Pharmaceutical Commerce - November/December 2011 - (Page 26)

Legal Regulatory Drug Shortages Continue to Rise, With No Near-term Resolution < continued from page 1 produce acceptable product, some causes are more systemic. In 2010, 74% of all shortages involved sterile injectables, which require both careful production steps and complex packaging steps. Specific problems among these: Fig. 1: National Drug Shortages 2001-2011 43% due to “significant” GMP issues such as particulates or impurities that most of the shortages are generics, and said that manufacturers are taking unnamed “aggressive actions,” while admitting at the same time that some shortages are caused by individual company decisions to discontinue specific medicines. GPhA, more on the firing line for these shortages, is looking for regulatory relief. In truth, the drug shortage situation has been building gradually over time (Fig. 1), reminding one of the cliché about the frog sitting in water that gets warmer and warmer until he boils to death. And it’s not that nothing has been done about it: a CDER Drug Shortage Program (which has a staff of five) has mitigated or sidestepped 38 potential shortages in 2010, and 99 shortages through September in this year by working with manufacturers to get needed production equipment approved for use, locating alternative suppliers, negotiating with DEA for necessary commercial arrangements and a few other strategems. FDA is authorized to allow the importation of unapproved drugs at its discretion, and that tactic, which few in the manufacturing community are comfortable with, is something of a last resort. The overall CDER process is highly dependent on manufacturers giving early notice of potential shortfalls, which isn’t always performed, or even possible. (Getting a required early notification is one of several items being discussed for legislative action in Congress.) The CDER program has also looked into causes of shortages, and while many of them are specific to manufacturers’ inability to 20% due to production delays and capacity issues 10% due to raw-material (API) issues 8% due to discontinuations and several lesser factors, including increased demand caused by another product’s shortage. Many of these products are indeed generics (although there are branded products suffering the same problem) and in some cases, the products are sole-sourced, of limited market size, and may simply be uneconomic to produce for a resource-constrained manufacturer. GPhA, in testimony at the September FDA hearing, listed three causes and potential solutions of current shortages: • “Insufficient early collaboration and communication between industry and FDA with respect to regulatory actions that could impact supply.” One of the potential solutions is “enhanced intra-agency dialogue within FDA”—but this seems to imply that a drugmaker with manufacturing deficiencies would get a bye from FDA inspectors because the drug could become short-supplied; GPhA also calls for a process where remedial actions could be taken without “completely disrupting the manufacturing of necessary products.” • “Manufacturers face a very extensive process to qualify an alternate API supplier … as a result, many drugs have only one API supplier or manufacturing site approved.” Credit: Univ. of Utah DIS To fix, GPhA suggest that alternate suppliers could be approved through a more “streamlined” process; also that a CBE-30 (Changes Being Effected) supplement—the regulatory mechanism to make production modifications—be expedited. • “Inability to source sufficient API for controlled drugs due to annual manufacturerspecific allocations … established by DEA.” But difficulties like this one have already been addressed by the FDA Drug Shortage Program; it just seems that everyone involved has to act faster. These solutions certainly make sense, but seem to be resolvable simply by heightened awareness by both manufacturers and FDA regulators. To which the question can be asked, if these haven’t been done extensively to date, what’s the holdup? GPhA also highlighted an “opportunity” for its own members: “Work with FDA to develop guidance that better outlines the News Flash: Obama signs executive order to reduce drug shortages ust as this story was wrapping up, the White House held a session to announce a Presidential Executive Order— something that the New York Times said hasn’t happened with FDA since 1985—directing that agency, plus the Dept. of Justice, to take actions to address the problem. According to the White House, while some manufacturers are currently obligated to report shortages to FDA, not all of them have done so; in addition, voluntary reporting of upcoming potential shortages is being sought. FDA is charged with bumping up its Drug Shortage Program staff (from the current five to 11-13). DoJ will look into the claims of “price gouging,” and Obama cited the Premier health alliance report mentioned here as one of the justifications. In conjunction with the Executive Order, HHS released a study of drug shortages, noting, among other things, that the market for sterile injectables (especially oncologics) is “robust and growing,” but manufacturing complexity constrains the number of companies that can enter the market, while GPOs, who concentrate the main buyers of sterile injectables, have gradually abandoned “failure to supply” clauses in contracts, which penalize contract suppliers who fail to meet commitments. And it suggests that GPOs could strengthen these clauses, in return for allowing higher prices for products to be entertained. An FDA report, updating some of its Drug Shortage progam results, was also released in conjunction with the Executive Order. One interesting finding: in a bit of a bureaucratic snafu, it turns out that while all sole-source CDER drugs approved under NDA and ANDAs have a prior-notification requirement when they become unavailable, hardly any biologics (managed by CBER) do. The definition of “medically necessary” drugs varies across FDA divisions as well. J process for suppliers to proactively report drug shortages to the FDA’s drug shortage staff.” This is a theme that nearly everyone looking into the situation has recommended. Currently, manufacturers can voluntarily report a potential shortage to FDA; the process could be made mandatory (or, alternatively, manufacturers could simply be more forthcoming than they have been). ASHP had advocated for this a year ago at a national meeting on drug shortages. A bill, “Preserving Access to Life-Saving Medications Act” (S 296) was introduced by Senator Amy Klobuchar (D-MN) in February, but has been sitting in committee since; a parallel House bill, HR 2245, was introduced in June. Both bills require manufacturers to notify HHS/ FDA at least six months prior to a planned discontinuation or interruption of production of “medically necessary” drugs; and for HHS to establish a schedule of monetary penalties for noncompliance. But these bills might take care of some, predictable, shortages, they wouldn’t address sudden or unexpected disruptions. (PhRMA, ever helpful, noted that shortages can be caused by “natural disasters.”) And the bills call for manufacturers both to have a grip on what overall supply and demand for a product is (thus tracking not only its own production, but that of its competitors), and to be able to factor in the availability of alternative medications—something that manufacturers probably could do, but which involves prescriber input as well. Cases of sole-source API would need to be evaluated as well. Given that many of the short-supply products are of low economic value, it’s hard to say that these measures would change the situation even if they were enacted. ‘Fragile’ supply chain Such economic constraints highlight another set of factors in the shortage situation: what Erin Fox, head of the Drug Information Service (DIS) at the University of Utah Health 26 November | December 2011

Table of Contents for the Digital Edition of Pharmaceutical Commerce - November/December 2011

Pharmaceutical Commerce - November/December 2011
Top News
Brand Marketing & Communications
Supply Chain/Logistics
Information Technology
Manufacturing & Packaging
Legal & Regulatory
Meetings and Editorial Index

Pharmaceutical Commerce - November/December 2011