Lately, there has been an influx of news reports regarding tainted medications reaching consumers from their favorite drugstores. These are medications that people like you and I might take on a regular basis. At the time of this writing, the dominant headline centers around raniditine, a common antacid for heartburn relief. The recall is widespread enough that consumers at the pharmacy may stop and wonder “is this safe?,” when reaching for their family’s medication. In fact, ranitidine is something I have at home right now. Are such purchases something I should start worrying about? The FDA issued a statement that the impurity found in this medicine, N-nitrosodimethylamine (NDMA), is classified as a probable human carcinogen, meaning that it could potentially cause cancer. Many manufacturers have voluntarily recalled the medicine while the FDA investigates the cause and risk of the contamination. Can this be attributed to poor employee scheduling in manufacturing?

 


What is the cause?

Ranitidine has been manufactured for decades without any known issue, which begs the question: what caused this to happen? The production process has been validated and ongoing since the early 1980’s. Assuming that it has not always had this contaminant present, identifying the contributing factors to this occurrence is critical. Because the drug creation mechanism is well understood, and there are known risks involved, there are mandated checks to ensure that there are no harmful byproducts. What would have caused the process to deviate?

From an equipment operator’s standpoint, it’s not a difficult oversight: these technicians, who may or may not have the intimate process knowledge to monitor for these risks, are scheduled shift after shift performing the same routine tasks. Their job is not to check to see if there has been an irregularity within creation process, but rather, to make sure they follow various sets of instructions correctly, such as adding correct volumes of media, opening and closing valves, and weighing reactor vessels. It is a requirement, however, that employees armed with this knowledge are always present during the production process, to identify and mitigate any anomaly. 
 

FDARecallsAnnually_Ranitidine
Figure 1: Number of FDA recalls issued to USA-based manufacturing sites annually. Class I is the most urgent, and poses serious risk of injury or death, class II is an intermediate threat level, and class III is the least serious

 

Not a new problem

It’s not the first time that this impurity has been identified as a byproduct in pharmaceutical manufacturing. You may remember last year a similar recall on certain blood pressure medications, valsartan and hydrochlorothiazide, due to NDMA levels outside the upper acceptable tolerance. A possible rationale in this instance is an undesirable side reaction from the degradation reaction of a solvent, dimethylamine, under acidic conditions. Whatever the reasoning, it’s important to remember that the FDA requires stress-testing of the manufacturing process before production, and risks in the process are identified and minimized during the design phase with Quality by Design (QbD). So how do we identify the root cause?

 

Where we can help

One factor with high potential to lead the manufacturing process astray is the workforce; specifically, constant change of employees, or lack thereof on the shop floor. When the primary focus is the creation of enough product volume to satisfy the market demand, balancing schedules for workers can become an oversight for the business – and clearly, a large one at that. It can be challenging to find workers with the correct skillset to work shifts to meet timelines during a continuous process, but it’s important to remember that people are not robots, and the longer and more frequently they work, the more likely they are to become fatigued and make mistakes.  It’s not necessarily the root cause of the ranitidine incident, but research has shown a high correlation between human error in manufacturing and repetitive tasks.

Additionally, other sources of contamination could include aseptic technique, like improper hand washing, leading to foreign debris, or poor equipment maintenance. In this realm, any mistake can cause catastrophic results. If overscheduling or managing resources is a problem, employee fatigue and errors are bound to happen – especially in these routine tasks. If resources are limited, it’s tempting to resort to scheduling the same resources - workers - who have demonstrated their capabilities, rather than seeking, onboarding, and training new employees to get them up to speed. Not all risks are preventable due to the volatility of these chemical processes, but when it comes to workforce management, there is always room for improvement.

This is where Kronos comes in. By leveraging machine learning and artificial intelligence algorithms, Kronos HCM solutions can assist in automating complex, time-intensive labor scheduling, particularly for workers who have non-routine schedules. Not only can supervisors free up their time from administrative tasks such as scheduling and managing shifts for more critical tasks, but also, supervisors can ensure that workers have balanced schedules with automated scheduling technology. Both employees and supervisors can get alerted of potential problems and excess overtime. By utilizing strategic labor scheduling, businesses can optimize efficiency and minimize risks. For consumers, that means a safer, more trustworthy product and improved reputation. Though the FDA has not yet identified the root cause of this contamination, why not stay vigilant to mitigate this area of potential risk?

Published: Thursday, October 17, 2019