What is Validation?

Validation is "that part of GMP (Good Manufacturing Practices) that ensures that facility systems, equipment, processes, and test procedures are in control and therefore consistently produce quality product" (World Health Organization). Validation is "the documented act of demonstrating that any procedure, process, and activity will consistently lead to the expected results" (Health Canada).

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The Canadian GMP, Division 2, Part C of the Food and Drug Regulations require that:

• All critical production processes be validated.
• Validation studies are conducted in accordance with pre-defined protocols. Written reports summarizing recorded results and conclusions are prepared, evaluated, approved and maintained.
• Changes to production processes, operating parameters, equipment or materials that may affect product quality and/or the reproducibility of the process are also validated prior to implementation.

Importers and distributors of drug products are expected to have documented evidence that their vendors (e.g., fabricators) meet validation requirements.

The first step is to determine the type(s) of validation required and the scope of this validation. We can help you identify your needs using The Validation Gap Analysis™. From the information gathered in this activity, we can develop a project plan that includes actions (validation initiatives) with targeted completion dates for the core components. It will:

• Provide a detailed long-term roadmap to compliance
• Prioritize validation activities
• Work as a communication tool for all parties involved

	What is a Validation Master Plan?

Once your validation needs have been established, you need to form your Validation Team and develop a Validation Master Plan, "an approved written plan of objectives and actions stating how and when a company will achieve compliance with the GMP requirements regarding validation" (Health Canada). This plan outlines your validation activities - how you plan to demonstrate that your procedures, processes, and activities will consistently lead to the expected results.

As a member of your multi-disciplinary Validation Team, we can conduct and/or supervise validation studies. Our associates are qualified by training and experience to excel in this capacity. We can help you develop your Validation Master Plan in a timely manner using either your company format or Quality & Compliance's template. We can interface with management to establish an approach that is agreeable to all parties.

	What is Protocol?

Your validation plan will include references to a number of protocols. A Protocol is a written plan of actions stating how the validation will be conducted; among other things, it includes who will do the testing, what specifications need to be met, sampling plans, testing methods, product characteristics, equipment to be used, and the minimum number of batches to be used for the study.

Validation plans and protocols are controlled documents that must be numbered, signed, and dated; any modifications must be documented through a change control process.

Confused yet?  See our

Validation Project Map for an overview.

	What is Process Validation?

Validation studies for processes and equipment are interconnected. Process Validation demonstrates the suitability and reproducibility of a whole process such as making product or maintaining refrigerated storage space. Qualification (of equipment or facility systems) is part of this validation. For example, when

validating a refrigeration process (process validation), you need to qualify the refrigeration units (equipment qualification). Equipment qualification is completed prior to process validation to ensure the final result of the process validation study is not impacted by poorly functioning equipment.

	What is Equipment Qualification?

Equipment Qualification is a validation study that establishes with confidence that the critical process equipment and ancillary systems are capable of consistently operating within established limits and tolerances. The studies must include equipment specifications and the following protocols:

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• Installation Qualification (IQ) - to demonstrate that process equipment and ancillary systems are appropriately selected and correctly installed.
• Operational Qualification (OQ) - to demonstrate that process equipment and ancillary systems work correctly and operate consistently in accordance with established specifications.
• Performance Qualification (PQ) - sampling and testing at various stages on process equipment and ancillary systems to ensure equipment specifications are met.

Equipment qualification should simulate actual production conditions,
including "worst case" (stressed) conditions. In some cases,
a combined IQ/OQ may be sufficient.

	What is Process Qualification?

Process Validation studies are conducted on a process using qualified equipment. Sampling and testing at various stages of the manufacturing process is performed to ensure product specifications are met. This is called Process Qualification.

Ideally, Process Validation is conducted prior to commercial distribution of a new product or a product made under a significantly modified process (Prospective Validation). Where this is not possible, it may be necessary to validate processes during routine production (Concurrent Validation). Processes that have been in use for some time without any significant changes may be validated according to an approved protocol (Retrospective Validation).

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Quality & Compliance can write your protocols and execute them if desired. Alternately, if you wish, we can work with your staff and guide them through
the execution phase. Our associates work well independently or as
part of a team.

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All validation work should be carried out in a structured way in accordance with documented standard operating procedures (SOPs). We can provide assistance in writing supporting SOPs that satisfy regulatory requirements and meet your company's unique needs. These SOPs will include, as applicable:

Equipment/Production Lines: • Operation • Start-up/Shut down • Changeover Cleaning Maintenance

Shipping and receiving Temperature monitoring/excursions Calibration of monitoring devices Alarm incident/ alarm testing

For further information about writing SOPs, go to our
Technical Writing Services page.

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To summarize the validation process, at various stages in a validation exercise there is a need for protocols, documentation, procedures, equipment, specifications, and acceptance criteria for test results. All of these need to be reviewed, checked, and authorized. Quality & Compliance associates can work with the various disciplines (Engineering, Research and Development, Manufacturing, Quality Control and Quality Assurance) to ensure everyone performs their part to move the validation study forward to successful completion.

Once your systems are fully validated, you are required to maintain them in a validated state. You must review all processes frequently to ensure there are no changes, deviations, failures, or modifications to the production process, and that all SOPs have been followed, including Change Control procedures. Your validation team monitors these to ensure there are no changes/deviations that require Re-qualification or Re-validation.

For more information, Health Canada has produced a guidance document,
Validation Guidelines for Pharmaceutical Dosage Forms (GUIDE-0029),
which outlines the requirements for validation.

	What is Temperature Mapping?

Temperature mapping is one of many tests used to qualify a facility or storage unit (e.g., warehouse, freezer, shipping container, etc.) where temperature must be controlled. Temperature control is a 'hot' topic with Health Canada. In fact, they recently published a guidance document to address this issue. See our Temperature Control Quick Note for more information about these guidelines. Quite simply, you must be able to ensure appropriate storage and transportation conditions are met throughout your GMP activities from the point of manufacture to the final distribution point. How do you achieve this? By validating your processes.

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If you transport temperature-sensitive product, we can help you prove your product is not exposed to temperatures or humidity levels outside its recommended storage conditions through Shipping Validation. We can perform:

• Packing configuration temperature mapping studies
• Shipping configuration temperature mapping studies
• Qualification of single-use monitoring devices/data loggers

If you transport temperature-sensitive product, we can help you prove your product is not exposed to temperatures or humidity levels outside its recommended storage conditions through Shipping Validation. We can perform:

• Temperature mapping studies
• Temperature monitoring
• Temperature alarm/excursion process/procedures
• Equipment Installation/Operational Qualification (IOQ) for refrigerators, freezers, etc., including:
  • Documentation/procedures
  • Functionality testing
  • Temperature mapping studies
  • Instrument calibration
  • Alarm function challenges
  • Open door tests
  • Power failure tests