Biopharmas Should Explore Better Ways to Make and Regulate Drugs to Avoid Shortages

August 10, 2011 – 3:36 pm | By Guest Contributor | No comments yet

What’s causing drug shortages in the U.S., and is it a matter of mechanisms of control or methods of drug production? In 2010, there were shortages of 178 drugs in the U.S., a record-high level. Many drugs on the 2010 list are still unavailable, and the number is growing. It has tripled in the last six years, according to the FDA.

Currently there are about 246 drugs in short supply, and that number has risen steadily since 2006. Severe drug shortages are endangering cancer patients, heart attack victims, accident survivors and others. Many people hold the FDA largely responsible for the problem.

FDA’s Rules as a Pebbles in the Innvation Stream
According to a summary report, several drug shortages are the result of “actual or anticipated action by the FDA as part of the Unapproved Drugs Initiative, which is designed to increase enforcement against drugs that lack FDA approval to be marketed in the United States,” those that were available before the Food, Drug, and Cosmetic Act: of 1938 was passed. Manufacturers are balking at “the cost and complexity of completing a New Drug Application (NDA),” as well as “the time for FDA review of Abbreviated New Drug Applications (ANDA) and supplemental applications.” Another major cause cited for the drug shortage was “inability to fully comply with GMP, which results in production stoppages or recalls.” The summary report was prepared by the American Society of Health-System Pharmacists, the American Society of Anesthesiologists, the American Society of Clinical Oncology and the Institute for Safe Medication Practices.

John Goodman at the Health Affairs Blog said “the FDA has been “stepping up its quality enforcement efforts — levying fines and forcing manufacturers to retool their facilities both here and abroad.” The “more rigorous regulatory oversight” has not only slowed production, but also, “the FDA’s ‘zero tolerance’ regime is forcing manufacturers to abide by rules that are rigid, inflexible and unforgiving.”

Economist Michael Mandel also cited rules and regulations as impeding innovation: “No single regulation or regulatory activity is going to deter innovation by itself, just like no single pebble is going to affect a stream. But if you throw in enough small pebbles, you can dam up the stream.”

Biotech Drugs Are a Different Breed (and Breeding Ground)
For biotech drugs, the problem of drug shortages is even more critical, and complex. According to an article in Nature:

Unlike the manufacture of small-molecule drugs, which typically relies purely on large-scale chemical synthesis, biomanufacturing usually involves massive cultures of live cells maintained in rich, contamination-prone media. Anyone who has struggled to keep a 1-litre laboratory cell culture sterile will appreciate the challenge of doing the same for a 10,000-litre reactor. Viruses are stealthy intruders and can lie undetected in a culture for weeks, while the infected cells move down the pipeline to spread the scourge through the manufacturing facility — into those 10,000-litre reactors and through million-dollar chromatography columns This means that viral contamination can shut down drug production for months and cost a company millions of dollars, interrupting drug supplies and leaving patients vulnerable.

At least 17 incidences of viral contamination in biologics have been reported, but many more have gone unreported, according to Nature.

According to the Biotechnology Industry Organization (BIO), the 10,000-liter tanks in sterile manufacturing facilities cannot be built fast enough to keep up with patient demand. In addition, pharmaceutical industry experts believe that since it takes three to five years, and about $450 million, to build a biotech facility, in order for biopharma companies to be prepared to meet the overwhelming patient demand, they would have to make risky investments before receiving FDA approval.

Solutions Sought in Research, Switching to Different Manufacturing ‘Plants’
Researchers at the Massachusetts Institute of Technology, of Cambridge, Mass., are forming a consortium with industry to draw lessons from contamination data that could benefit the industry as a whole, and to publish answers to questions, such as where viral contaminants originate and what the best way to detect and eradicate them is, or how to prevent them altogether. Currently, only six companies have signed up to participate in the pilot phase of the study. Organizers hope that more biotechnology companies will “embrace this rare and valuable opportunity to pool resources without compromising their business interests.”

One solution proposed by BIO is using plants to produce therapeutic proteins. According to a fact sheet:

Traditional methods of producing pharmaceutical materials using microbial fermentation or animal cells are limited by the time and money necessary to build the required manufacturing facilities, and production is limited to manufacturing capacity. It can take a total of five to seven years from laying the first bricks of a traditional biotech facility to extracting pharmaceutical proteins from cultivated cells.

BIO claims that it will “cost significantly less to grow plants with the ability to mass-produce pharmaceutical proteins because plant-based techniques don’t require the same costly capital investments.” In addition, such plant-made production can be expanded more easily if demand for a drug increases. Since “plants are renewable in nature and can produce pharmaceutical proteins within a single growing season, production can be quickly scaled up to meet patient needs.”

Whether drug shortages are caused by the process of producing the drugs, the procedures for approving them or both, it would behoove manufacturers and government officials to engage in dialogue to analyze the problems and attempt to find solutions. Time-consuming, expensive procedures for making biotechnology drugs and lengthy approval procedures are likely to continue, but technology and cooperation can be valuable allies in finding solutions.

By Ilene Schneider, BioWorld Perspectives Contributing Writer

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