Insider Solutions: Preventing the Next Heparin Scare

It was only one and a half years ago that a leading pharmaceutical company recalled several lots of a life-saving product after receiving numerous reports of adverse events, namely allergic reactions. The company ceased production of the drug and began investigating the cause of the incidents. Approximately one month later, the US Food and Drug Administration issued a Public Health Advisory to the medical community, warning them not to use this product. The company, Baxter (Deerfield, IL), recalled all lots of the product, heparin, which was ultimately linked to more than 350 serious adverse reactions and several patient deaths. Contaminated active pharmaceutical ingredient (API) supplied by a manufacturer in China caused the reactions.

Susan J. Schniepp

One of the most important issues facing the pharmaceutical and biotechnology industries today is securing the supply chain. None of us want to experience a similar event like the one described above. The problem is figuring out how to manage the supply chain with existing or dwindling company resources. Big companies have large auditing staffs, but even they are unable to audit all of their suppliers on a sufficiently frequent basis because of their diverse product line. Smaller start-up companies often do not have personnel with expertise in supplier qualification and auditing because they are focused on early-stage development, thereby leaving them to trust their contract research and manufacturing organizations (CROs and CMOs) with the integrity of their supply chain.

If the industry learned nothing else from the heparin incident, it learned to verify, qualify, and document everything regarding the suitability of all suppliers. The upside of this learning experience is that there is plenty of help available to companies that want to learn more about shoring up their supply chain.

The Parenteral Drug Association (PDA) offered a two-day conference in September 2008 in Washington, DC, to discuss the pharmaceutical supply chain from a global perspective. The initial conference was so successful that it was refined and repeated three more times: December 2008 in San Diego, March 2009 in Munich, and June 2009 in Shanghai. This series of conferences focused on identifying issues related to supply-chain management and discussing perspectives on how to address identified deficiencies. One key contributor to the series' content was the International Pharmaceutical Excipients Auditing (IPEA) organization.

Founded in 2000, IPEA is an independent subsidiary of the International Pharmaceutical Excipients Council of the Americas (IPEC–Americas). The organization's mission is "to facilitate the assessment of excipient manufacturers to appropriate GMP [good manufacturing practice] standards."

To achieve this goal, IPEA audits pharmaceutical and nutriceutical excipient manufacturing facilities following US Pharmacopeia (USP) and IPEC guidelines on a worldwide basis. IPEA's audit reports provide a basis for confirming that the quality systems used to produce the audited excipient meet the appropriate current GMPs. The leaders of IPEA hope that, "through CGMP audits, deficiencies in excipient manufacturing and packaging can be identified early and potential industry tragedies can be avoided," according to their mission statement. In additon, IPEA has been training industry professionals in CGMP auditing for excipients for several years, demonstrating how far ahead the organization was in recognizing vulnerabilities in the supply chain.

Also stemming from the PDA conferences was the desire of industry supply chain representatives to unite and stay informed of developing standards and current FDA thinking. This desire led to the formation of a new industry group called Rx-360, an international pharmaceutical supply chain consortium whose mission is to: "Create and monitor a global quality system that meets the expectations of industry and regulators that assures patient safety by enhancing product quality and authenticity throughout the supply chain."

This new group held its first formal meeting on June 4, 2009, in Washington, DC. It is unclear what the final role of the consortium will ultimately be, but its leaders indicate they intend to serve in four different capacities: Adopting standards and best practices, technology development to detect tampering in the supply chain, monitoring the supply chain for suspicious activities, and establishing auditing services which may ultimately lead to shared supplier audits.

In September, PDA will hold its annual PDA/FDA Joint Regulatory Conference in Washington, DC. Conference planners are devoting a plenary session and an entire two-day track to discussions about the supply chain. Guidance on constructing quality, technical, and cooperative agreements as well as discussions about products and services available for conducting supplier audits, and good distribution and import practices will be featured topics at the conference. Regulatory authorities are expected to speak in all the sessions to provide their perspective on industry initiatives.

It is important for the industry to secure the pharmaceutical supply chain from starting materials to final-product distribution so that patients can rest assured that they have received safe and effective medicine that does what it is intended to do.

Susan J. Schniepp is vice-president of quality assurance at Javelin Pharmaceuticals, and a member of the PDA/FDA Joint Regulatory Conference 2009 Planning Board, 125 CambridgePark Drive, Cambridge, MA 02140, tel. 617.499.4709, sschniepp@javelinpharma.com