Validation Tutorial - projects.ncsu.edu · Validation Tutorial ... the actual validation protocol,...

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Validation Tutorial Validation Tutorial This tutorial is designed to enhance knowledge of This tutorial is designed to enhance knowledge of biotechnological/pharmaceutical processes. The biotechnological/pharmaceutical processes. The topics covered within this tutorial will give preliminary topics covered within this tutorial will give preliminary explanations and conclusions. However, references explanations and conclusions. However, references for more in depth study will be provided. It is strongly for more in depth study will be provided. It is strongly suggested that you investigate these references. suggested that you investigate these references.

Transcript of Validation Tutorial - projects.ncsu.edu · Validation Tutorial ... the actual validation protocol,...

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Validation TutorialValidation Tutorial

This tutorial is designed to enhance knowledge of This tutorial is designed to enhance knowledge of biotechnological/pharmaceutical processes. The biotechnological/pharmaceutical processes. The

topics covered within this tutorial will give preliminary topics covered within this tutorial will give preliminary explanations and conclusions. However, references explanations and conclusions. However, references for more in depth study will be provided. It is strongly for more in depth study will be provided. It is strongly

suggested that you investigate these references.suggested that you investigate these references.

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OverviewOverview

What is Validation?What is Validation?–– This section will define validation and will put its meaning in This section will define validation and will put its meaning in

terms pertinent for a chemical engineer.terms pertinent for a chemical engineer.Food and Drug Administration (FDA) Food and Drug Administration (FDA) –– This section will explain the role of the FDA in validation and This section will explain the role of the FDA in validation and the the

guidelines it sets forth.guidelines it sets forth.Equipment ValidationEquipment Validation–– This section will explain what role unit operations equipment This section will explain what role unit operations equipment

plays in validation and why that is important.plays in validation and why that is important.Process ValidationProcess Validation–– This section will explain the implications of validation in the This section will explain the implications of validation in the

overall manufacturing process.overall manufacturing process.Applications to Facility DesignApplications to Facility Design–– This section will discuss considerations to facility design in lThis section will discuss considerations to facility design in light ight

of validation.of validation.

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What is Validation?What is Validation?

According to the Food and Drug Administration (FDA), the goal ofAccording to the Food and Drug Administration (FDA), the goal ofvalidation is to:validation is to:

““establish documented evidence which provides a high degree of establish documented evidence which provides a high degree of assurance that a specific process will consistently produce a assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality product meeting its predetermined specifications and quality attributes.attributes.”” [1][1]

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What is Validation?What is Validation?

What does this mean?What does this mean?–– An quantitative approach is needed to prove quality, An quantitative approach is needed to prove quality,

functionality, and performance of a functionality, and performance of a pharmaceutical/biotechnological manufacturing process.pharmaceutical/biotechnological manufacturing process.

–– This approach will be applied to individual pieces of equipment This approach will be applied to individual pieces of equipment as well as the manufacturing process as a whole.as well as the manufacturing process as a whole.

–– Guidelines for validation are set by the FDA, but the specifics Guidelines for validation are set by the FDA, but the specifics of of validation are determined by the pharmaceutical/biotech validation are determined by the pharmaceutical/biotech company.company.

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What is Validation?What is Validation?

Phases of ValidationPhases of Validation–– Validation is broken down into three phases:Validation is broken down into three phases:

Installation Qualification (IQ)Installation Qualification (IQ)Operational Qualification (OQ)Operational Qualification (OQ)Performance Qualification (PQ)Performance Qualification (PQ)

–– These three protocols are used to define tests that will These three protocols are used to define tests that will demonstrate that the process consistently and repeatedly demonstrate that the process consistently and repeatedly produces the desired productproduces the desired product..

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What is Validation?What is Validation?

Installation Qualification (IQ)Installation Qualification (IQ)–– This is the first step in validation.This is the first step in validation.

–– This protocol insures that the system/equipment and its This protocol insures that the system/equipment and its components are installed correctly and to the original components are installed correctly and to the original manufacturer’s specifications.manufacturer’s specifications.

–– Calibration of major equipment, accessory equipment, and/or Calibration of major equipment, accessory equipment, and/or utilities should be performed in this step as well.utilities should be performed in this step as well.

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What is Validation?What is Validation?

Operational Qualification (OQ)Operational Qualification (OQ)–– This step proceeds after the IQ has been performed.This step proceeds after the IQ has been performed.

–– In the OQ, tests are performed on the critical parameters of theIn the OQ, tests are performed on the critical parameters of thesystem/process. These are usually the independent and/or system/process. These are usually the independent and/or manipulated variables associated with the system/equipment.manipulated variables associated with the system/equipment.

–– All tests’ data and measurements must be documented in order All tests’ data and measurements must be documented in order to set a baseline for the system/equipment.to set a baseline for the system/equipment.

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What is Validation?What is Validation?

Performance Qualification (PQ)Performance Qualification (PQ)–– This is the third and final phase of validation.This is the third and final phase of validation.

–– This phase tests the ability of the process to perform over longThis phase tests the ability of the process to perform over longperiods of time within tolerance deemed acceptable. periods of time within tolerance deemed acceptable.

–– PQ is performed on the manufacturing process as a whole. PQ is performed on the manufacturing process as a whole. Individual components of the system are not tested individually.Individual components of the system are not tested individually.

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What is Validation?What is Validation?

An example validation protocol can be seen here: An example validation protocol can be seen here: sample validation sample validation protocolprotocol..

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FDAFDA

The FDA is a federal scienceThe FDA is a federal science--based law enforcement agency based law enforcement agency mandated to protect public health.mandated to protect public health.

The validation process is regulated by the guidelines and restriThe validation process is regulated by the guidelines and restrictions ctions set forth by the FDA. However, the actual validation protocol, set forth by the FDA. However, the actual validation protocol, documentation, and execution is the responsibility of the documentation, and execution is the responsibility of the manufacturer. More specifically, this is the responsibility of manufacturer. More specifically, this is the responsibility of the the engineer. engineer.

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FDAFDA

Code of Federal Regulations (CFR)Code of Federal Regulations (CFR)–– This is the body of regulations, created by the US government, This is the body of regulations, created by the US government,

that sets forth the guidelines pertaining to food and drugs.that sets forth the guidelines pertaining to food and drugs.

–– 21 CFR Part 210 21 CFR Part 210 concerns current good manufacturing practice concerns current good manufacturing practice in manufacturing, processing, packing, or holding of drugs.in manufacturing, processing, packing, or holding of drugs.

–– 21 CFR Part 211 concerns current good manufacturing practice 21 CFR Part 211 concerns current good manufacturing practice for finished pharmaceuticals for finished pharmaceuticals

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FDAFDA

–– 21 CFR Part 600 pertains to the safe production of biological 21 CFR Part 600 pertains to the safe production of biological derived products.derived products.

–– 21 CFR Part 610 pertains to the safe distribution of biological21 CFR Part 610 pertains to the safe distribution of biologically ly derived products.derived products.

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Equipment ValidationEquipment Validation

As mentioned earlier, each piece of must be validated in order tAs mentioned earlier, each piece of must be validated in order to o legally operate within the facility.legally operate within the facility.

The goal is to produce consistent results with minimal variationThe goal is to produce consistent results with minimal variationwithout compromising the integrity of the product and the personwithout compromising the integrity of the product and the persons s operating the equipment.operating the equipment.

A plan of validation should be drafted and executed by engineersA plan of validation should be drafted and executed by engineers in in order to satisfy guidelines. The validation plan generally consiorder to satisfy guidelines. The validation plan generally consists of sts of IQ and OQ sections.IQ and OQ sections.

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Equipment ValidationEquipment Validation

Any major equipment changes after the initial validation will reAny major equipment changes after the initial validation will result in sult in the need for subsequent revalidation.the need for subsequent revalidation.

In the end, equipment validation will create specification rangeIn the end, equipment validation will create specification ranges and s and tolerances that will be applied to the normal operation of equiptolerances that will be applied to the normal operation of equipment.ment.

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Process ValidationProcess Validation

The manufacturing process, in addition to the individual equipmeThe manufacturing process, in addition to the individual equipment, nt, must be validated.must be validated.

The goal is to create a robust manufacturing process that The goal is to create a robust manufacturing process that consistently produces a drug product with minimal variation thatconsistently produces a drug product with minimal variation thatadheres to quality criteria of purity, identity, and potency.adheres to quality criteria of purity, identity, and potency.

A validation plan for the manufacturing process should be drafteA validation plan for the manufacturing process should be drafted d and executed by engineers in order to satisfy guidelines. The and executed by engineers in order to satisfy guidelines. The validation plan usually involves just a PQ section.validation plan usually involves just a PQ section.

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Process ValidationProcess Validation

Just as equipment validation, major changes after the initial Just as equipment validation, major changes after the initial validation will result in the need for subsequent revalidation.validation will result in the need for subsequent revalidation.

In the end, process validation will ensure aIn the end, process validation will ensure a robust product that is robust product that is highly reproducible over timehighly reproducible over time..

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Applications to Facility DesignApplications to Facility Design

Facilities should be designed in order to facilitate any changesFacilities should be designed in order to facilitate any changes that that may arise after initial validation.may arise after initial validation.

In the case of retrofitting, current facilities services (WFI, CIn the case of retrofitting, current facilities services (WFI, CIP, SIP, IP, SIP, HVAC, etc.), equipment, and instrumentation should be assessed HVAC, etc.), equipment, and instrumentation should be assessed for revalidation. This assessment will be based on age of the for revalidation. This assessment will be based on age of the individual system and the needs of the new process. individual system and the needs of the new process.

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ResourcesResources

[1] [1] www.fda.govwww.fda.gov–– 21 CFR Part 210: 21 CFR Part 210:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearchttp://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRParh.cfm?CFRPart=210&showFR=1t=210&showFR=1

–– 21 CFR Part 211: 21 CFR Part 211: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearchttp://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRParh.cfm?CFRPart=211&showFR=1t=211&showFR=1

–– 21 CFR Part 600: 21 CFR Part 600: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearchttp://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRParh.cfm?CFRPart=600&showFR=1t=600&showFR=1

–– 21 CFR Part 610: 21 CFR Part 610: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearchttp://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRParh.cfm?CFRPart=610&showFR=1t=610&showFR=1

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ResourcesResources

[2] [2] www.validationworld.comwww.validationworld.com–– Information concerning IQ: Information concerning IQ: http://www.cqionline.com/knowledge/iq.htmlhttp://www.cqionline.com/knowledge/iq.html–– Information concerning OQ: Information concerning OQ: http://www.cqionline.com/knowledge/oq.htmlhttp://www.cqionline.com/knowledge/oq.html–– Information concerning PQ: Information concerning PQ: http://www.cqionline.com/knowledge/pq.htmlhttp://www.cqionline.com/knowledge/pq.html

[3] Patricia Stewart[3] Patricia Stewart--Flaherty. Performance Validation. Presentation. 13 Apr. Flaherty. Performance Validation. Presentation. 13 Apr. 2003.2003.

[4] Sofer, Gail and Zabriskie, Dane W., ed. [4] Sofer, Gail and Zabriskie, Dane W., ed. Biopharmaceutical Process Biopharmaceutical Process ValidationValidation. New York: Marcel Dekker, 2000.. New York: Marcel Dekker, 2000.

[4] Avis, Kenneth E., Wagner, Carmen M., Wu, Vincent L., ed. [4] Avis, Kenneth E., Wagner, Carmen M., Wu, Vincent L., ed. Biotechnology: Quality Assurance and ValidationBiotechnology: Quality Assurance and Validation. Buffalo Grove, Illinois: . Buffalo Grove, Illinois: Interpharm Press, Inc., 1999.Interpharm Press, Inc., 1999.

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ResourcesResources

[5] Carleton, Fredrick J. and Agalloco James P. ed. [5] Carleton, Fredrick J. and Agalloco James P. ed. Validation of Validation of Pharmaceutical ProcessesPharmaceutical Processes. New York: Marcel . New York: Marcel DekkerDekker, Inc., 1999., Inc., 1999.