4 Strategies To Prevent Manufacture And Distribution Of Substandard Medications

By Michael Esposito, TrainReach Consulting, LLC

In my article “5 Strategies To Combat Counterfeit Drugs And Other Pharma Supply Chain Threats,” I dealt with drugs that were deliberate counterfeits. However, deliberately fake meds aren’t the only prescription drug-related threat to public health. If a legitimate product is not manufactured according to quality standards or becomes degraded as it travels through its supply chain, it can be ineffective at best or deadly at worst. Examples of potential dangers that can occur include temperature excursions, inappropriate use, and unsafe ingredients inadvertently added to the product.

Separating the issues of counterfeit and substandard medications is a difficult proposition. Because the harmful effects of both on consumers are similar, they are often dealt with together. Organizations such as the USP’s Promoting the Quality of Medicines (PQM) program combine the two instances within the scope of their work.¹ The major difference between the two is that much of the control of substandard medications resides with the company and its supply chain, whereas counterfeit products involve combating a rogue supply chain created and deliberately hidden from view by malicious actors.

However, in terms of effect, substandard pharmaceutical product is a worldwide issue on a par with counterfeiting. The following examples illustrate how the origins of such cases can vary but lead to similar deadly results. In the case of tainted cough syrup that caused at least 400 deaths in Panama in 2006, an inactive ingredient was the culprit when diethylene glycol, a poisonous substance used in antifreeze, was sourced by a Chinese manufacturer.² In another instance, heparin sourced from China and used in a product made by Baxter Laboratories led to 149 deaths in the U.S. in 2007 and 2008. While there was no deliberate malicious intent, there was a neglect of quality that led to the tragic result. These and other events have raised questions about the quality of active ingredients sourced from many countries and used in products manufactured and marketed in the U.S. Roger Bate, author of the book Phake: The Deadly World of Falsified and Substandard Medications, notes, “I have come across many examples of manufacturers, traders, and even pharmacists and doctors who think only about increasing profits by any means they can get away with, as if making, selling, or prescribing substandard medical products were no different from faking designer-clothing labels.”³

Substandard product can exist even if the product itself is manufactured according to quality standards. Muhammad H. Zaman, in his book Bitter Pills, recalls his visit to a warehouse in Ghana that had no climate control, with temperatures in the warehouse reaching 95 degrees Fahrenheit.⁴  Recently, Allergan’s Taytulla birth control products were recalled due to the packaging of active tablets and inert tablets in the wrong order, potentially leading to patients likewise taking the tablets in the wrong order and not obtaining the desired result. Allergan stated, “As a result of this packaging error, oral contraceptive capsules that are taken out of sequence may place the user at risk for contraceptive failure and unintended pregnancy.”⁵

Harm to patients and damage to a company’s reputation are the two most obvious consequences of substandard product. Yet, many companies pay too little attention to these problems, preferring short-term gain over long-term reputation and profitability. Within companies, it is common to hear the argument that quality is a cost center and does not directly contribute to the company’s profits. While the quality function is obviously not the same as sales and marketing, prevention of losses due to quality issues (e.g., product recalls) or remediation (e.g., addressing lawsuits or FDA enforcement actions) affects the bottom line every bit as much as sales.

Despite how these discussions often play out in the corporate world, profitability and quality can indeed coexist and complement each other. There are many tried-and-true examples of how an intelligent approach to quality can avert disaster and, even more, proactively address potential issues before they arise and save the company both money and damages to its reputation. In addition, other quality enhancements are available that can be incorporated by small and midsize companies as well as large companies. Here are four strategies that can help your company avoid inadvertently producing or distributing substandard medicines.

1. Maintain a robust quality system.

Your company’s proper oversight of its sourcing, manufacturing, and distribution is your first, best defense against substandard medication. You should already have a quality infrastructure in place, but it is worth highlighting a number of critical activities within quality that may be compromised in cost-cutting operations. These activities consist of, in part:

• Proper vetting of ingredient suppliers by a supplier quality unit.
• Quality incorporated into the entirety of the manufacturing, packaging, warehousing, and distribution process.
• Controlling temperature excursion by using appropriate packaging, particularly with products that require refrigeration throughout their life cycle (i.e., cold chain products).
• Traceability of product from its manufacture to its consumption by the consumer.
• Prompt and thorough investigation of deviations and complaints.

Unfortunately, the quality infrastructure is prone to staff reduction because its activities do not lead directly to profit. However, a middle ground can be obtained between profitability and quality by using a risk-based approach to help distinguish critical quality issues from those less likely to cause harm to patients. Dealing with similar resource issues, the FDA itself developed a risk-based approach to maximize the effectiveness of its oversight operations. The FDA asserts, “We believe we have created a framework that will streamline the quality review of many products, allowing us to use our valuable resources in a more efficient manner.”⁶

2. Join industry and governmental efforts to improve product quality worldwide. Most large pharma companies recognize the value of teaming up with other segments of their industry, as well as government agencies and transnational organizations such as the World Health Organization (WHO), to address common problems. In my article on combating counterfeiting, I highlighted the work of the organization GS1 in verifying product integrity at different points in the supply chain via barcoding and other methods. In addition to increasing product security, the solutions enable companies to track their products more effectively and assist healthcare providers in keeping accurate records of the products they dispense. GS1’s programs also enable participants to keep track of new regulatory requirements and learn how companies have addressed them.⁷  Another worthy initiative is the aforementioned USP’s PQM, which is dedicated to helping developing countries improve their ability to manufacture and test product according to accepted GMP standards, as well as strengthen regulatory oversight in those same markets, while avoiding costly measures that may not be sustainable in those markets.

3. Explore new technologies such as blockchain to bolster product integrity.

My article on counterfeit medicines explored the use of blockchain to impede counterfeiting. The same technology can be used to preserve vital data related to product manufacture and distribution that confirms its quality throughout the supply chain. China’s recent crisis in the safety and efficacy of its vaccines has led to the exploration of blockchain as a possible solution,⁸ following the example of major pharma companies partnering with Chronicled, Inc. and The LinkLab to create The MediLedger Project.⁹

4. Make a hardheaded assessment of risk and reward when assessing cost reduction initiatives.

Cost reduction is a vital activity of any company that wishes to stay profitable. Still, saving money by risking quality, in the long run, leads to spending more money. You’ve probably heard the expression, “Why is there enough time to do it over but not enough time to do it right?” Regardless of the size of your company, it cannot afford to take the hit of a damaged reputation, which can take years to overcome. Johnson & Johnson’s Consumer Healthcare division spent years and millions of dollars to address quality issues that led to a class-action lawsuit against the company, a consent decree of permanent injunction, and a Congressional investigation.¹⁰ The entire industry learned from Johnson & Johnson’s costly experience, which serves as a cautionary tale highlighting the importance of assuring product quality. You can likewise learn from these experiences and maintain the integrity of your products.

References:

1. PQM - Promoting the Quality of Medicines https://www.usp-pqm.org
2. Australian Broadcasting Commission (The ABC), “Five jailed in Panama over toxic cough syrup scandal that killed hundreds,” July 30, 2016, https://www.abc.net.au/news/2016-07-30/five-jailed-in-panama-over-toxic-medicom-cough-syrup-scandal/7674760
3. Roger Bate, Phake: The Deadly World of Falsified and Substandard Medicines (Washington, DC: AEI Press, 2012), pp. 11-17, 21.
4. Muhammad H. Zaman, Bitter Pills: The Global War on Counterfeit Drugs (Oxford: Oxford University Press, 2018), p. 2.
5. KFOR Channel 4 (Oklahoma), “Allergan birth control pills packaged in wrong order,” http://kfor.com/2018/05/30/drugmaker-recalls-birth-control-pills-packaged-in-wrong-order/
6. U.S. Food and Drug Administration, Pharmaceutical cGMPs for the 21st Century - A Risk-Based Approach: Final Report, September 2004 https://www.fda.gov/downloads/drugs/developmentapprovalprocess/manufacturing/questionsandanswersoncurrentgoodmanufacturingpracticescgmpfordrugs/ucm176374.pdf
7. GS1 Healthcare Event Information https://healthcare-event.gs1.org/
8. Angus Liu, “Could a dose of blockchain prevent China’s vaccine production data problem?”            Fierce Pharma, August 7, 2018, https://www.fiercepharma.com/vaccines/could-a-dose-blockchain-prevent-china-s-vaccine-production-data-problem
9. PR Newswire, “Chronicled and The LinkLab Announce The MediLedger Project, a Revolutionary Blockchain-backed System to Safeguard the Pharmaceutical Industry,” September 21, 2017, https://www.prnewswire.com/news-releases/chronicled-and-the-linklab-announce-the-mediledger-project-a-revolutionary-blockchain-backed-system-to-safeguard-the-pharmaceutical-industry-300522426.html
10. Warren Adis, “McNeil, a Johnson & Johnson Subsidiary FDA Case Study,” Communications of the IIMA: Vol. 14: Iss. 3, Article 2 (2014). Available at: http://scholarworks.lib.csusb.edu/ciima/vol14/iss3/2

About The Author:

Michael Esposito, principal at TrainReach Consulting, LLC, has over 30 years of experience in the pharmaceutical industry and 17 in GMP training and document management. He has worked for Wyeth Pharmaceuticals, Pfizer, and Johnson & Johnson's McNeil Consumer Healthcare Division in a variety of areas, including packaging, project administration, quality assurance, government contracts, translations, systems training, and international operations. He collaborated on the development and implementation of the training portion of the consent decree work plan for McNeil and revised its introductory GMP course. Esposito is a member of the training organizations GMP TEA and the Association for GxP Excellence (AGXPE). His areas of interest include systems training, training effectiveness, post-training user support, process improvement, and sustainable packaging. You can reach him at mesposito@trainreach.com.