Regulatory Roundup

June 2, 2013
Jill Wechsler
Pharmaceutical Technology
Volume 37, Issue 6

An overview of the latest regulatory developments for malaria drugs, biosimilars, and global standards.

Combating malaria

World Malaria Day, held on April 25, provided an opportunity to highlight several advances in biomedical research and healthcare initiatives to combat this deadly disease. One hopeful sign is success in producing a synthetic version of artemisinin, the ingredient derived from the Chinese wormwood plant that has proven effective in treating malaria. Sanofi is beginning to produce this ingredient at a plant in Italy, building on discovery of a new process developed by a collaboration of OneWorldHealth, Amyris, and the University of California, Berkeley. Initial funding from the Bill and Melinda Gates Foundation and support from PATH has led to a process that will yield 35 tons of artemisinin in 2013, using a complex photochemistry method to turn artemisinic acid into the active ingredient basic to antimalarial combination products.

There's also action to curb proliferation of fake and substandard malaria drugs. FDA is working with other government health agencies to test use of the Counterfeit Detection Device (CD-3), a handheld scanner developed by FDA scientists that can tell quickly if a product is real or counterfeit. The effectiveness of this tool in detecting bogus versions of two common malaria therapies will be piloted in Ghana, building on a United States Pharmacopeia program in that country to promote quality medicines; additional funding will come from the Skoll Global Threats Fund.

Drug spending down, prices up

Patent expirations leading to greater generic drug use continue to drive down US spending on prescription drugs, raising concerns about appropriate drug use and future development of the pharmaceutical industry. Total spending on medicines in 2012 declined by 3.5% on a real per capita basis according to a report from the IMS Institute for Healthcare Informatics released May 9, 2013. Outlays reached $325.8 billion, 1% less than the previous year. A main reason for the decline is that fewer patients went to the doctor and fewer prescriptions were dispensed, likely due to a rise in high-deductible health insurance policies and high coinsurance for specialty drugs.

While the drop in overall drug costs may be good news for US consumers, soaring price tags on new cancer drugs have prompted protests from oncologists. Doctors at Memorial Sloan-Kettering in New York said they won't prescribe certain medicines with more than $100,000 in annual costs that lack strong treatment benefits. Manufacturers have long claimed that they need high prices on important new products to offset the millions spent on unsuccessful research. The critics claim that industry profits are excessive, and that desperate patients should not have to shoulder the costs.

Measuring quality

FDA officials are talking more about the need for clear metrics on drug quality. But this does not mean developing "report cards" on manufacturers, says Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER). She noted at the April annual meeting of the Food and Drug Law Institute that the agency wants to develop "uniform and clear standards" for drug manufacturing for all types of medicines, with an emphasis on "clinically relevant" requirements. One aim is to ensure that senior management at companies is aware of quality problems, which she observed is often not the case.

Considering biosimilars

More manufacturers are meeting with FDA experts to discuss options and approaches for developing biosimilars, but the agency still had not received an application to test its proposed biosimilar pathway for these therapies as of late April. Manufacturers have filed 16 investigational new drug applications (INDs) for biosimilars, reported Steve Koslowski, director of CDER's Office of Biotechnology Products, at the April CMC Workshop sponsored by the Drug Information Association (DIA). The agency also has received 55 requests for meetings on biosimilars involving 11 reference products and has met with sponsors 38 times. The process has been facilitated by draft guidance published in March 2013 clarifying how sponsors should request and plan for formal meetings involving biosimilars. Koslowski clarified that a biosimilar may be proposed for fewer than all the conditions and routes of administration of the reference product, and that differences in formulation may be acceptable. There should be "no clinically meaningful differences," however, between a biosimilar and the reference product, which presents a challenge in determining "how close is close enough?"

Global regulatory standards

If a pharmaceutical manufacturer produces the same drug for international use, it should be able to work with globally accepted regulatory standards and filing requirements, says Ganapathy Mohan, executive director for global CMC pharmaceutical and devices at Merck, Sharp and Dohme. The goal should be a universally accepted set of control specifications, with common policies governing dissolution, assays, genotoxic impurities, among others. Instead, manufacturers face "a nightmare" of different filing requirements, inspection schedules, and clinical study policies, Mohan commented at the DIA CMC Workshop. Despite years of efforts to harmonize CMC requirements through the International Conference on Harmonization, regulatory authorities in key emerging markets are establishing diverse requirements for inspections, local clinical data, stability testing, and post-approval changes. Manufacturers need to demonstrate to regulatory authorities, Mohan advised, how such unique requirements generate high costs and regulatory hurdles that could block access to valuable medicines for their citizens.