Sterilization in the pharmaceutical industry

The pharmaceutical industry consists of different processes that affect the manufacturing process and product differently. Every process is critical and cannot be avoided or replaced by any other because it has a definite effect on product manufacturing.

Some processes are used as a manufacturing requirement; some are included to enhance & check the product quality; some are included to make the manufacturing process & product safe for human consumption, and so on. Sterilization is also one of many and is used to ensure the safety of a pharma product.

Sterilization removes hazardous living & non-living bodies from the item being sterilized. It is performed in a specified equipment. There are various techniques for performing sterilization, which also affect the equipment construction and application.

Sterilization is a mandatory process in pharma product manufacturing and is a process closely reviewed by regulatory bodies during their inspection. The sterilization record becomes part of the batch record, and no manufacturer is allowed to sell or market its product without sterilization.

Sterilization is used in many industries, such as Food & Beverages, but the pharma industry has its own sterilization requirements, types and applications.

Sterilization in the Pharmaceutical Industry 

Sterilization is the process of using high temperatures to remove contaminants, pyrogens, microbial spores, and any object (that could become potentially harmful to the pharma product) from the pharma product. It must also be applied to containers, equipment, accessories or any other item that could come in direct contact with pharma products at any manufacturing stage.

However, for executing sterilization, it is necessary determine its ability to tolerate high temperatures. If for any reason, the item cannot tolerate high temperatures, alternate methods are devised to remove harmful objects.

Its objective is to make patient products safe by removing all objectionable objects. It can be used in several stages where there is a potential for ingress of these foreign bodies.

Sterilization can be achieved using high temperatures through moist or dry heat. Each method has specific applications depending on the items being sterilized, characteristics and foreign objects in consideration.

Whatever the process is, it must be performed based on the guidelines of regulatory bodies or manufacturing principles. It must be suitable for the product and demonstrate efficacy in achieving the required sterilization conditions in all product dimensions.

The sterilization process is monitored by physical, chemical and biological indicators to confirm its authenticity and to detect anomalies in the sterilization equipment and process. Results of these monitoring mechanisms are must be recorded and made part of batch record.

Every item in the product lot must receive the sterilization mechanism. Otherwise, certain products in equipment will not be sterilized and become hazardous for its end user.

The sterilization process must be recorded for later review and presented to the regulatory bodies during their visit. The parameters in the record depend on the requirements of the regulatory bodies, but commonly, it includes the following

· Items being sterilized, such as filter assemblies, glass containers or products

· Time of sterilization

· Set temperature

· Actual temperature, it indicates the efficiency of temperature control system and ensures all items have received the required temperature

As with other equipment and processes in the pharmaceutical industry, both process & equipment for sterilization must be validated according to the regulatory guidelines, and records must be retained and presented to the regulatory bodies.  Please note that the validation is different from the Sterilization record, and is performed by quality department and consist of Installation Qualification, Operational Qualification and Performance Qualification

Types of Sterilization in the pharmaceutical industry

Several methods are being used in the pharma industry for the sterilization process. However, in this article, we will focus on the two most common methods, i.e. Moist Heat and Dry heat.

Most Heat Sterilization

Moist Heat Sterilization is the process of using steam to sterile the items. Water is converted into steam and then supplied to sterilization equipment.

Steam is applied to the equipment at high pressure to create high temperatures, typically 100⁰C to 131⁰C.

The effectiveness of moist heat sterilization depends upon various factors, briefly described below.

Time

Time is defined as the number of minute/seconds the steam is exposed to the sterilised items. Different contaminants or microorganisms have different resistance levels and cannot die or be removed at the same temperature. For this purpose, a D – value is determined, which is the time required to kill 90% of microorganisms. For every organism, D – values are different.

The sterilization time for each product and item depends on various factors, which are determined.

For efficient sterilization results, the time is determined after detailed studies and must not be altered without thorough research.

Temperature

Temperature is another factor that impacts the sterilization process in the pharma industry. It is directly proportional to the pressure of steam through which it is being applied in the equipment. If we increase the temperature of steam, it will reduce the time of sterilization.

Like steam, an item's sterilization temperature is determined after study and cannot be altered.

Dry Heat Sterilization

In Dry Heat Sterilization uses hot air to sterilize the items inside the equipment. The temperature of DHS is around 200⁰C, and the exposure time is around two hours. High temperature is achieved by continuous circulation of hot air. It is best suited for non-aqueous liquid or dry powder products.

It can also be used for glass and stainless steel. The items to be dry heat sterilized must be able to bear high temperatures.

Dry heat sterilization is used to sterilize from bacterial endotoxins, which resists other sterilization means. It is also used to sterilize glass containers before aseptically filing the product.

The circulation air is passed through HEPA filters and then enters the chamber. The function of HEPA is to filter out foreign bodies that may have ingresses into the non-product section of equipment.

Physical and biological indicators monitor the dry heat sterilization process to detect problems with the process or equipment. 

Equipment for sterilization

The two most common methods used in the pharmaceutical industry are autoclave and dry heat sterilizer.

Autoclave

An autoclave is a sterilization equipment that uses most steam to perform the sterilization process. It consists of an enclosed chamber with a jacket around it. It has several ports for different functions.

A centralized door facilitates the autoclave loading & un-loading, which can be closed airtight to prevent leakage in the Autoclave.

It has several physical monitoring sensors, such as Temperature and Pressure. A recording device records the sterilization process with its variables, which becomes part of the batch record for a specific product. Time is also monitored for the integrity of the sterilization process. Besides these parameters, other parameters are also monitored, which are used to track and monitor equipment performance.

The Autoclave can be run automatically (through the main controller) or manually. However, today, most autoclaves operate automatically.

When items are loaded and the door closed, the operator starts the process, commonly divided into the

following stages.

· Pre-Heating is before the sterilization stage, where equipment is heated to the desired temperature. First, a vacuum is created inside the autoclave chamber about 1 – 3 times. Its main purpose is to remove empty pockets created by product placement. The disadvantage of empty pockets is that they resist steam reaching these areas. As a result, temperature is not achieved, and sterilization is not performed. After the vacuum stage, steam is applied until the required temperature is achieved. At this stage, the sterilization phase starts.

· Heating (Sterilization): After the vacuum phase & temperature are achieved in the pre-heating stage, sterilization is started. In this stage, the required temperature is maintained for a specific period. When specific time lapses, the steam is released, and items can be taken out.

· Cooling: In this stage, the air is blown into the chamber so operators can safely handle the items inside.

After completing the autoclave cycle, items are taken out for further process. The record of the Autoclave is also attached in the desired document.

Dry Heat Sterilizer 

Dry Heat Sterilizer - DHS is a sterilizing equipment that utilizes dry heat to perform the sterilization process. It is an enclosed chamber with a provision of trays inside it.

A heater generates heat, and an air blower generates air volume sufficient to circulate throughout the chamber without blockage. The air passes through the heater and heats itself, which is then used to increase the chamber of the DHS chamber.

Like an autoclave, it consists of several sensors and instruments that monitor the process. A main controller is used to control the DHS process without human intervention. It can also be operated manually, but it's rare.

After completion of a sterilizing cycle, the record is maintained for future review.

Like the Autoclave, the sterilizing cycle is divided into three sections.

Pre-Heating - In this phase, the chamber is heated up to the desired temperature

Heating - This stage starts after the pre-heating stage is completed. The temperature is maintained inside the chamber for a fixed amount of time. After the specified time lapses, the heating phase shifts to the cooling phase

Cooling - in this phase, the chamber’s temperature is lowered so that items can be easily unloaded and personnel can easily move around without harm.

About the Author:

Muhammad Asim Niazi

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.