The pharmaceutical supply chain has been an increasing focus for regulators and the industry in the past couple of years. Drug shortages and counterfeiting have spurred the creation of legislation and industry guidelines to combat the situation and prevent suspect drug products from entering the market.
Regulators and Congress have stepped up in the fight against counterfeit and unsafe drugs by enacting legislation to ensure supply-chain safety. “The recent and upcoming changes to the FDA Safety and Innovation Act (FDASIA) have added a number of requirements intended to ensure a safe supply of medicines. Many of these enhancements are included in Title VII of the act, parts 701-718. The changes outlined in Title VII are important because they allow the agency to collect more comprehensive, accurate, and timely information about the pharmaceutical supply chain,” says Susan Schniepp, vice-president, Quality and Regulatory Affairs at Allergy Laboratories.
In addition, Schniepp explains that FDASIA helps establish the same requirements for foreign and domestic manufacturers, allowing the agency to work more effectively with their overseas counterparts. The Act gives FDA tools to protect the integrity of the global supply chain. FDA can collect and analyze product data to enable risk-informed decision making on incoming products and partner with foreign authorities to leverage resources through information sharing and recognition of foreign inspections of facilities. “These changes have already resulted in two draft guidance documents: Specification of the Unique Facility Identifier (UFI) System for Drug Establishment Registration and Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection,” says Schniepp
In June 2014, FDA issued draft guidance on how to identify suspect drug products in the supply chain (1). Developed under the Drug Supply Chain Security Act, the guidance describes potential signs that drug supply-chain stakeholders can look for to identify suspect drugs, including product labeling that may contain misspelled words or looks different than the standard labeling; packaging that has missing lot numbers or expiration dates or has been opened, damaged, or altered; or a change in shape or color from the standard product.
Supply-chain stakeholders are encouraged by FDA to be cautious when purchasing drugs from a new or unknown source, from the Internet, or purchasing drugs on the drug shortage list. Unsolicited offers for lower-priced drugs should also be avoided. The draft guidance provides supply-chain stakeholders with information on how to notify FDA of illegitimate products and details a process for stakeholders to follow when terminating previously made notifications.
Supply Chain Pilot Program
FDA initiated the Secure Supply Chain Pilot Program, in February 2014, to enhance the security of imported drugs. FDA published a notice in the Federal Register in August 2013 to solicit companies to voluntarily submit applications for participation in the program (2). Thirteen prequalified companies were designated to take part in the program. Participating companies received expedited entry for the importation of up to five selected drug products into the United States.
The companies met multiple participation conditions, including committing to comply with requirements of the Food, Drug, and Cosmetics Act; having a validated secure supply-chain protocol per the US Customs and Border Protection’s Customs-Trade Partnership Against Terrorism program; having a plan in place to quickly correct potential problems FDA identifies regarding importation of specific products; having effective recall and corrective action plans in place; and maintaining control over their drugs from the time of manufacture abroad through entry into the US.
“By creating incentives for manufacturers to adopt best practices for supply chain integrity, we can enhance the quality and safety of imported drugs,” said Carol Bennett, acting director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, in a press release. “The program also allows the FDA to focus resources on the areas with the greatest potential risk to consumers.”
“FDA’s Supply Chain Pilot Program is designed to help in addressing the increasing issues and problems associated with importations that have arisen from the globalization of the pharmaceutical supply chain. The goal of the program is to expedite the importation of legitimate materials, APIs, and product coming from abroad. The pilot program will collect data from 20142016. At the end of this period, the data will be evaluated to establish a system where there is an efficient use of time and resources to evaluate items of importation. The system would rely on specific code numbers that would require little human intervention. Instead, time can be spent on evaluating the questionable materials that require a more detailed human review,” says Schniepp.
Industry takes action
The pharmaceutical industry has also taken steps of its own to ensure the security of the drug supply chain. In 2009, the industry created Rx-360, a pharmaceutical industry supply-chain consortium that includes more than 80 companies and organizations. The consortium is committed to creating communication between pharmaceutical companies, suppliers, and contract manufacturers to better secure the pharmaceutical supply chain.
In an August 2013 interview with Pharmaceutical Technology, Rx-360 Chair Brian Johnson states, “Rx-360 believes that freely sharing information, such as alerts on potential supply-chain threats, is vital to the industry’s success. Industry collaboration on sharing audit information and jointly conducting audits is crucial to improving the transparency of our increasingly complex and global supply chains” (3).
The United States Pharmacopeial Convention (USP) is taking part in the “Fight the Fakes” campaign. The campaign is designed to spread awareness about the negative impact of fake medicines to create a global movement of organizations.
“Combating counterfeit and substandard products is an essential part of USP’s mission to improving public health by promoting quality medicines around the world,” said USP CEO Ron Piervincenzi in a press release. “The challenges we face today, with raw materials and finished products circling the globe before they reach the hands of patients and consumers, require collaboration to stem the tide of fakes” (4).
The campaign was established in 2013 and includes 25 healthcare groups, research institutes, foundations, non-profits, and private sector organizations including the Generic Pharmaceutical Association, the Global Pharma Health Fund, the International Federation of Pharmaceutical Manufacturers and Associations, and the Partnership for Safe Medicines.
These continued efforts by regulators and the industry will hopefully prove to be a positive impact on the availability of medicines and the ensurance of patient safety.
1. FDA, Guidance for Industry, Drug Supply Chain Security Act Implementation: Identification of Suspect Product and Notification, Draft Guidance (Silver Spring, Md., June 2014).
2. FDA, Federal Register, 78 FR 51192, Aug. 20., 2013.
3. A. Siew, Supplement to Pharm. Tech., s46 (August 2013).
4. USP, “USP Welcomes New Partners to ‘Fight the Fakes’ Campaign,” Press Release, USP.org.
About the Author
Susan Haigney is managing editor of Pharmaceutical Technology.