FDA Law Blog

FDA Announces Public Meeting and Request for Comments and Data on Nanotechnology

2008-08-07T11:11:43-07:00

On September 8, FDA will hold a public meeting to receive data and other information on the effects of nanoscale materials on quality, safety, and effectiveness of FDA-regulated products. FDA will consider the information that it receives in its development of guidance that addresses: (1) the data required to demonstrate safety and effectiveness of a product that contains nanoscale materials; and (2) the circumstances under which the use of nanoscale materials might change the regulatory status of a product. There will be breakout sessions that will address different product categories, including medical devices, prescription drugs, food and color additives, dietary supplements, and cosmetics.

The issues to be addressed in the breakout sessions include: (1) characteristics of materials to be identified and evaluated; (2) availability of tools to assess characteristics of nanoscale materials that could affect safety, effectiveness, and quality; (3) whether the manufacturing processes for nanoscale materials have unique features that merit evaluation; (4) whether there are aspects of formulation, processing, or storage that affect quality, safety, or effectiveness of products that contain nanoscale materials; (5) experience with, avoidance of, and concerns about products containing nanoscale materials; and (6) whether FDA should consider additional questions regarding characterization and manufacture of products containing nanoscale materials.

FDA also is requesting data that: (1) identify Over-the-Counter (“OTC”) drug products that contain nanoscale versions of ingredients in an OTC drug monograph; (2) identify nanoscale versions of food and color additives; (3) address the safety and effectiveness of both new FDA-regulated products and those that are reformulated to contain, or increase the content of, nanoscale materials; (4) address the effects of nanoscale versions of materials on bioavailability; and (5) address the effects of nanoscale materials on the manufacturing process for FDA-regulated products.

The importance of submitting comments to FDA as the Agency works to implement the recommendations in the 2007 Nanotechnology Task Force Report and sets a course for the future regulation of nanotechnology can hardly be overstated. Comments can be submitted to Docket No. FDA-2008-N-0416.

By Ricardo Carvajal

ADDITIONAL READING:

April 17, 2008 FDA Law Blog post

August 1, 2007 FDA Law Blog Post

Animal Drug User Fee Law Awaiting Enactment; New Law Reauthorizes ADUFA, Creates Generic Animal Drug User Fees, and Makes Technical Corrections to FDAAA

2008-08-06T06:04:38-07:00

In the coming days, President Bush is expected to sign into law H.R. 6432 – the Animal Drug User Fee Amendments of 2008. The new law reauthorizes and amends the Animal Drug User Fee Act (“ADUFA”) through Fiscal Year (“FY”) 2013, creates a new law for generic animal drug user fees (the Animal Generic Drug User Fee Act of 2008), and makes a couple of technical changes to the FDA Amendments Act (“FDAAA”), which was enacted in September 2007.

ADUFA was first enacted in 2003 (Pub. L. No. 108-130). Like its human drug counterpart, the Prescription Drug User Fee Act (“PDUFA”), ADUFA authorizes FDA to collect user fees to enhance the performance of the drug review process and ensure that new drugs are safe and effective. Under both laws, FDA has agreed to certain performance goals to review and act on applications. While human drug products under PDUFA are subject to three types of fees (application, establishment, and product fees), animal drug products approved under ADUFA are subject to four types of fees - application, product, establishment, and sponsor fees. FDA’s ADUFA website provides additional information on the law.

The House Report accompanying H.R. 6432 details the changes made to ADUFA I by ADUFA II. Among other things, the new law requires animal drug sponsors to submit annual reports to FDA on certain products containing antimicrobial active ingredients, and requires FDA to make summaries of the reports publicly available. The information is intended to support FDA’s continuing efforts to address antimicrobial resistance.

Unlike PDUFA, which does not cover human generic drug products approved under Abbreviated NDAs (“ANDAs”), H.R. 6432 establishes a generic animal drug user fee system under the Animal Generic Drug User Fee Act of 2008 (“AGDUFA”). Under AGDUFA, generic animal drug applicants are subject to three types of fees – application, product, and sponsor fees. The enactment of AGDUFA will fulfill the Bush Administration’s FY2009 budget proposal to create such a law. It is possible that the creation of a user fee system for generic animal drugs might lead to the creation of such a system for generic human drugs. Indeed, the Bush Administration’s FY2008 and FY2009 budget proposals recommended the creation of generic human drug user fees. While it is unlikely that a generic human drug user fee system will be proposed in Congress this year, it could happen once the 111th Congress convenes in January 2009.

In addition to handling animal drug user fees, H.R. 6432 makes a few technical corrections to FDAAA. FDAAA added FDC Act § 505(q) concerning certain types of citizen petitions that could delay generic competition. H.R. 6432 clarifies that “[c]onsideration of the petition shall be separate and apart from review and approval of any application.” FDA has been criticized for its implementation of FDC Act § 505(q), and, in particular for not decoupling ANDA approval from responding to an applicable petition that could delay generic competition. Despite this criticism, FDA has in at least one post-FDAAA instance decoupled ANDA approval and petition response. Specifically, FDA approved ANDAs for generic CAMPTOSAR (irinotecan HCl) Injection in February 2008, notwithstanding a January 29, 2008 petition requesting that FDA stay further ANDA approvals. FDA formally responded to the petition late last month. H.R. 6432 also makes minor clarifying amendments to the clinical trial registry and results data bank provisions of Public Health Service Act § 402(j) added by FDAAA § 801.

An earlier version of the so-called “FDAAA fix” language that was circulated on Capitol Hill would have made more significant changes to FDAAA, including adding a provision creating Hatch-Waxman benefits for “old” antibiotics – i.e., antibiotic active ingredients (and derivatives of such ingredients) included in an application submitted to FDA for review or approved prior to the enactment of the 1997 FDA Modernization Act on November 21, 1997. The proposal circulated on Capitol Hill mirrored § 1111 of the Staff Agreement version of FDAAA. Section 1111 was stripped from FDAAA hours before the House of Representatives voted on the bill, reportedly due to costs concerns. The same provisions in a proposed FDAAA fix addition to H.R. 6432 were removed, but for reasons that are unclear.

By Kurt R. Karst

Another Court Hammers an Off-Label Use Case

2008-08-05T04:36:38-07:00

Off-label use cases have certainly become the rage. Last week, the federal government’s Government Accountability Office released a report that outlined the government’s enforcement efforts in this area. The report casts doubt on FDA’s ability to monitor off-label drug promotion.

In addition, a number of individuals have filed federal False Claims Act “qui tam” lawsuits, seeking monetary rewards for lawsuits they have initiated against drug manufacturers which have allegedly engaged in unlawful off label promotional practices. However, most of these lawsuits have been rejected by federal courts.

On August 1, 2008, Magistrate Judge Thomas G. Wilson of the U.S. District Court for the Middle District of Florida (Tampa Division) joined the list of federal judges who have rejected off-label use qui tam cases. In United States ex rel Hopper and Hutto v. Solvay Pharmaceuticals, Inc., Magistrate Judge Wilson issued a 27-page Report and Recommendation in which he recommended that the District Court dismiss this action under Fed. R. Civ. P. 12(b)(6). Magistrate Judge Wilson found that although the qui tam relators’ amended complaint had gone into detail about allegations of a purported fraudulent scheme involving off label sales, the relators had utterly failed to comply with the requirements set forth in Fed. R. Civ. P (9)(b) to include specific allegations of actual false claims that were submitted to the government. The relators acknowledged that they had no evidence of any false claims being submitted. The Magistrate Judge rejected the argument that the court could infer that false claims were submitted because of the purported off label marketing scheme that was identified in the amended complaint.

The court’s ruling relied on three published decisions from the United States Court of Appeals for the Eleventh Circuit, which had collectively rejected qui tam cases where the relators had not submitted evidence that false claims had actually been submitted to the government. However, the court did not need to rely on any of the four other court ruling which have dismissed off label use qui tam actions. See e.g., United States ex rel. Rost v. Pfizer, Inc., 446 F.Supp. 6 (D. Mass 2006), a ruling later affirmed by the U.S. Court of Appeals for the First Circuit. (Additional information on this case is available from Pharmalot.)

These qui tam off-label use cases, culminating in Hopper and Hutto establish a very demanding threshold for qui tam relators to meet in order to move forward with this type of case. For instance, it seems very unlikely that current or former sales people can meet the 9(b) requirements even if, as in Hopper and Hutto, the sales people were allegedly involving in the off-label marketing practices of a company.

By John R. Fleder

Update: FDA Globalization Act Discussion Draft Revised

2008-08-04T10:31:23-07:00

Representative John Dingell (D-MI) has revised several of the drug-related sections of the Discussion Draft of the FDA Globalization Act (“FDAGA”). We first reported on the Discussion Draft, which has received significant attention from industry and stakeholder groups alike, in April 2008.

Updated sections of the FDAGA were recently posted on the U.S. House of Representatives’ Energy and Commerce Committee’s website. The updated draft does not significantly alter any sections of the original Discussion Draft, but it does include several new provisions of interest – many of which appear to be aimed at ensuring the purity of drugs. Several of the new additions are blank placeholders left for further updating.

First, the updated draft calls for inspections of drug, active ingredient, device, and device part manufacturing establishments every two years. However, FDA can permit inspections once every four years if such a timeline would be appropriate when considering the class of the products, associated risks of the products, shipping volume, the history of the facility, and any other factors the Agency finds relevant. The draft discussion also adds a section calling for reports to Congress on “the risk-based process for conducting surveillance of 8 current good manufacturing practices” under FDC Act § 510(h)(4).

The revisions also include several sections on risk management. If these revisions are enacted, the FDC Act would be amended to hold that a drug is adulterated if it is manufactured in a plant that fails to have a risk management plan. The risk management plan must “provide for an assessment, prior to contracting with a person to supply raw materials or ingredients . . . of the suitability and competence of such person to carry out such activity,” explain the quality control process, “provide for the monitoring and review through periodic on-site audits of the facility,” “provide for the monitoring of incoming materials,” and explain quality control measures to ensure that the drugs manufactured are pure. FDA would have authority to inspect this risk management plan during facility inspections.

In addition, the updated draft adds a requirement for the documentation of the supply chain for all steps in the chain of drug manufacturing. Each establishment registered with FDA must also be able to provide the Agency with an electronic statement that documents the chain of supply for the drug.

Several other provisions are aimed at giving FDA greater authority. For example, the revised Draft Discussion contains sections that would give FDA greater recall authority. Perhaps to alert FDA to the need for a recall, a provision was added that requires that a person, other than a consumer, who “has reason to believe that a drug intended for human use would cause serious, adverse health consequences or death, shall” notify FDA as soon as practical of the danger. The bill, if enacted, would require penalties for those who manufacture counterfeit drugs and provides for greater civil penalties for those who violate the FDC Act (although the actual dollar amounts of the penalties were mostly left blank).

Finally, the end of the updated draft contains two very interesting additions. First is a blank section titled “FDA Bonuses.” Text below this heading indicates that the language will be added later. Rep. Dingell has been a vocal critic of FDA bonuses and has launched an investigation into the Agency’s compensation practices. Second is a section stating that FDA has “extraterritorial Federal jurisdiction over any violation of this Act relating to any food, drug, device, or cosmetic intended for import into the United States.” It remains to be seen what, if anything, will be added to or deleted from these sections.

Although the latest revisions to the FDAGA Draft Discussion are not extensive, they do indicate that the bill continues to receive the attention of Rep. Dingell and others in Congress. We will continue to monitor this legislation and report on any further updates.

By Susan J. Matthees

ConsumerLab Red Yeast Rice Product Review Creates Potential Safety and Regulatory Problems

2008-08-03T09:52:29-07:00

On July 1, 2008, ConsumerLab.com, LLC published a product review titled “Red Yeast Rice Supplements.” Hyman, Phelps & McNamara, P.C. sent an 8-page letter to ConsumerLab on July 17 to inform the company that, as confirmed in FDA warning letters, the product review created potential safety issues for consumers as well as regulatory issues for the dietary supplement industry.

The ConsumerLab product review of red yeast rice supplements makes incorrect statements about the law and FDA enforcement policy, and creates general confusion about the marketing of red yeast rice products. Most important, the review encourages consumers to purchase dietary supplements with high levels of lovastatin, the active ingredient in the prescription drug Mevacor™, that FDA has determined to be unsafe. In addition, FDA has repeatedly warned industry that the marketing of products with levels of lovastatin represented as “high” or “moderate” in the ConsumerLab review is illegal.

Although ConsumerLab has updated its product review, ConsumerLab has not corrected the safety and regulatory issues addressed in FDA’s warning letters and this firm’s July 17 letter. In a telephone call with counsel to ConsumerLab on July 30, this firm was informed that ConsumerLab did not intend to make further changes to the red yeast rice product review. For this reason, we are posting a memorandum based on the firm’s letter to ConsumerLab as a warning to industry and consumers that the ConsumerLab review is in conflict with FDA’s view of the law.

By A. Wes Siegner

New Legislation Seeks the Creation of a Government-Sponsored Counter-Detailing Force to Subvert Prescription Drug Messaging by Drug Companies

2008-08-01T08:43:33-07:00

Yesterday, Pharmalot reported that U.S. Senator Herb Kohl (D-WI) and several co-sponsors introduced the “Independent Drug Education and Outreach Act of 2008.” A similar version of the bill has reportedly been introduced in the U.S. House of Representatives. According to a press release from the U.S. Senate Special Committee on Aging, the bill is intended “to provide doctors with unbiased information on prescription drugs,” and “will provide an important alternative to the way doctors currently get their information about drugs.”

If enacted, the bill would amend the Public Health Service Act to add § 904 – Prescription Drug Education and Outreach – to establish a program to award grants or contracts:

For the development and production of educational materials concerning the evidence available on the relative safety, relative effectiveness, and relative cost of prescription drugs, non-prescription drugs, and non-drug interventions for treating selected conditions, for distribution to healthcare providers who prescribe such drugs and their patients; and

For the development and implementation of a program to appropriately train and deploy health professionals to educate physicians and other drug prescribers concerning the relative safety, relative effectiveness, and relative cost of prescription drugs, non-prescription drugs, and non-drug interventions for treating selected conditions.

By Kurt R. Karst