1. VALIDATION METHODS OF EQUIPMENT AND PROCESSING
TECHNIQUES FOR MIXING, GRANULATION, DRYING, COMPRESSION,
FILTERATION AND FILLING
Presented By
AQSA FATIMA
M.Pharmacy 1st Year 2nd Semester
15451S0602
Under the guidance of
V.M BALARAM
M.Pharm, PhD
SULTANUL ULOOM COLLEGEOF PHARMACY
2. VALIDATION
Validation is a key process for effective quality
assurance.
“Validation is establishing documented evidence
which provides a high degree of assurances that a
specific process or equipment will
consistently produce a product or result meeting its
predetermined specifications and quality attributes.”
3. PROCESS VALIDATION:
Process validation can be defined as means of challenging
a process during development to determine which
variables can be controlled to ensure the consistency
production of a product or intermediate.
It is based on the concept that the processed employed
has been optimized, so that the data generated through the
testing program may be considered credible and evaluated
for consistency as well as relevance.
4.
5. Types of Process Validation
• Prospective validation:
-Conducted prior to market the product.
- Documented evidence which provides a high degree of assurances
that a specific process or equipment will consistently produce a
product meeting its predetermined specifications and quality
attributes.
• Concurrent validation:
- Based on information generated during actual implementation
of the process.
- Establishing documented evidence that the process is in a state of
control during the actual implementation of the process. This
normally performed by conducing in- process testing.
6. • Retrospective validation:
All the processes and subsystems should be validated,
which have been used for the production of batches of
numerical data of both process and the end product
testing of which are included in retrospective validation
7. Process equipment used in the development phase is
assessed relative to its suitability for large scale
manufacture.
This protocol can be divided into
• Design qualification
• Installation qualification
• Operation qualification
• Performance qualification
• Maintenance (calibration, cleaning, repair)
qualification
8. Design qualification (DQ):
Documented verification of the design of equipment and manufacturing
facilities.
Installation qualification (IQ):
Documented verification of the system design and adherence to
manufacturer’s recommendations.
Operational qualification (OQ):
Documented verification of equipment or system performance in the
target operating range.
Process performance qualification (PQ):
Documented verification that equipment system operates as expected
under routine production conditions. The operation is reproducible,
reliable and in a state of control.
9. EQUIPMENT VALIDATION:
A typical Validation Blueprint of Equipment validation:
1. Installation qualification
Facilities
Utilities
Equipment
2. Operation qualification
Testing Protocols for Utilities and Equipment
3. Validation
Testing protocols for products and Cleaning systems
4. Documentation
5. Validation of the QA testing laboratory
6. SOPs
7. Training of personnel
8. Organization charts
9. Schedule of events.
10.
11. INDUSTRIAL PROCESS OVERVIEW OF SOLID DOSAGE
FORMS
Steps &Process parameter are following-
MIXING OR BLENDING:
Material have similar physical properties will be easier to form a
uniform mix or blend as compare to difference in properties.
Techniques-1.Diffussion(tumble)
2.convection(planetary or high intensity or fluid bed).
Mixing and blending depends upon various factors-
1.Mixing speed-
Mixing of drug and excipient requires more intense mixing than
adding the lubricant to the final blend.
12. 2.Mixing Time-
depends on mixing technique and speed.
3.Drug and excipient uniformity-
handling of material is key in obtaining valid content
uniformity results. Sample should be equivalent to the
weight of a single tablet.
4.Equipment capacity -
the bulk density of material will affect the capacity of the
equipment.
13. WET GRANULATION
what type of wet granulation to be used
LOW SHEAR/ HIGH SHEAR/ FLUID BED
wet granulation parameters are
• Binder addition:
Adding the binder dry avoids the need to determine the
optimal binder concentration and a separate manufacture for
the binder solution.
14. • Binder concentration:
The optimal binder concentration will need to be determined
for the formulation. If the binder is to be sprayed, the binder
solution needs to be dilute enough so that it can be pumped
through the spray nozzle.
• Amount of binder solution:
The amount of binder solution is related to the binder
concentration.
• Granulation end point:
Determined by ammeter and wattmeter equipment.
15. Drying is a most important step in the formulation and development of
pharmaceutical product. It is important to keep the residual moisture
low enough to prevent product deterioration and ensure free flowing
properties.
Factors-
• Inlet/outlet temp-
inlet temp is set to high to minize drying with out effecting
physical/chemical parameters.
• Airflow-
insufficient air flow prolongs drying
• Moisture uniformity-
moisture content could vary in the granulation
• Equipment capacity-
high the load high moisture should be removed
DRYING
16. TABLET COMPRESSION-
After the preparation of granules (in case of wet
granulation) or sized slugs (in case of dry granulation) or
mixing of ingredients (in case of direct compression), they are
compressed to get final product.
The compression is done either by single punch machine
(stamping press) or by multi station machine (rotary press).
Factors-
• compression speed-
range of compression speed to determine the operating range
of the compressor.
• compression or ejection force-
determined optimal compression force to obtain the desired
tablet hardness.
17. The following in-process tests should be examined during the
compression stage-
• Appearance
• Hardness
• Tablet weight
• Friability-0.5-1%
• Disintegration
• Weight uniformity
19. FILLING
Perform installation qualification
Product contact surfaces must be compatible with the
product
Rate of filling should be readily controllable
Physical characteristics of the powder
Powder hopper agitation speed
Vibration rate
Vacuum setting
Machine filling speed
The need for lubricant fluids should be minimized by use
of limited friction bearing surfaces
20. EQUIPMENT EVALUATION
• Selection of equipments is based on;
1. Formulation.
2. Safety requirements.
3. Handling / production efficiency.
4. Commercial demands.
• Equipment should be qualified.
• Cleaning procedure should be available.
21. MIXER / GRANULATOR:
1. What is the method of mixing?
2. Capable to provide high / low shear?
3. Can mixing be varied?
4. Availability of monitoring system OR capability to
accommodate one?
5. Working load range and capacity?
6. How is material charged and discharged from the
unit?
7. Are there options to introduce granulating fluid?
22. BLENDER:
1. Type of blender?
2. Positioning of the axis of rotation?
3. Working load range and capacity of the equipment?
4. Features for the ease of handling of powders?
5. Can samples be easily taken from the unit? Can
samples be taken from more than one location?
6. Are there dead spots?
7. Can the equipment be easily cleaned?
8. Can the equipment heat the powder if needed? What
is the heating source?
23. DRYER:
1. What is the operating principle?
2. Will the wet material be static or fluid?
3. Working load range and capacity?
4. Heating range and airflow capabilities?
5. What is the heat distribution of the unit? Are there
any hot &/or cold spots?
6. Can the unit pull a vacuum? What is the vacuum
range of the unit?
7. Can the equipment handle different types of filter
bags?
8. Filter bag shaking mechanisms with options?
24. MILLS:
1. Type of mill?
2. What is the configuration of the impact mill or screen
mill?
3. What type or size of hammers or pin / disc can be used
on the unit?
4. Can the impeller be positioned in different ways?
5. What size screens or plates can be used on the unit?
6. Is the speed on the impeller/screen variable? What is the
rpm range?
7. What type of feed system is required? What feed rate
can unit handle?
8. Can the unit handle wet &/or dry mill material?
9. Does the unit generate a significant amount of heat,
possibly affecting the product?
10. Is the unit portable?
25. TABLET COMPRESSION:
1. How many compressing stations does the compressor have?
2. What is the operating & output range of the unit?
3. Will the unit meet the future demand?
4. What kind of powder feeding capabilities does the equipment
have? Can this capability be altered/controlled?
5. What is the compression force range of the equipment?
6. Is the equipment capable of monitoring compression and
ejection force?
7. Does the unit have pre-compression capabilities?
8. How long can the equipment operate without routine
maintenance?
9. Does the equipment require special tooling or tools from
other equipment can fit?
10. Protection to operator?
26. CONCLUSION
• Solid dosage form validation should be part of
comprehensive validation program within an industry.
• The multidisciplinary validation team must identify
the product and process characteristics that must be
studied and incorporate specific validation tests to
ensure that product will meet all quality,
manufacturing and regulatory requirements.
• Continuous awareness of validation will produce
reproducibility.
27. REFERENCES
Pharmaceutical process validation, page no.: 170 – 184, 1 – 12; an international
3rd edition, revised & expanded, edited by: Robert A. Nash, Alfred H. wachter,
MARCEL DEKKER INC.
Pharmaceutical dosage forms: tablets, volume 3, 2nd edition, revised and
expanded, edited by: Herbert A. Liebermann, Leon lachman, Joseph B.
Schwartz, MARCEL DEKKER INC.
Agalloco James, Carleton J. Fredric “Validation of Pharmaceutical Processes”
FDA. "Guidelines on General Principles of Process Validation".
Validation of Analysis Procedures. International Conference on Harmonization
(ICH) of Technical Requirements for the Registration of Pharmaceuticals for
Human Use
