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technology poses a financial risk to the company. Cost of the rapid system combined with potential product obsolescence is also a concern.
More recently, regulatory agencies have demonstrated a greater willingness to accept rapid technologies and encourage the adoption of these technologies when appropriate. One example is encouragement of the vaccine industry to implement rapid sterility methods to support testing vaccines for pandemic flu strains.
Growth-based, nondestructive rapid methods with the appropriate sensitivity are available today while greater clarity around the expectations for demonstrating equivalency between the rapid method and compendial gold standard method make implementation possible. For example, a rapid sterility equivalency study that utilizes a growth-based, nondestructive method that produces results in seven or less days, detects stressed organisms in inhibitory matrices and has a demonstrated detection limit of 1 CFU, has a strong possibility of achieving regulatory acceptance.
Initiative encourages innovation and ICH Q10 PQS mentions innovation numerous times. In this sense, RMMs are a perfect fit. Pharma users are actively examining RMMs as a way to be competitive, due to their potential to immediately provide improved efficiencies, enabling time and cost savings while maintaining patient safety.
TR:
Delays in adoption are due to many factors, such as regulatory authorities encouraging RMMs but not detailing them in aseptic processing guidance. Additionally, smaller companies do not want to be the first to adopt and are waiting for the large pharma companies to lead the way. Conversely, some larger companies do not want everyone to know when they adopt RMMs preferring to maintain a competitive advantage.
Delay is also inevitable when a new technology has the potential to be more sensitive than existing methods. Existing active air sampling and culturing could not be validated if it was new technology being introduced today.
One driver of RMM is regulators wanting to see pharma adopt 21st century best practices and technology.
The US FDA PAT
processes. So while it seems like adopting rapid micro methods should be a no-brainer, this move is happening more slowly than expected. First of all, microorganisms are extremely diverse and many are still completely unknown. To be widely adopted, a method should provide a one-size-fits-all protocol detecting the largest variety of bugs. Very few techniques provide such benefits. Moreover the cost associated with alternative methods is often handled by the Pharmaceutical microbiologist whereas the benefits and return on investment are actually beneficial to the manufacturing process. By building transversal teams in the pharmaceutical industry, the benefits are better understood and the costs are easier to justify.
Discuss reasons for microbiological-related recalls in recent years as well as key prevention efforts.
Review article (Feb 2012). Generally, in the area of sterile products, recalls seemed to indicate that the products were recalled due to either a lack of adequate demonstration of validated sterilization practices or potential non-sterile conditions of packaging, such as pinholes or other defects. Adequate process validation and documentation are the best approach to preventing these types of recalls. The the concerns developed from compounding pharmacy recalls in the last two years are more complex than just process validation as a corrective measure.
DS:
A colleague, Scott Sutton, co-authored (with Luis Jimeniz) a comprehensive review of recalls in an American Pharmaceutical
In the latter Similarly, there is not a single new method which is perfect.
Therefore, it is important to understand the strengths and limitations of any measurement technology, new or old. Laser Induced Fluorescence, used to detect airborne viable particles in real-time, is an example of a new RMM. It is a different from the culture-based method and as such is going to give a different result.
PB:
The key drivers for turning to Rapid Microbiological Methods (RMMs) are needs for accuracy and short time-to-result. Genotypic
RMMs are famous for their ability to deliver this. The DNA sequence of the organism is not influenced by external factors. Genotypic methods allow more confidence and greater accuracy. The customer gets answers in a shorter period of time. In general, in big facilities with high throughput, these methods are attractive, because they allow for workflow automation.
Traditional methods often continue to be used because they are familiar, with inexpensive running costs, and provide good enough results in many scenarios.
In addition, RMMs generally require a change in the way
microbiology is routinely conducted and a certain amount of knowledge in molecular biology methods. When a greater need for improved accuracy of results is realized, that’s when a lab moves from culture-based methods to modern molecular methods.
microbiologist are like everybody, they want answers immediately so that they can make the right decisions. These decisions help improve patient safety and drive, in a scientific manner, the efficiency of manufacturing
RJ: 74 | | September/October 2013 - 15TH ANNIVERSARY ISSUE
Nobody wants to wait fourteen days to get an answer. Would we accept such a delay when searching the Internet? Pharmaceutical
instances, better oversight and responsibility are important measures, along with separation and understanding the differences between GMP manufacturing and good pharmacy compounding practices. One must realize that a pharma manufacturing operation has a Quality role for oversight of GMPs and product quality, whereas a compounding pharmacy may understand quality only as an attribute and not as a preventative activity. These troubling events took us by surprise, I think, and thus many stakeholders have begun to generate a more robust plan for improvement in this area, including the FDA, the USP and the APhA.
Packaging integrity is a sterile and non-sterile product attribute. Building a better understanding of how package integrity relates to product protection from microbial contaminants is an active field. Often, we have taken for granted the packaging components and processes used to seal packages. We’re learning more about weaknesses in the supply chain and challenges brought by more complex processes and package designs.
If
we continue to learn and be aware of potential integrity loss root causes, we will be more pro-active in our design for quality thinking. Be on the lookout for revised guidance from the USP (Chapter <1207>) and the PDA (revision of former TR27 document).
define the requirement for absence of objectionable organisms in these types of products, there continues to be a lack of clarity on this issue. To avoid regulatory issues, companies need well-developed procedures to address objectionable organisms. The compendial microbial limit tests as written are not adequate to detect objectionable organisms, and additional modifications to the compendial methods are necessary. One approach is to streak the enrichments prepared in the compendial test to non-selective media in addition to the required selective media. The next step is to identify isolates and evaluate the organisms using a risk- based approach that considers a number of factors such as, dosage form, intended use, potential of the isolate to degrade the product and infection risk associated with the isolate.
MK:
The majority of recalls of non-sterile products are associated with objectionable organisms. While GMP regulations clearly
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