Industrial Biotechnology Impact Factor

July 14, 2014
In Industrial Biotech with

Mark Warner HeadshotBy Mark Warner, PE, creator, Warner Advisors LLC, specialized towards the Digest

Two concerns have actually ruled the answers obtained after my Lessons Learned show on commercializing manufacturing biotechnology (right here) therefore the deep-dive into the manufacturing biotechnology commercialization process (right here), the questions are and of course just how can risk be low in the method? Looking back within products, there are some areas that need to be broadened in increased detail to answer those questions.

Through the sessions Learned series, the 3rd concept “there isn't any replacement for a totally built-in pilot process” created plenty of conversation on the reason why this is certainly therefore. Many within our advanced biotechnology industry come from the chemical or petrochemical industries, which are rooted in procedure modeling because their primary scale-up device. That is substantially distinct from advanced level biotechnology, in which scale-up is dependant on prolonged pilot functions. The fee and schedule to build an integrated pilot, or demonstration scale plant, challenges ventures wanting to bypass these tips, which could end badly. Allow me to target why is biotechnology processes unique and just why pilot evaluating is really critical to an effective scale-up.

Initially, let’s understand how old-fashioned substance processes are scaled-up by modeling as an assessment. As a chemical procedure professional just who spent the first part of his profession inside chemical business, i've been up against most standard substance scale-up challenges. Processes including synthesis of a natural compound and subsequent refinement from an assortment of solvents, in which all of the compounds had well-documented substance and real properties. If there were chemical responses, it had been usually between a small quantity of substances with well-known reaction kinetics and a brief listing of contending negative reactions become considered. This is modeled extremely precisely by process simulation computer software like Aspen or CHEMCAD. Modeling didn't completely change the necessity for piloting, but usually minimal the range of pilot testing to verification of key variables. This reputation for success in making use of modeling procedures then verifying several individual operating conditions with piloting, provided confidence in this strategy.

Now, let’s compare that to professional fermentation based procedures. Industrial fermentation typically starts with feedstocks being less pure plus complicated from a reaction viewpoint than a normal chemical response. Anyone who has heard of huge wall surface posters of metabolic pathways in very small font understands the things I in the morning speaking about. Its usually not practical to model the entirety regarding the specific responses (and contending negative responses), but instead only useful to build the average price equation when it comes to total process. While this may be used to portray the method from a “macro” viewpoint, you won't accurately anticipate the small constituents in the fermentation broth that will affect both the fermentation and data recovery productivity. This instance is specific to fermentation, however the principle similarly relates to various other bio-based processes.

Given this incapacity to precisely model biotechnology processes, pilot and demonstration plant operation is the only dependable solution to create the info necessary to measure and design equipment. This is why built-in pilot operation can be so important to project success. Here are a number of my lesson’s discovered specific to scale up of biologic processes:

Understand your feedstock – if you should be intending to make use of standard industrial sugars like liquid dextrose at commercial scale, you need to ensure your laboratory and pilot examination precisely presents the feedstock. As one example, if you're purchasing bags of commercial dextrose crystals to perform inside pilot plant, you may be surprised to discover that crystal sugar has actually a much greater purity (>99.5percent) than standard fluid dextrose. Typical liquid dextrose is 95% dextrose and has now 3-5% of other (frequently unfermentable) sugars including maltose and higher saccharides. These could cause working problems both in fermentation and downstream data recovery. Neglecting to utilize representative feedstock during scale-up assessment can set you right up for huge issues later on.

Exactly the same dilemmas occur when performing fermentation with syngas or digester fuel as a feedstock. Frequently, the commercial business model is to produce syngas by gasification of biomass or MSW, the laboratory or pilot will work on syngas generated from gas for convenience. Just as the sugar example above, if the feedstock utilized in the pilot doesn't portray the reality of commercial scale, there will be businesses problems that happen.

The liberal news – a reference to the fermentation news, of course. This might be an assortment of trace vitamin supplements included with liquid and inoculum at the start of the fermentation. Just like humans, most organisms require some trace amount of these to guide metabolic activity. The difficult component is determining exactly how much is required and not only liberally adding it to ensure there's plenty. Optimization of news isn't generally a priority at laboratory or pilot scale, but can be a substantial expense and offer constraint in a commercial operation. Just as the dextrose instance, commercial supplies of this nutrients are less pure and will deliver contaminants as well as other compounds that will adversely impact the process.

The “other” problem – as talked about above, it's not practical in a commercial biotechnology process predict all substances created during fermentation, or which come combined with the feedstock. Typical substance analysis used in manufacturing scale-up will recognize key compounds, but then everything else that simply cannot be identified gets lumped into a category of “other”, usually labeled throughout the design process as “OS” or “other stuff”. It's important to keep in mind that these substances are not inert and in most cases impact the method. The biggest issue often arises from the unfermentable sugars together with co-compounds that are produced from negative responses. This will be one more situation where in fact the only way to look for the impact of these substances is always to run the pilot procedure.

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