35th Anniversary Special: The Transformation of Regulation and Global Standards

How FDA, USP, and ICH have redirected industry practice.
Jul 02, 2012
Volume 36, Issue 7

Since the initial introduction of Pharmaceutical Technology in 1977, many regulatory and compendial initiatives have transformed the way the industry does business not only in terms of global partnerships and supply chain management, but also in the laboratory and on the manufacturing floor. PharmTech's reports and special-themed issues have offered invaluable guidance and interpretation to the industry over the years when new standards and guidances are released. Some of the events and issues discussed in this publication have had long-term impact with respect to how the industry operates today. This roundup article highlights some of the organizations and key influential events that have shaped the pages of PharmTech and the way our industry works.

US Food and Drug Administration (FDA)

Tamper-resistant packaging regulations (1983). In September 1982, several deaths resulted from cyanide poisoning in Chicago, IL, and its suburban area. The investigation determined that the common denominator between the victims was taking Tylenol. Johnson & Johnson, the manufacturer of Tylenol, was ruled out as the source of contamination but on Oct. 5, 1982, the company issued a nationwide recall of an estimated 31 million bottles. This incident prompted the passing of tamper-resistant packaging regulations, which made it a felony to tamper with packaged consumer products. The industry developed standards for tamper-resistant packaging that are still used today.

Orphan Drug Act (1983). The Orphan Drug Act was passed in 1983 to encourage pharmaceutical companies to develop medicines for patients with rare diseases. Companies were given 7 years of exclusivity and tax incentives for pharmaceuticals that qualified for orphan-drug status. This act has lead to the successful treatment of or medical management of diseases such as multiple myeloma and cystic fibrosis. Before this law was passed, there were approximately 38 drugs approved to treat rare diseases. From 1983 to 2010, FDA approved 353 orphan drugs and granted orphan designations to 2116 active compounds.

Generic-drug scandal (1989). The generic-drug scandal began when a generic-drug manufacturer submitted a complaint to regulators after experiencing repeated delays in approval of its ANDAs. The complainant charged that FDA was discriminating against the generic-drug firm in favor of other companies. Three FDA officials plead guilty to accepting bribes from companies and two companies plead guilty to offering bribes to FDA officials. Ultimately, 13 generic-drug manufacturers were investigated for fraudulent practices and several products were recalled. This incident resulted in an increase in requirements for ANDA submissions. Today, about 65% of the prescriptions written are for generic-drug products, but it has taken this segment of the industry about two decades to recover from the 1989 scandal.

The Barr decision (1991). The Barr decision was the direct result of FDA investigations into questionable quality control practices for the handling of out-of-specification (OOS) results. FDA took Barr Pharmaceuticals to court for the perceived practice of testing products into compliance. Judge Wolin of the US District Court for the District of New Jersey presided over the proceedings. The result of the Barr decision changed the practice of how manufacturers' investigate laboratory results that do not meet specifications, and on how the industry determines whether a product meets it quality attributes.

Heparin adulteration (2006–2008). In late 2006, a leading pharmaceutical company recalled several lots of life-saving heparin after receiving numerous reports of adverse events, namely allergic reactions. The company ceased production of the product and began investigating the cause of the incidents. Approximately one month later, FDA issued a Public Health Advisory to the medical community, warning the public and healthcare providers not to use heparin. The company recalled all lots of the product, which was ultimately linked to more than 350 serious adverse reactions and several patient deaths. Contaminated API supplied by a manufacturer in China caused the reactions. This incident impacted the industry because it expanded the definition of supply chain and made companies responsible for the quality of all the ingredients going back to their root source, which in some cases turned out to be several layers deep. New focus was given to the importance of supplier audits, and several trade organizations began focusing on developing third-party audit capabilities to assist the industry in dealing with the vast amount of suppliers sourcing material to the pharmaceutical industry. The incident, for example, spawned a new trade organization, Rx–360, an international supply chain consortium, and redefined the concept of supply chain integrity.

Biosimilars guidances (2012). In February 2012, FDA issued three draft guidance documents regarding biosimilars. The agency announced that "the draft documents are designed to help industry develop biosimilar versions of currently approved biological products, which can enhance competition and may lead to better patient access and lower cost to consumers." These documents opened the door to generic-drug products in an area where there has been little competition to innovator products.

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