Latest revision as of 16:20, 27 October 2010

UCL IGEM 2010

Doxycycline Economic Analysis

Doxycycline Biorocess Flowsheet

Cost

Estimate of Doxycycline cost for an industrial scale fermentation based on the 1,000L mammalian cell model

From Sigma Aldrich website for Doxycycline hyclate cost is $ 32.20 for 1 gram of Doxycycline

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

Bioprocess Flowsheet

A bioprocess flowsheet was constructed with regards to the mammalian cell system, in order to define all the necessary upstream and downstream steps and assess whether this choice is a feasible one.

The main steps for the antibody production expressed in mammalian cell culture are the primary recovery, primary purification, viral inactivation, secondary purification and viral exclusion prior to formulation, as indicated by the following SuperPro flowsheet.

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	%