Process Validation

November 4, 2015

Joseph Tartal

Postmarket and Consumer Branch Chief

Division of Industry and Consumer Education

Office of Communication and Education

Center for Devices and Radiological Health

U.S. Food and Drug Administration
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Learning Objectives 

• Understand the Background and Definitions of Process 

Validation (PV)

• Recognize when Validation is Required

• Understand PV Regulatory Requirements

• Identify Guidance and Installation, Operational and 

Performance Qualifications

• Understand Requirements for Process Monitoring, 

Process Changes and When to Revalidate
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References and 

Regulatory Requirements

21 Code of Federal Regulations (CFR) 820: 

Quality System Regulation

21 CFR 820.75: Process Validation

Preamble to 1996 Quality System (QS) Regulation 
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Background: Regulatory Requirements

The Quality System Regulation, 

21 CFR 820.75

http://www.ecfr.gov/cgi-bin/textidx?SID=5f15fc6205369484e218941accf68eeb&m

c=true&node=se21.8.820_175&rgn=div8 

 
GHTF Guidance: Quality Management System 

Medical Devices – Process Validation Guidance; 

SG3; 2004

http://www.imdrf.org/docs/ghtf/final/sg3/technicaldocs/ghtf-sg3-n99-10-2004-qms-processguidance-04010.pdf 

Background: Guidance 
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Linkage to Other Sections of the 

Quality System

• Design Controls: Using Risk Analysis and Identifying 

Essential Design Outputs 

• Purchasing Controls: Selecting Suppliers on their ability 

to meet specified requirements

• Personnel: Training and Qualifications

• Production and Process Controls: Using software and 

software automated processes 
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Quality System Regulation: Definitions

Definitions 21 CFR 820.3 (aa)

 Verification: confirmation by examination and 

provision of objective evidence that specified 

requirements have been fulfilled. 
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Quality System Regulation: Definitions

Definitions 21 CFR 820.3 (z)

 Validation: confirmation by examination and 

provision of objective evidence that the 

particular requirements for a specific intended 

use can be consistently fulfilled. 
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Quality System Regulation: Definitions

Definitions 21 CFR 820.3 (z)(1)

 Process Validation: establishing by objective 

evidence that a process consistently produces a 

result or product meeting its predetermined 

specifications. 
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Regulatory Requirement

Where the results of a process cannot be fully 

verified by subsequent inspection and test, the 

process shall be validated with a high degree of 

assurance and approved according to established 

procedures.

 21 CFR 820.75(a)
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Examples: Is Validation Required?

1.) Sterile Package Sealing Processes?

Yes; limitations and destructive 

2.) Dimensions of a Manual cutting process?

No; manual process, can be fully verified. 

3.) Filling processes?

Maybe; need additional information

2004 GHTF QMS PV Guidance, also see Figure 1: Process validation decision 

tree and examples
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When to Start? Earlier the Better 

No specific requirement in design, but requirement under 

21 CFR 820.80 is that process validation is completed prior 

to finished device release. Items to consider... 

• When to initiate PV in the design process

• Translation of design output criteria into production 

parameters and specifications

• Addressing design, process and purchasing changes 
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Where to Start? 

Master Validation Plans 

Not a 21 CFR 820 requirement, but is recommended per 

GHTF Guidance. The plan should...

• Define the product and process flow

• Identify what needs to be validated

• Consider protocols and specifications

• Be documented and approved 
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Regulatory Requirement

The validation activities and results, including the 

date and signature of the individual(s) approving 

the validation and where appropriate the major 

equipment validated, shall be documented. 

 

 21 CFR 820.75 (a)
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Regulatory Requirements:

Personnel Performing Validation

• Each manufacturer shall ensure that validated processes 

are performed by qualified individual(s) . 

 21 CFR 820.75(b)(1)

• Personnel who perform verification & validation activities 

shall be made aware of defects and errors that may be 

encountered as part of their job functions. 

 21 CFR 820.25(b)(2)
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Regulatory Requirement

Equipment. Each manufacturer shall ensure that 

all equipment used in the manufacturing process 

meets specified requirements and is appropriately 

designed, constructed, placed, and installed to 

facilitate maintenance, adjustment, cleaning and 

use.

 21 CFR 820.70(g)
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Installation Qualification (IQ) 

Simply put in guidance, is everything installed correctly. 

Things to consider...

• Equipment design features

• Installation and Environmental Conditions

• Safety features

• Supplier documents, Calibration, preventative 

maintenance and spare parts. 

http://www.imdrf.org/docs/ghtf/final/sg3/technical-docs/ghtf-sg3-n99-10-2004-qms-process-guidance04010.pdf (Guidance - Definitions Pg. 5 & Section 5.3)
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Operational Qualification

Challenge process parameters to assure the process will result 

in product that meets requirements. Things to consider...

• Process control limits

• Material specifications and handling

• Process change control and training

• Potential failure modes, action levels and worst case scenario 

• Software V&V for intended use

http://www.imdrf.org/docs/ghtf/final/sg3/technical-docs/ghtf-sg3-n99-10-2004-qmsprocess-guidance-04010.pdf (Guidance - Definitions Pg. 5 & Section 5.4)
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Determining Process Validation 

Parameters, Criteria and Limits 

 GHTF Guidance, Example: heat sealer

 Design Output – a sealed pouched as measured by seal 

thickness and strength

 PV Parameters, 

1. Temperature

 2. Pressure

 3. Time
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Performance Qualification (PQ)

Demonstrate the process will consistently produce 

acceptable product under normal operating conditions. 

Things to consider...

• Procedures and limits from OQ

• Acceptable product

• Actual manufacturing conditions

• Process repeatability and long term stability 

http://www.imdrf.org/docs/ghtf/final/sg3/technical-docs/ghtf-sg3-n99-10-2004-qmsprocess-guidance-04010.pdf (Guidance - Definitions Pg. 5 & Section 5.5)
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How Many Runs or Samples are Enough?

The requirement for testing from the first three production 

lots or batches has been deleted... 

Comment #85 to Preamble to 1996 QS Regulation

The challenges should be repeated enough times to assure 

that the results are meaningful and consistent. 

 GHTF Guidance Section 5.5 PQ
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Stable and Capable Process

Stable Process – produces a consistent level of 

performance, total variation is reduced and is more 

predictable.

Capable Process – When consistent performance is 

achieved the remaining variation must be made to fit within 

the upper and lower specification limits.

GHTF Guidance Annex A Statistical Methods and tools for 

process validation.
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Regulatory Requirement

Each manufacturer shall establish and maintain 

procedures for monitoring and control of process 

parameters for validated processes to ensure that 

the specified requirements continue to be met. 

 

 21 CFR 820.75(b)
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Process Validation Monitoring

Monitor and control process parameters for 

validated processes so the specified requirements 

continue to be met.

• Robustness of Process

• Statistical Process Control

• Use of Action Limits and Control Charts
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Production and Process Changes

Establish and maintain procedures for changes to 

a specification, method, process or procedure. 

Such changes shall be verified or where 

appropriate validated according to 21 CFR 820.75 

before implementation...Changes shall be 

approved in accordance with 21 CFR 820.40

 21 CFR 820.70(b)
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Regulatory Requirement: 

Revalidation

When changes or process deviations occur, the 

manufacturer shall review and evaluate the 

process and perform revalidation where 

appropriate. These activities shall be documented.

 21 CFR 820.75(c)
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Revalidation Continued

Examples of Reasons for Revalidation

• Change(s) in the actual process

• Negative trend(s) in quality indicators

• Change in product design that affects process

• Transfer of process to another facility

• Change of the application of the process

 GHTF Guidance Section 6.4 
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Use of Historical Data

Data used from device history records such as 

batch records, control charts and testing and 

inspection data can be used. Also any 

validation type can use historical data.
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Summary

• Manufacturers are legally obligated to meet the requirements 

for process validation in 21 CFR 820

• The GHTF Guidance is a useful educational tool for 

understanding how to validate a process 

• Performing process validation activities ensures that the 

process output is predictable and predetermined

• The completion of appropriate process validation activities 

can help reduce waste, reduce cost and reduce the time it 

takes to get a medical device on to the market.
Providing Industry Education

1. CDRH Learn – Multi-Media Industry Education

 over 80 modules - videos, audio recordings, power point presentations, software-based 

“how to” modules

 accessible on your portable devices: http://www.fda.gov/Training/CDRHLearn

2. Device Advice – Text-Based Education

 comprehensive regulatory information on premarket and postmarket topics:

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance

3. Division of Industry and Consumer Education (DICE) 

 If you have a question - Email: DICE@fda.hhs.gov 

 Phone: 1(800) 638-2041 or (301) 796-7100 (Live Agents 9am – 12:30 pm; 1-4:30 pm EST)

 Web Homepage: 

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ContactUs-- DivisionofIndustryandConsumerEducation/default.htm 

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