Pengantar Farmasi Industri

(UNIT PROSES)

Yoga Windhu Wardhana

Department of Pharmaceutics and Pharmaceuticals Technology
Faculty of Pharmacy - UNPAD
Pharmaceutical Product
TIMELINE
Criticals Product Reputation
Quality Assurance
 PHARMACEUTICAL Engineers need
to understand all physical treatment
such as:

• Transport (flow and mixing of molecules)

 rheology
• Thermodynamics (energy and heat)
 transform & stability
• Material and Energy Balances (conservation laws)
 momentum & impulse
PROCESS & OPERATION UNIT
PROCESS & OPERATION UNIT

Some Processing UNIT

Some
Operations
UNIT
PROCESS & OPERATION UNIT

Wet Granulation (process unit)

Some operation units

involved :
 Dry Mixing
 Wet Mixing GRANULES
 Filtration 1
 Drying
 Filtration 2
 Understanding pharmaceutical
manufacture process
Fundamentals
1. Fluid Flow
2. Heat Transfer
3. Mass Transfer
4. Momentum Transfer
5. Powders

10. Filtration
Processes
5. Air Conditioning and Humidification 11. Size Reduction and Classification
6. Drying 12. Mixing
7. Solid–Liquid Extraction
13. Solid Dosage Forms
8. Crystallization
9. Evaporation and Distillation 14. Sterilization
15. Bioprocessing
PROCESS & OPERATION UNIT
 Raw
materials
Drug Formulation
Excipients
Oven
Milling drying
Filtration /
drying
Crystallization

Blending

Lubrication

Granulation Coating
Compression

Finished products

Adapted from: Glasser and Pedersen, Pharmaceutical Bulk Drug Production, ERC 11
Educational Modules, www.pharmaHUB.org/resources/286, 2009
PROCESS & OPERATION UNIT
PROCESS & OPERATION UNIT
Facts:
• Drugs are materials
• Pharmaceutical production processes are
a series of unit operations
• They are governed by the same chemical
and engineering principles that operate in
other manufacturing processes

 We need to treat them that way

 Quality by Design
Accept from a recent FDA warning letter.
(not issued to Pfizer)

“Product testing alone is not sufficient to assure

that a process consistently produces a product
with predetermined specifications. Adequate
process design; knowledge and control of factors
that produce process variability: and successful
process validation studies, in conjunction with
product testing, provide assurance that the
process will produce a product with the required
quality characteristics.”

http://www.fda.gov/foi/warning.htm
 FDA Definition of PAT

• FDA Guidance – September 2004

PAT – A Framework for Innovative Pharmaceutical
Manufacturing and Quality Assurance

 Line 158:
“For the purposes of this guidance document, PAT is
considered to be a system for designing, analyzing,
and controlling manufacturing through timely
measurements (i.e., during processing) of critical
quality and performance attributes of raw and in-
process materials and processes with the goal of
ensuring final product quality.”
 Why do PAT?
Improved quality.
RFT
(Right First Time)
Improved safety.
Well Controlled Process Cost savings.
Fundamental Goals

Process Control
Process Knowledge
Use of PAT to Achieve RFT Benefits

• Reduce/eliminate deviations
• Improve customer service (product availability)
• Reduce cycle times (operational efficiency)
• Reduce inventory levels
• Reduce costs (reworks, resample, retesting, etc)
• Improve capacity utilization
• Improve compliance (reduce deviation reports)
• Improve assurance of quality
 PAT System Qualification
• PAT System Qualification and Method Validation
should be based on intended use of data.

Three Levels Quality Impact

1. Development or Proof of Concept No Impact
2. Information Only Indirect Impact

3. Release Decisions Direct Impact

 Validation or Commissioning and Qualification

must conform to applicable:
 Corporate Quality Standards
 Site Procedures
 Six Questions
do you want to measure?
 What ?
Chemical or physical property.
 How ? do you want to measure it?
Analytical technology.
 Why ? do you want to measure it?
Process Knowledge or Process Control?
 Where ? do you want to measure?

Before, during, or after a process step?

 When ? do you want to measure it?
Sampling frequency.
 Who ? will look at the results?
Validation…..
 Quality Impact Assessments
• Process Knowledge
• No Impact or Indirect Impact (validation perspective)
• Short term study used to assess process variability,
and potential need for a permanent PAT
• Process Monitoring
• Indirect Impact, requiring “Commissioning of Equipment”
• More permanent implementation.
• Monitors process to assure RFT, but not used for decision
making; i.e., registered or validated assay already exists.
• Process Control
• Direct Impact, requiring “Qualification of Equipment”
• Used for
• Material Release or Parametric Release
• GMP Decisions for Critical to Process Parameters (CPP)
• Advanced Process Control