An Ugly Reality, Failed Batches

Have you ever wondered how your batch success, or failure rate compares to others in the industry?

Sooner or later everyone involved in bioprocessing faces the ugly reality of a failed batch. Whether its a small bench scale bioreactor batch testing a new process parameter, a pilot scale bioreactor being used to generate product for early downstream testing and analytical development or a manufacturing scale bioreactor being used to produce product for use in an important clinical trial, a failed batch can really ruin your day.

The 5th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production was published earlier this year and some of the findings are summarized in a recent article in Genetic Engineering News. Its a short article that is worth reading to gain some overall perspective on industry trends but I thought I would highlight a couple of main points here.

The results of the survey indicate that the overall total batch failure rate among 434 biopharmaceutical developers was 7% and that the difference in failure rate was fairly similar between small and large scale facilities. For facilities operating at scales of less than 1,000L the failure rate was 6.6% while for those operating at scales larger than 1,000L the rate was 7.6%.

The article in GEN also listed the top four causes of batch failures for both large and small-scale facilities.

Large-Scale (1,000L or greater)

1. Contamination
2. Operator Error
3. Equipment Failure
4. Failure to meet specification

Small-Scale (less than 1,000L)

1. Material Failure
2. Equipment Failure
3. Product Cross-contamination
4. Contamination

I would imagine that with the adoption of disposable systems for both upstream and downstream applications the incidence of product cross-contamination should start to decline.

The fact the operator error was the second leading cause of batch failures in larger scale facilities indicates the importance that proper employee training can have on overall success rates.

Update: See the September 2008 issue of BioProcess International for another article summarizing the findings from the survey mentioned in the above post... slightly more detail is provided in this article.