A tragic incident involving the poisonings of multiple Chicago-area residents due to adulterated Tylenol capsules occurred 30 years ago. This tragedy led to new tamper-resistant packaging regulations, many of which are still in place today (1-4).
These current practices, adopted for drug and food packaging, are crucial to production safety standards and security controls to ensure patient safety.
On September 29, 1982, 12-year-old Mary Kellerman from Elk Grove, Illinois, died of cyanide poisoning after taking extra-strength Tylenol capsules (5). Within days, three more similar deaths, seemingly unrelated, occurred in Arlington Heights and Lisle, Illinois. Investigators took notice when even more deaths began cropping up in other Chicago suburbs. With leads from local workers, they discovered the common link between all of these events; all seven victims had ingested extra-strength Tylenol capsules laced with extremely lethal doses of potassium cyanide.
As the details unfolded, it appeared that the adulteration did not occur within the manufacturing plant, but transpired in the retail stores that sold the product (5). Evidence showed that the bottles had been taken from the shelves and the capsules removed. The capsules were then opened, adulterated with cyanide, closed, and replaced in the bottles. Packages were then reassembled and returned to the store. At this time, commercial packages were not glued shut, overwrapped, or otherwise sealed. There were no obvious indications that packages had been opened and product adulterated.
Figure 1: Acetaminophen.
Tylenol (: see Figure 1) is a widely used analgesic and antipyretic indicated for relief of minor aches, pains, and reduction of fever (6). Acetaminophen was very popular during the 1980s at the time of the tragedy (7).
The usual dose of Tylenol ranges from 325-650 milligrams (mg) every four to six hours with a maximum of four grams in 24 hours (6). In peripheral tissues, acetaminophen is a weak cyclo-oxygenase-1 (COX-1) and COX-2 inhibitor. Acetaminophen does not exhibit anti-inflammatory properties or inhibit platelet function. Tylenol was revered as being a “safe” alternative to other pain medications such as aspirin due to its decreased gastrointestinal (GI) adverse events and safety profile (5). Acetaminophen’s half-life is two to three hours. It is metabolized primarily through hepatic conjugation with glucuronide. A small amount is metabolized to N-acetyl-p-benzoquinoneimine (NAPQI), a potentially toxic intermediate if overdose or ingestion with alcohol occurs (6).
The capsule dosage form ingested by victims of the Tylenol
scare has since been replaced by tamper-resistant, gelatin-enrobed capsules, or “gelcaps,” which were among the first of its kind (8).
These “gelcaps” were adopted largely due to the Tylenol
tragedy, as were the tamper-evident, triple-sealed safety containers that have greatly influenced packaging and consumer safety (4).
Many food manufacturers have implemented the practices used for acetaminophen and other over-the-counter (OTC) medications.
Figure 2: Cyanide.
Cyanide (Figure 2) is a highly toxic compound containing the chemical moiety cyano, which involves a carbon atom triple-bonded to a nitrogen atom (9). Potassium cyanide is the substance that was used in the Tylenol murders. Ingestion of toxic amounts of cyanide inhibits cellular respiration by blocking the mitochondrial enzyme cytochrome c oxidase. Low doses of cyanide can lead to weakness, confusion, vertigo, and difficulty breathing, eventually resulting in loss of consciousness and coma. High doses of cyanide are ultimately fatal with pulmonary edema or cardiac arrest possibly preceding inevitable death. A toxic cyanide dose in humans can be as low as 1.5 mg/kg body weight. The amount used in the Tylenol incident was 65 mg/capsule. The victims had no possible recourse for antidote or recovery.
Upon learning of the poisonings, Johnson & Johnson’s subsidiary, McNeil Consumer Products Company, swiftly initiated a total recall of all Tylenol products, one of the largest recalls in American history (8). Roughly 31 million bottles were collected, costing the company $100 million (9, 10). All advertising and promotion for Tylenol ceased and production was permanently halted pending a thorough investigation of the incident. Once it was discovered that the tampering had occurred with capsules, Johnson & Johnson offered to send tablet replacements to anyone who had purchased extra-strength Tylenol capsules. The company also used media facets to notify the nation not to take Tylenol capsules. The Chicago police paraded through neighborhood streets with loudspeakers to warn the public of the potential Tylenol danger.
In the aftermath of these tragic events, Johnson & Johnson was commended for its efforts to prevent further poisonings (8). Commentators remarked how safety was of utmost concern and that Johnson & Johnson put the needs of the public before the financial concerns of the company. The firm also collaborated with other organizations such as US Food and Drug Administration, Federal Bureau of Investigations (FBI), and Chicago Police Department to form a Tylenol task force of more than 100 agents to apprehend the perpetrators (5). However, despite promising leads during the past 30 years, the criminal’s identity is still unknown (10, 11). The initial loss of public confidence notwithstanding, Johnson & Johnson was able to regain market share and sell Tylenol once again due to their diligence that led to positive media attention. For example, according to the Washington Post on October 11, 1982, “Johnson & Johnson has effectively demonstrated how a major business ought to handle a disaster.” (12)
FDA established new packaging guidelines within two months after the Tylenol tragedy (1, 4). By early as November 5, 1982, requirements published in the Federal Registrar mandated tamper-resistant packaging (TRP) for OTC products (2). By 1989, the amended 21 Code of Federal Regulations (CFR) stated that “Each manufacturer and packer who packages an OTC drug product…shall package the product in a tamper-evident package (1).” These regulations and policies implemented after the Tylenol scare fall under two major categories: tighter and more stringent tamper-evident packaging, and innovations for tamper-resistant dosage forms. For example, the hard gelatin capsules tampered with in the Tylenol incident were no longer acceptable under the new compliance guidelines. “Any two-piece, hard gelatin capsule…must be sealed using an acceptable tamper-evident technology (2).” Options listed in the compliance policy guides (CPG) under “capsule-sealing technologies” include “sonic welding, banding, and sealing techniques employing solvent and/or low temperature heating.” (2). Moreover, capsules dosage forms were required to have at least one additional tamper-resistant mechanism on the packaging. All OTC products, with a few exceptions, were now required to have tamper-resistant packaging. Some TRP examples include film wrappers, blister packs, bubble packs, heat shrink bands, foil pouches, container mouth inner seals, breakable caps, sealed metal tubes, and aerosol containers. In addition to the TRP and capsule-sealing technologies, new labeling requirements were implemented. All products with tamper-resistant packaging would alert the consumer on the packaging to the tamper-evident feature. For example, a warning reading “do not use if safety seal is broken” might appear on the bottom of a tablet bottle (2).
OTC medications as well as food, other drugs, and cosmetics currently require multiple layers of tamper-evident packaging to varying degrees (1, 2). The Tylenol murders paved the way for revolutionary techniques within the packaging industry. While initial incidents of copycat criminal tampering increased, these types of events have since decreased due in large part to the actions of Johnson & Johnson as well as FDA. While the nation mourned the victims of the infamous Tylenol scare, the pharmaceutical industry and the US government reacted quickly and responsibly to implement packaging precautions that, to this day, positively impact consumer safety.
- FDA, “Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.”Code of Federal Regulations. Title 21, sec. 211.132, 1989, available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr...
- FDA, “Tamper-Resistant Packaging Requirements for Certain Over-the-Counter Human Drug Products,” Compliance Policy Guides (CPG) Sec. 450.500, available at: http://www.fda.gov/iceci/compliancemanuals/compliancepolicyguidancemanua...
- Fletcher, Dan, “A Brief History of the Tylenol Poisonings.” Time Magazine, Feb. 2009, available at: http://www.time.com/time/nation/article/0,8599,1878063,00.html.
- Persinos, John F., “Consumers Will Pay Little for More Capsule Safety,” Chicago Tribune, May 1986, avaiable at: http://articles.chicagotribune.com/1986-05-25/business/8602070615_1_tamp...
- Beck, M., Monroe, S., Prout, L., Hager, and M. LaBreque, R., “The Tylenol Scare.” Newsweek: United States Edition, Oct. 1982, available at: http://classes.colgate.edu/rbowman/core145/Tylenol_Newsweek.pdf
- Facts & Comparisons, available at: http://online.factsandcomparisons.com/MonoDisp.aspx?monoID=fandc-hcp1002...
- Salazar, D., “The 1982 Tylenol Murders and the Packaging Industry’s Response.” Salazar Packaging Inc., Feb. 2009, available at: http://blog.salazarpackaging.com/sustainable-perspective/the-1982-tyleno...
- Susi, R., “THE TYLENOL CRISIS, 1982,” Effective Crisis Management. Np., 2002, available at: http://iml.jou.ufl.edu/projects/fall02/susi/tylenol.htm
- CDC, “Facts About Cyanide,” Centers for Disease Control and Preventation, 2004, available at: http://www.bt.cdc.gov/agent/cyanide/basics/facts.asp
- Bell, R., “The Tylenonl Terrorist: Death in a Bottle.” Crime Library: Criminal Minds And Methods, Time Warner, 2012. available at: http://www.trutv.com/library/crime/terrorists_spies/terrorists/tylenol_m...
- Friedman, E., “James Lewis, Suspect in the 1982 Tylenol Killings, Submitted DNA, Print Samples,” ABC NEWS, Jan. 2010, available at: http://abcnews.go.com/WN/suspected-1982-tylenol-killer-james-lewis-subpo...
- Kaplan, T., “The Tylenol Crisis: How Effective Public Relations Saved Johnson & Johnson,” Pennsylvania State University, Jan. 1998, available at: http://www.aerobiologicalengineering.com/wxk116/TylenolMurders/crisis.html
- Fox News, “Possible Breakthrough in Tylenol Poisoning Case,” Foxnews.com, Associated Press, Jan. 2010, available at: http://www.foxnews.com/story/0,2933,582534,00.html
- Federal Register: 47 FR 50442, 05 November 1982.
- Spink, J., “Tamper-Evident Packaging in Brand Protection,” A-CAPPP Backgrounder Series 1-4, 2012: available at: http://acappp.msu.edu/files/Spink_Tamper.pdf GXP