Team:UCL London/Economic Evaluation

Economic Evaluation

Through means of auto induction, we hope not only to revolutionize the biopharmaceutical industries approach to protein expression, but we also hope to bring a wave of economic benefits;

1. Cost of IPTG is approximately $600.00 for 10,000L fermentation.

2. Average Facility of a pharmaceutical plant: 50 batches per year, total of $30,000 saving.

3. Industry wide savings of millions of dollars.

4. Two tons of CO2 are produced for each innocculum volume of IPTG. (Source: BIA)

5. Saving an average facility 100 tons of CO2 annually

Calculations

Estimate of IPTG cost for an industrial scale fermentation - say 1000L

From Sigma Aldrich (readily available): Isopropyl-Beta-D-thiogalactopyranoside (IPTG) solution costs £32.30p for 200 mM IPTG

IPTG’s molar mass= 238.3 g/M

200* (1 M/ 1000 mM) = 0.2 M
0.2 M * (238.3 g/M) = 47.66 g

So its £32.30p for 47.66 grams, therefore £ 0.68 pence /gram

From literature: 0.1 mM (This value is usually used for a high FAb production)

So using 0.1 mM, how much IPTG you need in grams: 0.1 mM * (1M/1000mM) = 0.0001 M

238.3 g/M * (0.0001 M) = 0.02383 grams<<< this is
how many grams of IPTG you need per a kg of a feedstream.

Finally for a 1,000 L fermentation batch

Using SuperPro Designer you can assume kg = L

So for 1,000 kg/batch, this is how much IPTG you need:

1,000 * 0.02383 g * (1 kg/ 1,000 g) = 0.02383 kg /batch

Cost of IPTG per a batch:

0.02383 (kg/batch) * 0.6777 (£/ gram) * (1,000 gram / 1 kg) = £ 16. 15 p / batch

Below we have summarized the Economic Advantages and Disadvantages of Auto-Induction:

Advantages

• Simple procedure, expression strain inoculated in the auto-inducing media

- No holding tank required for IPTG, therefore cost saving in equipment costs (Note: lowering the equipment costs, also lowers the capital investment)

- And maybe a slight reduction in CIP and SIP costs

• High titres achieved when auto-inducing compared to using IPTG as proven by our circuit simulation

- Reduces size of fermenter required (as there is more target protein per volume of culture), which lowers the USP equipment costs.

- Also number of batches produced per year would be less

Disadvantages

• Auto-induction uses complex medium

- Complex medium, more expensive

- Could increase the Cost of Goods (COG’s), dependent on the prices of IPTG and complex media.

• At high titres, nature of the feedstream has an impact on the purification steps

- Protein A resin required to capture more product

- High titres bring about more impurities, purification steps may struggle to remove this higher level of impurities.

- Resin lifetime reduces due to fouling, therefore more resin required

- Protein A resin expensive and a significant cost driver for DSP costs

• Possibility of unintended induction

- Could potentially kill cells and produce unexpected impurities that cannot be removed downstream or require further purification steps

• Cultures grown using auto-inducing media may not be suitable as frozen stocks.

- Limited time for use

- Potential risk; loss of stocks due to decrease in viability