Heparin and Quality by Design

The Wall Street Journal February 19, 2008 published an article on Heparin.

Following are some excerpts.

“Baxter, which supplies about half the U.S. heparin market, said last week it had temporarily stopped production because of about 350 bad reactions, including four fatalities, potentially tied to the drug. About 40% of the reactions were classified as serious, ranging from stomach pain to vomiting and diarrhea, low blood pressure, speeding heartbeats and fainting.”

In pharmaceutical business, the current methodology to produce consistent performance quality drug is to follow “quality by analysis,” which is analyze everything. In the case of Baxter International, casualties and bad reactions are a clear failure of the prevailing “quality by analysis” culture.

Legislators and consumers are demanding increased inspections. The FDA does not have enough staff to inspect every drug that is imported in US. FDA inspects only 7% of the incoming drugs (FDA inspections). It will not only take increased funding but also time to train inspectors to achieve 100% inspection. We have neither luxury.

Even if FDA could do 100% inspection, they would be following “quality by analysis” methods, which FDA wants the pharmaceutical companies to abandon. It is well known that “quality by analysis” is an inefficient and expensive method of producing drugs. Consumer pays for every mistake, rework, and disposal, if the drugs do not meet their respective specifications.

It has been mentioned that USFDA or EU regulatory agencies should be stationed in China, India and/or other countries exporting drugs. This can only happen if there are agreements in place between various governments. We are nowhere close to such agreements.

If a supplier/manufacturer is behind schedule, there is pressure to release the drug to the market as soon as it is produced. In such circumstances, mistakes like Heparin are going to happen. As more drugs are imported in the future, we are going to hear more about the mistakes. Heparin mistake also suggests that there is a failure on part of the pharmaceutical importer to set up strict standards and stringent protocols. Laxity has to be completely eliminated.

Pharmaceutical industry has to move from “quality by analysis” culture to “quality by design (QBD)” methods. Until this happens, increasing FDA inspectorate and passing new legislation is not going to solve situations similar to the current situation. QBD builds quality in the product from onset. It will change the culture, improve quality and will significantly reduce pressure on FDA and/or any regulatory bodies. Someone has to make a move.