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UCL IGEM 2010

Doxycycline Economic Analysis

Doxycycline Process Flowsheet

Estimate of Doxycycline cost for an industrial scale fermentation - say 1,000L

I looked on Sigma Aldrich website for Doxycycline hyclate cost • $ 32.20

• For 1 gram of Doxycycline

Finally for a 1,000 L fermentation batch, this is how much Doxycycline you need: 0.012 kg per 1,000 L batch

Cost of Doxycycline per a batch: 12 (gram/batch) * 32.20 ($ / gram) = $386.40 per a 1,000 batch

Mammalian cell process using Doxycline

Production Volume (L)	Titre (g/L)	Product Generated (kg/batch)	Annual Production (kg/yr)	Batches (per a year)	Centrifugation Yield (%)	Filtration Yield (%)	Purification Yield (%)	Overall Yield (%)	No. Bioreactors	Scale of Bioreactors (L)
40,000	2	6.3	132.4	21	94	100	70	67	1	7000

Note: 7,000 L fermenter example

Executive Summary

Capital Investment ($)	42,013,000
Operating Costs ($/yr)	16,210,726
Product Unit Cost ($/kg)	122,475
Labour Cost ($/yr)	1,805,307

After removing Doxycline from the production process

'	Before	After
Capital Investment ($)	42,013,000	41,820,000
Operating costs ($/yr)	16,210,726	16,153,925
Cogs ($/g)	122.5	122.1

Annual Operating Cost

Annual Operating Cost	'	'
Cost Item	$	%
Raw Materials	5,477,726	34
Labour-Dependent	1,805,000	11
Facility-Dependent	6,050,000	37
Laboratory/QC/QA	903,000	6
Consumables	1,966,000	12
Wste Treatment/Disposable	6,000	0.0
Utilities	3,000	0.0
Total	16,210,726	100
Cogs ($/g)	122.47

Could this be because of Doxycline? No, doxycline makes up only 1% of the total raw material costs

Material Cost

Material Costs	Unit Cost ($/kg)	Annual Amount (kg)	Annual Cost ($)	%
Media	300	16	4,860	0.088722951
SerumFree Media	300	17,184	5,155,169	94.11148327
Doxycline	32200	1.764	56,801	1.03694128
Water	0	335	0	0
WFI	0.15	517,650	77,647	1.417504323
Air	0	88,694	0	0
H3PO4 (5% w/w)	0.14	121,071	17,253	0.314966478
NaOH (0.5M)	0.25	99,042	24,271	0.44308534
Protein A Equil	0.15	144,251	22,063	0.402776641
Protein A Eluti	0.15	65,347	10,029	0.18308693
Prot- A Reg Buffer	0.17	39,230	6,580	0.120122844
NaOH (0.1M)	0.24	135,799	33,015	0.60271363
IEX -Eq-Buffer	0.19	21,491	4,000	0.073023005
IEX-Wash-Buffer	0.22	21,586	4,766	0.087006911
IEX-El-Buffer	0.35	1,217	423	0.007722183
NaCl (1M)	0.37	13,196	4,860	0.088722951
Amm. Sulfate	8	919	7,354	0.134252795
HIC-Eq-Buffer	0.91	8,522	7,744	0.141372538
HIC-Wash-Buffer	0.54	20,256	10,898	0.198951178
HIC-El-Buffer	0.31	19,645	5,985	0.109260672
NaOH (1M)	0.34	65,709	22,094	0.40334257
PBS	0.18	15,255	1,913	0.034923252
Polysorbate 80	1.83	1	1	1.82558E-05
Total	-		5,477,726	100

Consumable Costs

Consumable Costs	Unit Cost ($)	Annual Amount	Annual Cost ($)
Dft DEF Cartridge	1,000	63	63,000
Dft Membrane	400	10 m2	4,008
50 L Bag	5	210	1,050
Viral Exclusion Membrane	13,356	21	280,476
Protein A	6,000	167 L	1,000,337
SP-Sepharose High Performance	1,200	98 L	117,915
HIC Butyl Sepharose High Performance	2,050	9 L	18,332
Total	-	-	1,485,118

Equipment Cost $

Doxycline is added from a holding tank, absence of doxycline will make minimal difference to USP costs.

DSP costs are very high, that a cost reduction in the USP section has no significant difference to the total equipment costs

USP	DSP	Total Cost	USP:DSP
732,000	2,607,000	3,339,000	0.28

USP	'	'
Equipment Name	Cost ($)
Stirred tank reactor	539,000
Blending Tank	193,000
DSP
Blending Tank	191,000
Blending Tank	159,000
Diafilter	26,000
Chromatography Column	148,000
Blending Tank	137,000
Chromatography Column	144,000
Dead-End Filter	32,000
Blending Tank	134,000
Diafilter	22,000
Dead-End Filter	32,000
Disposable Container-Skid	0
Disk-Stack Centrifuge	370,000	Most expensive piece of equipment downstream
Dead-End Filter	32,000
Chromatography Column	192,000
Dead-End Filter	32,000
Blending Tank	134,000
Dead-End Filter	32,000
Blending Tank	127,000
Dead-End Filter	32,000
Unlisted Equipment	677,000
Total	3,385,000

Waste Treatment/Disposal Cost

Waste disposal costs are mainly for CEX and HIC

Waste Category	Unit Cost ($/kg)	Annual Amount (kg)	Annual Cost ($)	%
Solid Waste	-	0	0	0
Aqueous Liquid	-	156,691	6,268	100
IEX - Waste	0.04	87,190	3,488	55.64
HIC- Waste	0.04	69,500	2,780	44.36
Organic Liquid	-	0	0	0
Emissions	-	88,584	0	0
Total	-	245,275	6,268	100

Throughput Analysis

On SuperPro it assumes it would take 60 minutes to set up the Doxycline inlet This is 0.3 % of the overall process, delay in set up doesn't have a profound effect.

Process Data	'	'
Annual Operating time	7,104.66	Hours
Annual Throughput	132.36	Kg/MP
Batch Throughput	6.3	Kg/MP
Plant Batch Time	397.49	Hours
Number of Batches per a year	21	Batches
Time Bottleneck Equipment	Production Fermenter	PBR1
Throughput Utilization	90	%

@@ Line 3: / Line 3: @@
 =Doxycycline Economic Analysis=
+==Doxycycline Process Flowsheet==
 Estimate of Doxycycline cost for an industrial scale fermentation - say 1,000L
@@ Line 17: / Line 18: @@
 (gram/batch) * 32.20 ($ / gram) = $386.40 per a 1,000 batch
+[[Image:Ucl-doxylcien.png|800px|left]]
 ==Mammalian cell process using Doxycline==
@@ Line 323: / Line 325: @@
 |}
-==Doxycycline Process Flowsheet==
-[[Image:Ucl-doxylcien.png|800px|left]]

Team:UCL London/Doxycycline