1.What is Validation and Why do you Validate ?

Validation is a Quality Assurance process. It strives to establish evidence that

provides a high degree of assurance that a product accomplishes its intended
requirements consistently.

Basic principle of Quality Assurance is the product should be built in with quality
,safety and efficacy( effectiveness)which cannot be tested or inspected so process
validation is the key element in ensuring these Quality Assurance requirements are
met.

a. To meet User Requirements Specification.

b. To meet scientific evidence that a process is capable of consistently

delivering quality product
c. Validation is required by law within the life science industry.
d. If a company is a medical device company and it does not validate the process it
is deemed a criminal act so a medical device manufacturer who does not validate a
process will not get permission to manufacture or sell their product in the market
place.
e. If a customer knows that a process is validated then that have a good assurance
that each product is consistently meet user requirement specification. Happy
customer repeats business.

If the Output cannot be verified we redesign the process or we Validate.

Key elements of Process Validation

a. Verifying the equipment is installed and operating correctly.
b. Developing a process that can produce product to meet specifications.
c. Verifying that the process can produce product and give results that meet
specifications consistently over time.

2. What is Verification?
Verification is a quality control process . It is used to evaluate whether or not a
product complies with specifications. verification is comparing conformity to a
defined specification. An example of verification in medical device industry would
be measuring the distance between the marker bands on a catheter. This can be done
in medical device industry by using a smart scope software , this can confirm if
the measurement matches the specification. If you cannot verify the output then you
must validate.

In medical device industry bonding is utilized to join parts together, this can be
done with adhesives or bonding heat. The only way to verify the strength of the
bond would be a destructive test so we must Validate the process.

DESIGN VERIFICATION MUST BE SUCCESFULLY COMPLETED BEFORE PROCESS VALIDATION

COMMENCE.

what do you know about FDA Regulations?

A. FDA (THE FOOD AND DRUG ADMINISTRATION) has a stringent guidelines for medical
device testing and validation including 21CFR PART 820 for quality system
regulations(QSR)
2. How do you design a validation plan?
A. I start by understanding the User Requirements and regulatory standards.
3.validation and verification
validation is a quality assurance process which aims to meet the customer needs
and expectations.
verification is a quality control process which aims to meet design specified
requirements and development specifications.
5 Stages of Validation Process
1. User Requirement Specification(URS)
2. Design Qualification(DQ)
3. Installation Qualification(IQ)
4.Operational Qualification(OP)
5. Performance Qualification.(PQ)

1.URS

THE PRODUCT USER REQUIREMENT SPECIFICATION AND PRODUCT FUNCTIONAL SPECIFICATION

WILL LEAD TO DESIGN INPUT OF THE PRODUCT.
The Product Design will have
1.Design Input
2.Design process
3.Design Output
These three steps will create the Design of the Product. The Design will be
Verified and Validated
Design verification is done before the validation process commences.
Design Validation can be done during the performance qualification stage

2.Design Qualification

is to verify that the process has been designed to meet URS and FRS and meet CGMP
Current Good Manufacturing Practices and wants to meet the Regulatory Requirements
or the standards of the industry.
design qualification can be defined as document review of the Design and is the
only document that is going to confirm that this design will work.
Design Qualification will ensure correct equipment is chosen to meet the process
validation requirements.
It will ensure the utilities will be able to satisfy the process validation.
1.clean room
2.heat ventilation
3.air conditioning system
4.water supply.
5.power supply.

3. Installation Qualification

IQ is a systematic check of all installed components against equipment suppliers

specifications and against any specific criteria set out in the URS.
It is important to confirm that the equipment complies with URS/FS.

IQ will Establish Design features

Installation conditions like wiring ,utilities, venting
environmental conditions
calibration, PM and cleaning schedules
safety features
all supplier documentation, prints, drawings and manuals
software documentation
spare parts list
supplier manuals
Piping and instrumentation diagram should be updated at this point(graphical
representation of the physical flow in designing manufacturing process)
All gauges and other parts should be given serial numbers which are recorded by the
engineering department.

FACTORTY ACCEPTANCE TEST (FAT) and SITE ACCEPTANCE TEST(SAT) can form a part of
Installation Qualification plan.
The equipment verification vs user requirement specification and functional
specification is performed at suppliers factory.
It gives the opportunity to the buyer to confirm the suitability of the equipment
or utility before delivery to buyer's site.
SIT is once the equipment has been delivered the equipment verification vs user
requirement specification and functional specification is performed.

It is important to confirm that the equipment complies with URS/FS.

4. OPERATIONAL QUALIFICATION (OQ)

OQ determines whether the process is capable

All the items in the test plan are tested individually and their performance is
documented. This is a prerequisite for technical acceptance of the equipment and
can only be performed once the IQ has been successful. This will form the basis for
sustaining manufacturing.

OQ will establish Process Control Limits and Action Levels and what input
parameters create the desired output
control limits= (eg: time, temperature, pressure, line speed)
Action levels = give a warning that the input process parameters may be going out
of control and action need to be taken to control the input process parameter by
the validation engineer
The main output achieved in OQ is to establish the upper control limit and lower
control limit of process input parameters.
The outputs that can be achieved from an operational qualification is
manufacturing materials specifications, raw material specification. component
specifications ,standard operating procedures, material handling requirement
procedures and training operating procedures.

5.PERFORMANCE QUALIFICATION (PQ):

This stage may be called as PPQ Process Performance Qualification.

Before the qualification begins, a detailed test plan is created based on the
process description. PQ is to verify that the system performance satisfies the
performance requirements including the user requirements specifications. PQ is best
carried out by the people who will use the equipment/system routinely.

Rather than testing each instrument individually, the process is together tested as
part of an overall process.
This stage is the final step in qualification process for equipment and this step
involves verifying and documenting that the equipment is working reproducibly
within a specified working range.

The main output of performance qualification is proving that the process is

capable and in control.
stress levels chosen should be within regulatory limits. Three possible runs are
required to approve.

PQ is the final QC test to be carried out. same as routine QC tests but at a higher
sampling frequency
THE PROCESS WILL HAVE A VARIATION AND THE GOAL IS TO CONTROL THE VARIATION

Process data and product data should be analyzed to determine what the normal range
of variation is for the process output and is in control. One of the outputs of OQ
and PQ is the
development of attributes for continuous monitoring and maintenance. This will
enable process stability.
if the process behaves consistently over time, then we say that the process is
stable or in control.

P The Attributes here are

1.Accuracy ----The Measurement system error which is closeness to the true value
2.Precision---consistent measurements when repeat under same conditions. High
precision is repeated measurements close to each other even if they are not close
to true value.
3.Repeatability
4.robustness----how well equipment performs under challenging conditions like
change in environmental conditions, inputs.
5.response time
6.Alarm Systems

variables are
1. Time
2. Pressure
3. Temperature
4. Material

PROCESS VALIDATION IS CONSIDERED AS DESIGN TRANSFER ACTIVITIES, ASSURES THAT DESIGN

SPECIFICATIONS CAN BE REPRODUCED BY THE MANUFACTURING PROCESS.
(PQ)PERFORMANCE QUALIFICATION PHASE OF PROCESS VALIDATION CAN BE USED FOR DESIGN
VALIDATION.

PROCESS CAPABILITY

we know the process can be adjusted to realize the required levels of performance
this assurance is described as standard process capability indices.
The process will have a variation and the goal is to control the variation.
one of the outputs of OQ and PQ is the development of process input parameters and
continuous monitoring and maintenance of these process input parameters can assure
the PROCESS CAPABILITY.

We develop the process input parameters to stay within an upper and lower control
limit, if this happens we can assure our output will meet customer requirements.

The two main process capability indices are CP and CPK values. These can be
measured to see if the process is in control

Process Capability ratio is the measure of variance. Higher the Cp Value, the less
variation in the process.
Cp = Upper specification limit- Lower specification limit
---------------------------------------------------
6 sigma(standard deviation)

Cp>=1.33 variation is less and process is in control and there is room for
improvement
Cp>2 variation is minimum. process is in good control and needs monitoring.
Cpk is the variation in Centering

Action Limits are values that trigger action on the process parameter to prevent
it from exceeding the process control limits. This part of process validation takes
place in OQ

D O E: Design of Experiments

Helps to develop the capability of the process

Its is a technique where we manipulate the process to observe the interactions

between its variables and the results.
we manipulate the process input parameters in order to achieve our desired output.

Risk Management
risk management fits in process validation

Design Validation is meeting the device specifications as per the user needs this
is also a part of performance qualification

ISO13485 is the standard that is used to prove a medical device is safe and
effective to market in regions such as Europe

ISO14971 Standard Risk Management

product realization = creating the product from design to manufacture.

product produced during performance qualification can be used to validate the
design of the product.
The Risk Traceability summary can be used as feedback mechanism to make changes in
the input of the design of the product

Risk Management is a part of DESIGN VALIDATION PROCESS

If the Risk Management during Design Validation Process creates an action, this
will have a impact on Validation of the Manufacturing Process.
so Risk Management needs to be a part of Quality Management System

Life Cycle of Product

Design and Development------

RISK ASSESSMENT AND RISK CONTROL
Process Validation------------

Production-----------------------------
PRODUCTION INFORMATION
Pick , Pack and Ship------------------- (RISK MANAGEMENT)

Warehouse--------

Activate--------POST PRODUCTION INFORMATION

Use-----------

Dispose----------

TEST METHOD VALIDATION

measurement system analysis is important in process validation
validation needs to ensure that the measurement system will be accurate so we
create a Test Method Validation
Test equipment operates consistently and delivers consistent results
operational qualification and performance qualification depend on obtaining correct
data. Therefore we need to do measurement system analysis to ensure the data is
accurate.

Measurement System Analysis,

Accuracy and Precision are metrics that measure and quantify the measurement
system is accurate
Accuracy is The Measurement system value which is closeness to the true value
2.Precision---consistent measurements when repeat under same conditions. High
precision is repeated measurements close to each other even if they are not close
to true value.

Gage Repeatability and Reproducibility,(a method for testing if the measurement

system is precise)( If R and R leads to high variation in measurements then the
measurement system is wrong)

TEST METHOD VALIDATION TYPES IN OQ and PQ

Test Method can separate Conforming from Non Conforming product

There are two types of Test Methods that are used in Operational qualification and
Performance qualification depending on the type of data that is

1.Attribute Test Method Validation ( Pass/ Fail scenario)( visual defects which
are categorized as Fail)to determine if a process is in control.
2.Variable Test Method Validation( Data is measured)( It can be weight , length or
strength of the bond)

ATTRIBUTE TEST METHOD VALIDATION(Destructive and Non Destructive)

VARIABLE TEST METHOD VALIDATION( Destructive and Non Destructive)
The Attribute Test Method Validation is a check on a system that is using attribute
data. It is usually pass/fail scenario.
Design Input Document is required.

The Variable Test Method Validation means the data is measurement. It can be a
weight, a length, or the strength of a bond

The Acceptance Criteria for Variable Test Method Validation

% of tolerance < 30%
If Fail The Variation is coming from
operators
equipment
test instructions
samples

Calibration
refers to the process of comparing the measurements of an instrument or device
under test (DUT) with a known standard or reference to determine any deviations and
adjust the instrument accordingly. The goal of calibration is to ensure the
accuracy and reliability of the measurements made by the instrument.

Non Conformance
Failure to meet the specified requirements.
with in a company the product has a defect

CAPA(out of company)

class 1 devices
class 2 devices
class 3 devices