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Manufacturers face new rules for tracing drugs through the supply chain and compounders face stricter standards.
FDA Center for Drug Evaluation and Research (CDER) director Janet Woodcock’s top priorities for 2015 are to establish new rules to ensure safe drug compounding, while also implementing a new track-and-trace system for monitoring drugs and ingredients moving through the pharmaceutical supply chain. CDER staffers have been working hard to meet tight deadlines for launching the compounding and tracing programs set by the Drug Quality & Security Act (DQSA) of 2013, Woodcock noted at the FDA/CMS Summit in December 2014. As with such broad regulatory initiatives, proposed policies for both programs have been raising questions from stakeholders on all sides. Compounding Crackdown A sign that federal authorities are serious about halting unsafe drug compounding practices is the recent indictment of the owners and key employees of the New England Compounding Center (NECC) for murder and other serious crimes. NECC has been charged with distributing tainted injectable steroids linked to the meningitis outbreak of 2012 that killed more than 60 patients and sickened hundreds across the country (1). Both “traditional” compounders still regulated by states and the new class of “outsourcing facilities” that agree to register with FDA have to meet new standards and rules, which have generated objections to the scope and tone of tougher inspections and broader reporting requirements (2). A new Pharmacy Compounding Advisory Committee (PCAC), which was announced in December 2014, will have 14 experts from compounding, manufacturing, pharmacy, and medicine to help oversee these programs, including development of a “difficult-to-compound” list of drugs that are off limits to compounders (3). Pharmaceutical manufacturers are watching closely the process for leveling the playing field with large-scale outsourcing compounders, which may continue to produce and distribute certain sterile injectable drugs, provided they register and pay fees to FDA, undergo inspection, and comply with GMPs and other standards. While more than 50 compounders have signed up for FDA oversight, many have concerns about agency draft guidance documents, according to presentations at a December 2014 conference on Implementation of DQSA sponsored by the Food and Drug Law Institution (FDLI). Compounders cited significant hurdles in meeting GMPs and overly burdensome documentation and release and stability testing requirements. One result, the panel speculated, is that outsourcers may shift to producing larger batches of fewer products, which would reduce their ability to respond quickly to drug shortage situations and to meet specific patient needs. In addition, the thousands of “traditional” pharmacy compounders that remain under state regulation claim that FDA is overstepping its new legislative authority and that its onerous rules will limit physician and hospital access to vital “repackaged” formulations and needed emergency room supplies. A key bone of contention is that FDA is blocking the compounding of drugs for “office use” in advance of receiving a patient-specific prescription, a procedure that a coalition of pharmacists and medical associations claimed is still permitted under DQSA in a December 2014 letter to Congressional leaders (4). Meanwhile, pharmaceutical manufacturers joined with the Pew Charitable Trusts and public health organizations in opposing such advance compounding without a prescription by unregistered compounders. In a Nov. 20, 2014 letter to commissioner Margaret Hamburg, the group voiced strong support for “robust enforcement” of the new law by FDA (5). Launching Track & Trace DQSA set Jan. 1, 2015 as the date for FDA and industry to take the first step in establishing a comprehensive system for tracking prescription drugs from manufacturers to distributors and pharmacy dispensers. To meet this tight deadline, FDA issued a number of guidance documents and rules in 2014 to clarify standards for the interoperable exchange of tracing information and how manufacturers and distributors should identify and report evidence of suspect or illegitimate products. The agency also developed procedures for wholesalers, distributors, and third-party logistics providers to be licensed and to register with FDA or with states that meet federal standards. Initially, the program will track products by lot number, to be followed by item-level product serialization and a fully inter-operative, electronic product tracing system by 2023 (6). Flexibility has been key for all parties to get the system up and running. FDA issued guidance on Dec. 24, 2014 indicating that it would not fully enforce new requirements for the exchange of drug tracing information until May 2015. Manufacturers still must verify and report suspect and illegitimate products and provide lot-level identifiers on products. The delay is not that crucial for most pharmaceutical companies, which have established advanced computer systems able to track production lots, and some already are moving forward with unique serialized identifiers. But many smaller wholesaler distributors and third parties raised concerns last year that they would not be fully compliant with DQSA standards by January and that strict enforcement could block the continued flow of drugs to customers. Their complaints had some legitimacy, as FDA draft guidance on standards for interoperable exchange of information did not appear until November 2014, and annual reporting requirements for distributors were not published until December. Many specific questions about how the system actually will operate remain unanswered. There’s confusion over identifying and reporting suspect or illegitimate medicines and what high-risk situations warrant manufacturer notification to FDA. Important for pharmaceutical companies is how the program affects reporting responsibilities of exclusive distributors and of contract, co-licensed, and virtual manufacturing partners; resolution of these issues may require new definition of just what is a “manufacturer” under DQSA. Some states, moreover, have been slow to recognize DQSA pre-emption of state drug pedigree laws and to revise licensing requirements to meet federal standards. FDA will be busy in the coming months finalizing draft guidance documents and developing policies for meeting serialization requirements in 2017. Further guidance is needed on standardization of data and documentation practices; on waivers, exemptions and exceptions; and on dealing with grandfathered products, explained Ilisa Bernstein, deputy director of CDER’s Office of Compliance, who heads up track-and-trace implementation at the agency. Bernstein noted at the FDLI conference that FDA has established a new portal for wholesaler distributors and third parties to report licensing information to the agency, and for that data to be added to FDA’s broader registration database. FDA also will launch at least one pilot project to test interoperable methods for exchanging unit-level information to help prepare for implementing the more specific tracking system in a few years. Further examination of supply chain security as related to strategies for dealing with counterfeit drugs and regulated products will take place at an FDLI conference in Washington, DC on Feb. 25, 2015. Pharmaceutical companies would like to see more harmonization of US standards for product identification and tracking with other regions to facilitate establishing a global system to detect fraudulent and substandard drugs. Bernstein noted that FDA is discussing standards for product identification with European authorities and with other countries developing serialization and tracking systems. But different legal policies in other countries, she noted, will allow FDA to “only go so far” in harmonizing tracking requirements. References
1. J. Wechsler, “Meningitis Outbreak Linked to Contaminated Vials of Steroid Injectables,” PharmTech.com (Oct. 9, 2012), www.pharmtech.com/meningitis-outbreak-linked-contaminated-vials-steroid-injectables.
2. FDA, Compounding, FDA.gov,www.fda.gov/Drugs/GuidanceCompliance RegulatoryInformation/PharmacyCompounding/default.htm, accessed Jan. 2, 2015.
3. FDA, Pharmacy Compounding Advisory Committee, FDA.gov,www.fda.gov/AdvisoryCommittees/Committees MeetingMaterials/Drugs/Pharmacy CompoundingAdvisory Committee/default.htm, accessed Jan. 2, 2015.
4. D. Anderson, “Broad Provider and Pharmacy Coalition Urges Congress to Fix Drug Quality and Security Act,” iacprx.org (Dec. 10, 2014), www.iacprx.org/news/206444/Broad-Provider-and-Pharmacy-Coalition-Urges-Congress-to-Fix-Drug-Quality-and-Security-Act.htm, accessed Jan. 2, 2015.
5. PhRMA, Letter to Commissioner Margaret Hamburg regarding FDA oversight of drug compounding and enforcement of federal law (Nov. 20, 2014),
, accessed Jan. 2, 2015.
6. FDA, Are you ready for the Drug Supply Chain Security Act?, FDA.gov, www.fda.gov/Drugs/DrugSafety/DrugIntegrityand SupplyChainSecurity/DrugSupplyChain SecurityAct/ucm427033.htm, accessed Jan. 2, 2015.
Article DetailsPharmaceutical Technology
Vol. 39, No. 2
Citation: When referring to this article, please cite it as J. Wechsler, “FDA Sets Policies to Enhance Drug Security and Safety,” Pharmaceutical Technology 39 (2) 2015.