General Overview on Qualification and Validation
Quality
Quality is a standard of how good something is as measured against other similar things.
According to American Society, quality can be defined in following ways:
➢ Based on customers perceptions of product
➢ The ability of a product
➢ Achieved by conforming to established requirements within an organization
Basic criteria of quality: The criteria of quality are safety, potency, efficacy, stability, purity,
Identify.
Quality control (QC)
The term quality control refers to the sum of all procedures undertaken to ensure the identity and
purity of a particular pharmaceutical product. It involves in chemical, physical and sometime
microbiological testing of a pharmaceutical product.
Quality control involves testing of units and determining if they are within the specifications for
the final product.
In Quality Control there are different sections like Raw Material (RM), Finished Products (FP),
Good Laboratory Practices (GLP), Calibration, Specification and Stability etc.
Quality control (QC) vs. and Quality assurance (QA)
Answer: QC is the operational technique and activities that are used to fulfill requirements for
quality or to measure the quality of a products. On the other-hand QA is a set of systematic
activities necessary to provide adequate confidence that a product will satisfy given requirements
for quality.
Responsibilities of QC
• Ensure compliance with current Good Laboratory Practices (GLP) and current Good
Manufacturing Practices (GMP).
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
• Preparation of Certificate of Analysis (COA).
• Preparation of Stability reports after analysis.
• Status labeling of Quality control instruments, Chemicals & Glassware.
• Analysis of Raw Materials (API / Excipients), finished Product, Stability Sample etc.
• Daily Calibration and Monthly Calibration of Analytical Balances and other Instruments.
• Sampling and analysis of process validation and cleaning validation samples.
• Review and checked all analytical Document like Test Data sheet, Daily and monthly
instrument calibration, GLP record etc.
• Preparation of Standard Test Procedure (STP) for Raw, Finished products etc.
• To follow the laid down safety precautions while working in the laboratory.
Standard Operating Procedure (SOP)
A Standard Operating Procedure (SOP) is a certain type of document that describes in a step-by-
step outline form how to perform a particular task or operation. Everyone in a company must
follow the same procedures to assure that tasks are performed consistently and correctly. Most
companies have a wide variety of SOPs that describe how to do different tasks. In many
companies’ technicians and operators are trained in how to follow individual SOPs and their
training record specifies which SOPs they are trained on and are authorized to use.
User requirements specification (URS)
User Requirements Specification (URS) describes what users require from the System. User
requirement specifications are written early in the validation process, typically before the system
is created. It is written by the System Owner and End Users, with input from Quality Assurance.
Requirements outlined in the URS are usually tested in the Performance Qualification. User
Requirements Specifications are not intended to be a technical document; readers with only a
general knowledge of the system should be able to understand the requirements outlined in the
URS.
Validation/pharmaceutical validation
Pharmaceutical validation is a systematic process in the pharmaceutical industry to ensure that
processes, equipment, and analytical methods consistently produce products meeting
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
predetermined quality standards. It's crucial for maintaining product quality, safety, and efficacy,
as well as ensuring regulatory compliance
Validation plan
Validation Plans define the scope and goals of a validation project. Validation plans are written
before a validation project and are specific to a single validation project.
Validation Plans can include:
• Documents to be generated during the validation process.
• Resources/Departments/Personnel to participate in the validation project.
• Time-Line for completing the validation project.
Validation master plan = Design qualification (DQ) + Installation qualification (IQ) + Operational
qualification (OQ) + Process Validation or Performance qualification (PQ).
VMP= DQ+IQ+OQ+PQ
Validation Summary Report
Validation Summary Reports provide an overview of the entire validation project. When
regulatory auditors review validation projects, they typically begin by reviewing the summary
report.
The validation summary report should include:
• A description of the validation project.
• All test cases performed, including if those test cases passed without issue.
• All deviations reported, including how those deviations were resolved.
The report should include at least the following –
• Title and objective of study
• Reference to protocol
• Details of material
• Details of procedures and test methods
• Equipment’s
• Results (Compared with acceptance criteria)
• Recommendations on the limit and criteria to be applied on future basis.
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
Validation Protocol
Validation Protocol is a written statement to conduct the validation process along with the
procedure, test method, equipment handling, specifications, acceptance criteria, report and
approval. Validation protocol must be written before carrying out a validation activity.
Content of a validation protocol
A validation protocol should contain following parts –
▪ Protocol approval
▪ Objectives
▪ Scope
▪ Reasons for validation
▪ Revalidation criteria
▪ Responsibilities
▪ Reference documents
▪ Procedure
▪ Deviations
▪ Conclusions
▪ Report
▪ Report approval
Process validation
Process validation is the collection and evaluation of data, from the process design stage through
commercial production, which establishes scientific evidence that a process is capable of
consistently delivering quality products.
The entire manufacturing process and its control, during a batch production, is a part of process
validation.
According to the WHO guideline, process validation should be performed for -
New premises and equipment's
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
New utilities and systems
Processes and procedures at periodic intervals and
When major changes have been made
Types of process validation
There are many ways to carry out process validation but the most common forms are –
1. Prospective process validation
2. Retrospective process validation
3. Concurrent validation
4. Revalidation
Prospective Validation: When validation works are done before marketing a product, it is called
prospective validation. In prospective process validation, an experimental plan called the
validation protocol is executed before the process is put into commercial use.
Retrospective Validation: When validation works are done after successful marketing a product it
is called retrospective validation. But today it’s unlikely to still have products whose processes
haven’t been subjected to prospective validation.
Concurrent Validation: It is used to provide documentary evidence that facilities or processes
actually work the way they are said to be working. In this process, critical processing steps are
monitored and the end products from the current production line are tested to prove that the process
of manufacture is running in a controlled state.
Revalidation: When a major change is made in unit operation of the manufacturing system, then
it is necessary to perform revalidation. Revalidation is necessary when –
▪ Change a critical component (refers to raw materials)
▪ Change or replacement a critical piece of capital equipment
▪ Change a facility and/or plant (location or site)
▪ Significant increase or decrease in batch size
▪ Sequential batches that fail to meet product and process specifications
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
Steps of a process validation
A typical process validation exercise involves the following steps:
▪ Studying the entire system
▪ Drawing up a process flow sheet
▪ Identification of critical steps of operation
▪ Designing experiments to prove that the system works
▪ Designing the in-process testing protocols
▪ Drawing up the validation protocol and schedule
▪ Performing relevant tests
▪ Finalization of all relevant operating procedures
▪ Issuing the validation report
Process validation studies need to be done on full scale production batches
Process validation parameters for manufacturing a tablet by wet granulation process
Determining critical control point
Particle size distribution of the active
Blending time for the powder
Granulating time and speed
Amount of granulating fluid-binder concentration
Drying time
final moisture content
Granule particle size distribution
Granule active content and homogeneity
Blending time of external phase
Homogeneity in blending – the key to quality!
Sampling strategy
Sample site, label, container
Storage
Transport
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
Tablet compression
Tablet compression variables:
Fill volume
Pre-compression force, compression force
Turntable speed
Dwell time
Granule size and feed
Ejection force
Lubrication
Tablet compression parameters:
Mass
Hardness
Moisture
Friability
Disintegration
Dissolution
Thickness
▪ Tablet coating variables
Spray rate
Inlet and outlet air temp
Coating weight
▪ Manufacturing room
Temperature
Humidity
Variations in electrical supply
Environmental contaminants
Light
Human factors
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
Wear and tear of equipment
Verification
Verification is the evaluation of whether or not a product, service, or system complies with a
regulation, requirement, specification, or imposed condition. It is the comparison of results against
specifications. It is intended to check that a product, service or system meets a set of design
specifications. For example, if the specification limit of the solvent pH is 4.0-4.5 and the value
shown by the pH meter is 4.6, then we can say the result is failed against the specifications.
Validation vs. Verification
Verification and validation are quite different. Validation is used when a method developed
internally is evaluated, and the term Verification is used when the laboratory is evaluating a
compendial method (such as USP, BP etcetera).
Qualification
It is the action of proving that any instrument is properly installed, performs correctly and leads to
the expected results. If the instrument is not qualified, then all the work based upon the use of that
instrument becomes suspicious.
Design qualification (DQ): A documented verification that a system consistently produces results
meeting predetermined acceptance criteria in an operational environment. It focuses on verifying
the design specifications, documentation, and design intent to ensure they align with user
requirements and relevant standards.
Installation Qualification (IQ): A documented verification that equipment or systems are installed
according to design specifications. It ensures that all the important aspects of process equipment
together with ancillary system installation follow the approved specification of a manufacturer and
what the supplier recommends.
Operational qualification (OQ): It is the executed test protocol documenting that a system meets
the defined functional requirements, or that the system does what it's supposed to do. Testing
whether a system operates within established parameters.
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
Performance Qualification (PQ): It is a documented verification process that ensures equipment,
systems, or processes consistently operate as intended under real-world conditions.
Qualification protocol
A qualification protocol is a written plan that details how to demonstrate that equipment, systems,
or processes meet predefined quality standards and requirements. It's a crucial step in ensuring that
manufacturing processes consistently produce products that meet quality expectations.
Qualification report
Qualification reports are documents that provide evidence that equipment used in pharmaceuticals
operates as intended and meets predefined specifications.
Importance of qualification
• It ensures that the specific equipment or system and its ancillary components are installed
correctly and fit for intended use.
• It will be performed for all existing/new instruments, facility, system.
• It is directly related to the equipment, system.
• URS, FAT, SAT, DQ, IQ, PQ and OQ are the parts of qualification.
Calibration
It is a process of comparing the measurement of an instrument with a known measurement
(Reference Standard). Thereby, adjust the instrument response close to the value shown by the
reference standard.
For example, if applied voltage is 1.50 V but the value shown by the instrument is 1.45, then the
error will be -0.05 V. So, we can adjust the instrument response by removing that error to 0.00.
This is called calibration.
Calibration vs. Validation
Calibration:
• Calibration is a process that compares between standard (known) and sample (Unknown).
• It means system performance checking.
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
• It ensures that instrument or equipment is working well.
• It ensures that the system is ready to use for any analysis.
On the other hand, Validation:
• It means methods of analysis performance checking.
• It ensures that analytical method is working well.
• It ensures that the method is ready to use for its intended purpose or not.
• It is done to ensure that consistency of expected results of method or procedure.
Qualification vs. Calibration
Compendial analytical procedure
Compendial analytical procedures are standardized methods for testing pharmaceutical products,
ensuring quality and consistency. These procedures are found in official publications like the
United States Pharmacopeia (USP) and are used to verify the identity, strength, quality, and purity
of drug substances and products. They cover a wide range of testing, from basic physical properties
to complex chromatographic separations.
Non-compendial analytical procedure
Non-compendial analytical procedures are those not officially published in recognized
pharmacopeias like the United States Pharmacopeia (USP). These procedures are typically
developed for specific products or materials, focusing on their unique quality attributes. They are
essential when compendial methods don't adequately address the specific needs of a product or
when analyzing novel substances or formulations.
Sampling
The process of taking a small portion from a batch for test and analysis.
Reference sample
A sample of a batch of starting material, packaging material or finished product which is stored
for the purpose of being analyzed should the need arise during the shelf life of the batch concerned.
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
Retention sample
A sample of a fully packaged unit from a batch of finished product. It is stored for identification
purposes. For example, presentation, packaging, labeling, patient information leaflet, batch
number, expiry date should the need arise during the shelf life of the batch concerned.
Qualification vs. validation
Md. Shafiul Hossen, Lecturer, Department of Pharmacy, State University of Bangladesh
