Burkholderia cepacia: This Decision Is Overdue

FDA Believes Now is the Time to Remove the Bug from Pharmaceutical Manufacturing

The FDA recently published an article wherein they discuss the rationale for removing B. cepacia from the pharmaceutical arena.  They cite a number of reasons why they believe that this bacterium and its variants should no longer be permitted.  These discussions are continued by S. Sutton, Ph.D. in a Letter to the Editor PDA (J Pharm. Sci. Technol March/April 2012 66: 91-95) where he argues that the FDA is perhaps extending this concept too far.  Enclosed are Dr. Sutton’s concluding remarks as well as Raccasi et.al. counterpoint to this Letter to the Editor (PDA J Pharm Sci Technol March/April 2012 66:96-97).  Please view the entire recent research article by Friedman et al., Burkholderia cepacia: This Decision Is Overdue. PDA J. Pharm. Sci. Technol. 2011, 65 (5), 535–543.

Dr. Sutton’s concluding remarks include:

“I looked for a scientific justification of the unwritten policy of viewing B. cepacia (Bcc) as a pathogenic organism whose presence alone justified recall of batches. As has been amply documented, this has been the de facto standard for years. Unfortunately, this proof is lacking. The discussion presented in this article states that B. cepacia is a pathogen because of recalls involving it and that these recalls involving Bcc prove its status as an objectionable organism. This circular argument is not what is to be hoped for in a rational risk analysis.

In conclusion, then, I appreciate the opportunity to read the opinions of FDA scientists whom I admire, but have to point out not only does the article “Burkholderia cepacia: This Decision Is Overdue” employ questionable logic in risk assessment, it does not adequately support the arguments presented with relevant scientific data or case studies. If it is the intent of the agency to move towards requiring all pharmaceutical, OTC, and personal care products be sterile, this intent should be stated clearly to allow for discussion. If it is the intent to protect CF patients and those at risk for pneumonia from B. cepacia, then this should be done by cost-effective procedures in patient care. There are clearly some products that must be free of B. cepacia (inhalants, for example, and perhaps others based on demonstrated risk to the target population), but this article failed to provide convincing evidence or arguments that would lead to the conclusion that B. cepacia complex must be excluded from all product formats, or that we need to establish procedures for “objectionable organisms” in our manufacturing environment.”

S. Sutton, Ph.D. Letter to the Editor: PDA Journal of Pharmaceutical Science and Technology March/April 2012 66: 91-95

In the Author Response, the FDA comments as follows:

“In closing our paper, we concluded, “The evidence for the objectionable nature of this microorganism is substantial and supported by other independent research (2). B. cepacia is a clear and present danger to patient health and safety. The challenge is undeniable; now is the time to remove B. cepacia from our pharmaceutical manufacturing areas and products.” This conclusion would require manufacturers and application holders to establish specifications for products and criteria for manufacturing areas with sensitivity to the end use of product, and would be a concern for most aqueous, non-sterile products. We are not proposing that the environmental presence of B. cepacia is a batch release criterion, but should be cause for investigation and mitigation. We are proposing that aqueous drug products undergo a risk assessment of the presence of B. cepacia in the product, and analysis of its potential sources with the goal of keeping it out of the process stream.

We believe we are in agreement with Dr. Sutton on most of his points and appreciate his directing our attention to areas that may need more clarity. We appreciate the opportunity for these collegial discussions and to clarify our expectations.”

2) Halls, N. Burkholderia (Pseudomonas) cepacia—a brief profile for the pharmaceutical microbiologist. Eur. J. Parent. Pharm. Sci. 2006, 11 (2), 53.

Author Response PDA J Pharm Sci Technol March/April 2012 66:96-97

I encourage each of you to review the initial article as well as Dr. Sutton’s and the FDA’s response and form your own opinion.  Should B. cepacia have the same status of other “specified” microorganisms listed within USP<62> or should that status be reserved for selected monographs as per USP<1111>?  I encourage you to voice your opinions.