Validation is a concept that has evolved in united states in 1978. The word validation simply means assessment of validity or action of proving effectiveness. Validation is a team effort where it involves people from various disciplines of the plant.
Overview of Pharmaceutical Process Validation:
HISTORY OF VALIDATION
The concept of validation was first proposed by two FDA officials, Ted Byers and Bud Loftus, in the mid 1970’s in order to improve the quality of pharmaceuticals. U.S.F.D.A. was the pioneer in advocating the concept of process validation, but till 29th September 1978 the definition of process validation did not appear in any part of literature of U.S.F.D.A. no cGMP regulations talked anything about process validation.
Definitions
European commission 1991 –Validation- “Act of proving, in accordance of GMPs that Any” process actually leads to expected results. 2000 - “Documented evidence that the process, operated within established Parameters, can perform effectively and reproducibly to produce a Medicinal product meeting its predetermined specifications and quality attributes”.
US FDA Definition “Process validation is establishing documented evidence which provides a high degree of assurance that a specified process will consistently produce a product meeting its pre-determined specifications and quality characteristics.”
ICH Definition “Process Validation is the means of ensuring and providing documentary evidence that processes within their specified design parameters are capable of repeatedly and reliably producing a finished product of the required quality.”
WHO Definition “The documented act of proving that any procedure, process, equipment, material, activity or system actually leads to expected result.”
Need of Pharmaceutical Validation
Validation is an integral part of quality assurance; it involves the systematic study of systems, facilities and processes aimed at determining whether they perform their intended functions adequately and consistently as specified. Validation in itself does not improve processes but confirms that the processes have been properly developed and are under control
Scope of Validation
Systematic look at the pharmaceutical operations will point out at least the following areas for pharmaceutical validation;
- Analytical
- Instrument Calibration
- Process Utility services
- Raw materials
- Packaging materials
- Equipment
- Facilities
- Manufacturing operations
- Product Design
- Cleaning
- Operators
Phases in Process Validation
|
Master Plan or Outline
of a Process Validation Program |
|
|
Objective |
Proving or
demonstrating that the process works |
|
Type of
validation |
Prospective,
concurrent, retrospective, revalidation |
|
Type of
process |
Chemical,
pharmaceutical, automation, cleaning |
|
Definition of
process |
Flow diagram,
equipment/components, in-process, finished product |
|
Definition of
process output |
Potency,
yield, physical parameters |
|
Definition of
test methods |
Method,
instrumentation, calibration, traceability, precision, accuracy |
|
Analysis of
process |
Critical
modules and variables defined by process capability design and testing
program |
|
Control
limits of critical variables |
Defined by
process capability design and testing program |
|
Preparation
of validation protocol |
Facilities,
equipment, process, number of validation trials, sampling frequency, size,
type, tests to perform, methods used, criteria for success |
|
Organizing
for validation |
Responsibility
and authority |
|
Planning
validation trials |
Timetable and
PERT charting, material availability, and disposal |
|
Validation
trials |
Supervision,
administration, documentation |
|
Validation
finding |
Data summary,
analysis, and conclusions |
|
Final report
and recommendations |
Process
validated, further trials, more process design, and testing |
Importance of Validation
- Assurance of quality
- Time bound
- Process optimization
- Reduction of quality cost
- Nominal mix-ups, and bottle necks
- Minimal batch failures, improved efficiently and productivity
- Reduction in rejections
- Increased output
- Avoidance of capital expenditures
- Fewer complaints about process related failures
- Reduced testing in process and in finished goods
- More rapid and reliable start-up of new equipments
- Easier scale-up form development work
- Easier maintenance of equipment
- Improved employee awareness of processes
Standard operating procedure for validation and re-validation of manufacturing process to produce the quality product consistently.
OBJECTIVE
The purpose of this SOP is to lay down the minimum requirements for validation or revalidation of manufacturing processes applicable to marketed drug products in order to provide documented evidence that each specific process will consistently yield a product meeting all quality and design specifications.
SCOPE
Process validation may be prospective, retrospective or concurrent and is based on the assumption that equipment, environment and material validation have been completed prior to commencing process validation for any product.
RESPONSIBILITIES
3.1 Officer-Quality Assurance
3.1.1 To prepare validation protocol
3.1.2 To ensure the activities to be followed as per the approved protocol.
3.1.3 To withdraw the sample as per sampling program.
3.2. Executive-Quality Assurance
3.2.1 To evaluate the analytical report.
3.2.2 To prepare the validation report.
3.3 Officer-Quality Control
3.3.1 To analyze the samples
3.4 Executive- Quality Control
3.4.1 To review the protocol
3.4.2 To check the result of the analysis.
3.5 Manager Quality
3.5.1 To approve the protocol
3.5.2 To co-ordinate the activity.
3.5.3 To review and approve the validation report.
3.5.4 To organize the training and impart the training before validation.
3.6 Manager-Production:
3.6.1
To review validation protocol & report & organize the activity.
3.7 Executive-Maintenance:
3.7.1 To review the protocol and provide the required services.
4.0 ACCOUNTABILITY
4.1 Head Quality Assurance
5.0 PRODUCTION
5.1 Draw up a detailed flow chart of the process to be validated with each major and minor stages being differentiated (incorporate sub-stages, if required in the event of any major stage). 5.2 Prepare detailed flow sheet for each stage corresponding to individual operations in the process.
5.3 Define the critical factors/operations, which assure the reliability of the process. Note: Critical factors/operations may be defined as a step(s) of the operation whose variability has to be controlled to produce a quality product.
5.4 Prepare a written validation protocol for each critical operation/stage for any related minor operation/stage.
5.5 A validation protocol includes the following:
5.5.1 Purpose
5.5.2 Scope
5.5.3 Reference & Attachments
5.5.4 Responsibility Matrix
5.5.5 Equipments required
5.5.6 Training
5.5.7 Critical stages
5.5.8 Flow diagram of the process
5.5.9 Specification of active material, In process material, Finished product.
5.5.10 Product details including batch details.
5.5.11 Operation 5.5.12 Test(s) to be performed.
5.5.13 Stability 5.5.14 Summary & conclusion
5.5.15 Approval & Comments.
5.6 Run the test as per the written protocols and under conditions conforming to the actual production condition.
5.7 Verify the performance of the critical factors by evaluation of data for conformance to specifications.
5.8 Interpret the results and in case the process performs as per the predetermined specification, consider the process validated.
5.9 For non-confirming validation data, critically scrutinize the data collected, recommend the corrective actions and revalidate the process.
5.10 File the completed validation document of the process along with the test results of analysis and interpretation confirming its satisfactory performance in a master file for validation of the process along with such other data like stability studies for the process or product.
5.11 Get the approval of the Quality head for each validation performed
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