Cleanroom is a controlled environment in which particulate contamination is controlled and used to minimize the generation and retention of particles inside and in which the temperature, humidity, air flow pattern, air motion and pressure are controlled to a specified limits. Thus, a cleanroom is a room that is clean.

The US Federal Standard 209E defines a cleanroom as `a room in which the concentration of airborne particles is controlled and which contains one or more clean zones.' According to ISO 14644-1, it is defined as, `a room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimize the introduction, generation and retention of particles inside the room and in which other relevant parameters, e.g. temperature, humidity, and pressure, are controlled as necessary'.

In pharmaceutical industries; the cleanrooms are used to control airborne particulate materials which contain living organisms that would produce undesirable bacterial growth in the production of biological, pharmaceutical and other medical products as well as for the research. Other manufacturing and R&D sectors use cleanroom include electronics (semiconductor) industries, aerospace research, advanced material research, laser and optics, food and beverage and of course hospitals.

Requirement of cleanroom
Micro-organisms had been known since the19th century which cause infections and hospitals were aware the problems of contamination. Between the 1940 and 1960, studies were performed in hospitals to demonstrate the relationship between airborne micro-organisms and infections. In the early 1960s, the cleanroom standards for hospitals were written. Subsequently, other industries also adopted the cleanroom concept with similar standards or with minor modifications as per their requirement.

The requirement for cleanroom can be broadly divided into two areas. The first area is that in which inanimate particles are undesirable and where their presence, even in submicron size, may prevent a product functioning or reduce its useful life. The second area requires the absence of microbe-carrying particles whose growth in the product could lead to human infection. It may also be seen that many of the examples given are recent innovations and this list will certainly be added to in the future, there being a considerable increase in the demand for cleanrooms.

Classification of cleanrooms
Cleanrooms are classified based on the degree of cleanliness of the air in the controlled environment. The method most easily understood and universally applied is the one suggested in versions of U.S. Federal Standard 209 up to edition `D' in which the number of particles equal to and greater than 0.5 w m is measured in one cubic foot of air and this count is used to classify the room. Federal Standard 209E has been published in 1992 in metric version and the corresponding International Standard Organisation's (ISO) standard is ISO-14644-1.

What is contamination?
Contamination is a process or act that causes materials, surfaces or environment to be soiled or adulterated with contaminating substances. There are two broad categories of surface contaminants: film type and particulates. These contaminants can produce a “killer defect” in a miniature circuit. Film contaminants of only 10 nm (nanometers) can drastically reduce coating adhesion on a wafer or chip. It is widely accepted that particles of 0.5 microns or larger are the target. However, some industries are now targeting smaller particles.

Sources of contamination
The facilities, people (patients, nurse and even doctors in hospital and technicians, engineers in other sector), tools, fluids and the product being manufactured can all contribute to contamination. It is important to identify and list all such probable sources the contaminations can spread or to gain a better understanding of where contamination originates.

The sources of the contamination can be divided as external and internal sources. The external sources include air supply and air filtration system, wall penetrations for pipes, cables and ducts etc. The external contamination is primarily controlled by using i) High Efficiency Particulate Filter (HEPA), ii) maintaining slight positive pressure and iii) sealing of space penetrations. The people, process equipment and instruments, process and respiratory emission etc. contribute to the internal sources of contamination. This is controlled by adequate air changes in the cleanroom and restricted entry of people.

Applicable standards
For the design and maintenance of cleanroom, some industries follow an official national, or international, standard, while in other some other industries, the authorities have produced a recommendation, a specification or guidelines.

The most well-known and widely used cleanroom standard in the world, which was originally issued in 1963, is the United States Federal Standard 209. When this was first published it was not a complete standard in the accepted definition of the word, as a major part of it was not mandatory. However, the latest version of it, 209E, which was issued in September 1992, is a complete standard, but has a much more limited scope than the previous versions.

Standards written for the design of cleanrooms are part of a more comprehensive group of contamination control standards. There is a comprehensive survey of the many contamination control standards that are available and this was published by the Institute of Environmental Sciences and Technology (IEST) in the United States and known as the `Compendium of Standards, Practices, Methods and Similar Documents, Relating to Contamination Control; IEST-CC-009’. The 1993 version covers 276 standards, 143 from outside the United States. This document, IEST RP 009.2, has a helpful category listing and gives full addresses of where to buy the listed documents. This revised edition is much more complete than the earlier one, but we must consider that a list of all cleanroom standards will never be completed, as new or revised cleanroom standards are always being developed. During the last 5-10 years there were annually about 30 new or revised cleanroom standards presented in the major industrial nations, covering different applications and written in a dozen different languages. This rate of expansion will now be reduced due to the CEN and ISO work for common, international standards.

Up to the 1990s, the standards were mainly written for use in the countries where they were written. Much work was done by the national standards organizations in the United States, European countries and Japan. Their confederation, the International Confederation of Contamination Control Societies (ICCCS), promotes its international cleanroom standards. ICCCS is also a liaison partner in the International Standard Organization (ISO). Some international organizations like ISO, FIP (Federation International Pharmacie, The Haag, The Netherlands) and WHO (World Health Organization, Geneva, Switzerland), and European organizations like Eurovent and PIC, also wrote standards on cleanrooms at that time. Recently, much work has been done on European standards by CEN in the European Union and by ISO for world-wide standards. The following ISO cleanroom standards with the provisional titles are followed in many countries.

• WG1: Cleanliness Classification by Airborne Particulate Cleanliness
• WG2: Biocontamination
• WG3: Metrology and Testing Methods
• WG4: Design, Construction and Start Up
• WG5: Cleanroom Operation
• WG6: Terms, Definitions and Units
• WGT Enhanced Clean Devices
• WG8: Molecular Contamination

Design criteria
The design criterion for a standard cleanroom is the supply of unidirectional flow of clean air with face velocity of up 0.46 - 0.1 m/s. Air changes per unit of time should not be used with a unidirectional flow room as they are related to the volume of the room, which generally has no effect on the performance of the system. The GMP guides specify the building design, building material, care of personnel, etc and they may also give figures for the cleanliness classes of cleanrooms: particles, microorganisms, as well as the type of air filters and number of air changes per hour.

At present, cleanrooms are designed as per the standards. There are a number of cleanroom design standards available which should be considered. These are listed in Table 1.