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Regulatory Requirements

History Fermation Processing DetailsMicrobial Sources

Erythromycin was first produced by isolating it from the metabolic products of

strain of Streptomyces erytheus (Saccharopolyspora erythraea) by Eli lilys

research team led by J .M . McGuire in 1949.

Lilly filed for patent protection of the compound and U.S. patent 2,653,899 wasgranted in 1953. The product was launched commercially in 1952 under the brand name Ilosone. Erythromycin was formerly also called Ilotycin. Today this drug is manufactured 66 companies and is a component of almost

1200 drugs 4

Uses

References

The antibiotics market generated sales of US$42

billion in 2009 globally, representing 46% of

sales of anti-infective agents (which also include

antiviral drugs and vaccines) and 5% of the

global pharmaceutical market.7 Erythromycin belongs to Macrolides group which

made a sale of $4.8 million In USA, New York has the maximum market size

of $15.25 million, covering 22.7% of the country

sales and 4.2% of the world market. Globally, Paris has the largest market size of $7

million which is 2.7% of the world widesale.(2009)8

According to Federal regulation 16 CFR 1700.14(a) (10), erythromycin as a

prescription drug can only be administered orally and dispensed only upon

written or oral prescription of a licensed practitioner by law.2

Erythromycin ethylsuccinate granules for oral suspension and oral suspensions

in packages containing not more than 8 grams of the equivalent of

erythromycin2

Erythromycin ethylsuccinate granules for oral suspension and oral suspensions

in packages containing not more than 8 grams of the equivalent of

erythromycin2

Erythromycin is also subject to special packaging regulations outline under the

Poison Prevention Packaging Act (PPPA). Such regulations includes a

requirement for drugs like erythromycin to have special packaging which is

designed to be significantly difficultfor children under five years of age to

open3.

Through out the scaling up process, the

temperature is maintained constant, as it is the

optimal temperature for growth. On the other

hand the rotation of the impeller decreased with

every passage. The reason for the decrease is the

increase in bacterial density. With every increase

in density the bacterial is under greater pressure

therefore original speed of the impeller is more

likely to shear and lyse the bacterial. Another

parameter that varies is the aeration r ate. The

aeration carries oxygen and CO2, where

erythromycin production is enhanced by

dissolved CO2 and oxygen allows for aerobic

fermentation to occur.

1. [Webpage] ErythromycinNCBI2014. Retrieved on: February 13, 2014. Available from:http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=12560

2. 16 Cfr 1700.14. (2014) 1-1-12 Edition ed., US Government Printing Office,

3.Poison Prevention Packaging Act.(1970) October 14, 2008 Version ed., Consumer Product Safety Comission,

4. [Article] Cortes, J., Haydock, S. F., Roberts, G. A., Bevitt, D. J., and Leadlay, P. F. (1990) An Unusually Large MultifunctionalPolypeptide in the Erythromycin-Producing Polyketide Synthase of Saccharopolyspora Erythraea.

5. [Article] Garcia-Rey, C., Aguilar, L., Baquero, F., Casal, J., and Dal-Re, R. (2002) Importance of Local Variations in AntibioticConsumption and Geographical Differences of Erythromycin and Penicillin Resistance in Streptococcus Pneumoniae.J. Clin.

Microbiol. 40, 159-164

6. [Article] Ginsburg, C. M., and Eichenwald, H. F. (1976) Erythromycin: A Review of its Uses in Pediatric Practice.J. Pediatr.89, 872-884

7. [Article] Gonzales, R., Steiner, J. F., and Sande, M. A. (1997) Antibiotic Prescribing for Adults with Colds, Up per Respiratory

Tract Infections, and Bronchitis by Ambulatory Care Physicians.JAMA. 278, 901-904

8. [Article] Hamad, B. (2010) The Antibiotics Market.Nature Reviews Drug Discovery. 9, 675-676

9. [Article] Minas, W., Brnker, P., Kallio, P. T., and Bailey, J. E. (1998) Improved Erythromycin Production in a GeneticallyEngineered Industrial Strain of Saccharopolyspora Erythraea.Biotechnol. Prog. 14, 561-566

10. [Article] Zou, X., Hang, H., Chu, J., Zhuang, Y., and Zhang, S. (2009) Oxyg en Uptake Rate Optimization with NitrogenRegulation for Erythromycin Production and Scale-Up from 50L to 372m< Sup> 3 Scale.Bioresour. Technol. 100, 1406-1412

Challenges and Drivers

Market

Block Flow

Microbial Source: Erythromycin is produced from Saccharopolyspora erythraea

(formerly known as Streptomyces erythreus), which is a species of actinomycete

bacteria1.

Legend

Yellow Boxes: Flow of the erythromycin compound through the various

chambers

Green Boxes: Details the starting micro-organism and the final erythromycin

product

Blue Boxes: Describes facilitating processes and transitional steps

Figure adapted from Zou et al. study10.

Erythromycin is a broad spectrum antibiotic used to treat infections caused by

bacteria5 Conditions like bronchitis; diphtheria; Legionnaires' disease; pertussis

(whooping cough); pneumonia; rheumatic fever; venereal disease (VD); Renal

impairment, Hepatic impairment and ear, intestine, lung, urinary tract, and skin

infections

It is also used before surgery or dental work to prevent hospital acquired

infections6

Erythromycin Microbial Bioprocessing

Peter Leung, Akhila Nair & Roberto Rodriguez

ALS 420,Keck Graduate Institute, Claremont ,CA

Antibitoics market in USA8

Fermentation Specifications

2.5 m3Fermenter (FJ2102, HEC, China)

220 rpm

33C

1.0 vvm

25 m3Fermenter (FJ2203, HEC,China)

180 rpm

33C

1.2 vvm

132m 3Fermenter (FJ2303, HEC, China)

60-126 rpm

33 C

0.8-1.2 vvm

Axial impellar 1270mm

9

10

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=12560http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=12560