Introduction of Validation and

Qualification

Presented by Group 7:
Muhamad Bima Muria (14344143)
Ririn
(14344)
Ellen
(14344)
Sherly
(14344)
Apothecary Profession Program of ISTN Jakarta

What is Validation?
Validation is establishing of documented evidence
which provides a high degree of assurance that a
planned process will consistently perform
according to the intended specified outcomes
(WHO, 1997).
Validation is an essential part of GMP, and an element of
QA . The term of validation is normally used for processes

What Types of Validation?

Process Validation:
- Prospective Validation
- Concurrent Validation
- Retrospective Validation
Cleaning Validation
Analytical Method Validation
Qualification (DQ,IQ, OQ & PQ)
Re Validation/ Re Qualification

Why Validation Should be Implemented?

Needed to prove control of the critical aspects:
Facilities
Ex: HVAC, Water, Steam, Building, etc.
Equipment
Ex: Tablet Press, Autoclave, Fluid Bed Dryer, etc.
Process
Ex: Manufacturing Process, Sterile Filling, Sterilization, etc.
Which may affect the quality of product, should be validated.

Cont
Manufacturers should plan validation to ensure:
- regulatory compliance and
- product quality, safety and consistency
Need for confidence that the product will consistently meet
predetermined specifications and attributes.
An quantitative approach is needed to prove quality,
functionality, and performance of a pharmaceutical
manufacturing process.

Planning For Validation (Validation Master Plan)

All validation activities should be planned. The key elements of a
validation program should be clearly defined and documented in a
Validation Master Plan (VMP).
The VMP should contain data on at least the following:
Validation policy
Structure organization of validation activities
Summary of facilities, systems, equipment and process to be
validated.
Documentation format (protocol and report format, planning and
scheduling)
Change control
Reference to existing documents

Documentation (Validation Protocol)

Describe the study to be performed and include as a minimum:

The objectives of the study
The site of the study
The responsible of personnel
Description of SOPs to be followed
Equipment to be used
Standards and criteria for the products and processes
The type of validation

Protocol contents:
The processes and/or parameters
Sampling, testing and monitoring requirements
Predetermined acceptance criteria for drawing conclusions
Validation protocol should be established to specify and define the validation activity
that will be performed. It reviewed and approved by the head of Quality Assurance

Documentation (Validation Report)

A validation report should refer to validation protocol:
Summarizing the result obtained,
Commenting on any deviations observed
Describing the necessary conclusions
Recommending changes necessary to correct
deficiencies.
Any changes defined from protocol should be
reported and documented with appropriate justification

Process Validation
Process validation is defined as the collection and evaluation of
data, from the process design stage throughout production, which
establishes scientific evidence that a process is capable of
consistently delivering quality products.

Critical Process Steps Should be Validated

Process step
XIII
XIV
XV Sieve 3/
5
XVI Blend
3/5
granulate

Operation
Measure humidity with
humidity meter
Weigh granulate - balance

sieve with sieve type 1

mixer (speed 1, 1 minute)

XVI Blend 2
with 3/5
granulate

mixer (speed 1, 30
seconds)

XVIII

Weigh granulate

IQ/OQ/PQ requirements
IQ/OQ
calibration
IQ/OQ
calibration
I Q/OQ/PQ
Cleaning
validation

Critical
control
point

instrument
operation,
cleaning, care
and maintenance

Critical
control
point

Decision as to whether to
compress or not based on
expected yield and actual yield

Training
records for
technician

Cleaning, and Blend

uniformity required to be
established during validation

Prospective Validation
Prospective validation should be performed and completed
before the pharmaceutical product will be sale and
distributed. A minimum of three batches of product is
required.
Prospective validation should include:
Short description of the process
Summary of the critical processing steps to be investigated
List of the equipments/ facilities to be used (completed with
IQ,OQ & PQ document and its calibration status)
Finished product specification for release
List of analytical method

Prospective Validation
Proposed in-process controls with the acceptance criteria
Additional testing to be carried out, with acceptance criteria
Sampling plan (location and frequency)
Method for recording and evaluating method
Functions and responsibilities
Proposed and timetable
Batch size made for process validation (Prospective, Concurrent
& Retrospective) should be the same as the industrial scale batch.

Concurrent Validation
In exceptional circumstance it may be acceptable not to
complete a validation program before routine production
starts.
It can be performed during routine operation/production where
the product had been sale.
For example: when a process is being transferred to a third
party contract manufacturer/assembler.
Documentation requirements same as specified for
prospective validation
The completed protocols and reports should be reviewed and
approved before product is released for sale or supply

Retrospective Validation
Retrospective validation is only acceptable for well established
processes and will be inappropriate where there have been
recent changes in the composition of the product, operating
procedures or equipment.
Source of data should include:
Batch processing an packaging records
Process control chart
Maintenance log book
Records of personnel change
Process capability
Finished product data
Stability result

Retrospective Validation
For Retrospective validation, generally data from ten (10)
to thirty (30) consecutive batches should be examines
and to assess process consistency.
The steps involved in this type of validation still require
the preparation of a protocol, the reporting of the results
of the data review, leading to a conclusion and
recommendation

Cleaning Validation
Cleaning validation should be performed in order to confirm
the effectiveness of a cleaning procedure.
The objectives of Cleaning Validation include prevention of
possible contamination and cross-contamination.
Contamination by a variety of substances:
Contaminants {e.g. microbes, previous products (both API and
excipient residues), residues of cleaning agents, airborne
materials (e.g. dust and particulate matter), lubricants and
ancillary material, such as disinfectants}.
Also decomposition residues from product or detergents

Cleaning Validation
The aspect to be examined:
Visual inspection of the equipment / machinery cleanliness
Determination of residues of active ingredient (along with
degradation when necessary) and cleaning solutions
Examination of microbiological contamination
Inspection last rinse solution for parameters: TOC, pH and
conductivity, to ensure that no residual cleaning materials left
behind.
Validated analytical methods having sensitivity to detect residues
or contaminants should be used.
Cleaning of contact surfaces (machine or equipment) to be
validated, with consideration to non-contact parts. Critical areas
should be identified.

Cleaning Validation
The cleaning validation protocol should include:
Objectives and responsible of personnel
Description of the equipment or machine including model, serial
number, etc.
Time intervals and cleaning procedures;
Equipment used for routine monitoring (e.g. conductivity meters,
pH meters and total organic carbon analyzer);
Number of cleaning cycles; sampling procedures (e.g. direct
sampling, rinse sampling, in process monitoring and sampling
location).
Data on recovery studies (efficiency of the recovery of the
sampling technique should be established);
Analytical methods
Acceptance criteria

Cleaning Validation
Two methods of sampling:
Direct surface sampling (swab)
Rinse samples
Note: combination of the two - most desirable
The three most commonly used criteria are:
Visually clean No residue visible on equipment after cleaning.
Spiking studies to determine the concentration at which most
active ingredients are visible. (May not be suitable for high
potency, low-dosage drugs.)
No more than 10 ppm of one product will appear in another
product (basis for heavy metals in starting materials).
No more than 0.1% of the normal therapeutic dose of one
product will appear in the maximum daily dose of a subsequent
product.

Analytical Method Validation

The objective of analytical method validation (AMV) is to
demonstrate an analytical procedure suitable for its intended
purpose.
The most common type of AMV:
Identification test: intended to ensure the identity of analyte in a
sample, by comparing of sample property (e.g. spectrum,
chromatographic behavior, chemical reactivity, etc) to a reference
standard.
Quantitative and limit test for impurities content: both of tests is
intended to accurately reflect the purity in a sample
Quantitative test of API, medicinal product or other selected
components in the medicinal product.

Analytical Method Validation

Analytical Method Validation Characteristics:
Accuracy
Precision
Repeatability
Intermediate precision
Specificity
Detection limit (LOD)
Quantitative limit (LOQ)
Linearity
Range

Analytical Method Validation

Accuracy of an analytical method is the closeness of test results
obtained by that method to the true value.
Precision of an analytical method is the degree of agreement among
individual test results when the method is applied repeatedly to multiple
samplings of a homogenous sample.
Repeatability: a measurement is repeatable if the original experimenter
repeats the investigation using same method and equipment and
obtains the same results.
Intermediate precision: a measure of within-laboratory variations
(different days, different analysts, different equipment).
Specificity: The ability to measure accurately and specifically the
analyte in the presence of components that may be expected to be
present in the matrix

Analytical Method Validation

Limit of detection: The lowest concentration of an analyte in a sample
that can be detected, not quantified.
Limit of quantitative: The lowest concentration of analyte in a sample
that can be determined with acceptable precision and accuracy under
stated operational conditions
Peak B
LOQ

Peak A
LOD

Baseline

noise

Analytical Method Validation

Linearity: The ability of the method to obtain test results that are directly
proportional to concentration within a given range.

Precision: Interval between upper and lower levels of analyte demonstrated

by the method.