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Microbiological recalls have been increasing due to enforcement actions by federal agencies and recent contamination incidents
where major violations of GMP practices resulted in morbidity and mortality cases [1]. Previous studies reported an increase in the number of product recalls by the FDA.
The first study reported a disturbing trend in the
numbers of products recalled by microbial contamination [2]. The study was published in 2007 and covered a period of time from 1998 to 2006. This was the first comprehensive study looking at the types of microorganisms found in product recalls reported by the FDA describing the types of products and microbial contaminants.
Burkholderia cepacia was found to be the
number one microbial contaminant in non-sterile and sterile pharmaceutical formulations. Yeast and mold were found to be responsible for 23% of the recalls in non-sterile and 7% of sterile products. Unfortunately, mold was found to be the reason for product contamination during a recent meningitis outbreak due to contaminated syringes [1]. Of the 193 recalls in sterile manufacturing, 78% were due to lack of sterility assurance.
A new study was published in 2012 with a different time range. Recalls were analyzed from 2004 to 2011 [3]. The findings demonstrated that the lack of sterility assurance was still a major problem for sterile products. However, the data showed a significant increase in the numbers of recalls from 2009 to 2011 [Figure 1, reference 3].
B. cepacia remains
the number one microbial contaminant in recalls for non-sterile and sterile products. Although B. cepacia is an opportunistic pathogen for immunocompromised patients, the metabolic capacities of these bacterial species have been severely underestimated in pharmaceutical quality control [4]. B. cepacia is capable of growing on nitroaromatic and aromatic
compounds by the action of different enzymes such as monooxygenases and dioxygenases [5]. Therefore the health hazard to patients not only makes B. cepacia a real nightmare for quality control microbiologists but these bacterial species can compromise product stability and purity by degrading active ingredients and excipients resulting in sub potent formulations. Many pharmaceutical formulations are based upon nitro aromatic compounds [5]. For instance, antipsychotic and analgesic drugs are based upon aromatic structures sensitive to biodegradation attack by mono and dioxygenases from microbial contaminants. B. cepacia posses a diverse genotypic and phenotypic potential to break down pharmaceutical active ingredients and excipients [6].
Further discussions by industry and regulatory agencies will provide better conditions to control microbial contamination and reduce the incidents of recalls, morbidity, and mortality by optimizing training, regulatory guidance, and enforcement.
driven both by regulatory concerns and the manufacturers themselves – certainly account for a large portion of recalls. Among these precaution principles, the fear of Objectionable Organisms is key. The highest number of recalls incriminates B. cepacia, an organism that is resistant to many traditional antimicrobials and responsible for severe infections in immuno-compromised patients. This organism is absent from the list of compendial specific bugs to detect, thus it is not tracked systematically. The use of modified Total Viable Count testing designed to specifically
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In addition to the unfortunate and rare cases of improper manufacturing practices, increased scrutiny and precaution –
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