Like many industries today, the pharmaceutical industry is under enormous pressure to reduce its expenses and its prices. The industry acknowledges its responsibility to the environment, shareholder expectations, and society as a whole. This concept is called the triple bottom line, and it incorporates the company’s financial, social, and environmental performance. As a result, an increasing number of companies are investigating how sustainable, green technologies and practices can help them stay competitive in a challenging regulated market. 

Unlike other sectors, the pharmaceutical industry must comply with stringent current good manufacturing practice regulations. Decisions about green, sustainable, and energy-saving opportunities cannot be based on financial considerations alone. It is imperative that all systems, processes, equipment, and facility designs be reliable and not compromise drug efficacy and safety. Being green in the pharmaceutical industry begins at the intersection of business, innovation, compliance, and the environment. 

Establishing a sustainability team is a good way for a company to start being green. The sustainability team sets performance goals, benchmarks green practices, assesses employee awareness, and identifies the need for training. The team also monitors, analyzes, and reports on the progress the company is making in the program. 

The process of developing a sustainability program and incorporating it into a pharmaceutical operation should first identify the direct effect the operations have on the environment and establish a base line of the company’s greenhouse gas emissions (often referred to as its carbon footprint). Businesses must realize that they affect the environment both directly (e.g., through the emissions from their buildings and processes) and indirectly (e.g., through the amount and type of power they consume). Finally, the program must evaluate the supply chain’s effect on the environment, including impact from sources such as product transportation, commodity production, waste disposal, outsourced materials, contractor-owned vehicles, and employee travel. A sustainable procurement strategy can foster efficiency, conserve utilities, and reduce waste in the supply chain.

The techniques for improving sustainability, and their corresponding risk to the product, vary with their function and relation to the product. For example, a typical office building poses no product risk, but a sterile finishing facility has an immediate effect on the product. Accordingly, a company must assess the risk of all activities, including proposed green activities, within the sterile facility that could affect the product. 

The processes of designing, constructing, and renovating facilities offer many opportunities to improve sustainability. One way to track and assess the sustainability projects is by using the US Green Building Council’s (USGBC’s) Leadership in Energy and Environmental Design (LEED) certification program. The LEED program is a consensus document that uses a point system in various categories to score a building on its environmental impact. Although the LEED program is not specifically focused on pharmaceutical facilities, using the LEED scoring system to evaluate capital projects during their conceptual phase enables companies to identify green elements that can be incorporated into the project. The scoring system challenges companies to compare and evaluate alternatives to obtain more points and thus is a way to track green and sustainable features during the design phase. 

Another sustainable practice is green chemistry. Green chemistry has influenced research and product development for several years. The Environmental Protection Agency’s annual Presidential Green Chemistry Challenge has recognized companies such as Pfizer, Merck, Bayer, and Eli Lilly for finding green synthetic pathways and promoting green reactions. One of the keys of green chemistry is to analyze the process of synthesis early on during the development of a new chemical entity and incorporate the notion that it is better to eliminate waste in the beginning than to clean it up at the end. Using this guiding principle, a chemistry team can seek alternative synthetic methods that use less toxic and hazardous material and produce greener reactions.

On average, it takes 7–11 years to move a drug from development phase to approval, and many potential products fail. Manufacturers must follow the various regulatory steps for investigational new drug applications and file a new drug application. Once a product is approved by the US Food and Drug Administration, changes to the process are hard to implement. Thus it is imperative to perform a green assessment of the manufacturing process during the drug-development stage. Performing this assessment and incorporating sustainability early in development will yield benefits during the manufacturing process and for the company’s triple bottom line.

Mark A. Butler is a general manager of engineering services and principal at Integrated Project Services.

Articles

In the Mixer

The concept of the the triple bottom line incorporates a company's financial, social, and environmental performance. As a result, an increasing number of companies are investigating how sustainable, green technologies and practices can help them stay competitive in a challenging regulated market.

How to Be Green in a CGMP-Regulated Environment

Decontaminating pharmaceutical manufacturing facilities is essential for producing safe and pure drugs. The most commonly used decontaminant in the industry has been sublimated formaldehyde. In June 2004, however, the International Agency for Research on Cancer classified formaldehyde as carcinogenic to humans. The US and most world health organizations now recognize formaldehyde as a carcinogen or a possible carcinogen for humans. Although some companies still use formaldehyde, the pharmaceutical industry is looking for alternative decontaminants.

Chlorine dioxide and vapor-phase hydrogen peroxide (VPHP) have emerged as popular replacements for formaldehyde gas. These decontaminants share several characteristics. Both compounds can be used in an automated decontamination process, and a process using either agent can be validated easily. Neither chlorine dioxide nor VPHP leaves a residue or causes cancer. But is one agent superior to the other?

Mark Czarneski, director of technology at ClorDiSys Solutions (Lebanon, NJ), says chlorine dioxide “offers the most thorough decontamination possible in the safest manner.” Chlorine dioxide is a gas at room temperature, thus it achieves comprehensive distribution and good surface coverage throughout a room. Because chlorine dioxide gas is a small molecule, it penetrates into small areas. 

Another benefit of chlorine dioxide is its fast aeration time. Aeration removes a decontaminant from a room. Czarneski explains that 15 air exchanges bring the amount of gas in an area below the 8-h safety level set by the Occupational Safety and Health Administration. Fast aeration time results in a fast overall cycle time, which also enhances safety. Operators can decontaminate isolators in as little as 1.3 h, and rooms in 3.5 h. These characteristics make chlorine dioxide “an excellent decontamination agent, independent of external factors,” Czarneski adds.

Adam Warner, east coast sales manager for BIOQUELL (Horsham, PA), indicates that VPHP has certain advantages over chlorine dioxide. For example, VPHP can be used at a wide humidity range, but chlorine dioxide gas must be kept at a relative humidity of at least 70% to be effective. Also, containment is not a significant concern in VPHP decontamination, as it is for chlorine dioxide. It’s sufficient for personnel to seal entry and egress points with tape during VPHP contamination, but far more precautions must be taken to prevent chlorine dioxide gas from leaking from a room.

Warner also argues that VPHP is safer than chlorine dioxide. Unlike chlorine dioxide, VPHP breaks down without a catalyst. Its byproducts are water and oxygen, which are innocuous. In addition, he observes that the National Institute for Occupational Safety and Health set an 8-h exposure limit of 0.1 ppm for chlorine dioxide. In contrast, the 8-h limit for VPHP is 1 ppm. Furthermore, the level at which chlorine dioxide is considered immediately dangerous to life and health is 5 ppm, but that level is 75 ppm for VPHP.

VPHP decontamination has a long cycle time, however, which may lessen the safety advantage of the compound’s higher exposure limits. Often a room must be aerated overnight to remove the VPHP, Czarneski says. The aeration step accounts for the decontaminant’s long cycle time.

The nature of vapors themselves poses problems for VPHP decontamination, including poor penetration. Also, Czarneski explains that “hydrogen peroxide’s normal state at room temperature is a liquid, so it will always condense out,” which limits its distribution. A dry process of VPHP decontamination reduces condensation and thus offers better distribution. But the dry process “can only reduce the condensation and not eliminate it,” according to Czarneski.

An important similarity between the two compounds is that Steris’s (Mentor, OH) dry VPHP and ClorDiSys’s chlorine-dioxide processes are both registered as sterilants by the Environmental Protection Agency. This designation means both agents provide the maximum kill and are considered to be highly sporicidal under stringent test conditions. 

Chlorine dioxide and VPHP have different requirements, strengths, and weaknesses as decontaminants. But their designation as sterilants shows that the two compounds have equivalent efficacy. It is not clear that one agent is superior to the other, and a pharmaceutical manufacturer’s choice may be determined by preference.

Production Lines

Decontaminating pharmaceutical manufacturing facilities is essential for producing safe and pure drugs. The most commonly used decontaminant in the industry has been sublimated formaldehyde.

After Formaldehyde: Comparing Alternative Decontaminants

OYSTAR Manesty  
 Tablet press produces scalable results


 The fully automated, single-station “Flexitab” tablet press from OYSTAR Manesty (Fairfield, NJ) is designed to produce results similar to those of a rotary press. The device’s two punches are each controlled by one pneumatic and one hydraulic cylinder, which help the unit achieve the same punch travel velocity and force as a rotary press. Scientists can “optimize a formulation with only a small amount of material,” according to Nic Michel, vice-president of OYSTAR USA’s process division.

 In addition, the Flexitab machine produces single layer, bilayer, and trilayer tablets. Three hoppers are mounted on the press’s die table. Each hopper has a pneumatically driven slide-feeder mechanism that automatically fills each tablet layer and compresses between each layer.

 Michel adds that operators can set the unit’s dwell time and punch displacement and store various compression profiles in the device’s memory.

Hawk
 Detectors incorporate adjustable sensitivity


 Hawk (Melbourne, Australia) has added microwave-beam blockage-detecting systems to its “Gladiator” series of level-detection switches. The units use microwave energy, which penetrates plastic, glass, ultrahigh-molecular-weight polyethylene, PTFE, firebrick, and ceramic materials. The devices do not suffer from false tripping or fail to respond like traditional tilt switches, according to Hawk.

 The system’s sender transmits rapid bursts of microwave energy to a corresponding receiver, which can be mounted as far as 100 m away. The presence or absence of the signal at the receiver switches a relay for indication or control purposes. The detector’s sensitivity is adjustable, and operators can allow the system to tolerate buildup or changes in material properties. 

 Systems are available in remote and stand-alone configurations and are not intrusive to manufacturing processes. The product is suitable for blocked-chute detection in wet-, dry-, and bulk-material conveying and transfer systems. 

PharmTech's monthly newsletter, Equipment & Processing Report, reviews the Editor's Picks for the August 2008 edition from OYSTAR Manesty and Hawk.

Equipment and Processing Report-08-20-2008

How to Be Green in a CGMP-Regulated Environment

After Formaldehyde: Comparing Alternative Decontaminants

August 2008 Editor's Picks: Products from OYSTAR Manesty and Hawk