Ethical Dilemmas in Pharma: Pharma's Toughest Decisions

We want to hear about the ethical dilemmas you face on the job. The pharma sector occupies a crossroads of medicine, business and ethics, with numerous pitfalls and dilemmas.

At its core, the sector is dedicated to creating and providing lifesaving and life-enhancing medicines, making it one of the most influential sectors in the world. However, navigating the complexities of pharma ethics is not an easy endeavor. This includes balancing patients' rights, ensuring the safety and efficacy of drugs, managing the cost of drugs and managing access issues—especially in the constantly changing technological landscape involving artificial intelligence (AI) and big data. In my book "Protecting Patients at All Costs: The Drug Watch Dogs," I underscore the quality professionals' responsibility to guard patient safety and the importance of ethical decision-making in all aspects of the biopharmaceutical industry.

One of the most important ethical responsibilities in the pharmaceutical industry is protecting patient safety. Every drug produced must undergo rigorous testing to ensure its safety and effectiveness. Extensive development and validation are needed to ensure manufacturing is robust, reliable and sustainable so that every patient can depend on a safe and reliable drug supply. Millions of lives depend on the guarantee that medication will meet these criteria. As it is laid out in my book, quality professionals are on the front lines protecting patient safety. They ensure that drugs are manufactured by good manufacturing practices (GMP) and that any potential risk to patient health is quickly identified and addressed.

The goal of this article is not to provide advice on how to solve the following ethical dilemmas, but to stimulate conversation and discussions so we can learn from each other. I will state my views, and I know not all of them will be popular.

Dilemma 1: Speed to Market

We have all been there. The next big billion-dollar product is racing to gain U.S. Food and Drug Administration (FDA) approval and market introduction, or everyone is rushing to ensure their generic drug is first filed with the FDA. Both achievements are good for patients and financially good for the company. For example, a billion-dollar drug produces about $3 million daily sales. It can significantly increase a company's stock price, and failure to meet drug approval commitments to Wall Street would cause the stock price to crash. The first generic drug to gain approval receives 180-day market access exclusively, which provides a competitive advantage, greater profits and higher market share.

The tension between speed to market and ethical responsibilities is a daily challenge for pharmaceutical manufacturing, engineering and quality professionals. Upholding patient safety, product integrity and regulatory compliance should always precede business pressures, even when faced with tight deadlines or executive expectations. However, these pressures are daily and create many dilemmas to deal with like the following: the risk of inadequate process validation, cutting corners in equipment and facility qualification, accepting deviation justifications without proper investigation, supply chain shortcuts and ethical sourcing, pressure to override or expedite quality review, data integrity and compliance pressures.

Martin's View: First, let us not call this challenge the "speed to market" but "the speed to the patient." I have always led with the idea of " This sounds easy, but it is very hard and sometimes complex, producing counterintuitive solutions. The above challenge might be one of those situations. I embrace the concept of getting to the market as fast as possible, allowing patients to receive the benefits as soon as possible, which is good for patients if the drug is safe. This is a challenge in balancing the risk-benefit scale. What is important is to slow down for safety and when a risk can be taken to get to the patient faster.

Dilemma 2: Process Improvements Need Regulatory Approval

Nothing is more frustrating than completing a significant investigation and having the recommended corrective action to fix the process to improve process robustness, prevent imminent future out-of-specification results, improve line yields or even reduce costs, only to have regulations say the change cannot be implemented without regulatory approval. Over my 40-year career, regulatory departments have told me the change cannot be a “change being effective (CBE)” or CBE-30; they are too busy to make the submission or do not want to tarnish the company's reputation.

You probably have heard these excuses and many others. So, what would you do?

Martin's View: Remember, "do what is in the best interest of patients." Do not take these responses at face value. Challenge the status quo. Push using persuasion and eliminate excuses with data to take action or escalate your concerns up the management chain. I have a specific example where I was provided with all three of the above regulatory responses related to one improvement.

I was confident the change would qualify for a CBE-30. I did my research, and with determination, persistence and data, I repetitively went back to Regulatory Affairs with the case for the change and the benefit to patients. Eventually, I was successful, but Regulatory Affairs said they were too busy to make the change. So, I prepared the CBE-30 and presented it to Regulatory Affairs, who then told me they did not want to tarnish the company's reputation with the change.

I could not understand how making a science-based process improvement to protect patients would tarnish the company's reputation, so I pushed for an answer. The individual responded that the FDA might say "No." This response to me was illogical. Having someone say no should not be embarrassing. If they say no, nothing changes—the process cannot change—but we now have documentation that we could improve the process, but the FDA has said no.

It is unacceptable to me that a quality professional throws up their hands and says, "I don't have the power to make that change." There are many avenues to pursue to create change. It takes commitment, persistence, determination and some creativity to act.

Dilemma 3: Should a Recall be Recommended

Recommending the rejection of a batch in the pharmaceutical industry is a significant and often difficult decision that professionals face. The dilemma usually arises from a balance of competing priorities, such as patient safety, drug shortages, regulatory compliance, financial considerations and professional integrity.

The foremost responsibility of a pharmaceutical professional is to ensure patient safety. If a batch does not meet the required quality standards, rejecting it is necessary to prevent potential harm to patients. However, rejecting a batch can have significant financial repercussions, such as loss of revenue, production delays and negative impacts on market supply. Deciding between safeguarding patient health and preventing a business loss can be emotionally and professionally challenging, especially considering the potential consequences for the company and the market.

Pharmaceutical professionals may face pressure from management or stakeholders to approve a batch, especially if it is a high-value product, a time-sensitive release or a critical supply. Sometimes, this pressure can create conflict between professional ethics and company goals. Navigating this tension can be difficult, especially when upper management or stakeholders are concerned about the financial impact of rejection. This can lead to the potential compromise of safety for profitability.

Rejecting a batch can disrupt the supply chain, especially if the product is essential for patient treatment or if there are limited alternative sources. This can lead to shortages or delays that may affect patient care. Pharmaceutical professionals must weigh the consequences of a rejection on the supply chain and patient access to the medication, understanding that delays or shortages could lead to a loss of patient trust or even harm. Sometimes, the reasons for rejecting a batch may not be entirely clear-cut. Testing may show borderline results or data discrepancies that could lead to subjective judgment calls in certain cases.

Uncertainty may exist regarding the precise nature of the problem or whether it poses a true risk to patients. Deciding whether to reject a batch based on subjective or inconclusive evidence can be daunting, especially if the decision could be challenged later.

Martin's View: When individuals ask about taking a role in Quality, I have always said that as a Quality Professional, you must be prepared to make decisions that might cost you your job.

I used the following practices when I had to recommend or make such decisions:

• Prioritize Patient Safety
• Use Clear, Data-Driven Decision Making
• Communicate with Transparency and Professionalism
• Engage in Collaborative Problem-Solving
• Anticipate and Mitigate Supply Chain Impacts

To be better prepared to make such decisions, do the following:

• Engage in Ethical Reflection and Training
• Develop Strong Relationships with Management
• Understand and Address Financial Implications
• Foster a Culture of Quality

Dilemma 4: The Role of AI

AI use in drug development, manufacturing and supply has a number of advantages. In drug development, AI can accelerate the discovery process by analyzing huge amounts of data to identify potential drug candidates, predict their efficacy and streamline chemical formulations. This may reduce the cost and time of bringing new drugs to market. AI can optimize production processes by detecting inefficiencies, maintaining consistent quality control and automating repetitive tasks, which can enhance overall efficiency and minimize the risk of human error. AI's capacity to process and analyze real-time data also supports predictive maintenance of manufacturing equipment, avoiding expensive downtimes. In distribution and supply, AI can also make supply chains more rational by accurately projecting demand, tracking inventory, managing logistics for more efficient and timely medicine delivery to physicians and avoiding possible stockouts. I believe the largest impact will be within Quality and Regulatory organizations. I know that at least one company used AI to prepare an entire NDA, reducing the time to file for approval by months. I also know others who use AI to disposition batches, reducing product disposition cycle times by 90%.

However, the use of AI in these areas also poses some disadvantages. One of the primary difficulties is biased algorithms. AI is educated on accessible data, and if the data have underlying biases, the AI will also carry those biases in drug development, potentially missing populations or offering unequal access to treatment. There are legitimate concerns about how to validate AI applications and defend these systems from regulators. Moreover, job loss caused by AI, with automation potentially assuming some roles in manufacturing and distribution, raises questions surrounding the future of workers. Finally, while AI can potentially make a product more efficient, its effectiveness is contingent upon the quality of information it works with, and poor-quality or incomplete data can lead to faulty results in drug development, manufacturing or supply chain management. Hence, while AI promises a lot to revolutionize the drug industry, it must be implemented wisely, ensuring that ethical guidelines and security checks are in place to negate these risks.

Martin's View: AI will quickly be adopted in biopharmaceutical manufacturing. Some professionals will resist this change, but as the saying goes, "resistance is futile." I have embraced AI and am developing skills to use it to benefit my daily life. Those professionals who resist at every turn will become dinosaurs. The future for pharmaceutical professionals who do not embrace it is bleak, but the future for patients is bright.

Moving into the Future in Pharma

As the drug industry evolves, it is more and more important to re-evaluate its ethical conduct. The balance of profiting on the one side and ensuring the safety, affordability and availability of drugs is acceptable. Corporations are not only obligated to report profit but also to work towards world health and well-being. Transparency, honesty and commitment to the highest ethical standards are crucial in rebuilding public trust and ensuring that patients remain the business's highest priority.

Our actions should focus on the necessity of creating a "culture of quality" within pharmaceutical firms. We must engender an energetic patient safety strategy, one that is underpinned by vigilance, ethical leadership and the fortitude to act accordingly, even under intense corporate pressure.

For more, see Safety First: Human Safety in Pharmaceutical Companies. The responsibility to protect patients at all costs is not only a moral but also a professional one, requiring a continuous commitment to safety principles, integrity and patient-centered care.

Overall, the challenges for the pharmaceutical industry are complex and compounded. From safeguarding the patient's safety and well-being to addressing the growing frustrating issue of drug pricing and access, the industry must seriously address these issues. The development of AI and data analytics adds new risks and opportunities, making it even more critical for the pharmaceutical industry to be transparent, accountable and conducted ethically. In this manner, they can continue serving as trusted guardians of public health, ensuring that patients are safeguarded and access to life-saving drugs is maintained.

Summary

To address these multifaceted ethical dilemmas, the industry must prioritize transparency, patient safety and integrity. Implementing comprehensive ethics training, fostering open dialogue among stakeholders and adhering strictly to regulatory standards are essential steps. How would you handle each situation? I encourage you to comment on the challenges faced by biopharmaceutical professionals on the PDA LinkedIn page.