CALIFORNIA ST ATE UNIVERSITY SAN MARCOS

PROJECT SIGNATURE PAGE

PROJECT SUBMITTED IN PARTIAL FULFILLMENT

OF THE REQUIREMENTS FOR THE DEGREE

MASTER

OF

BIOTECHNOLOGY

PROJECT TITLE: Validation Document and Standard Operating Procedure (SOP) Creation of
Incubator Shaker for Vial Thaw and Shake Flask Manufacturing Operations

AUTHOR: Doug Chung

DATE OF SUCCESSFUL DEFENSE: 1\

April 24 1 2018

THE PROJECT HAS BEEN ACCEPTED BY THE PROJECT COMMITTEE IN

PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF
BIOTECHNOLOGY.

Betsy Read
PROJECT COMMITTEE CHAIR

Mike Fino d1-Y4',/#

PROJECT COMMITTEE MEMBER SIGNATURE DATE

John Sarandos so1-=\\'R\ t,

PROJECT COMMITTEE MEMBER DATE
 EXECUTIVE SUMMARY

Validation document and Standard Operating Procedure (SOP) Creation of Incubator Shaker for Vial
Thaw and Shake Flask Manufacturing Operations

Gilead Sciences

Doug Chung

April 25th, 2018

Professional Science Masters

California State University, San Marcos

This Semester-in-Residence project was conducted at Gilead Sciences, Biopharmaceutical Company, in

Oceanside, CA within manufacturing department. The goal of the project was to generate User
Requirement Specifications (URS), Standard Operating Procedure (SOP) and Installation
Qualification/Operational Qualification (IQ/OQ) documents for Incubator Shaker validation. Equipment
validation is one of the most important activities that need to be performed prior to equipment operation
in a cGMP setting. The first step of the validation process is to create documents that are required to
perform validation. New incubator shakers are being validated at Gilead Sciences, and URS, SOP and
IQ/OQ documents need to be created prior to validation. URS is needed to identify the minimum
requirements of incubator shakers with respect to the functionality and operating environment in which
the incubator will operate. A SOP is required to give specific instructions to operators for robust operating
processes, while IQ/OQ document is necessary to confirm the minimum installation and operational
requirements of incubator shakers. Overall, URS, SOP and IQ/OQ documents for the incubator shakers
were generated successfully. All the documents were reviewed and approved by personnel from
manufacturing, validation, engineering and quality assurance department. URS and SOP are ready to be
used as supporting documents for validation, and IQ/OQ document is ready to be executed to complete
validation process in cGMP environment. Recommendations for future work include the implementation
of remote alarms and the execution of IQ/OQ documents.
Validation Document and Standard Operating Procedure (SOP) Creation of
Incubator Shaker for Vial Thaw and Shake Flask Manufacturing Operations

Doug Chung
1
Gilead Sciences in Oceanside B400 is a clinical
biopharmaceutical manufacturing site

2
 Incubator and shaker are used to optimize cell culture
process for Vial Thaw and Shake Flask expansion process

Incubator and shaker

Inoculum Train Production Harvest

Vial Thaw Shake flask 20L scale-up
expansion

1mL
Vial

125mL 1L 3L 20L 20L 100L 500L 2750L Centrifuge

Shaker Shaker Shaker Bioreactor Bioreactor Bioreactor Bioreactor Bioreactor

3
 Current process is inefficient as it requires
separate incubator and shaker unit

• HIGH number of preventative maintenances

• HIGH amount of manpower hours.
How do we make it better?

4
 New incubator shaker will function as both
incubator and shaker

• Single unit will control temperature, CO2 and agitation speed.

• Will improve efficiency by combining two separate unit into one equipment.

5
 Introducing new equipment into a cGMP
environment requires validation

• Equipment validation provides documented evident of intended function

• Improves efficiency and quality

• Reduces risk of non-compliance

6
Validation failure can lead to serious consequences

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 Three tasks are required to validate an equipment

1. Creation of User Requirement Specification (URS) document

2. Generation of Standard Operating Procedure document (SOP)

3. Making Installation Qualification (IQ) and Operational Qualification

(OQ) document

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User Requirement Specification (URS) specifies
the minimum requirements for equipment

PROCESS REQUIREMENTS CRITICALITY

Incubator shaker shall maintain a temperature range of: 35 ºC to 40ºC. CRITICAL

Incubator shaker shall control increments of 0.1ºC with an accuracy of

CRITICAL
± 1ºC at 37ºC

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 SOP was written after reviewing the vender’s
Instrument Manual and Gilead’s cleaning procedures

• General operation
• Changing set points and alarms (CO2, temp, spped)
• Cleaning Process (frequency, solutions)
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Installation Qualification (IQ) / Operational Qualification (OQ)
are the two main steps of Validation

TESTS verification of correct equipment Installation

IQ ENSURES correct installation of system per specs

ESTABLISHEDS baseline for equipment

TESTS verification of correct equipment operation

OQ ENSURES correct operation of system per specs

VERIFIES system meets claims from parameters

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25 Activities have to be performed for Incubator
Shaker IQ/OQ process

Example
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 URS, SOP and IQ/OQ documents of the incubator
shakers have been created and ready for cGMP Use.
• Upon document reviews, all the documents are deemed to meet the compliance
requirement in manufacturing setting

• Remote alarm/automation system will be integrated to incubator shaker within Gilead

Oceanside facility in the future.

• IQ/OQ document will be executed by manufacturing and validation department prior to

use for GMP operation.

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 Pharmaceutical companies spend a large amount of
money and time to validate their process and equipment

QUALITY PRODUCT

PATIENT SAFETY

GOOD REDUCES EQUIPMENT REPLACEMENT

VALIDATION
REGULATORY REQUIREMENT

RELIABILITY

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 Acknowledgment
• Dr. Betsy Read

• Mike Fino

• John Sarandos

• Gilead Validation Department

• Gilead Manufacturing Department

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