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Regulatory bodies, standard-setting organizations, and industry seek to tackle the problem of counterfeit drugs and securing the flow of pharma ingredients.
Securing the pharmaceutical supply chain is of crucial importance to drug companies, suppliers, and consumers. The problem of supply-chain security has taken center stage with a number of recent initiatives.
Patricia Van Arnum
Although the problem of counterfeit drugs traditionally has centered on solid dosage drugs, recent drug shortages for injectable cancer medications have triggered concerns over counterfeit versions of these types of drugs. In January 2012, FDA advised that current shortages of injectable cancer medications may present an opportunity for introduction of non-FDA approved products into the drug supply (1). FDA advised healthcare providers to obtain and use only FDA- approved injectable cancer medications purchased directly from the manufacturer or from wholesale distributors licensed in the United States.
FDA advised in January 2012 of promotions and sales of unapproved injectable cancer medications direct-to-clinics in the US, which most likely were administered to patients. Products purchased include a high percentage of sterile injectable medications and medications whose quality could be adversely affected if they are not stored or transported under specific temperatures. Examples of products include unapproved versions of FDA-approved medications, such as Faslodex (fulvestrant), Neupogen (filgrastim), Rituxan (rituximab) and Herceptin (trastuzumab).
In certain circumstances, FDA may authorize limited importation of medications that are in short supply. Such medications are imported from approved international sources and distributed in the US through a controlled network and would not be sold in direct-to-clinic solicitations. If FDA has arranged for limited importation of the foreign version of a medication, information on obtaining that medication is available on the FDA drug shortages website (1).
FDA's notification in January was followed by another problem of a counterfeit version of an injectable drug, Avastin (bevacizumab). In mid-February 2012, FDA warned healthcare professionals and patients about a counterfeit version of Roche's/Genentech's anticancer drug Avastin 400 mg/16 mL, which may have been purchased and used by some medical practices in the US. Avastin is an injectable medicine and is administered to patients in clinics, hospitals, and doctors' offices. The counterfeit version of Avastin does not contain the medicine's active ingredient, bevacizumab, which may have resulted in patients not receiving needed therapy (2).
In a related action, FDA issued letters to 19 medical practices in the US that purchased unapproved cancer medicines that may include the counterfeit Avastin. The counterfeit version is labeled as Avastin, manufactured by Roche. Roche is the company that manufactures Avastin approved for marketing outside of the US. The only FDA-approved version of Avastin for use in the US is marketed by Genentech (a member company of Roche). The FDA-approved version does not include the Roche logo on the packaging or vials. In addition, Genentech's FDA-approved version of Avastin vials and packaging have a 6-digit numeric batch number and expiration dates in a three-letter month and four-digit year format (e.g., JAN 2014). Genentech's Avastin products are safe and effective for their intended uses.
The 19 medical practices in the United States purchased unapproved cancer medicines and, potentially, the counterfeit Avastin, from Quality Specialty Products (QSP), a foreign supplier that may also be known as Montana Health Care Solutions, according to FDA documentation (2). Volunteer Distribution in Gainesboro, Tennessee, is a distributor of QSP's products. FDA requested that the medical practices stop using any remaining products from these suppliers. FDA cannot ensure the safety or efficacy of any of these unapproved products. Based on information to date, FDA determined that none of the unapproved cancer medicines received by these medical practices from Volunteer Distribution are in shortage in the US. FDA-approved versions of these medicines are available in adequate supply to meet current demand.
Coordinating US efforts
In March 2011, several US government agencies and departments—FDA, the Office of the Intellectual Property Enforcement Coordinator, the US Customs and Border Protection (CBP), US Immigration and Customs Enforcement, the US Departments of Justice, State and Commerce, and the Agency for International Development—issued a joint report recommending a series of items to combat the problem of counterfeit medicines entering the US (3). The report called for better data and information-sharing among government agencies and departments to address counterfeit medicines entering the US. For example, as part of a process for developing an Import Operation Strategic Plan, FDA and CBP examined the flow of imported pharmaceutical products through different ports of entry, identified available legal authorities, and worked to develop best practices to enhance collaborative enforcement efforts. (3).
CBP and FDA are engaged in ways to ensure that only compliant pharmaceuticals are imported into the US and that appropriate enforcement action is taken against illegal pharmaceuticals. For example, FDA and CBP will explore ways to ensure that, under appropriate circumstances, products are destroyed rather than returned to the sender. CBP and FDA also are exploring ways to improve targeting of counterfeit pharmaceuticals. And CBP, in coordination with FDA, will access civil penalties to deter repeat offenders of importation of counterfeit medicines (3).
Part of this effort also involved the development of a Secure Supply Chain (SSC) pilot program by FDA's Center for Drug Evaluation and Research and Office of Regulatory Affairs. The program is part of FDA's risk-based approach to ensure the safety of imported drugs. The program is designed to help expedite shipments of drugs that meet the SCC pilot criteria because FDA has greater confidence in the drugs that are imported by a company in control of its supply chain.
The Counterfeit Pharmaceutical Inter-Agency Working Group Report also called for increased measures for improving coordination among international bodies for combating counterfeit medicines, improving public awareness of counterfeit medicines, and improving government-to-government enforcement training. The report also called for continued involvement and support by FDA in the World Health Organization's International Medical Product Anti-counterfeiting Task Force (IMPACT). IMPACT brings together private and public sector experts to address the public health aspects of drug counterfeiting and is developing technical tools for countries to use and adopt to fight drug counterfeiting. These tools can be used to strengthen legislative, regulatory, technological, enforcement and communication infrastructure and build capacity for surveillance, identification, and prevention of counterfeit drugs from reaching patients. (3).
WHO and FDA are collaborating to build global rapid alert surveillance/monitoring systems for combating counterfeit and falsified medicines and risks in supply-chain security. The goals of this effort are to generate sound and reliable evidence of where the incidence of falsified medicines is most serious, and promote exchange of information (e.g., case reports and descriptions of actions taken) and expertise between countries to stimulate action. Also, FDA and WHO are partnering to make available a system to be used for collecting and disseminating information based upon the requirements shared by all partners (3).
In January 2012, the US Pharmacopeial Convention (USP) proposed a set of recommended best practices to help ensure that medicines can be traced back to their original manufacturer, are not adulterated or counterfeited, and are transported to their intended destination with their quality intact. USP is seeking broad feedback on these recommendations on supply-chain integrity. The new standard being proposed is not mandatory and is contained in the proposed USP General Chapter <1083> Good Distribution Practices—Supply Chain Integrity. The proposal is intended to serve as a central guidance document outlining the essential elements of an effective strategy.
"While individual pharmaceutical companies have their own approaches to addressing this issue, the size and sophistication of companies and their suppliers vary widely, as do their quality systems and risk management approaches," noted USP in a Jan. 4, 2012, press release in announcing the proposed standard. "Broad consensus around issues such as track-and-trace technology does not exist, and smaller companies that may be relied upon for sourcing pharmaceutical ingredients may or may not have security approaches comparable to their larger counterparts. Supply-chain integrity involves minimizing risks that arise anywhere along the supply chain, from sourcing pharmaceutical raw materials to their manufacture and distribution," noted USP in its release.
"There is incentive for all players in the pharmaceutical industry—large and small companies, regulators and standards-setting bodies—to come to some agreement on hot-button issues such as track-and- trace technology and, at the larger level, to codify what constitutes a solid, universal approach to global supply-chain integrity," said Praveen Tyle, chief science officer for USP, in the release. "USP has developed an initial proposal that we expect to evolve as industry, FDA and others weigh in. Our role as an independent body provides an opportunity to convene all these parties and advance this critical issue. While some pockets of information are available via FDA guidances, trade organizations and other sources, an overall approach is lacking. USP can move forward something more concrete than a technical report, as part of a mechanism that can be regularly updated to best meet the needs of all."
The proposed standard covers four main areas:
USP envisions the general chapter will be of use to all organizations and individuals involved in the global supply chain, including manufacturers; transportation companies involved in automobile, truck, rail, sea and air services; third-party logistics providers, freight forwarders and consolidators; brokers, importers, and exporters; packaging and repackaging operations; wholesalers and distributors; retail, mail-order, hospital, nursing home and other pharmacies; and mail distributors, including the US Postal Service and other expedited shipping services.
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The formal proposal will be published in Pharmacopeial Forum38 (2), March–April 2012. This is the vehicle through which USP accepts public comment on its standards. The draft general chapter and comments submitted to USP will be a central topic of a Supply Chain Integrity Workshop that USP is convening May 22–23, 2012, in Rockville, Maryland. This meeting will be a further opportunity to provide input, including whether additional information needs to be included in the chapter.
Patricia Van Arnum is a senior editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072, firstname.lastname@example.org.
1. FDA Statement, "FDA Notifies Healthcare Providers about the Risks of Purchasing Unapproved Injectable Cancer Medications from Unlicensed Sources" (Rockville, MD, Jan. 13, 2012).
2. FDA Statement, "Counterfeit Version of Avastin in US Distribution" (Rockville, MD, Feb. 14, 2012).
3. Counterfeit Pharmaceutical Inter-Agency Working Group, "Counterfeit Pharmaceutical Inter-Agency Working Group Report to the Vice-President of the United States and Congress (Washington, DC, March 2011).