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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.
Overview
Overview
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 Validation Equipment 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 Validation Process 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 Design Applications to Facility Design
This section will discuss considerations to facility design in l This section will discuss considerations to facility design in light ight
of validation. of validation.
What is Validation?
What is Validation?
According to the Food and Drug Administration (FDA), the goal of According to the Food and Drug Administration (FDA), the goal of
validation 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]
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.
What is Validation?
What is Validation?
Phases of Validation Phases 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 product produces the desired product
.
.
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
manufacturers specifications. manufacturers 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.
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 the In the OQ, tests are performed on the critical parameters of the
system/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.
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 long This phase tests the ability of the process to perform over long
periods 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.
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
protocol protocol. .
FDA
FDA
The FDA is a federal science The 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 restri The 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.
FDA
FDA
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
FDA
FDA
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 biological 21 CFR Part 610 pertains to the safe distribution of biologically ly
derived products. derived products.
Equipment Validation
Equipment Validation
As mentioned earlier, each piece of must be validated in order t As 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 variation The goal is to produce consistent results with minimal variation
without compromising the integrity of the product and the person without 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 engineers A plan of validation should be drafted and executed by engineers in in
order to satisfy guidelines. The validation plan generally consi order to satisfy guidelines. The validation plan generally consists of sts of
IQ and OQ sections. IQ and OQ sections.
Equipment Validation
Equipment Validation
Any major equipment changes after the initial validation will re Any 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 range In the end, equipment validation will create specification ranges and s and
tolerances that will be applied to the normal operation of equip tolerances that will be applied to the normal operation of equipment. ment.
Process Validation
Process Validation
The manufacturing process, in addition to the individual equipme The 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 that consistently produces a drug product with minimal variation that
adheres 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 drafte A 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.
Process Validation
Process 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 a In the end, process validation will ensure a robust product that is robust product that is
highly reproducible over time highly reproducible over time. .
Applications to Facility Design
Applications to Facility Design
Facilities should be designed in order to facilitate any changes Facilities 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, C In 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.
Resources
Resources
[1] [1] www.fda.gov www.fda.gov
21 CFR Part 210: 21 CFR Part 210:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearc http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPar h.cfm?CFRPar
t=210&showFR=1 t=210&showFR=1
21 CFR Part 211: 21 CFR Part 211:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearc http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPar h.cfm?CFRPar
t=211&showFR=1 t=211&showFR=1
21 CFR Part 600: 21 CFR Part 600:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearc http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPar h.cfm?CFRPar
t=600&showFR=1 t=600&showFR=1
21 CFR Part 610: 21 CFR Part 610:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearc http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPar h.cfm?CFRPar
t=610&showFR=1 t=610&showFR=1
Resources
Resources
[2] [2] www.validationworld.com www.validationworld.com
Information concerning IQ: Information concerning IQ: http://www.cqionline.com/knowledge/iq.html http://www.cqionline.com/knowledge/iq.html
Information concerning OQ: Information concerning OQ: http://www.cqionline.com/knowledge/oq.html http://www.cqionline.com/knowledge/oq.html
Information concerning PQ: Information concerning PQ: http://www.cqionline.com/knowledge/pq.html http://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
Validation Validation. 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 Validation Biotechnology: Quality Assurance and Validation. Buffalo Grove, Illinois: . Buffalo Grove, Illinois:
Interpharm Press, Inc., 1999. Interpharm Press, Inc., 1999.
Resources
Resources
[5] Carleton, Fredrick J. and Agalloco James P. ed. [5] Carleton, Fredrick J. and Agalloco James P. ed. Validation of Validation of
Pharmaceutical Processes Pharmaceutical Processes. New York: Marcel . New York: Marcel Dekker Dekker, Inc., 1999. , Inc., 1999.