Contamination control strategies:Types of contamination in Pharma industry

Contamination in Pharma manufacturing facilities is an integral topic of interest and significant concern for manufacturers and regulatory bodies. While Pharma manufacturers are responsible for implementing contamination control strategies, regulatory bodies are responsible for establishing such guidelines.

In this regard, the role of regulatory bodies is crucial because pharma manufacturers are responsible for following guidelines laid down by regulatory bodies. If regulatory bodies fail to establish an effective contamination control strategy, all efforts of both these bodies and pharma manufacturers will result in vain.

What is contamination control?

Contamination control is the processes, steps, or controls that prevent, minimize, or reduce contamination in pharma manufacturing processes. Since there are a number of stages and processes involved, there are various types of controls to prevent contamination.

Contamination control is implemented for every part or component directly or indirectly involved in pharmaceutical manufacturing processes. For example, the building in which Pharma manufacturing is being carried out must also be part of the contamination control strategy.

Regulatory guidelines

As mentioned above, contamination control strategies are defined by various regulatory bodies that must be adhered to by Pharma manufacturers that intend to market or sell their products in their jurisdiction. Compliance to these guidelines is closely monitored by the regulatory bodies during routine inspection, and deviation from the guidelines, could result in warning, and even can result in shut down of operations.

This article will focus on the Unites States FDA, and some common regulatory guidelines related to contamination control are mentioned below.

21 CFR 211.42

It is the United States FDA regulation for finish pharmaceuticals. It's sub part c “buildings and facilities".  Provides guidance to contamination control in their section (b) and c.

This regulations emphasis on adequate space for orderly placement of equipment and material to prevent mix-ups and contamination. Its part [c], emphasis on separate or defined areas or space for operations to prevent contamination or mix-ups

21 CFR 211.46

It is the United States FDA regulations for ", building and facilities", and provides guidance related to ventilation, air filtration air heating and cooling.

It's a part (b) mentions prevention techniques for contamination in production area, by having a proper design of material flow through the buildings.

Additionally it's part b States requirement for controlling dirt microorganism humidity and temperature, which are an important contributor in contamination in an area.

21 CFR 211.63

It is the United States FDA, regulation for GMP "equipment". Selection of equipment design, size and location shall provide basic qualities of machine involved in Pharma processes for cleaning and maintenance.

21 CFR 211.65

It is the United States FDA regulation for GMP finished pharmaceuticals. It's a part (a) provides guidance related to part of equipment surface that contacts Pharma product during manufacturing process, and it shall not be reactive, additive or absorptive to alter the product characteristics.

21 CFR 211.67

It is the United States regulation for equipment cleaning and maintenance. It emphasizes on cleaning of equipment and utensils at regular interval to prevent contamination

21 CFR 211.113

It is the United States the regulation for control in microbial contamination. It's part b, emphasizes on written procedure to prevent microbial contamination of sterile drug products

Types of contamination in Pharma industry

There are various types of contamination which are described below.

Physical contamination

Physical contaminants are the types that have a physical existence, i.e., having a particular size, shape, or area. These are generated by any object interacting with the process or area in which production occurs. Usually, they are a small part of a significant object or body that releases these containments due to various material phenomena such as breakage or conversion.

Examples of physical contaminants include hair, foreign objects, and dust particles.

Chemical contaminants

Chemical contaminants have a chemical nature in them. They are reactive and cause reactions when interacting with the product during favorable conditions.

Chemical contaminants affect the therapeutic effects of medicine, cause changes in chemical properties, or even become dangerous for patients. In some cases, chemical contaminants affect the physical appearance of a product, such as color or odor.

Microbiological containments

Microbiological containments are tiny organisms that are not visible to the human eye. Examples include bacteria and fungus spores. These are commonly present in the environment and can interact with the pharmaceutical product through various mediums such as human contact, cross-contamination, and any contaminated objects.

Cross-contamination

Cross-contamination is caused by the material of another batch or product not intended to be part of a particular product. Its primary disadvantage is that the product becomes dangerous for patients, as it does not remain pure, and its constituents differ from the label mentioned on the packaging.

Some common causes of cross-contamination include the following.

·        Sufficient cleaning of a machine, after completion of batch or at the end of the day, traces from the previous product batch in the machine contaminate the current production process and product.

·        The inadequate exhaust system in the area causes traces of products from other products and from the environment to interact with the product. Because inadequate exhaust causes the traces of development to remain in an area instead of being kept out

·        Improper gowning and protective measures by personnel. They must have and use separate gowning for the production area and other areas. Every time they go out of the production department, they must change their gowning, and in any case, must not use gowns for the production department in other areas or departments. Otherwise, the gown will contaminate the product from the contaminants in the area they visit.

·        Improper separation between production areas regarding area, exhaust system, personnel equipment, and accessories.

How to establish an effective contamination control strategy

Many general approaches for implementing a contamination control strategy mainly depend upon the type of process, product, and everything related to these.

However, some common strategies can be defined as follows.

Root cause analysis

This is the first step in implementing a contamination control strategy. Its main purpose is to identify all possible sources of contamination in the Pharma industry. This is an integral step as it forms the basis of strategy. Root cause analysis enables a Pharma manufacturer to determine specific remedial actions.

Risk assessment

After the determination of root cause, the next step is to assess the risk associated with each root cause. For this purpose, a person must have deep knowledge and understanding of the process.

Risk assessment is carried out by calculating the probability of the impact associated with risk. Risk assessment helps determine the impact of the specific risk and subsequent corrective actions.

Strategy

After the above steps, develop a comprehensive strategy to prevent contamination in critical areas such as processes and facilities.

Some strategies that help establish an effective contamination control strategy are described below.

Facility design

Contamination can be controlled by designing adequate facilities. It includes providing each area of the manufacturing process with required accessories and requirement that prevents contamination in the process and product.

Some common procedures to implement in facility design include the following.

·        Controlling air quality being supplied to production areas

·        Adequate filtration system in each manufacturing and associated phones

·        Monitoring airflow patterns to detect unusual activity and the presence of contaminants

·        Controlling physical variables such as temperature and humidity in different production areas according to the process and product requirement.

Process

Contamination control must also be incorporated in process design to prevent products from different types of contamination. It includes

·        Implementing the latest and innovative technologies, such as continuous manufacturing in critical areas such as sterile production, effectively restricts contamination compared to conventional methods.

·        Implementing various contamination techniques, such as sterilization during product manufacturing

·        Effective cleaning practices according to product requirements

Personal

Personnel working in the area are an easy and frequent source of contamination. Human error can lead to significant contamination in pharma industries.

An important strategy to prevent personnel from introducing contamination in the production area is to train them, enabling them to prevent contamination in the production process.

Personal training can include

·        Importance of contamination control in the pharma industry

·        Impact of contamination on Pharma products

·        Using adequate gowning and PPE

·        Personal hygiene and behavior

Environmental control

The environment is an important source of contamination in the pharma industry. Contamination particles can easily travel from one department, process, or equipment to another without being noticed.

To prevent contamination in the environment, some steps that are integral in controlling contamination include the following.

·        Monitoring environment of critical process for contamination sources. Typical examples include a particle measuring system that helps to determine particle concentration and size in the area. Both automated and manual systems must be used simultaneously. Because, in case of problems with automated systems, manual system can be effectively used

·        An effective Air Handling Unit, complete with all accessories and functionalities, can significantly help to prevent contamination in the production area.

Cleaning

Cleaning involves both equipment and machine, especially after

·        Completion of each product so that its traces do not remain on equipment and area and contaminate other product

·        Cleaning area or equipment after being shut down for a long time. Because it can lead to various problems such as rust and accumulation of dirt, thorough cleaning, in this case, helps to prevent contamination.

About the Author

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.