Cleanroom Validation: Design, Certification, and Maintenance

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Cleanroom Validation
Student Name
Institutional Affiliation

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Table of Contents
1 Introduction..............................................................................................................................3
2 Designing Cleanrooms.............................................................................................................4
2.1 Strategy and Purpose of design.........................................................................................4
2.2 Cleanroom Layout.............................................................................................................6
2.3 Changing room..................................................................................................................9
2.4 Material distribution technology.....................................................................................10
2.4.1 Air supply................................................................................................................10
2.4.2 Air distribution.........................................................................................................11
2.4.3 Air Filtration and supply..........................................................................................15
2.4.4 Construction Materials.............................................................................................16
2.4.5 Operating procedures...............................................................................................17
3 Cleanroom Validation............................................................................................................17
3.1 Lifecycle of Cleanroom Validation.................................................................................18
3.1.1 DQ (Design Qualification)......................................................................................19
3.1.2 IQ (Installation Qualification).................................................................................19
3.1.3 OQ (Operation Qualification)..................................................................................21
3.1.4 PQ (Performance Qualification)..............................................................................22
3.2 Cleanroom Certification..................................................................................................23
3.3 Monitor and Control........................................................................................................23
4 Maintenance and Control of Cleanroom Areas......................................................................24
5 Cleanroom Clothing...............................................................................................................26
6 Cleaning instructions..............................................................................................................27
6.1 General regulations of a cleanroom................................................................................27
6.2 Airborne Particle Measurement......................................................................................28
7 Conclusion..............................................................................................................................28
Reference List................................................................................................................................30

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1 Introduction
Presently cleanrooms are utilized in several industries such as biotechnology, pharmaceuticals,
defense industry, microelectronics and nanotechnology. Cleanrooms may vary from small to
large multilevel structures with big serviced utilities and equipment. Cleanroom is a managed
placement where various goods are produced and airborne particles concentration is managed to
particularized limits. As such, the killing process of contaminants of ultrafines need to be
controlled. Contaminations are created by processes, equipment, people and facilities. They must
be constantly eliminated from the air. The air cleanliness level in a room should be controlled by
standards. ISO 14644 is the most regularly applied standard (Brahm, 2012).
The primary cleanroom function is to safeguard the produced product from contamination. In
manufacturing of a biotechnology drug, manufacturer economic survival relies on the protection
of the manufactured product. Therefore, a potential contamination source should be identified,
including the working environment. Supply air quality requirements have increased as a result of
the development of advancing and new technologies in various sectors of human operations.
Major factors of operation which symbolize air quality are humidity, cleanness, temperature and
pressure. Conditions are selected on settings to support each process of technology. Thus general
ventilation systems cannot be used in manufacturing a biotechnology drug in a cleanroom if
maintenance of these parameters is expected to be permanent. Systematic techniques are needed
to develop unique engineering designs. Cleanroom requires complex tools of technology that
support set-up air quality parameters. The context will focus on Remicade. It is a biotechnology
drug utilized to treat particular types of arthritis such as spine arthiritis, rheumatoid arthritis and
psoriatic arthritis, along with other diseases of bowel such as ulcerative colitis and Crohn’s
disease as well as skin disease (Vasilyev et al., 2014, p. 19). The paper will evaluate the

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cleanroom design, steps for validating cleanrooms, and the process required in maintaining the
validated state of the cleanroom.
2 Designing Cleanrooms
The main function of a cleanroom is to protect the product from being contaminated. In
manufacturing Remicade, the manufacturer reputation and the patients’ lives relies on the
product purity. It is thus essential to determine the potential contamination source. They may
include the raw materials, manufacturing personnel, working facilities and process equipment.
As such, it should be acknowledged that management of the operating process in the
environment, means that process equipment, raw materials and production personnel, is a setting
of successful operation of the cleanroom (Ginty et al., 2014, p. 44). Cleanroom is an environment
where the air distribution, construction materials, air supply, air supply filtration and operating
processes are controlled to regulate concentration of airborne particles to meet proper levels of
cleanliness. The department of design needs to address most challenging issues: optimum cost
against minimum risk. It refers to the cleanliness level needed to reduce risk contaminating the
product while concurrently developing a facility which operates without adding constraints to the
unit cost of the product and is economical to design.
2.1 Strategy and Purpose of design
The following are the purposes of a pharmaceutical cleanroom design in a production facility:
 Eliminating the environment external to cleanrooms suite
 Dilution or removal of contamination emerging from the process of manufacturing
 Dilution or removal of contamination emerging from production personnel
 Controlling hazards emerging from the product
 Containment of cross-contamination of product-to-product

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 Personnel protection
 Management and control of the flow of material via the procedure processes through
configuration and layout
 Management and control of the movement of personnel by improving the connection and
arrangement of each rooms
 General operation safety by managing egress and entry of materials and personnel
 Establishing best comfort conditions for employees
 Developing unique products environmental conditions
 Adaptation of process equipment and plant to guarantee easy utilization, safety and good
maintenance access
 Efficient control of room conditions
All of the above purposes are essential, and cleanrooms should be structured to function and
overlap well. Thus, it is essential to examine all requirements and establish the solution in an
organized way (Fernández-Pérez et al., 2017). A simple step plan can be outlined as follows:
 Evaluate the stages of production
 Develop flow diagrams of processes
 Define operations connected to the rooms
 Define requirements of environmental quality
 Measure process, production and space requirements
 Develop association diagrams of the room
 Define the needs of accommodation
 Create schemes and layouts
 Develop specifications and designs

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 Carry out a comprehensive construction and design process.
The above steps can be conducted at various detail levels due to the scale, physical size and
complexity of a facility. It is essential to define roles of all the involved parts (Fischer et al.,
2013, p. 5475).
2.2 Cleanroom Layout
Cleanrooms are constructed as suite of rooms which have defined purposes in
pharmaceutical manufacturing. The figures 1 and 2 illustrates this phenomenon. Figure 1 shows
a designed of cleanroom suite that meets the requirements manufacturing the drug that can be
sterilized terminally. Any worker should go through the clean changing area before entering the
cleanroom suite. In the clean changing area, the worker changes the clothes and wear the
cleanroom attire. Components and other raw materials are brought in through their respective
entry airlocks. Standard procedures are employed in the airlocks to reduce contamination from
outside. Preparation of solutions is done in the ‘Solution Preparation’ room and then indirectly or
directly transferred via mobile containers or pipes to the ‘Clean Filling’ room for filling
procedures to be undertaken. The closures and containers are cleaned and prepared in the
‘component preparation’ room and transferred using conveyor system or manually to the filling
stage. In the ‘Clean Filling’ room, which is unidirectional flow clean zone, containers are filled
and packed and transferred via the autoclave terminal sterilization.

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Figure 1: Cleanroom Suite Layout
(Source: Flaherty, 2011)
Figure 2 below shows the cleanroom suite typically setup for the manufacturing of a drug
using the technique of aseptic filling. Requirements variations refer to the following differences:
the rooms are distinguished into aseptic rooms and clean rooms. Autoclave, oven, and transfer
hatch are the barriers created to for products getting into the aseptic rooms, and via the
separation of aseptic filling rooms and solution preparation rooms. The aseptic suite is provided
with more exact and separate changing room control because of variations in aseptic and clean

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suites environmental control. Unidirectional flow workstation can be used as a substitute of
isolator.
Figure 2: Aseptic Filling Room Suites
(Source: Flaherty, 2011)
Method, quantity, and quality of air in the room, amount if incoming contamination from
neighboring rooms, and the amount if contamination released in the rooms makes it difficult to
achieve the correct internal environment cleanliness level.