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detect such an organism could help to improve the safety of drugs and limit the number of recalls.
Describe challenges of maintaining GMP and the advantages these guidelines present.
control must be robust, consistent and appropriate for the manufacturing operation. We are learning more about the relevance of microbiological monitoring to product quality. Both the activity of monitoring and the intent of a controlled environment are related to GMPs. My view is that we should be designing and implementing a microbiological control program based on patient and product risk. This should be sufficient for a GMP-compliant environment. Yet, there are still a few influences in the regulatory field who continue to portray monitoring programs as a means of building GMP compliance in the name of ‘product quality’. We should be cognizant of this misdirected influence, and continue to improve and convey that a well-understood manufacturing process and environment is only partially based on monitoring data and mostly based on good design. In fact, maybe we should coin another industry acronym , ‘GMDP…good manufacturing design practices’; improvement strategies.
DS: this could be more advantageous to
What are your expectations for the next 15 years in this field?
What are the complications associated with control of microorganisms in biopharmaceutical manufacturing? How are these addressed?
conditions can either lead to optimal production of an intended biological substance or a disastrous contamination event.
DS:
catamount to ensuring that we prevent the latter type of event. biopharmaceutical manufacturing has brought learning with regards to microbiological control.
biological substances cannot tolerate classical ‘destructive’
In simple terms, one could think that the use of growth media, live cells, and large equipment with optimal microbial growth
Our knowledge is In fact,
to us a continuum of Since many of these terminal
sterilization methods, we have seen development of the most robust designs for prevention or removal of microorganisms in an upstream process.
The techniques used to remove microbial cells, bacterial
endotoxin and viral contaminants are commonly understood by biopharm manufacturing scientists and provide the customized design parameters for microbiological control. Challenges of biological substance stability have led to more awareness of package integrity as it relates to impact during cold storage conditions.
The hold time of a bulk substance
preparation during manufacturing is scrutinized closely as it relates to the growth potential of contaminants. Viral contaminants and mycoplasma are also ongoing concerns for removal or inactivation.
This wide
spectrum of microbiological contaminants make it mandatory to design a biopharmaceutical process with holistic thinking for control, to assure purity and safety of products.
PB: 76 |
Bioburden is omnipresent no matter how sterile the environment is. Quick and correct identification of problem microorganisms is
therefore crucial to contain contamination events. Having proper systems in place, such as environmental monitoring programs can have a big impact on potentially problematic situations such as loss of large volumes of samples facility shut down in event of contamination. An accurate and
| September/October 2013 - 15TH ANNIVERSARY ISSUE DS: in-process tools, rather than release methods.
I believe we are just beginning to accept the potential of alternative technologies for routine /monitoring use as If suppliers can make
these tools more economical and if industry users can lower their expectations for level of ‘validation’ scrutiny, there will be a flurry of implementation over the next 10 years. Since we are already in an era of digital technology, I can see us routinely using tablets and bar-coding in 10-15 years to track environmental samples (plates), record results and trend the data in a mobile format. Some companies have begun this journey. Another interesting area that may need at least the next 15 years for acceptance is development and understanding of non- classical means of terminal sterilization for materials that are sensitive to the current strict classical approaches.
with highly controlled processes/environments. At least two diverging philosophies describe the role of microbiology within this evolution. Some believe that, as automation expands, so as to virtually eliminate routine human interaction with the process/environment, an increasing reliance can be placed on parametric factors (laminar air rates, temp/RH, TOC, etc.) to ensure a system is under control and achieves a validated level of quality. This approach is aligned with tenets of Parametric and Real-Time Release initiatives. Another viewpoint is that microbiological measurements will always be necessary to demonstrate acceptable microbiological quality, and most sampling would necessarily require intrusion. Given established microbiological practices, these approaches seem mutually exclusive.
PN:
RMMs which offer data beyond simply faster compendial results, however, create an opportunity to bridge the philosophical gap. Some RMMs can be operated remotely, reducing the need for manual sample collection. Furthermore, online RMM systems can be integrated with process controls (e.g. HVAC system) to automatically maintain a predetermined state of control. An RMM-enabled future would reduce the need for
I believe a major theme in biopharmaceutical manufacturing will be increased automation, following other tech sectors
Briefly, and with passion, I can say that microbiologists view GMPs with a more focused perspective.
Microbiological
rapid microbial identification method that is set up within the facility also supports efficient control of microorganisms.
antibodies or Enzymes. In order to produce such high-value biologics the conditions must be highly favorable to living organisms, meaning nutrient sources such as oxygen, energy and, of course, water must be abundant. As such, unwanted microorganisms love to take advantage of this friendly environment. The length of these aseptic processes reaching up to two months and the absence of final sterilization method make biopharma manufacturing one of the highest risk processes for microbial contamination.
RJ:
In order to prevent bad surprises at the end of the process, regular in- process controls are needed. Mitigating the risk by early and systematic analysis provides a rationale to move safely from one step of the process to the next. Alternative methods are tools of choice to provide such valuable information. They do not aim at replacing final compendial testing but to complement it. Microbial controls should target product and raw material bioburden, but also environment. Robust sampling plans allow for the definition of a clear baseline and help the team take action before systemic failure occurs.
Biopharmaceutical manufacturing requires living organisms for the manufacture of biological drugs such as monoclonal
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