According to U.S.Food and Drug Administration 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.

1. Process ValidationProcess Validation
Department of Pharmacy (Pharmaceutics) | Sagar savale

2. ContentContent
 Introduction .
 Strategy for Process Validation.
 Steps in Validating a Process.
 Process Validation Options.
 Guidelines for Process Validation of solid Dosage forms.
 Validation of Non Sterile Product.
 Tablets.
 Summary of Tablet Manufacturing.
 References.
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3. IntroductionIntroduction
According to U.S.Food and Drug Administration
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.
According to the FDA
Assurance of product quality is derived from careful and systematic attention to
a number of important factors, including selection of quality components and
materials, adequate product and process design and control of the process
through in-process and end product testing.
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4. Conventional quality control procedures for finished
product
testing includes 3 basic steps:
• Establishment of specifications and performance characteristics.
• Selection of appropriate methodology, equipment and instrumentation,
using validated analytical and testing methods to ensure that finished
product meets specifications.
• Testing of the final product, using validated analytical and testing
methods to ensure that finished product meets specifications
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5. STRATEGY FOR PROCESS VALIDATIONSTRATEGY FOR PROCESS VALIDATION
The strategy selected for process validation should be simple and straight
forward.
1.The use of different lots of raw materials should be included.
2. Batches should be run in succession and on different days and shifts.
3.Batches should be manufactured in the equipment and facilities
designed for eventual commercial production.
4.Critical process variables should be set within their operating ranges
and should not exceed their upper and lower control limits during
process operation.
5. Failure to meet the requirements of the validation protocol with
respect to process input and output control should be subjected to
process requalification and subsequent revalidation following an
thorough analysis of process data and formal discussion by the
validation team.
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7. Steps In Validating Process.
Develop validation protocol
Conduct installation qualification
Conduct Operational qualification
Conduct performance qualification
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8. PROCESS VALIDATION OPTIONS -PROCESS VALIDATION OPTIONS -
Prospective Process Validation
 An experimental plan called validation protocol is executed before the
process is put into commercial use.
 Done During the new product development stage
 During this, the input resource are selected and clearly specified.
 Profile of all inputs and the operating parameters both are decides and
recorded.
 Limits of variations of the process parameters are identified.
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9. Retrospective ValidationRetrospective Validation
 The retrospective validation option is chosen for established products
whose manufacturing processes are considered stable.
 Prior to undertaking retrospective validation the numerical in process
and or end product test data of historic production batches are
subjected to statistical analysis, the equipment, facilities and
subsystems used in connection with the manufacturing process.
 Retrospective validation is achieving validation by documenting all the
historical information (e.g. release data) for existing products and
using that data to support the position that the process is under
control.
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10. Concurrent ValidationConcurrent Validation
In process monitoring of critical processing steps and end product
testing of current production can provide documented evidence to
show that the manufacturing process is in a state of control. Such
validation documentation can be provided from the test parameter .
Batch to batch study to each every parameter.
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11. Revalidation.Revalidation.
 Conditions requiring revalidation study and documentation are listed
 Change in a critical component(usually refers to raw materials)
 change or replacement in a critical piece of modular equipment
 Change in facility and or plant(usually location or site
 Significant increase or decrease in batch size
 Sequential batches that fail to meet product and process specifications
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12. Guidelines For Process Validation of SolidGuidelines For Process Validation of Solid
Dosage Forms.Dosage Forms.
 Numerous factor should be considered when developing and
validation solid dosage forms.
 There are validation flow chart of new processes and existing
processes.
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13. Validation of Non Sterile products.Validation of Non Sterile products.
Non Sterile
Products.
Tablets.
Capsules. Creams.
Ointments.
Suspensions. Syrups.
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14. TabletsTablets
A) Tablet Composition:
 Identify physicochemical properties such as:
1.Solubility
2.Particle size distribution and surface area
3.Morphology
4.True and bulk density
5.Mrerial flow and compressibility
6.Hygroscopicity
7.Melting point
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15. B) Process Evaluation and selectionB) Process Evaluation and selection
1.Mixing or Blending :
 It may occur once or several times during the tablet manufacture.
 Some physical properties of drug and excipients are factors in creating a
uniform mix or blend and will not segregate as readily as materials with
large differences.
a) Mixing or blending technique:
b) Mixing or blending speed:
c) Mixing or blending time:
d) Drug uniformity:
e) Excipient uniformity:
1.Lubricant
2.Color
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16. 2.Wet Granulation2.Wet Granulation
 Wet granulation parameters to be considered during development and
validation are such like that
1. Binder addition
2. Binder concentration
3. Amount of binder solution
4. Binder solution addition rate
5. Mixing time
3.Wet Milling
 It need to be milled to break up the lumps and enhance drying of the
granulation.
 Milling will reduce particle size of dried granulation
 Factors to consider are:
1. Equipment size and capacity
2. Screen size
3. Mill speed
4. Feed rate
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17. 4.Drying4.Drying
 Type of drying tech. may be dependent on such factors as drug or formulation
properties and equipment availability.
 Changing dryer tech. could affect such tablet properties as hardness,
disintegration, dissolution and stability.
 Parameters to consider during are:
1. Inlet/outlet temperature
2. Airflow
3. Moisture uniformity
4. Equipment capacity
5.Milling
 Reduce particle size of dried granulation.
 Factor to consider in milling are:
1. Mill type
2. Screen size
3. Mill speed
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18. 6.Tablet Compression6.Tablet Compression
 Materials being compress need to have adequate flow and compression
properties.
 Factors to consider during compression are:
1. Tooling
2. Compression speed
3. Compression force
 Following I.P.Q.C. tests should be performed during the compression stage:
1. Appearance
2. Hardness
3. Tablet weight
4. Friability
5. Disintegration
6. Weight uniformity
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19. • Summary of Tablet manufacturing.
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20. • ConclusionConclusion
Process validation result in fewer product recalls and
troubleshooting assignments in manufacturing operations and
more technically and economically sound batches and their
manufacturing processes.
Thus through careful design and validation of both the
process and its control system can establish a high degree of
confidence that all individual manufactured units of a given
batch or succession of batches that meet specifications will
be acceptable.
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21. ReferencesReferences
 R.A. Nash & A.H. Wachter, Pharmaceutical Process Validation,
Mercel Decker Inc., New York, Page no:1-82,170-178.
 Pharmaceutical Quality Assurance, M.A. Potdar, Nirali Prakashan,
Pune ,Page no:8.20-8.22.
 Sidney H. Wachter, Good Manufacturing Practices for
Pharmaceuticals, A Plan for Total Quality Control from
Manufacturer to consumer, Marcel Dekker Inc.,New York, Page
no:110-115.
 Validation Standard Operating Procedures: A step by Step Guide
for Achieving Compliance in the Pharmaceutical, Medical Device,
and Biotech Industries, Syed Imtiaz Haider, St. Lucie Press, 2002.
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22. List Of WebsitesList Of Websites
• www.fda.gov/cdrh/qsr/intro.html
• www.fda.gov/cdrh/comp/guidance/938.html
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23. Thank
Thank
You…
You…
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