot to be desired.

When establishing a PQS, it is better to start with something to what we’ve depicted here, and customize it as needed for the organization.


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How 21 CFR Part 11.3(7) Applies to Electronic Batch Records [Video]

When dealing with Part 11 it’s important to understand what an electronic signature actually means

The definition of electronic signatures or e-sigs can be found in 21 CFR Part 11.3(7).

Electronic Signature

An electronic signature or e-sig means a computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual’s handwritten signature.

Handwritten Signatures

We also need to understand what a handwritten signature means in the context of Part 11.
The definition of handwritten signatures can be found in 21 CFR Part 11.3(8).

Handwritten signature means the scripted name or legal mark of an individual handwritten by that individual and executed or adopted with the present intention to authenticate a writing in a permanent form.

The act of signing with a writing or marking instrument such as a pen or stylus is preserved. The scripted name or legal mark, while conventionally applied to paper, may also be applied to other devices that capture the name or mark.

Electronic Batch Records

Eric works in a Pharmaceutical company and he is responsible for the filling process of the batch been manufactured.

Each time Eric performs the filling process he has to populate a batch record with the appropriate details

After each step Eric must also fill in his signature and date to verify that he actually performed each task.

Eric is manually handwriting these details and they are legally binding to Eric.

21 CFR Part 11.3(8)

This is when 21 CFR Part 11.3(8) applies.

Fast forward 12 months and Eric’s company has implemented a brand new Manufacturing Execution System (MES) where all details around the batch manufacturing process are recorded electronically.

21 CFR Part 11.3(7)

Now when Eric performs the filling process he now populates everything electronically and signs with his username and password combination to verify that he has performed those tasks.

This is when 21 CFR Part 11.3 (7) applies.



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