Challenges faced by a Biochemical Engineer

o Biochemical engineering
e The extension Of engineering
principles to systems using a biological
catalyst to bring about desired chemical
transformations
Bio-reaction engineering
Bio-separations
• Bioprocess engineering
Design of processes based on living cells or
cellular components
Range of Microbial Products
Chemical industry
Lactic acid, acetic acid, ethanol or acetone.
Degrade petroleum products
Foods industry
Yogurt, cheese, buttermilk,sour cream, and butter,
pickles, beer, tequila
Plants resistant to certain pests, herbicides, and diseases
Pharmaceutical industry
Antibiotics such as tetracyclines, erythromycin,
streptomycin; vaccines against diphtheria, whooping
cough, tetanus, typhoid fever, cholera, drugs such as
insulin and human growth factor; human proteins such as
interferon, interleukin-2, and tumor necrosis factor.
Bioprocesses: Regulatory
Constraints
o Mandatory:
Regulatory compliance
Critical:
Minimization of manufacturing costs
o In the U.S. production of biological
products for human use is regulated by
the Food and Drug Administration(FDA)
o In Canada, Health Protection Branch of
Health Canada
Drug Development and the
Approval Process
• Discovery takes this much years to develop
6.5 years
Pre-clinical (animal) testing
Phase I clinicåtrials human clinical trails
At least 1 year duration
it involves 3 phases here
Involve 20-80 healthy, normal volunteers 1.about1year
2.2 years
Test product safety 3.3years
• Phase Il clinical trials
At least 2 years duration
Involve 100-300 patients
Test product efficacy and safety
 The approval process
Phase Ill clinical trials Approved!
At least 3 years duration
Involve 1000-3000 patients
Test efficacy, safety, also dose-finding
• Data review by the FDA at every stage before
approval is granted to move on cost of this 15yearsworkis 5400
million dollars (1996)
Discovery through approval generally takes
—15years and costs hundreds of millions of
dollars; only 1 in 10 drugs that enter human
1 in 10 refers,the 10percentis
clinical trials will actually make it to marke t success ratio
FDA approves product & process together
since small process change —may allow toxic
compound to form —incorporated in final product
—--resultingin severe side effects including
death.

Separate clinical trials also to be done

GMP- good manufacturing
practices
Manufacturing Drugs
• Any product used in clinical trials or sold
commercially must be manufactured in
accordance with cGMPs (current Good
ManufacturingPractices)
• GMPs are a series of "rules"that govern:
Manufacturing facility design and layout
Equipment
Procedures
Training
Raw materials testing and use
Handling of product
 • Plant layout and design must prevent
Manufacturing Drugs contamination of the product and dictate
the flow of material, personnel and air
• Equipment and procedures must be
validated
Procedures govern operation of equipment,
as Wellas cleaning and sterilization
All procedures are documentedby SOPs
(Standard Operating Procedures)
Validation
o "Process validation is establishing
documented evidence which provides a
high degree of assurance that a specific
process will consistently produce a
product meeting its predetermined
specifications and quality characteristics"
Meaning, every time you operate your
process within specs, you will produce a
product with the expected aptivity, purity and
yield (i.e. product will meet specifications)