Validation PRINCIPLES AMDR SEMINAR 2017 SURABAYA, …gakeslabindonesia.id/id/wp-content/uploads/2017/10/13.-Validation... · VALIDATION PRINCIPLES AMDC SEMINAR 2017 SURABAYA, INDONESIA

VALIDATION PRINCIPLES AMDC SEMINAR 2017

SURABAYA, INDONESIA

Chua Sook Peng

Johnson & Johnson

Snr Director SEA Business Quality

“ THIS MATERIAL IS TO BE USED FOR TRAINING PURPOSE ONLY”

OUTLINE Implementing a Validation Program

Background and Definitions

Essential Requirement/Testing

Example of an Equipment IQ,OQ,PQ


REASONS FOR VALIDATION

Customer Satisfaction

Market Requirement

Product Liability

Cost of Non Conformance

Supports Improvement


ISO 13485 REQUIREMENT

Requirements according to 7.5.6 of ISO 13485:2016 • The organization shall validate any processes for production and service provision where the resulting output cannot be verified by subsequent monitoring or measurement……..

General requirements ...

Validation shall demonstrate the ability of these processes to achieve the planned results consistently. The organization shall document procedures for validation of processes, including:

a) Defined criteria for review and approval of the processes,

b) Equipment qualification and qualification of personnel

c) Use of specific methods, procedures and acceptance criteria

d) As appropriate, statistical techniques with rationale for sample sizes of the equipment

and qualification of the operators,

e) Application of defined methods and procedures

f) Requirements for records

g) Revalidation, including criteria for revalidation

h) Approval of changes to the process


WHERE DO WE START?

GOAL

Consistently produce product that are fit for intended use.

Process validation is a key element in ensuring the principles and goals are met.

Many technologies are used in the manufacturing of the device. The details of the Process Validation will vary according to the type (sterile or non-sterile) and the nature and complexity of the process

Process must be designed according to the design controls (ISO 13485 Section 7.3) and validated


BASIC PRINCIPLES

Process Specifications (Parameter) are derived from the Device/Component Product Specification. The process is developed such that the required parameters are achieved.

Establish that the process equipment has the capability of operating within the required parameters.

Demonstrate that controlling, monitoring measuring equipment and instrumentation are capable of operating within the parameters prescribed for the process equipment.

Perform cycles/runs representing the required operational range of the equipment to demonstrate that the processes have been operated within the prescribed parameters for the process and that the output or product consistently meets predetermined specifications for quality and function.

Monitor the validated process during routine operation. As needed requalify and recertify the equipment.


WHEN SHOULD A PROCESS BE VALIDATED Where process results cannot fully verified during routine production by inspection and

test, the process must be validated according to established procedures.

Processes which should be validated • Sterilization processes

• Clean room ambient conditions

• Aseptic filling processes

• Sterile packaging sealing processes

Processes which may be covered by

verification • Manual cutting processes

• Testing for color, turbidity, total pH for solutions

• Visual inspection of printed circuit boards

Model useful in determination Certain cleaning processes

Certain human assembly processes

Is Process

Output

Verifiable

Validate

Redesign

Product or

Process

Is Verification

Sufficient &

Cost Effective

Verify &

Control the

Process

YES YES

NO

Source: IMDRF


DEFINITIONS

Installation Validation

Operational Validation

Performance Validation


TESTS

► Verification Of Correct

Equipment Installation

______________________

ENSURES

► Correct Installation of

System Per Specs

______________________

ESTABLISHES

► Baseline of Equipment

Studies which are conducted to show that all equipment (whether purchased or build in-house) relevant to the process was installed correctly and is capable of meeting supplier’s or manufacturer’s specification

INSTALLATION QUALIFICATION


INSTALLATION QUALIFICATION

Installation conditions (utilities, wiring, etc)

Installation check (ball bars, laser alignment, vibration analysis)

Verification of installation drawings or instructions

Equipment documentation (drawing, schematics, spare pats list, manuals)

Purchased software documentation

Critical equipment features (i.e materials of construction, cleanability)

Environment conditions (such as clean room requirements, temperature, humidity)

Preventative maintenance schedule

Calibration requirement

Identification of repair operations that require requalification


OPERATIONAL QUALIFICATION Studies designed to challenge the process and

process equipment, and establish objective evidence that the process meet predetermined requirements throughout all the anticipated operating ranges.

Monitoring equipment (instruments) should be calibrated at the beginning of the OQ and the calibration should be checked at the end of the study to establish confidence in the validation of the process. Where required, independent measurement instrument used as part of a validation shall have an acceptable and current calibration status.

In situation where these independent instruments might be affected by the actual testing (such as thermocouples exposed to high temperatures), the instruments should also be calibrated upon completion of the study.

TESTS


Equipment Operation

______________________

ENSURES

► Correct Operation of

System Per Specs

______________________

VERIFIES

► System Meets Claims

From Parameters


OQ EXAMPLES

Verification of all systems and subsystem functions

Confirmation of all safety devices and systems

Software qualification

Evaluate impact of key parameters on the process (DOE, worst case testing)

Measurement system suitability

Bias and/or repeatability and reproducibility of measurement systems

Operator training and qualification


PERFORMANCE QUALIFICATION

Studies conducted to demonstrate

the process will consistently

produce acceptable product under

normal operating conditions.

Challenges should simulate

conditions that will encountered

during actual manufacturing.

TESTS


Equipment Performance

______________________

ENSURES

► Correct Performance of

System Per Specs

______________________

VERIFIES

► System Meets Customers

Intended Purpose


EXAMPLES OF PQ

Verification of released process documentation (manufacturing procedures, inspections procedures, product specifications, engineering drawings, tool drawings, material specifications, related forms)

Dimensional verification (first article, layout inspections)

Process stability (x-bar and R charts)

Process capability (Cp, Cpk)

Fault seeding

Product performance evaluation (impact of the process on follow-on operations, product functionality, material and physical properties, etc)

Cleanliness tests (extraction tests, ESCA)

Product Sterility

Biological Tests (Bioburden, Hemolysis, Cytoxicity etc)

Manned and Unmanned of Controlled Environmental


TESTS

► Verification Of

Correct Equipment

Installation

____________________

ENSURES


System Per Specs

____________________

ESTABLISHES


TESTS


Equipment

Performance

_____________________

ENSURES


System Per Specs

_____________________

VERIFIES

► System Meets

Customers Intended

Purpose

TESTS


Equipment Operation

_____________________

ENSURES


System Per Specs

_____________________

VERIFIES


From Parameters

IQ OQ PQ


SUMMARY

Develop validation

summaries and compile

validation results

EXECUTION • Installation Qualification

• Operational Qualification

• Performance Qualification

PLANNING

Develop the validation

plan, IQ, OQ, PQ

protocols and

requirements

VALIDATION DOCUMENTATION


USER

REQUIREMENT

DETAILED

Design (How it

is built)

FUNCTIONAL

DESIGN (How it

should work)

Qualification of

Results

Qualification of

Operation

Qualification of

Installation

CONSTRUCTION

PQ TEST PLAN

OQ TEST PLAN

(Includes FAT)

IQ TEST

PLAN

VALIDATION DOCUMENTATION


PACKAGING EQUIPMENT VALIDATION EXAMPLE

Validating the heat sealing process is critical both to comply with regulatory requirement and to be confident in the quality of the final product.

Sealing equipment must perform the heat sealing function in a repeatable, invariable manner such that final product quality is consistent with predetermined standards.

The relevant regulatory standard for validation of the heat sealing process for medical applications is ISO 11607, Part 2.


EXAMPLE OF A CONTINUOUS BAND SEALER WITH INDIVIDUAL TEMPERATURE

CONTROLLERS FOR EACH HEATING BAR


TESTS

► Verifies heat sealing equipment is installed and

calibrated correctly to ensure that critical process

control and can perform consistently over time.

--------------------------------------------------------------

ENSURES

• CPP are defined so that they can be controlled and

monitored.

• Alarms, machine stops, and warning systems are

tested to trigger alerts when tolerances are

exceeded.

• All instrumentation, sensors, displays, and controllers

are certified as calibrated.

• Software systems are validated to ensure they

function as intended.

• Gauges should show actual temperature, line

pressure into the sealer, and have a method of

reflecting real dwell time.

ESTABLISHES


TESTS

► Verification Of

Correct Equipment

Installation

____________________

ENSURES


System Per Specs

____________________

ESTABLISHES


IQ


TESTS


Equipment Operation

_____________________

ENSURES


System Per Specs

_____________________

VERIFIES


From Parameters

OQ TESTS

• The sealing process can produce a sterile

package at the extremes of set operational

parameters.

• Qualifications are performed at upper and

lower limits to determine tolerances for error

and the threshold for machine stops and alarms.

For example, a particular package will have a

range of settings for temperature, pressure and

dwell time that will provide a good seal.

--------------------------------------------------------------

ENSURES

• A “good seal” should be intact.

• This range is specified to accommodate

variability eg different materials.

Combination of 3 variables

eg high speed/low temperature/low pressure

value is set as “worst case” and a low speed/high

temperature/high pressure value is set as “best

case.”


TESTS


Equipment

Performance

_____________________

ENSURES


System Per Specs

_____________________

VERIFIES

► System Meets

Customers Intended

Purpose

PQ TESTS

• The sealing process will consistently produce

sterile packages under the specified

operating conditions set out in the OQ.

• Three or more production runs are

conducted with different operators and

variation within the actual production

environment. Typical variations are caused

by changes in materials, operators, and

environment

__________________________________

ENSURES

• Given these difference, the machine still

performs within tolerances. Appropriate

operator training is important to guarantee

consistency across different shifts and users.

The PQ often uses real or simulated product

and is the closest approximation to a

genuine production run


INPUT VS OUTPUT

HI ALARM LIMIT

LOW ALARM LIMIT

FAILURE/ DEFECT

LTL Parameter

FAILURE/DEFECT

HTL Parameter

SET PARAMETER AIMED

MEAN

VALUE

HTL

LTL

3

3

Verified

during OQ

Verified

during OQ


SAMPLING What is representative as a sample from a population of data: – Samples distributed

over the whole range of a typical production run – Normality is typically shown per run

to make the samples representative – Sample amount shall be sufficient to assure to be

representative at a high confidence:

LTL LTL LTL

LTL LTL LTL

HTL

HTL HTL

HTL

HTL


WORST CASE TESTING

Set of conditions encompassing upper and lower processing limits and circumstances, which pose the greatest chance of process or product failure when compared to ideal conditions. Such conditions do necessarily induce product or process failure

SAMPLING

Established in the test plan based on the criticality of the process

Based on level of confidence desired to ensure the certain portion of the population is within the sample range.

Eg Sample size of 30 covers 90% of the population with 80% confidence


SPECIFIC TESTS Process Capability

Comparison of the variance to the tolerance

Cp = (USL – LSL/6)

USL = Upper specification limit, LSL = lower specification

= measured standard deviation

Provides potential capability

If the process mean is not centred, discrepant [product may still result. Another parameter may be more relevant CpK which is sensitive to where the mean lies in the tolerance band.

CpK = Min {(USL-Xbar) or (Xbar – LSL)}/3

Cp >1 (mean can be adjusted)

CpK >1.33 (mean cannot be adjusted)


F & T TESTING Often, the effects of a process change will be determined by comparing product from the

new process to that of the old process

For two individual groups, T & t testing is appropriate. The F test first compare the variance from each group and then the t test compares the means based on equal or unequal variance

Inspection process that only yield a pass/fail result cannot be qualified using standard R&R technique

and fault seed testing should be used. Evidence that the process is capable of rejecting products that

do not meet specification

Conducted by randomly testing unacceptable product units and verifying the inspection process rejects

this product

Inspector should not be aware which unit is acceptable or process is being tested

Acceptable results are then based on the criticality of the attribute being inspected. For automated

processes, generally all fault seeded product must be rejected.

FAULT SEED TESTING

“” THIS MATERIAL IS TO BE USED FOR TRAINING PURPOSE ONLY”

SPECIFIC TESTS

X BAR & R CHARTS

Prior to evaluation of process capability, the process must first be

demonstrated to be in state of control

Xbar charts plot the mean of successive groups, and compares these values to

established control limits

R charts plot the range of successive groups, and compares these values to

established control limits.

Points which lie outside of the control limits should be evaluated for potential

causes. If the cause is identified and corrected, then the point may be

excluded from the graph or repeat the reading.


Documents

Validation PRINCIPLES AMDR SEMINAR 2017 SURABAYA, …gakeslabindonesia.id/id/wp-content/uploads/2017/10/13.-Validation... · VALIDATION PRINCIPLES AMDC SEMINAR 2017 SURABAYA, INDONESIA