PREPARED BY : CHRISMITA S. M.PHARMACY RR COLLEGE OF PHARMACY BANGALORE

1. © R R INSTITUTIONS , BANGALORE 1
MODERN PHARMACEUTICS
VALIDATION
RR COLLEGE OF PHARMACY
Submitted by:
Chrishmitha sequeira
1st sem. M.Pharm.
Department of pharmaceutics
Submitted to:
Mrs. Sujatha p
Associate professor
Department of pharmaceutics

2. © R R INSTITUTIONS , BANGALORE
2
Contents:
 Government regulations in pharmaceutical validation
 Manufacturing process model
 User requirement specification(URS)
 Qualification of facilities

3. GOVERNMENT REGULATION IN PHARMACEUTICAL VALIDATION
 A regulation is a binding instruction issued by an agency (in our case,
the FDA) that tells you how to interpret and comply with law.
 The most important regulations, applying to validation are good
manufacturing practices(cGMP) and good laboratory practices (GLP).
The best-known quality standards are ISO 9000 series. Which provide
general standards for development, manufacturing and services.
© R R INSTITUTIONS , BANGALORE 3

4. Regulation for validation under USFDA
 Section 211.100(a): Written procedure/deviations,” There shall be written procedures for
production and process control designed to assure that the drug products have the identity,
strength, quality and purity.”
 Section 211.110: Sampling and testing of in-process materials and drug products
 Control procedures shall be established to monitor the output and validate the performance
of those manufacturing processes that may be responsible for causing variability in the
characteristics of in-process materials and drug product.
 21CFR211.133: Control of microbiological contamination: “appropriate written
procedures, designed to prevent microbiological contamination of drug products purporting
to be sterile, shall be established and followed. Such procedures shall include validation of
any sterilisation process.”
 FDA must inspect every drug manufacturing establishment at least once every 2 years.
© R R INSTITUTIONS , BANGALORE 4

5. Regulatory requirement for validation in cGMP
 The first cGMP regulations, based largely on the Pharmaceutical Manufacturers Association’s
manufacturing control guidelines.
 The Medicines Act (1968) covers most aspects of cGMP in what is commonly referred to as
“The Orange Guide”.
 Validation under document of cGMP covers procedure, process qualification, equipment and
facilities.
 211.68: Validation of automated process.
 211.84(d)(2): Validation of supplier’s test results for components.
 211.84(d)(3): Validation of supplier’s test results for container and closures.
 211.110(a): Validation of manufacturing process to ensure content uniformity and integrity.
 211.113(b): validation of sterilization process.
 211.165: validation of analytical methods.
© R R INSTITUTIONS , BANGALORE
5

6. Validation requirement under WHO
 WHO (World Health Organisation) cGMP Guidelines for validation studies are
an essential part of current good manufacturing practice and should be
conducted in accordance with predefined protocols.
 WHO validation definition: The documented act of providing any procedure,
process, equipment, materials, activity or system which actually leads to the
expected results.
 Design Qualification
 Installation Qualification
 Operational Qualification
• Performance Qualification
© R R INSTITUTIONS , BANGALORE 6

7. Validation requirements under EU
Strategies of validation under EU includes:
 1)Traditional process validation: Process validation should focus on the control strategy,
which primarily includes critical process parameters and other relevant studies
demonstrating that the process is capable of delivering the desired product quality.
 2)Continuous process validation: An alternative approach to process validation in which
manufacturing process performance is continuously monitored and evaluated.
 3)Critical process parameter: A process parameter whose variability has an impact on a
critical quality attribute and therefore should be controlled to ensure the process
produce the desired quality.
 4)Critical quality attributes: a physical, chemical, biological or microbiological property
should be written an appropriate limit, range to ensure product quality.
© R R INSTITUTIONS , BANGALORE 7

8. Manufacturing process model
 According to FDA assurance of product quality is derived from careful and systemic attention to a
number of important factors, including:
 Selection of quality components and materials, adequate product and process design and control of
process through in-process and end -product testing. Thus, it is through careful qualification and
validation of both the process and its control systems that a high degree of confidence can be
established that all individual manufactured units of a given batch or succession of batches that
meet specifications will be acceptable.
 This guidance describes process validation activities in three stages:
 Stage 1: Process design: The commercial manufacturing process is defined during this stage based
on knowledge gained through development and scale-up activities.
 Stage 2: Process qualification: During this stage, the process design is evaluated to determine if the
process is capable of reproducible commercial manufacturing.
 Stage 3: Continued process verification: Ongoing assurance is gained during routine production
that the process remains in a state of control.
© R R INSTITUTIONS , BANGALORE 8

9. PROCESS VALIDATION
© R R INSTITUTIONS , BANGALORE 9

10. USER REQUIREMENTS SPECIFICATION(URS)
 User requirement specification (URS) is a list of all the requirements from the
user, like equipment to be purchased. After the preparation of the list, the
documents are sent to the manufacturer to get the required materials as per the
given criteria.
 The user department will raise the indent for his requirement regarding machine
equipment or software. He/She will give all the requirements in the format of URS,
which include the functional and technical specifications for the machine
equipment or software. This specification in the written format is defined as URS.
 It shall be very specific. URS is a supporting document for the preparation of
design qualifications.
© R R INSTITUTIONS , BANGALORE 10

11. The following point must be included in URS:
• Name of the user department
 Location
 machine/equipment/software name
 Purpose of the machine/equipment/software
 Other areas of impact (AHU, movement, and space)
 Parameters to be considered for the URS.
 Model making Name with specification, and quantity with the remark.
 Capacity: give the detailed specification and quantity likes requirement in Kilogram or litres.
 The material of construction: give details about the material of construction like Stainless steel and
its grades.
 Give details about Instruments on machine likes Metal detector, Camera inspection system, and
pinhole detector, etc.
© R R INSTITUTIONS , BANGALORE
11

12.  Critical control points Required calibration details with the specification with remarks
 Details specification: baffles, Die, punches, Guide track, cutter, and channel.
 Specified details about required tools
 Documentation like FAT(factory acceptance test)/ SAT/ Qualification/ manuals
 Environmental: (Include the temperature and humidity of the area) / health safety requirements (like
safety Guard) and Control (Specify needs of equipment, interfaces, output forms (e.g., USB)
• Utilities: Define the kind of power supply to use for the equipment, the requirement of UPS, or
other utility requirements. Include water system, quality, or compressed gas, if required.
 Availability: Limitation of operation time for the equipment
 Supporting Documents: Operating manuals, warranty, parts, spare parts, circuit diagrams.
 User requirement specification document Shall be signed by an authorized person in the column
prepared by, reviewed by, and approved by. In the end, review, revise, and approve the URS. The
next step is the design qualification.
© R R INSTITUTIONS , BANGALORE
12

13. QUALIFICATION
 Definition: It is the action of providing and documenting that equipment or ancillary systems is
properly installed, work correctly and actually lead to the expected results.
 Qualification Vs Validation: - Qualification and validation are essentially components of the same
concept. The term qualification is normally used for equipment, utilities and systems. The term
validation is normally used for processes. In this sense, qualification is part of validation.
 There are 4 phases of qualification:
 1. Design qualification
 2. Installation qualification
 3. Operational qualification
 4. Performance qualification
 DQ, IQ, OQ, PQ protocol are methods for demonstrating that equipment being used or installed will
offer a high degree of quality assurance such that production processes will consistently manufacture
products that meet quality requirements.
© R R INSTITUTIONS , BANGALORE 13

14. Design Qualification
 It is the documented verification that the proposed design of the facilities, systems and
equipment is suitable for the intended use.
 DQ is performed when new equipment is being purchased, or when existing equipment
is being used for a new application.
 The scope of design qualification protocol should include:
 Verification that the design will achieve the URS requirements
 The design is cGMP complaint and where software is used, conforms to the life cycle
model requested in the VMP
 The design complies with the VMP
 The utility services required are available and validated
 All the required support documentation is specified
 The system will be calibratable
© R R INSTITUTIONS , BANGALORE 14

15. Installation qualification
 It is documented evidence that the premises, supporting utilities, equipment have been built and installed
in compliance with design specification.
 It verifies that the equipment is Installed in accordance with the manufacturer’s recommendation,
confirms equipment specification and verifies the condition of installed equipment.
 Installation qualification protocol:
 Engineering drawings and documents
 Building finishes
 Process and utilities
 Process and instrumentation diagrams
 Equipment and instrument specification
 Manufacturers drawing, equipment maintenance and operating manuals
 Spare lists
 Maintenance schedules
© R R INSTITUTIONS , BANGALORE
15

16. Operational qualification
It is documented evidence of activities necessary to demonstrate that an instrument will function
according to its operational specification testing in the specific environment
 Operation qualification protocol:
 A complete description of the purpose, methodology and acceptance criteria for the operational tests to
be performed
 Ensure that instrumentation is in current calibration
 Ensure that detailed control parameters have been established and recorded for each instrument loop
 Ensure change control systems are in operation
 Ensure that standard operating and maintenance procedure have been developed for each system, to
ensure continued operation under defined conditions
• Ensure that training modules and training sessions for production, engineering and support personnel
have been developed, conducted and documented during this stage
© R R INSTITUTIONS , BANGALORE
16

17. Performance qualification
 The performance qualification is a documented program to demonstrate that an
operation, when carried out within defined parameters, will consistently perform to
meet predetermined acceptance criteria.
 The objective of PQ is to ensure that the instrument is performing within specified
limits.
 PQ consideration include:
 Actual product and process parameters and procedures established in OQ
 Acceptability of the product
 Assurance of process capability
 Process repeatability, long term process stability.
© R R INSTITUTIONS , BANGALORE 17

18. Reference
 Modern pharmaceutics: by Gilbert and S. Banker
 Pharmaceutical Process Validation: By Fra.R.Berry and Robert a Nash
 Google.com
30-04-2022
© R R INSTITUTIONS , BANGALORE 18

19. 30-04-2022
© R R INSTITUTIONS , BANGALORE 19