Controlled area in Sterile Pharmaceutical Manufacturing : Pharmaguideline

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Controlled area in Sterile Pharmaceutical Manufacturing

All pharmaceutical products are manufactured in controlled areas where the environmental conditions are controlled and product remain safe from temperature, humidity and contaminants during manufacturing.
A controlled (classified) area is an enclosed environment or room with a flawless control over particulate contamination. More specifically, the areas have a controlled contamination level, which is specified regarding the number of particles for every cubic meter, for a specified particle size. The restricted areas are constructed with impeccable humidity, temperature and pressure control to minimize the generation, introduction, and retention of particulate matter inside the rooms.

Used for sterile pharmaceutical manufacturing, the controlled areas ensure low levels of environmental pollutants, such as airborne microbes, dust, aerosol particles and chemical vapors. The classified rooms help the sterile pharmaceutical industry to manufacture products that are free from particulate and microbial contamination. Indeed, sterile pharmaceutical controlled rooms are clean rooms that are fitted with HEPA filters, and dehumidifier systems to allow preparation of pharmaceutical products in a moisture-free and contamination-free environments. Today, controlled area (classified area) and its use in sterile product manufacturing have grown in leaps and bounds.
Controlled Area

Objectives of Using Controlled area in Sterile Pharmaceutical Manufacturing

In the sterile pharmaceutical industry, the core objective of using controlled rooms is preventing contamination and ensuring that preparations are completely sterile. The rooms help to eliminate contamination with chemicals, bacteria, electrostatic charges, particles, and fibers. Since, sterile pharmaceutical products should not introduce undesirable particles, chemicals, and bacteria into the patients, the controlled area (classified area) and its use in sterile product manufacturing have become a critical quality assurance step for every drug company. Similarly, because most surfaces of controlled rooms are made of poor conductors, they can easily develop and retain undesirable electrostatic charges. Hence, the surfaces are cleaned and controlled in such a fashion that the charges can be conducted away as soon as they are formed.

Sections and Classification of Controlled area in Sterile Pharmaceutical Manufacturing

A sterile pharmaceutical controlled area is principally divided into two sections: the general area and the critical area. The general area is the section of the rooms where the existence of contaminants will not directly influence the sterility of products. The general area should, however, be properly cleaned and controlled to avoid the transfer of contaminants into the critical area.

The critical area is the section around the production point, where any contaminants may gain direct access to the preparations. The critical area is usually protected using localized Laminar-Flow workstations and clean benches.

Ensuring Complete Sterilization

To manufacture completely sterile products, various stages of product processing such as component preparation, filling and product preparation should be performed in separate sections of the controlled area. Hence, manufacturing operations should be divided into stage-wise sterilization (for every stage) and terminal sterilization (for the completed preparations).

To achieve thorough stage-wise sterilization, the controlled room should allow for at-rest and in-operation states. At-rest state means the production equipment in the classified room operates without the presence of personnel. On the otherhand, in-operation state means the manufacturing processes are run by a specified and limited number of personnel.

Therefore, the sterile pharmaceutical company should grade its controlled production into four levels: A.B, C and D. Grade A should be the zone for high-risk operations such as the filling zone and the zone for making aseptic connections, open vials and ampoules.

The zone should have laminar airflow systems with homogenous air speeds. Grade B should be the background environment for grade A, allowing for aseptic preparation and filling. Grade C and D should be classified areas that handle the less critical stages of sterile product manufacturing.

Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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