September 2006

Regulations

FDA Boosts User Fees 17–19% for FY 2007

In an Aug. 2 Federal Register announcement (1), the US Food and Drug Administration (Rockville, MD, www.fda.gov) announced its Prescription Drug User Fee Amendments of 2002 (PDUFA III) fees for fiscal year 2007 (Oct. 1, 2006–Sept. 30, 2007). The new fee schedule for drug and biological products will be:

• $896,200 for an application requiring clinical data, up 17% from $767,400 for FY 2006;

• $448,100 for an application not requiring clinical data or a supplement requiring clinical data, up 17% from $383,700;

• $313,100 for establishment fees, up 19% from $264,000;

• $49,750 for product fees, up 18% from $42,130.

PDUFA user fees charged in four categories for each of the years 2000–2007.

The agency will begin issuing invoices for establishment and product fees under the new schedule this month.

The 2007 schedule represents the biggest fee increases since 2003, when fees rose by an average of 60%. Fees have increased by an average of 175% since 2000. Fees for applications requiring clinical data, for applications not requiring clinical data, and for supplements requiring clinical data have increased by nearly 214% since 2000. All fees have increased to varying degrees each year, with two exceptions. In 2002, establishment fees declined by 4% and product fees declined by 1% (2–8).

Indexed user fees for the years 2000–2007. The fees charged for each year are shown as percentages of the 2000 fees.

References

1. US Food and Drug Administration, "Establishment of Prescription Drug User Fee Rates for Fiscal Year 2007," Federal Register 71 (148), 43780–43784 (Aug. 2, 2006). DOCID:fr02au06-96.

2. FDA, "Establishment of Prescription Drug User Fee Rates for Fiscal Year 2006," Federal Register 70 (146), 44106–44109 (Aug. 1, 2005). DOCID: fr01au05-49.

3. FDA, "Establishment of Prescription Drug User Fee Rates for Fiscal Year 2005," Federal Register 69 (147), 46165–46168 (Aug. 2, 2004). DOCID: fr02au04-55.

4. FDA, "Establishment of Prescription Drug User Fee Rates for Fiscal Year 2004," Federal Register 68 (148), 45249–45252 (Aug. 1, 2003). DOCID: fr01au03-75.

5. FDA , "Establishment of Prescription Drug User Fee Rates for Fiscal Year 2003," Federal Register 67 (149), 50448–50451 (Aug. 2, 2002). DOCID: fr02au02-75.

6. FDA, "Establishment of Prescription Drug User Fee Rates for Fiscal Year 2002," Federal Register 66 (11), 2222–2226 (Jan. 16, 2001). DOCID: fr16ja02-78.

7. FDA, "Establishment of Prescription Drug User Fee Rates for Fiscal Year 2001," Federal Register 65 (243), 79107–79111 (Dec. 18, 2000). DOCID: fr18de00-100.

8. FDA, "Establishment of Prescription Drug User Fee Rates for Fiscal Year 2000," Federal Register 64 (248), 72669–72673 (Dec. 28, 1999). DOCID: fr28de99-104.

–Douglas McCormick and Erik Greb

REGULATIONS

FDA Forms Internal Nanotechnology Task Force

The US Food and Drug Administration (Rockville, MD, www.fda.gov) has formed an internal nanotechnology task force for determining regulatory approaches to encourage the continued development of innovative, safe, and effective FDA-regulated products that use nanotechnology materials.

Table I: National Nanotechnology Initiative fiscal year 2007 budget request.

The task force will identify and recommend ways to address knowledge or policy gaps to better enable the agency to evaluate possible adverse health effects from FDA-regulated products that use nanotechnology materials. FDA will continue to address product-specific nanotechnology-related issues on an ongoing basis.

Public meeting

One of the task force's first functions will be to chair a public meeting on Oct. 10, 2006 to help FDA further its understanding of developments in nanotechnology materials that pertain to FDA-regulated products, including new and emerging scientific issues such as those pertaining to biological interactions that may lead to either beneficial or adverse health effects. Details of the meeting may be found at http://www.fda.gov/OHRMS/DOCKETS/98fr/06n-0107-nm00002.pdf.

The task force also will be assessing the current state of scientific knowledge pertaining to nanotechnology and exploring opportunities for innovation using nanotechnology materials in drugs, biologics, devices, foods, feeds, and cosmetics. The task force will further evaluate the effectiveness of the agency's regulatory approaches to meet unique challenges raised by the use of nanotechnology materials in FDA-regulated materials. In addition, it will consider appropriate vehicles for communicating with the public about the use of nanotechnology materials in FDA-regulated products.

FDA will submit its initial findings and recommendations to the FDA Acting Commissioner within nine months of the October 10th public meeting.

Collaborations and budgets

FDA says it will continue to strengthen its collaborative relationships with other federal agencies participating in the National Nanotechnology Initiative (NNI, www.nano.gov) and other stakeholders. The NNI is a federal research and development (R&D) program established to coordinate the multiagency efforts in nanoscale science, engineering, and technology. Twenty-three federal agencies participate in the NNI, 11 of which have an R&D budget for nanotechnology.

The 2007 NNI budget request for nanotechnology R&D across the federal government is nearly $1.3 billion, an increase of 21% over the 2006 request (1) in seven program component areas (see Table I).

Reference

1. National Nanotechnology Initiative, Supplement to the President's Fiscal Year 2007 Budget, (Subcommittee on Nanoscale Science, Engineering and Technology, Committee on Technology, National Science and Technology Council, July 2006), http://www.nano.gov/index.html,, accessed August 14, 2006.

–Douglas McCormick and Patricia Van Arnum

EDUCATION

Biomanufacturing Training and Education Center Rises at North Carolina State

At the end of July, North Carolina State University (Raleigh, NC, www.ncsu.edu) celebrated the completion of the steel skeleton of its new Biomanufacturing Training and Education Center (BTEC, Raleigh, NC, www.engr.ncsu.edu/btec) with a topping-out ceremony attended by the construction workers and leaders from BioNetwork, BTEC, and the NC State Facilities Division.

BTEC is the result of a collaboration between local biomanufacturing-industry leaders and university faculty who had a strong interest in biotechnology and bioprocessing. The venture received support from the state government as well as from local universities, industry, and community colleges and was made possible by a substantial contribution from The Golden LEAF Foundation, a nonprofit organization based in Rocky Mount, North Carolina. This group is dedicated to helping North Carolinians make the transition from a tobacco-dependent economy by making investments that will positively affect the state's long-term economic advancement.

When completed, the 86,000-ft² facility will house a fully equipped laboratory training space and classrooms and will offer instruction in cell and protein harvest and recovery, protein purification, product characterization, and sterile filling and packaging. It will be the largest pilot-scale protein manufacturing facility in academia in the United States.

"I believe [BTEC is] unique on two counts," says Peter Kilpatrick, PhD, BTEC's director. "It's the largest CGMP protein manufacturing lab in a university in the country and the only CGMP facility that will be used exclusively for education and not contract manufacturing."

As work on the building moves forward, Kilpatrick is concentrating on recruiting faculty and staff. The search includes current NC State faculty members who have research or teaching interests related to biomanufacturing as well as new PhDs, faculty from other universities, and members of the biomanufacturing industry.

"It is a unique facility, so we want to develop unique programs and unique people," says Kilpatrick. "We want to develop a reputation as being the preferred place in the world to obtain biomanufacturing and bioprocessing science and engineering education."

BTEC is expected to be completed and ready for process validation in May or June of 2007.

–Brianne Harrison

LEGAL

Wholesaler Files Complaint Against 21 Pharma Manufacturers and Distributors

Seeking more than $580 million in damages and recovery of nearly $1.8 billion in punitive damages, RxUSA Wholesale (Port Washington, NY, www.rxusawholesale.com) filed a complaint against 16 major US pharmaceutical manufacturers and 5 drug wholesalers.

The 163-page complaint appears to target emerging distribution practices prompted by drug-pedigree requirements in state and federal regulations, measures intended to halt gray-market profiteering and to keep counterfeit products off the US market by closing points of entry.

According to a release issued by RxUSA, the company alleges "violations of various provisions of the US antitrust laws, New York State Donnelly law violations, restraint of trade, illegal boycott, and . . . violations of the federal RICO statutes and Federal Securities' laws and regulations."

Among its allegations, the company charges the existence of a "concerted effort" to "eliminate competition in the pharmaceutical industry by destroying the 'secondary wholesale' class of trade." This effort has kept drug prices "artificially high" and is claimed to have weakened "the integrity and security of the nation's drug supply."

In an interview, RxUSA president Robert C. Drucker said that the company (which had revenues of $295 million last year) has contracted for an e-pedigree system and is ready to comply with pedigree requirements as they go into effect. The lawsuit, he says, is not an attack on anti-diversion measures, but a response to manufacturer and distributor decisions not to sell products to secondary wholesalers such as RxUSA, whether or not they comply with pedigree and antidiversion practices.

The complaint names 16 manufacturers (Alcon, AstraZeneca, Boehringer, BMS, Eisai, Forest, GSK, Kos, Merck, Novartis, Organon, Pfizer, Sanofi-Aventis, Schering-Plough, Takeda, and Wyeth) and five national and regional distributors (McKesson, Cardinal, AmerisourceBergen, H.D. Smith, and Bellco) and the Healthcare Distribution Management Association (HDMA). HDMA did not respond to a request for comment.

–Douglas McCormick and Maribel Rios

EXPANSION

Novartis To Build Vaccine Manufacturing Plant in North Carolina

Novartis (Basel, Switzerland, www.novartis.com) will build a cell culture-derived influenza vaccines manufacturing plant in Holly Springs, North Carolina. Construction is expected to begin in 2007.

Novartis will invest $600 million in the facility, which includes a $220-million award from the US Department of Health and Human Services (Washington, DC, www.hhs.gov). Novartis also is making additional investments at its Marburg, Germany site to expand capacity for cell culture-derived influenza production.

In announcing its investment plans, Novartis reported that it had submitted a marketing application for cell culture-derived influenza vaccine to European regulatory authorities, specifically the Committee for Medicinal Products for Human Use of the European Medicines Agency (London, www.emea.eu.int). Novartis says it is seeking to become the first company to commercially produce and market a cell culture-derived influenza vaccines for the European market.

"We are taking the lead in moving flu cell culture vaccine manufacturing closer to a commercial reality now that the site for a US manufacturing plant has been chosen and the first EU submission for cell culture vaccine have been completed," said Daniel Vasell, chairman and CEO of Novartis, in a company release.

Once completed and approved for production, the planned Holly Springs site is expected to produce up to 50 million doses of seasonal trivalent flu vaccines, which will be for use in the United States. In the event of influenza pandemic, the site is planned to have a capacity as much as 150 million monovalent doses annually within six months of a pandemic declaration, says Novartis.

Novartis says that cell culture technology for vaccine production offers advantages over traditional chicken-egg based methods, including shorter production lead times and improved reliability of supply, issues that are of importance in the event of a influenza pandemic.

US clinical trials for the cell culture-derived influenza vaccines, which began in 2005, are ongoing. The vaccines for the EU and US clinical trials have been produced at Novartis' site in Marburg, where the product was developed.

–Patricia Van Arnum

GlaxoSmithKline Progresses on H5N1 Pandemic Flu Vaccine

GlaxoSmithKline (GSK, London, www.gsk.com) has developed a vaccine against the H5N1 bird flu strain that, the company says, shows better immune response than other vaccines in development. "All being well, we expect to make regulatory filings for the vaccine in the coming months," said JP Garnier, GlaxoSmith Kline's CEO in a company release.

GSK says its H5N1 pandemic flu vaccine achieved a high immune response at a low dose of antigen. The vaccine, which uses a proprietary adjuvant, enabled more than 80% of subjects who received 3.8 micrograms of antigen to demonstrate a strong seroprotective immune response. This level of seroprotection meets or exceeds target criteria set by regulatory agencies for registration of influenza vaccines, says GSK. The company says efficacy at these levels of antigen dosage has not been reported for any other H5N1 vaccine in development to date, including those using other adjuvants such as alum.

GSK will continue the development of its vaccine, including assessing the ability of the vaccine to offer cross-protection to variants of the H51N strain.

–Patricia Van Arnum

EXPANSION

$900-Million Biopharmaceutical Park Planned for Shenzhen

The city government in Shenzhen in southern China's Guangdong province is planning to build a 2.92-mile² national biopharmaceutical park in the Shenzhen Grand Industrial Zone.

The center will be designed for biopharmaceutical research and development and will house businesses in the biomedical engineering, marine biotechnology, biopharmaceuticals, modern Traditional Chinese Medicines, and chemical drugs industries.

The RMB 7.2-billion (USD 900-million) project will be funded by government and nongovernmental organizations and is subject to approval by China's National Development and Reform Commission (NDRC). The base is expected to have annual revenues of RMB 100 billion (USD 12.5 million).

The NDRC also has approved two other biopharmaceutical bases in Changchun (Jilin province) and Shijiazhuang (Hebei province).

–Kaylynn Chiarello–Ebner