FDA Faces Controversy Over Quality Metrics and Biosimilars

FDA officials have been busy addressing some difficult drug regulatory issues important to biopharma manufacturing, marketing, and R&D. In July 2015, the regulators rolled out a much-discussed proposal for how companies should collect and submit data to measure the quality and reliability of manufacturing systems, only to meet strong objections from industry (1, 2). FDA followed the metrics program with a highly controversial plan for naming biosimilars and innovator biotech therapies, which continues to divide innovator and generic firms (3, 4).

A stated goal of these and related FDA policies is to facilitate patient access to needed medicines, a process that involves preventing and reducing critical drug shortages. The FDA Safety & Innovation Act (FDASIA) of 2012 addressed shortages-in addition to providing FDA authority to collect additional manufacturing data for its metrics program-by enabling the agency to require early manufacturer notification of expected supply disruptions for life-saving medicines. FDA issued a final rule in July 2015 that addresses shortages by requiring a broad range of companies to provide advance (six months) notification of an event likely to cause a “meaningful disruption” in the supply of critical medicines (5). Biotech manufacturers had protested extending the initiative to vaccines and other biologics, and generic-drug makers complained that even a five-day notification requirement may be a burden, but those concerns did not stop FDA from implementing what it considers a practical early notification policy.

Slightly different biosimilar names
Much more contentious is FDA’s proposal for addressing the hot-button issue of how to identify biosimilars related to innovator products. Biosimilar makers and payers want their new products to carry the same proprietary names as reference drugs to encourage prescribing and reimbursement; brand companies argue that different names are necessary to prevent inadvertent substitution and confusion regarding adverse events.

FDA appears to lean towards the “ensure safety” camp by establishing a new biosimilar naming policy that adds a unique, four-digit suffix to a “core” name for all biotech therapies (3).

This approach aims to prevent erroneous prescribing and dispensing of biosimilar and reference products and to facilitate tracking of postmarketing safety issues, a process that FDA says can’t rely on national drug code numbers (NDC) because many biologics are administered in hospitals and clinics. Biosimilar advocates fear that even slightly different names will discourage product uptake, but analysts note that the similar core names will permit brands and biosimilars to be grouped together on health system databases, which will encourage their use.

While innovators may support FDA’s approach for differentiating biosimilar names, they are up in arms about the agency’s unexpected related proposal for adding suffixes to all biotech therapies, including those already on the market. To start what is sure to be a lengthy process of revising product names retroactively, FDA issued a proposed rule that specifically applies the new naming policy to six licensed biologics facing near-term competition from biosimilars (6). Requiring new names for old products has never occurred before, says Gillian Woollett of Avalere Health, noting that significant database and software changes may be needed to accommodate the new system.

Still unclear is how FDA will apply the new naming policy to biosimilars that achieve “interchangeable” status, which is a drug that can be substituted by the pharmacist without prescriber permission; while this may be the case for most conventional generics, biosimilars may be approved as similar. One option is to permit the same suffixes for these products, and FDA seeks comments on this issue, as well as its broader naming policy.

Go slow with metrics
Both brand and generic firms are troubled by FDA’s plan for collecting data on a range of measures for the reliability and quality of drug-production operations and resulting products. After three years of workshops and white papers on developing quality metrics, FDA finally spelled out its program in a draft Request for Quality Metrics guidance document (1). Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), opened an Aug. 24, 2015 public meeting to discuss the plan by suggesting that the proposed metrics are what “any manufacturer would want to know” and that FDA had worked hard to keep the new data collection initiative manageable and useful. The guidance outlines a number of data points that CDER and the Center for Biologics Evaluation and Research (CBER) believe will help field inspectors assess the ability of an operation to reliably produce high-quality medicines; firms with good reports may merit less frequent plant inspections and reduced reporting of post-approval manufacturing changes.

Somewhat surprising after such extensive FDA-industry collaboration were the many objections raised by manufacturers about the metrics proposal being too broad, unclear, and moving towards mandatory implementation too quickly. Industry reps stated at the August 2015 meeting that gathering and reporting the data will be costly and time-consuming and voiced fears about the program generating “report-card” listings and superficial comparisons open to misinterpretation by patients and payers.

Genentech Vice-President Diane Hagerty, representing the International Society for Pharmaceutical Engineering (ISPE), advised FDA to phase in the initiative, starting with higher risk facilities and products, and to drop for now a measure for on-time completion of annual product reviews. Camille Jackson, director for science & regulatory advocacy at the Pharmaceutical Research and Manufacturers of America (PhRMA), questioned FDA’s use of guidance, as opposed to more formal notice-and-comment rulemaking, to provide sufficient authority for the agency to require metrics reporting in advance of inspections. Similarly, David Gaugh, senior vice-president of the Generic Pharmaceutical Association (GPhA), speculated whether FDA can require metrics reporting by foreign companies, a limitation that he said could encourage US firms to shift drug production overseas.

Excipient makers objected to the idea of collecting metrics on “high risk” excipients, while API producers raised a host of questions about providing quality measures on products made for many drug companies. Non-prescription drug firms want to limit initial metrics to high-risk medicines, as opposed to hand creams. And Gil Roth, president of the Pharma & Biopharma Outsourcing Association, voiced uncertainties about how contract manufacturers can submit data on a facility making drugs for multiple clients. Richard Johnson, president of the Parenteral Drug Association (PDA), optimistically described the FDA proposal as “a good place to start,” but cited challenges in assessing the “quality culture” at companies-potentially the next phase for the program, but now apparently on the back burner.

All these objections clearly disappointed FDA officials, who said they sought an objective list of measures that companies already collect internally and that could be assessed easily by field inspectors. FDA believes the program will assist in inspection scheduling and in efforts to avoid supply disruptions. But staffers acknowledged the need to clarify terms, how data will be used, and reporting relationships for contractors and suppliers. Issuing final guidance “is a high priority,” said Russell Wesdyk, acting director of the Office of Surveillance in CDER’s Office of Pharmaceutical Quality, but FDA extended its comment period through November 2015, and no one expects any revisions until 2016, at the earliest.

References
1. FDA, Draft Guidance, Request for Quality Metrics(CDER, CBER, July 2015).
2. J. Wechsler, “Industry Responds to FDA Metrics Program,” PharmTech.com, Aug. 24, 2015.
3. FDA, Draft Guidance, Nonproprietary Naming of Biological Products (CDER, CBER, August 2015).
4. R. Hernandez, “FDA Releases Guidance on Biosimilar Nomenclature, Requests Comments on Interchangeable Product Naming,” PharmTech.com, Aug. 27, 2015.
5. FDA, Federal Register, 80 (130), July 8, 2015.
6. FDA, Federal Register, 80 (167), August 28, 2015.

Article Details
BioPharm International
Vol. 28, No. 10
Page: 8–9
Citation: When referring to this article, please cite it as J. Wechsler, “FDA Faces Controversy Over Quality Metrics and Biosimilars,” BioPharm International 28 (5) 2015.