ispe office space analysis - farmasi industri · 2019. 4. 13. · 2011: collecting large quantities...

PROCESS VALIDATION NEW CONCEPT

Jakarta, 29-30 March,2016

Speaker: MIMI VIRLANY SYAHPUTRI

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FITHRUL FARMASIINDUSTRI.COM

Process Validation Definition

1987

• establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality characteristics

2011

• the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products

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Shifted the focus :

Documented evidence Scientific evidence


Product Life Cycle

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PRODUCT DEVELOPMENT

PROCESS QUALIFICATION

CONTINUOUS VERIFICATION

PRODUCT DISCONTINUATION


Concept Differences 1987 2011

Collecting large quantities of data

from validation batches

Collect data throughout the

product life cycle and evaluate it scientifically

and assess if it supports a quality process

Validation as individual parts of a

process,

• Collective ‘process validation’ effort that

takes a more holistic view of process

• Highlights the GxP critical parts of the

process

• Focuses efforts and resources on the most

critical aspects.

Stand alone validation activities • Stage 1 – Process Design

• Stage 2 – Process Qualification

• Stage 3 – Continued Process Verification

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Process Validation Concept 2011

Stage Intent Typical Activities

Stage 1

Process

Design

• Build product knowledge

through development

and scale up activities

• Established design of

process for robust

process for routine

manufacturing activities .

• Quality by Design

• Product development

activities

• Experiments to determine

process parameters,

variability and necessary

controls

• Risk assessments

• Design of Experiment

testing

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Stage 2

Process

Qualification

To confirm the process

design as capable of

reproducible commercial

manufacturing

• Facility design

• Equipment & utilities

qualification

• Process Performance

qualification

• Strong emphasis on the

use of statistical analysis

of process data to

understand process

consistency and

performance

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Stage 3

Continued

Process

Verification

Ongoing assurance

that the process

remains in a state of

control during routine

production

through quality

procedures and

continuous

improvement

initiatives.

• Proceduralised data collection

from every batch.

• Data trending and statistical

analysis

• Product review

• Equipment and facility

maintenance

• Calibration

• Management review and

production staff feedback

• Improvement initiatives through

process experience

• Integrated CAPA and Change

Control Management

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1987

• Consistently meet specification

2011

• Consistently meet specification

• Understand process consistency and performancence

• Remains in a state of control during routine production


Process Validation New Concept

PROCESS UNDERSTANDING

PROCESS DESIGN PROCESS

QUALIFICATION COMMERCIAL

MANUFACTURE MONITORING AND

IMPROVEMENT

•STAGE 1

•Process Design

•STAGE 2

•Process

Qualification

•STAGE 3

Continuous Process

Verification

•Based on product •Quality and Patient Safety

•Know the process

•Know the variable

•Know the confidence level

•Vigilance


Process Validation Definition

Establishing documented evidence which provides a high degree of

assurance that a specific process will consistently produce a product

meeting its pre-determined specifications and quality

characteristics

the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products

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• Focus on document as evidence

• As long as meet specification and

quality characteristics

• Based data collection and evaluation

• Process design stage required

before process validation

• Established scientific evidence


HOW TO :

• Literature study

• Data Collection

• New product : development stage

• Mature Product : APR/PQR, product history

• Data evaluation Tools

• Established process understanding

• Critical Quality Attribute

• Critical Process Parameter

• Set up process control

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DATA EVALUATION VS

PROCESS VALIDATION : • Strong process understanding

• Understand process capability by considering all variable

• Design space

• Operation range

• Proven Acceptable Range

• Understand data collection rule

• Purpose and scope

• Same condition as much as possible

• Data integrity

• Data evaluation

• Use proper tools (Simple statistic to advance)

• Common sense

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EXAMPLE

• Change to new compressing machine

• Data taken from validation process to

uniformity of mass

• Specification 85% – 115%

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Parameter Acceptance

Criteria Batch 1 Batch 2 Batch 3

Uniformity of mass

(20 tablets)

Ind. weight:

18/20 : Avg ± 7.5%

20/20 : Avg ± 15%

197 202 199 205 208 201 197 196 206 219* 196 200 197 206 203 203 204 204 193 204 205 190 200 201 193 199 197 207 203 198

198 204 204 199 203 205 203 206 201 194 203 203 201 202 206 199 198 192 197 194 208 203 209 220 201 197 201 197 198 201

202 204 207 196 201 198 200 206 200 206 195 197 197 200 201 202 201 199 198 204 200 202 204 210 198 203 198 194 210 197

204 198 196 195 197 200 199 205 200 208 196 205 206 191 201 200 195 198 197 198 197 198 200 195 206 192 188 194 198 208

201 214 196 200 198 207 204 216 200 202 204 205 204 203 200 204 199 203 207 202 208 196 194 192 200 206 207 205 195 207

209 194 205 204 202 195 205 200 202 204 202 200 205 202 197 197 205 201 198 198 202 193 197 198 204 203 198 201 201 205

204 202 198 206 202 199 209 211 200 197 201 203 197 206 198 206 194 207 192 198 203 207 209 212 209 202 201 204 201 196

204 202 203 208 206 207 201 202 205 202 196 204 205 201 197 200 197 197 201 205 192 190 194 206 202 206 205 193 201 202

196 207 199 208 203 194 214 195 194 202 197 206 202 203 195 204 204 209 202 204 206 196 199 195 201 191 195 195 199 197

202 196 198 201 201 200 195 204 198 202 212 201 203 212 209 193 193 198 204 205 196 198 191 194 196 190 198 209 196 195

Minimum 194 mg 195 mg 194 mg 195 mg 194 mg 195 mg 191 mg 193 mg 192 mg 192 mg 190 mg 191 mg 190 mg 188 mg 195 mg

Dev: NLT (Avg - x%)

-4.0% -3.2% -3.7% -4.1% -4.0% -3.1% -5.5% -3.9% -4.0% -4.0% -4.8% -5.0% -5.0% -5.7% -2.7%

Maximum 214 mg 208 mg 208 mg 216 mg 219 mg 212 mg 212 mg 209 mg 209 mg 207 mg 208 mg 220 mg 209 mg 209 mg 210 mg

Dev: NMT (Avg + x%)

+5.9% +3.3% +3.3% +6.2% +8.4%* +5.3% +4.9% +4.1% +4.6% +3.5% +4.3% +9.5% +4.5% +4.8% +4.8%

Avg:

192.5 - 207.5 mg 202.0 mg 201.4 mg 201.4 mg 203.4 mg 202.1 mg 201.3 mg 202.2 mg 200.8 mg 199.9 mg 200.1 mg 199.5 mg 201.0 mg 200.0 mg 199.4 mg 200.4 mg


QUESTION

• Has the process consistently produced the

product that meet specification?

• Are we confidence and understand process

consistency and performancence?

• Are we confidence that the process

remains in a state of control during routine

production?

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What’s the statistic tool says???

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ANSWER

• Has the process consistently produced the

product that meet specification? YES

• Are we confidence and understand process

consistency and performancence? YES

• Are we confidence the process remains in a

state of control during routine production?

YES

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SUMMARY

TO ADDRESS NEW VALIDATION CONCEPT

2011 :

• Process/product understanding

• Know quality target product profile, critical quality

attribute, critical process parameter

• Proper tools to evaluate and how to provide scientific

evidence

• Trial historical data (process by design)

• Statistic approach

• PAT

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POINT TO REMEMBER

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ispe office space analysis - farmasi industri · 2019. 4. 13. · 2011: collecting large quantities...

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