DEPARTMENTS
RISK
A Holistic Approach to Risk, Part 2
Interviews with Leaders in the Pharmaceutical Industry
BY JULIE ROTH
Editor's note: Read part 1 of this series in the May digital Synergist.
The content in this article stems from separate interviews with risk leaders from the pharmaceutical industry. To preserve their anonymity, the article refers to these leaders by initials only. Their responses have been edited.
QUESTIONS AND ANSWERS
What is your company’s overall approach to risk management?
J.D.: Our company can be broken into two parts, with significant differences in risk. The first business unit is our finished dose sites, which essentially bring all the components together. The components are mixed together to form granules and then the finished form (for example, tablets, capsules, or powders in a bottle). The second business unit comprises the chemical plants. The plants create an active pharmaceutical ingredient, or API, which provides the therapeutic effect. This API is what goes into the finished dose to form the finished product, which the patient receives.
For finished dose sites, our risk management across the organization is a bit siloed. The EHS department manages our overall risks. Our Quality department manages risks related to patients, and our Engineering department looks at fire and environmental risks associated with geographic regions or major disasters. In some cases, our departments will interact with each other when we assess risk; however, risk assessment is largely done independently.
Within the EHS department we utilize a risk matrix to prioritize the greatest risks and find ways to reduce these risks. The use of the risk matrix was largely driven by our European sites, which have regulatory requirements for implementing risk assessments.
Risk assessments are conducted for each new project that we work on. Assessments address ingredients that are going into the process; the categorization of the API using a banding system; any flammable liquids being used; combustible dust properties; changes or modifications needed to existing equipment; containment at source of pharmaceutical powders to meet any containment requirements; personal protective equipment; air emissions; wastewater discharge; waste disposal requirements; and any changes that might be needed to existing training requirements.
For our chemical plants, the API group utilizes a similar risk matrix approach. The assessment is much more detailed for new projects at the chemical plants than for the finished dose sites. Examples include:
- Testing conducted on thermal properties of various chemical reactions
- The calculation for pressure relief valves is evaluated for new and existing equipment
- Evaluations of the potential for runaway reactions and systems to stop those reactions
Hazard and operability studies or similar techniques are used to identify hazards. Risk assessments address air discharge, waste generation, wastewater discharges, handling of the contents of residual tanks or reactors, and cleaning of equipment.
B.N.: Pharma companies take a holistic approach to risk. Occupational toxicologists focus on understanding the dataset for the API and impurities. Industrial hygienists and engineers determine how best to effectively implement the results of the hazard characterization and risk assessment. We have the benefit of human data, which allow us to develop assessments tailored toward the end user. Occupational exposure bands are developed first and are followed by numerical occupational exposure limits. Controls are implemented using parameters that are developed for design of new facilities or processes. Exposure monitoring is conducted to verify that controls are working as designed. Risk communication is critical. Occupational health risk assessments are completed by toxicologists and occupational physicians to put potential exposures into perspective.
How do you manage perceptions of your industry from workers, consumers, and the general public?
B.N.: Risk communication for the consumer (that is, the patient) is achieved through the product labeling (for example, the package insert), which is reviewed by the FDA and other agencies. Patients are also under the care of a physician who understands and communicates the additional factors that may play a part in how a drug interacts with the individual.
Risk communication in R&D and manufacturing operations within the pharmaceutical industry is also important. The therapeutic effect that the drug produces in the patient may be considered an adverse effect in workers. Off-target side effects are also possible in both patients and workers handling the drugs.
Risk communication in the pharmaceutical industry can be challenging. Drugs that can have an adverse effect on workers are often therapeutic to the consumer.
JULIE ROTH, CIH, is a health, safety, and environmental manager with Baker Hughes, a GE Company based in Minden, Nev. She is currently the secretary of the AIHA Risk Committee.
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J.D.: We provide training and direction on safe handling practices for each chemical and each process. For API sites, a specific training and dry walk-through are completed prior to the start of each step of a process. Batch records are created, which include important process safety steps. Our Quality organization manages the risks related to manufacturing quality products.
What do you focus on today that was not on your risk radar five or ten years ago?
B.N.: With the upward trend in the use of biologicals, more products are manufactured in solution. This has reduced the amount of powder used within our manufacturing processes. Of course, some biologicals are lyophilized, so exposure to solids has not been eliminated.
With new formulations, drugs are often more potent than they were in the past, which in turn drives the company to institute more rigor around engineering controls. This trend has actually spanned decades.
Within the industry there is a stronger focus on how pharmaceuticals may impact the environment. It is critical to anticipate potential exposure in drinking water from improper disposal methods. Pharmaceutical companies are now setting guidelines for safe levels of exposure via the environment. Risk communication has been important to provide proper perspective when levels of pharmaceuticals are identified within the environment.
The potential impact of antibiotics on the gut microbiome is becoming another area of focus within the industry. Researchers are investigating how the interactions between antibiotics and the microbiome may increase susceptibility to other diseases.
J.D.: Containment at source for potent compounds has been the primary focus over the last 20 years in the pharmaceutical industry. Only in the last five to ten years have vendors provided solutions that help keep powders contained within the equipment. We still have challenges in this area.
In the last ten years, combustible dust has been on the radar. Although there are standards we can use to reduce the risk, there are still a lot of unknowns. Most standards do not differentiate among the specific properties of a combustible dust, such as the minimum ignition energy, which is the minimum amount of energy required to ignite a combustible vapor, gas, or dust cloud. We have some compounds with an MIE less than 10 millijoules (mJ) and some that are greater than 1,000 mJ. The risk of ignition can be substantially different, and therefore controls are needed for materials with low MIEs.
Does your industry talk about risk collectively? If so, how do you share these discussions?
B.N.: External partnerships and various forums allow us to share best practices for banding and setting exposure limits, which results in some consistency within the industry. We leverage ideas for limit setting through participation on expert committees such as the ACGIH TLV and the Occupational Alliance for Risk Science (OARS) WEEL (Workplace Environmental Exposure Level) committees. The NIOSH hazardous drug alert task force has provided another opportunity to interact with stakeholders.
For over 30 years, the annual meeting of the Occupational Toxicology Roundtable has helped drive a consistent approach to setting OELs for APIs and process intermediates. The International Society for Pharmaceutical Engineers, or ISPE, with the help of industry toxicologists and industrial hygienists, has developed a baseline guide called Risk-MaPP that the industry can leverage. This roadmap describes how to incorporate quality requirements from FDA and other countries’ FDA equivalents, but it also includes guidance for protection of operators in manufacturing operations.
J.D.: As an industry, there are areas where we have worked closely together, such as banding systems. Most pharmaceutical companies have a banding system; the systems are similar, but not the same. Toxicologists from the various pharma companies get together to discuss categorization systems and toxicity of materials being handled.
From an industrial hygiene perspective, the pharma companies participate in an annual conference to discuss industrial hygiene activities.
There doesn’t seem to be a forum to discuss combustible dusts at this time, but there could be some benefits to this.
ISPE also provides an opportunity for the industry to standardize.
DRIVING CONSISTENCY
I am grateful to J.D. and B.N. for offering their unique insights into the industry’s overall risk strategy. It is evident that the pharmaceutical industry has an all-inclusive risk approach, with multiple functions within organizations working together to ensure both workers and consumers are protected. The pharmaceutical industry’s avenues to sharing best practices and driving consistency are critical elements for managing risk in an ever-changing industry.
