Pharmaceutical validation for manufacure of quality products and documentation.

1. Guided by,
Dr. A.B.Gangurde
Head of Department
Department of Pharmaceutics
INTRODUCTION TO
PHARMACEUTICAL
VALIDATION,SCOPE &MERITS
OF VALIDATION.
Presented By,
DEORE SEJAL SURESH
F.Y.M.Pharmacy
Department of Pharmaceutics

2. Contents:
 Introduction
 Need of validation
 Types of validation
 Prospective validation (or premarket validation )
 Retrospective validation
 Concurrent validation
 Revalidation
 Importance of validation
 Scope of validation
 Merits of validation
 Conclusion for validation
 References

3. Introduction:
 The concept of validation was first proposed by two Food and Drug
Administration (FDA) officials.
 Byers and Bud Loftus, in the mid 1979s in(USA )order to improve the
quality of pharmaceuticals. It was proposed in direct response to several
problems in the sterility of large volume parenteral market.
 The first validation activities were focused on the processes involved in
making these products, but quickly spread to associated processes including
environmental control, media fill, equipment sanitization and purified water
production.

4. Validation is the process of establishing documentary evidence
demonstrating that a procedure, process, or activity carried out in testing
and then production maintains the desired level of compliance at all stages.
 In the pharmaceutical industry, it is very important that in addition to final
testing and compliance of products, it is also assured that the process will
consistently produce the expected results.

5. Definition:
 Validation is the documented act of proving that any procedure, process,
equipment, material, activity or system actually leads to the expected
result.
 ISO definition :Validation is the confirmation by examination and the
provision of objective evidence that the particular requirements for a
specific intended use are fulfilled.

6. NEED FOR VALIDATION:
 Customer satisfaction.
 Customer mandated.
 Product liability.
 Control production cost.
 Development of new generation Safety.

7. CUSTOMER SATISFACTION:
 Customer satisfaction is defined as a measurement that determines how
happy customers are with a company’s products, services, & capabilities.
 Customer satisfaction information ,including surveys and ratings, can help a company
determine how to best improve or changes its products and services.

8. CUSTOMER MANDATE:
 Customer mandate means the forms completed by the client at the time the account
is opened or as amended by agreement between the client and the bank from time
to time.

9. PRODUCT LIABILITY:
 Product liability is a doctrine that gives plaintiffs a cause of action if they
encounter a defective consumer item.

10. CONTROL PRODUCTION COST:
 Production cost is based on the actual performance during production.
 Production cost control is done by comparison of actual cost with the standard cost,
budget cost or aimed cost.

11. DEVELOPMENT OF NEW
GENERATION SAFETY:
 In future validation play’s important role in development for new
pharmaceutical product.

12. TYPES OF VALIDATION:
The major
types of
validation
Process
validation
Cleaning
validation
Equipment
validation
Validation
of analytical
method

13. PROCESS VALIDATION:
As per FDA, the process validation is defined as:
“The collection of data from the process design stage throughout
production,which establishes scientific evidence that a process is capable of
consistently delivering quality products.”

14. ►Process validation life cycle/flow chart:

15. TYPES OF PROCESS VALIDATION:
Prospective validation (or premarket validation)
Retrospective validation
Concurrent validation
Revalidation

16. PROSPECTIVE VALIDATION:
 This is performed for all new equipment, product and processes.
 It is a proactive approach of documenting of design, specification and
performance before the system is operational.
 This is the most defendable type of validation.
 It is compulsory for sterile products.
 The activity continuous till first 3 batches are manufactured at full
scale.

17. .
• Formation of validation team
• Preparation of validation master plan and validation protocol
.
• Formulation development (preformulation studies and optimization)
• Process development (process design, control & challenges in critical
parameters etc.)
.
• Facility development (building, support systems, staff)
• Product qualification
• Process qualification
• Change control
STEPS IN PROSPECTIVE VALIDATION:

18. RETROSPECTIVE VALIDATION:
 Retrospective validation is used for facilities, processes, and process controls in
operation use that have not undergone a formally documented validation process.
 Validation of these facilities, processes, and process controls is possible using
historical data to provide the necessary documentary evidence.
 Therefore, this type of validation is only acceptable for well-established
processes and will be inappropriate where there have been recent changes in the
composition of product, operating processes, or equipment.
 This approach is rarely been used today because it's very unlikely that any
existing product hasn't been subjected to the Prospective validation process. It is
used only for the audit of a validated process.

19. CONCURRENT VALIDATION:
 Concurrent validation is used for establishing documented evidence that a
facility and processes do what they claim to do, based on information
generated during actual imputation of the process.
 This approach involves monitoring of critical processing steps and end
product testing of current production, to show that the manufacturing
process is in a state of control.

20. REVALIDATION:
► Revalidation means repeating the original validation effort or any part of
it, and includes investigative review of existing performance data. This
approach is essential to maintain the validated status of the plant,
equipment, manufacturing processes and computer systems. Possible
reasons for starting the revalidation process include:
► The transfer of a product from one plant to another.
► Changes to the product, the plant, the manufacturing process, the cleaning
process, or other changes that could affect product quality.

21. ► The necessity of periodic checking of the validation. results.
► Significant (usually order of magnitude) increase or decrease in
batch size.
► Sequential batches that fail to meet product and process
specifications.
► The scope of revalidation procedures depends on the extent of the
changes and the effect upon the product.

22. CLEANING VALIDATION:
Definition:
"A process of attaining and documenting sufficient evidence to give
reasonable assurance, given the current state of Science and
Technology, that the cleaning process under consideration does, and/or
will do, what it purpose is to do."

23. OBJECTIVE:
To minimize cross contamination.
To determine efficiency of cleaning process.
To do troubleshooting in case if problem is
identified in the cleaning process and give
suggestions to improve the process.

24. Source of contamination:
 Cross contamination of one product into another.
 Product contamination by a foreign material.
 Microbial contamination.
Cleaning methods:
 Manual cleaning method.
 Semi automated procedures.
 Fully automated procedures.

25. Factors Influencing Cleaning
validation:
Product.
Equipment.
Facilities.
Cleaning methods.
Cleaning agents.
Sampling.
Testing, Limits, and acceptance criteria.

27. EQUIPMENT VALIDATION:
Definition:
As per FDA, "Action of proving that any equipment works correctly and
leads to the expected result is equipment validation. It is not a single step
activity but instead result from many discrete activities. “
Steps involved:
• User requirement specification
• Design qualification
• Installation qualifications
• Operational qualifications
• Performance qualification

29. VALIDATION OF ANALYTICAL METHODS:
 Definition:
 "The process by, which it is established, by laboratory studies, that the performance
characteristics of the method meet the requirements for the intended analytical
application".
 Accuracy: The closeness of test results obtained by that method to the true value.
This accuracy should be established across its range.
 Precision: The degree of agreement among individual test results when the method is
applied repeatedly to multiple sampling of a homogenous sample.

30.  Specificity: The ability to assess unequivocally the analyte in the presence of
components that may be expected to be present, such as impurities, degradation
products and matrix components.
 Limit of Quantitation: A characteristic of quantitative assays for low levels of
compounds in sample matrices such as impurities in bulk substances and
degradation products in finished pharmaceuticals. It is the lowest amount of
analyte in a sample that can be determined with acceptable precision and
accuracy under the stated experimental conditions.

31.  Range: Interval between the upper and lower of analyte (including these levels) that
have been demonstrated to be determined with a suitable level of precision, accuracy
and linearity using the method as written. The range is normally expressed in the
same units as test results obtained by the analytical method (e.g. Percentage, parts per
million, etc.)
 Ruggedness: The degree of reproducibility of test results obtained by the analysis of
the same sample under a variety of conditions such as different laboratories, different
analysts, different instruments, different lots of reagents, different elapsed assay
times, different assay temperatures, different days, etc.

32. SCOPE OF VALIDATION:
 Validation requires an appropriate and sufficient infrastructure
including:-organization, documentation, personnel and finances.
 Involvement of management and quality assurance personnel
 Personnel with appropriate qualifications and experience
 Extensive preparation and planning before validation is performed.
 A specific programme for validation activities in place.

33.  Validation done in a structured way according to documentation
including procedures and protocols.
 Validation should be performed:-for new premises, equipment, utilities
and systems, and processes and procedures; at periodic intervals; and-
when major changes have been made.
 Validation in accordance with written protocols.

34.  A written report on the outcome to be produced.
 Validation over a period of time, e.g.-at least three consecutive batches
(full production scale) to demonstrate consistency.
 Process, materials and equipment to prove consistent yield of a product
of the required quality.
 Manufacturers to identify what validation work is needed.
 Significant changes (facilities, equipment, processes) - should be
validated
 Risk assessment approach used to determine the scope and extent of
validation needed.

35. MERITS 0F VALIDATION:
 Assurance of quality compliance.
 Optimization of resources and manufacture product at lowest possible
cost.
 Fewer failures, fewer rejects, fewer retests, fewer reworks, fewer
wastage.
 It is a practice that must be followed for manufacturing, distribution,
selling or license.
 Efficient production operation.

36. CONCLUSION FOR VALIDATION:
►Validation has been proven assurance for the process efficiency and
sturdiness and it is the full fledged quality attributing tool for the
pharmaceutical industries.
►Validation is the commonest word in the areas of drug development,
manufacturing and specification of finished products.
►It also renders reduction in the cost linked with process monitoring,
sampling and testing.
►Apart from all the consistency and reliability of a validated process to
produce a quality product, it is very important for an industry.

37. REFERENCES:
 Fundamental of quality assurance techniques...by Ramesh Sawant and Sandip Hapse,
First edition Dec 2011, Career publications.
 Pharmaceutical Quality Assurance...by Manohar Potdar, Second edition Dec 2007,
Nirali Prakashan.
 IJRPC 2011 An overview of pharmaceutical validation: quality assurance view point'
by Nandhakumar et al.
 IJPR Review Article An Overview of pharmaceutical Validation and Process Controls
in Drug Development" Elsie Jatto and Augustine O. Okhamafe.
 P. P. Sharma, "Validation in Pharmaceutical Industry- concepts, approaches &
guidelines", 1 edition, 2007 Vandana Publication House.

38.  B. T. Loftus & R. A. Nash, "Pharmaceutical Process Validation", Drugs and
Pharm Sci. Series, Vol. 129, 3rd Ed., Marcel Dekker Inc., N.Y.
 https://www.slideshare.net/Manikant PrasadShah/validation-scope- of-
validation-urs-who-guidelines-for-validation
 https://www.slideshare.net/shettyue/new-who-guidance-on-process-
validation
 https://www.slideshare.net/Anshul2593/ich-guidelines-
72292250https://www.slideshare.net/rks19761/pharmaceutical-process-
validation?next slideshow-1
 https://www.slideshare.net/dalvirabul16/pharmaceutical-validation-ppt
 https://www.slideshare.net/sagarsavale 1/cleaning-validation- 62056468

39.  https://www.who.int/medicines/areas/quality safety/quality
assurance/Supplementary GMP Validation TRS937Annex4.pdf?ua
 https://www.slideshare.net/ssuserfe3019/ich-who-guidelines.