Humidity Consideration in Pharma Industry

The pharmaceutical industry is governed by various restrictions in drug manufacturing during the entire product life cycle to achieve product quality and safety. One of many is humidity, which effects the product, process and equipment.

Like other requirements, humidity control is also enforced by regulatory bodies.

Humidity in the pharma industry

Humidity is a critical criterion when designing a manufacturing facility and planning production. Because too much humidity in the environment affects the product, process, and equipment in many ways. If controlled, the product and process can be useful, preventing loss for the pharma organization. 

Normal humidity levels provide optimum product quality conditions and equipment working conditions. 

For these reasons and many more, regulatory bodies worldwide have devised guidelines on humidity control in all critical areas of pharma facilities. In addition to product safety, regulatory bodies review humidity control and other requirements during their routine inspection.

What can go wrong if humidity levels are not maintained?

Some disadvantages of not maintaining humidity in the pharma industry include but are not limited to 

Microbial Growth

Increased humidity causes the temperatures to warm, which is ideal for microbial growth. At low temperatures, microbial growth halts, and they can be effectively prevented from affecting the production process in an area. 

Humidity acts as a an accelerator for microorganisms to grow; if conditions are sustained, they can multiply in large numbers. It has been proved that microorganism causes damage to production process in many ways, and humidity among others is the main cause.

In a complex pharma working environment, it can become difficult to trace them, making them one of the deadliest hazards for the pharma industry.

Microorganisms can affect the environment, floors, and equipment in increased humidity, directly affecting the product being processed. 

It has become a standard and essential requirement to control humidity within specified limits to prevent microorganisms from growing in pharma-critical areas, making it difficult for microorganisms to grow and multiply.

Hazardous for pharma product

High humidity levels cause the pharmaceutical product to absorb moisture from the environment, changing its basic chemical structure and altering the properties of pharma drug products, and making them ineffective. 

Its basic science is that the volume of water in any chemical compound is critical, and if not adequately controlled (not too much and not too little), it changes its properties. Similarly, humidity alters the moisture content of pharma chemical compounds, and the product deviates from its intended applications. As a result, therapeutic effects of a product are changed. 

In some cases, abnormal humidity causes hazardous organisms such as bacteria and fungi to grow, making the product toxic for human consumption. 

In every case, whatever the scenario is, the product becomes useless for its end user, and the pharma manufacturer has to recall it from the market and destroy it.

Poor equipment performance

High humidity levels affect the equipment's performance during production because the product changes its physical characteristics, such as mass distribution and physical appearance. Since the equipment is designed to operate and perform under specific physical characteristics, these abnormal changes have negative effects. Any abrupt change in normal characteristics makes equipment or its various sub-components problematic during production.

Changes in product characteristics cause frequent clogging in the equipment, especially in bins, piping, and pneumatic components, which are built to handle particular product specifications.

Clogging and blockage also result in vibrations and abnormal noise, further damaging the machine structure. Humidity can also erode or degrade metals used in various equipment, instruments, production accessories, and machine parts. 

Pharma humidity requirements

For the pharma humidity requirements, there are two factors to consider when determining humidity levels: Product and Human comfort.

Human Comfort

Human comfort means humidity at which humans are the most comfortable and can perform their duties without difficulties. Human comfortability becomes more important, because in some areas, personnel have to wear protective clothing and gear

Non – Comfortability often occurs at extremely low humidity levels, as it can make humans feel cold. High humidity levels are not an issues, because high humidity levels are not maintained in the pharma industry.

Product

For the product, the humidity levels must be maintained depending on the product requirements specified by the manufacturer.

Where no humidity range is specified, the humidity must be maintained at less than 60%. Otherwise, manufacturer’s recommendations are considered for a particular product.

How humidity is maintained

The most effective way to control humidity in the pharma industry is by using dehumidifiers. They are specialized equipment capable of maintaining area or product-specific humidity.

Although Heating, Ventilation, and Air Conditioning - HVAC are used in the pharmaceutical industry for maintaining different environmental parameters, they are often designed to provide generalized environmental conditions in required areas.

When stringent requirements are mandatory for specialized products such as vaccines, HVAC can't generate them, or more resources are needed to create specific humidity levels. Dehumidifiers can cost-effectively generate particular humidity levels.

There are two common types of dehumidifiers used in the pharmaceutical industry:  Desiccant dehumidifiers and Condensing dehumidifiers, which we will discuss here.

Desiccant dehumidifier

The desiccant dehumidifier uses a desiccant material that has the natural tendency to absorb moisture. It is used in the form of wheel, which rotates during its operation. Air is made to pass through the wheel, and the absorbing property of desiccant absorbs moisture from the passing air, reducing the humidity of the air. The de-humidified air is returned to the area. 

In another cycle, desiccant is heated through a heater to remove moisture, which is effectively exhausted from the vent. Its purpose is to restore the absorbing capability of the desiccant and continuously provide the required humidity levels.

Desiccant dehumidifiers are capable of generating extremely low humidity levels.

Condensing dehumidifier

Condensing dehumidifiers incorporate the refrigeration circuit for dehumidification purposes, resulting a cold surface upon which moisture condenses, reducing the humidity. It consists of a condenser, evaporator and compresses, much like the refrigeration unit. 

Air is directed the air into the unit, and flows into the evaporator. Liquid refrigerant flowing into the evaporator evaporates the heat from the air, making it cool below its dew point, creating condensate into it. Moisture in the form of water is collected from the appropriate point. 

In the last stage, cool, humid air flows into the area through the condenser of the dehumidifier. 

Condensing dehumidifiers are not able to provide ultra-low humidity levels and are only able to maintain humidity levels at around 45% RH.

What regulatory bodies say about humidity in pharma facility

Let's discuss some regulatory body guidelines for the pharmaceutical industry

United States FDA

21 CFR 211.42 Design and construction features

21 CFR 211 is the FDA guideline for Current Manufacturing Practices for finished pharmaceutical products. Two sections provide guidelines related to humidity

Sec 211.42, “Building and construction feature”, provides the following

Operations shall be performed within specifically defined areas of adequate size. There shall be separate or defined areas or such other control systems for the firm's operations as are necessary to prevent contamination or mixups during Aseptic Processing, including temperature and humidity control

Its subpart C, sec “Ventilation, air filtration, air heating, and cooling, provides the following guidelines.

Equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature shall be provided when appropriate for manufacturing, processing, packing, or holding a drug product.

21 CFR 211.142 Warehouse Procedures

This guideline is about developing and following the warehouse's written procedures. It shall include

Storage of drug products under appropriate temperature, humidity, and light conditions so that the drug products' identity, strength, quality, and purity are not affected.

European Union

The Good Manufacturing Practices -  GMP guidelines for the European Union provide the following guidelines regarding humidity in pharma facilities.

Part 1 - Basic requirements for medicinal products, its chapter 3 “Premise and Equipment” 

According to this guideline, section 3.3

Lighting, temperature, humidity and Ventilation should be appropriate and such that they do not adversely affect, directly or indirectly, either the medicinal products during their manufacture and storage or the accurate functioning of equipment.

Annex 1 Manufacture of sterile medicinal products

8.75 - Before exposure to the gas, materials should be brought into equilibrium with the humidity and temperature required by the process. Where steam is used to condition the load for sterilisation, it should be of an appropriate quality. The time required for this should be balanced against the opposing need to minimize the time before sterilization.

9.6 - Other characteristics, such as temperature and relative humidity, should be controlled within ranges that align with product/processing/personnel requirements and support the maintenance of defined cleanliness standards.

Humidity Monitoring Systems

To monitor and validate humidity in it is necessary to monitor humidity in all critical areas, especially time and temperature sensitive product requiring humidity control.

According to World Health Organization – WHO guidelines, “Temperature and humidity monitoring systems for fixed storage areas”

● Humidity monitoring systems and devices should be used in temperature controlled rooms

● Monitoring sensors should be accurate to ± 5% relative humidity

● Located to monitor worst-case humidity levels within the qualified storage volume

● They should be positioned so as to be minimally affected by transient events such as door opening

● Humidity alarm systems should be linked to the monitoring system(s) with high and low alarm set points

● There should be a visual alarm and preferably also an audible alarm

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.