Complaints and Recalls

Now u can type with ur eyes

Dr.K.Kathiresan.,M.Pharm.,Ph.D.,M.B.A.
Associate Professor
Department of Pharmacy
Annamalai University
v r going to deal with an area of very great
importance
 Product complaint principle

“ All complaints & other information concerning

potentially defective products must be carefully
reviewed according to written procedures”
Do not place the patient at risk because of
inadequate safety, quality or efficacy
 Objectives

• To identify the key issues in product complaint and recall

handling

• To understand the specific requirements for organisation,

procedures & resources.

• To understand & develop actions to resolve current issues

applicable to u
Complaints as a tool for overall quality improvement
 Complaints Handling Principle

• Handle Positively & carefully review

• Must be seen as important work
• Managed by a senior staff member
• Thorough investigation of the cause is essential
• A major source of information & learning
The result of investigation r used to improve the situation
and prevent recalls & complaints in the future
 Complaints Procedure - I

• Designated responsible person

• Written procedure describing action to be taken
• Acknowledge and respond to complainant within a
reasonable period
• Record written and verbal comments
 Responsible Person

– May be authorized person

– If not, must advise authorized person of results
– Sufficient support staff
– Access to records
 Decision from a Complaint Investigation

Complaint justified

• Actions to prevent reoccurrence

• Ongoing observation of process
• Recall product may be required

Complaint not justified

• Advise customer of findings
• Appropriate marketing response
For example, when the product has expired for a long
time or the product was not kept at the storage
conditions stated by the manufacturers.
 Other issues

• Regular review of trends required

– Reoccurring problems
– Potential recall or withdrawal

• Inform competent authority of serious quality

problems
 Classification of Defects

• If complaint is justified, then there has been a failure of

the quality system

• Once defect has been identified, company should be

dealing with it in an appropriate way, even recall.

• The definition of defects is useful.

• The following system has been found in some
countries (but it is not a WHO guideline):
– Critical defects
– Major defects
– Other defects
 Critical Defects

Those defects which can be life threatening and require the

company to take immediate action by all reasonable
means, whether in or out of business hours

Examples
– Product labelled with incorrect name or incorrect
strength
– Counterfeit or deliberately tampered-with product
– Microbiological contamination of a sterile product
 Other Defects

Those defects which present only a minor risk to the

patient — batch recall or product withdrawal would
normally be initiated within a few days

Examples
– Readily visible isolated packaging/closure faults
– Contamination which may cause spoilage or dirt
and where there is minimal risk to the patient
 Reasons for Recall

• Customer complaint
• Detection of GMP failure after release
• Result from the ongoing stability testing
• Request by the national authorities
• Result of an inspection
• Known counterfeiting or tampering
Detection of GMP failure
 Product Recall Principle

“There should be a system to recall from the market

promptly and effectively, products known or suspected
to be defective.”
 Definition

Recall
– Removal from the market of specified batches of
a product
– May refer to one batch or all batches of product

Responsible person
 SOP for Recall

• Established, authorized
• Actions to be taken
• Regularly checked and updated
• Capable of rapid operation to hospital and pharmacy
level
• Communication concept to national authorities and
internationally
 Distribution Records

• Available to designated person for recall purposes

• Accurate
• Include information on:
– Wholesalers
– Direct customers
– Batch numbers
– Quantities
Collect 3 examples of complaints
or recalls from your experience
Thank you
QUALITY AUDIT

Dr.K.Kathiresan,M.Pharm., Ph.D.,M.B.A.,
Associate Professor
Department of Pharmacy
Annamalai University
AUDITING IN THE PHARMACEUTICAL INDUSTRY
 Medicinal products have to be of high quality

People’s lives depend on it. While end product testing of samples from each batch
(to ensure compliance with a release specification) is important, it is not enough to
ensure quality, which must be built into the manufacturing processes.

To ensure quality, all pharmaceutical manufactures are required to establish and

implement an effective pharmaceutical QA system, involving the active
participation of the management and personnel of different services involved.
To assess the effectiveness of this QA system and ensure that it follows good
manufacturing practice (GMP), regular audits must be performed. Audits may be
performed by the manufacturer on itself (internal), or on its vendors (external).
Alternatively, audits may be conducted on a manufacturer by its customers or by a
regulatory body (regulatory).
 INTERNAL AUDITS

Internal audits are carried out by an organization on its own systems, procedures
and facilities. European legislation requires the Pharmaceutical manufactures:
‘conduct repeated self-inspections as part of the QA system, to monitor the
implementation and respect of good manufacturing practice and to propose any
necessary corrective measures. Records of such self-inspections and any
subsequent corrective action shall be maintained’.
Aside from the legal requirement, internal audits are vital from a business
perspective. As well as monitoring the current compliance status, well-conducted
internal audits help to spread the message that quality is everybody’s responsibility
and to catalyse continuous improvement.
The Organisation of internal audits depends on the size and complexity of the
organization. A procedure and programme of internal audits should be available
and may be requested during regulatory audits. Responsibility for the management
of internal audits should be assigned to ensure that they occur and are effectively
followed up (always a challenge). One possible system is a three tier approach.
Tier one - audits carried out by the staff of a section or department on themselves.
Such audits will typically be short and limited in scope, focusing on ‘visibles’, such
as housekeeping and documentation.

Tier two - audits typically led by a local QA group, comprising staff independent of
the department under audit. Such audits will typically be longer, but less frequent
and are likely to focus more on systems than housekeeping.
Tier three - audits carried out by a corporate compliance group. Alternatively,
external consultants may be used. Such audits are often carried out to assess
readiness for a regulatory audit, but may also be used to obtain an expert view on a
specific critical activity.
For tier one audits, are usually selected on the basis of knowledge and experience
of the area to be audited, though they should also receive some basic training on
the reasons for audits and particular areas for examination. More extensive audit
training will be required for tier two auditors, with more detail on quality systems
and audit techniques. Tier three auditors are likely to be highly trained and
experienced specialists, with an expert knowledge of GMP and other regulatory
requirements for pharmaceuticals.
 EXTERNAL AUDITS

External audits are audits carried out by a company on its vendors or

subcontractors. There is no legal requirement to conduct such audits, but the need
is implicit, since manufacturers are required to have a thorough knowledge of their
suppliers. Furthermore, if work is contracted out, they must ensure that
contractors are complement to complete it, in accordance with GMP.
There are also strong business benefits to be derived from performing these audits:

• Building knowledge and confidence in the partnership arrangement.

• Ensuring that requirements are understood and met.
• Enabling reduction of certain activities (e.g. in-house qc testing of starting
materials).
• Reducing the risk of failure (and, by implication, its costs).
The scope of these audits will vary, depending on the relationship between the two parties,
which may range from a simple vendor-purchaser transaction to a strategic joint venture
partnership. Confidentiality and technical agreements are likely to influence this.

Typically, there will be an initial evaluation audit of the capabilities and general suitability of
the vendor / contractor. Subsequently, regular audits will be carried out to assess compliance
with agreed contractual standards, the frequency of which will depend on the initial findings
and the critically of the vendor and materials supplied. As confidence in the vendor increases
through auditing, confidence in the vendor’s own internal auditing systems, third-party audits
and vendor history – it should be possible to reduce the level of external auditing.
External auditors typically have a broad practical experience of GMP and receive
quality systems auditing training equivalent to that of ISO 9001 lead auditors. Audit
teams may also include specific technical experts. Depending on the size of the
facility and the scope of the audit, an audit team of one or two other people will
usually accompany the audit leader.
Many Pharmaceutical industry suppliers are ISO 9001 or ISO 9002 – certified and
are regularly audited by their certification body. IQA’s Pharmaceutical Quality
Group has published codes of practice for Pharmaceutical suppliers, under the
banner ‘PS 9000’, detailed the additional requirements for the Pharmaceutical
industry, concerning the manufacture of product contact packaging materials,
printed materials and raw materials (active ingredients and excipients).
Pharmaceutical contract manufacturing or packaging companies will need to be
licensed and will be subject to regulatory audits.
 Regulatory Audits

These audits are carried out by regulatory bodies against relevant regulations for the
manufacture and supply of Pharmaceutical products. National regulatory bodies, such as
the Medicines Control Agency (MCA) in the UK and Food and Drug Administration (FDA) in
the USA, are statutorily responsible for carrying out such audits. All licensed
Pharmaceutical manufactures periodically receive them (as may their contractors). These
audits may be unannounced (MCA currently performs about ten percent of its UK
inspections like this) as manufacturers are expected to be complying with GMP at all times.
Regulatory bodies from other countries in which products are sold may also audit
companies (i.e. FDA audits European manufactures).
Regulatory inspectors are extensively trained and are knowledgeable and professional. All
MCA medicines inspectors are relevantly qualified and have a minimum of five years
appropriate experience in a manufacturing operation. They will be on the registers of
persons eligible to act as qualified persons (QP) and lead auditors.

Failure to pass a regulatory audit can lead practical experience of GMP and receive to
restrictions on (or the withdrawal of) a manufacturing or import / export license. (FDA has
recently imposed punitive financial ‘consent decrees’ on companies which failed to
respond adequately to audit findings and comply with GMP). Therefore, it is vital that
companies have defined processes for handling audits and that staff are well trained as
auditors. Internal audits can provide valuable practice opportunities.
Currently, different regulatory bodies have distinct audit styles and requirements, but to
reduce costs and the audit burden on manufacturers, there have been moves towards
sharing and mutually recognizing audit findings between these bodies, a practice likely to
increase in the future.

There has been a Pharmaceutical Inspection Convention (PIC) since 1971. Based in Geneva,
PIC is open to any member of the UN that satisfies PIC officials of its adequate legislation
and inspections relating to medicinal products. Under PIC, the health opportunities of
member countries agree that, if the manufacturer consents, information obtained during
inspections may be exchanged. PIC holds regular meetings for the representatives of
member countries to discuss common standards.
Launched in November 1995, the Pharmaceutical inspection co-operation scheme
is an informal, flexible arrangement between the inspectorates of PIC contracting
states, which is run in parallel with PIC and is open to inspectorates from other
countries.

The scheme retains and improves on the convention’s main features:

• Networking and confidence –building between national inspection authorities
• Development of quality systems
• Training of inspectors and related experts
• Work towards global harmonization of GMP
Regulatory audits vary considerably in scope, frequently and duration. Audits by
the national regulatory body are likely to be regular and to cover systematically all
areas of a facility, over a period. There may be additional audits (or Visits) as a
result of specific events, which may be company – specific (for example the recall of
a product) or industry – wide (a recent example being checks on compliance with
transmissible spongiform encephalopathies regulations by the MCA).
Audits by the regulatory body of another country may be general, or linked to a
specific regulatory event: the Pre-approval inspections of the FDA are linked to
submission of a new drug application. Depending on the scope, up to three,
inspectors may visit, for a period of between half a day to two weeks.
After a regulatory audit, a formal report will be delivered , the format of which will
depend on the regulatory body concerned. MCA provides verbal feedback at the
exit meeting, then a brief, action-oriented, written report shortly afterwards, FDA
provides a ‘form 483’ at the exit meeting, if there are points of concern, followed
by a more detailed establishment inspection report. The regulatory body will
expect a timely, formal response to the audit report and typically, will check that
corrective action has taken place, as part of the next audit, it is wise business
practice to take regulatory audit findings seriously and ensure that timely and
effective corrective action is taken.
Thank You
 HANDLING OF RETURNED PRODUCTS

Drugs are an important component of Health Care System

Definition of Finished Product:

A Product that has undergone all stages of Production, including Packaging in its final container and
Labeling.

Returned Good / Product.

The Finished Product sent back to the manufacturer
Disposal of Finished Product from Factory Premises
Storage at Depots
Sales and Distribution

A Returned Drug Product is the Distributed F.P. that has been returned to the manufacturing
following reasons,
COMPLAINT
DAMAGE
EXPIRATION OF VALIDITY.

A Salvaged drug product is that product which has been subjected to improper storage
conditions like extremes of Temperature, Humidity, Smoke, fumes, radiation, fire accidents or
equipment failure but may be reprocessed or recovered after laboratory validation to meet the
approved specification laid down for that product.

CLASSIFICATION OF RETURNED DRUG PRODUCTS

Drug products that still comply with all acceptable standards according to investigation by
quality control department.
Drug products which can be reprocessed to comply with appropriate specifications.
Drug products which are Un-acceptable.

Dr.K.Kathiresan, Department of Pharmacy Annamalai University

DISPOSITION OF RETURNED DRUG PRODUCTS

• returned drug products shall be counter checked at the Security and informs the concerned
department –i.e. Warehouse

• Receiving bay then records amount and identification of returned drug products

• Returned drug products are handed over to In – charge ware house

• Returned drug products shall be kept in QUARANTINE area

• Q.A. shall come for Physical Verification

• Holds in place until further decision

To be RECOVERED – QA & Validation dept. for reprocessing

To be DESTROYED – Destruction shall be done in the presence of QA officer and Excise Official

Destruction shall be done in such a way that No Pollution hazards shall be caused and prior approval
from ETP (Effluent Treatment Plant) and Biomedical Waste Dept.

Records of Returned Drug Product & Destruction Details:

A. Name of Product
B. Batch No.
C. Label Claim
D. Dosage Form
E. Qty & Date Of Receipt
F. Origin of returned goods
G. Storage conditions
H. Transportation

A Destruction Certificate shall be signed and commented by warehouse person and QA person.

This certificate should be a part of the batch document.

Dr.K.Kathiresan, Department of Pharmacy Annamalai University

 QUALITY REVIEW

The prime motto of any Pharmaceutical industry, as a vital segment of health care
system, should be of producing a product of good quality in terms of safety, purity and
efficacy.

NECESSITY FOR QUALITY PRODUCT

As all the countries are marching towards globalization. This globalization in turn
forces the companies to produce a product which meets the quality specifications set by the
respective countries, and because of increasing complexity of modern Pharmaceutical
manufacturing arising from a wide variety of unique drugs and dosage forms. The
Pharmaceutical company has set a department called quality assurance ( QAD) in order to
install the quality aspects in each and every product.
It is the responsibility of the QAD to install all the quality aspects of a product in each
and every product with the help of the other departments like production, quality control
dept, stores and maintenance. It does it duty by reviewing various steps involved in
manufacturing of products.

QUALITY REVIEW
Quality means purity, safety and efficacy, whereas review means counter checking.
As a whole, quality review in a Pharmaceutical company, represents counter checking
each and every step starting from acquiring raw material to releasing finished products,
including market complaints.

QUALITY REVIEW TEAM

A systematic and effective review team includes knowledgeable, professional and
experienced persons from each and every department. A typical QR team includes:
Quality assurance -1 person
Production -1 person
Quality control-1 person
Regulatory affairs -1 person

Dr.K.Kathiresan, Department of Pharmacy Annamalai University

Supply chain management -1 person
Team leader – Generally president or vice president (tech)
OBJECTIVES OF QRT
To minimize the errors those arise during various stages involved in production and to
minimize the market complaints and mainly to install safety, purity and efficacy in each and
every product.
RESPONSIBILITIES OF QRT
In the way to achieve the objectives, QRT will take various variables into
consideration for reviewing, which includes
A. Raw material review
B. Production records review
C. Packaging and Labelling review
D. Finished product record review

A. RAW MATERIAL CONTROL REVIEW

Quality review team will take decisions for the approval of quality of raw material from
a vendor by auditing the manufacturing premises of vendor and documenting the auditing
reports and then the reports will be sent to QRT leader for final approval of vendor to supply
the raw material.

B. PRODUCTION RECORD REVIEW

B1. Dispensing: In dispensing, each and everything has to be documented like r/m name,
batch no., quantity, A.R.N., approval signature.
B2. In process checks: The number of units assayed at the end of the process is not likely to
be representative of more than a small portion of the actual portion and so as to minimize
batch to batch and within batch variation, it is important to ensure that finished products
have uniform purity and quality within batch and between the batches.
This is accomplished by identifying critical steps involved in manufacturing process
like checking parameters of tablets (hardness, weight , thickness , friability , DT) and pH
adjustments in case of parenterals.
Each and every thing in process checks has to be documented for further reviewing.

Dr.K.Kathiresan, Department of Pharmacy Annamalai University

C. PACKAGING AND LABELING RECORD REVIEW
After manufacturing a product, QA member will check that correct labels have
been used for correct products and see that no mix-ups had occurred, and the approved labels
should be attached to the BMRs.

D.FINISHED PRODUCT RECORD REVIEWS

Final testing of f/p is done in Quality control dept. The finished product is tested for
compliance with predetermined standards prior to release of product for packaging and
subsequent distribution. All the tests and results should be documented. QRT will review the
documents before approving for market release.
This finished product testing along with in process checking assures that each and
every unit contains the amount of drug claimed on the label, that the entire drug in each unit
is available for absorption, that the drug is stable in the formulation in its specific final
container, and that dosage units themselves contain no toxic foreign substances.

FREQUENCY OF QUALITY REVIEW

It varies from company to company starting from once in a month to quarterly
reviewing, in some instances emergency reviewing.

COMPLIANCE TO Q.R.
Compliance with respect to quality review department can be achieved only by
following standard operational procedures by concerned officials of respective departments.
I.e. they should document each and everything they do and do as per given in SOP.

RESPONSIBILITY OF QUALITY REVIEW DOCUMENTS

Quality assurance dept will take the responsibility of all the quality documents concerning
quality aspects of products

Dr.K.Kathiresan, Department of Pharmacy Annamalai University

INTRODUCTION TO VALIDATION

Dr.K.Kathiresan.,M.Pharm.,Ph.D.,M.B.A.
Associate Professor
Department of Pharmacy
Annamalai University
 QUALITY
PURCHASE
CONTROL PRODUCTION

ADMINISTRATION QUALITY
ENIGINEERING
& HR ASSURANCE

REGULATORY
VALIDATION WHAREHOUSE
AFFAIRS

R&D
 WHY VALIDATION?

The pharmaceutical industry uses expensive materials, sophisticated facilities & equipment's
and highly qualified personal.

The efficient use of these resources is necessary for the continued success of the industry. The
cost of product failures, rejects, reworks, recalls, complaints are the significant part of the total
production cost.

Detailed study and control of the manufacturing process – validation is necessary if failure cost
is to be reduced and productivity improved.
V ery
A rduous
L engthy
I nvolved
D etailed
A ttempt to
T est
E verything
 Def.

“Establishing Documented Evidence, which provides a high degree of assurance

that a specific process will consistently produce a product meeting its pre-
determined specification and quality attributes”.

USFDA
There are different approaches for validating a pharmaceutical industry

• Prospective validation
• Retrospective validation
• Concurrent validation
• Revalidation
Prospective Validation

• pre-planned protocol.

• This approach to validation is normally undertaken whenever a new formula, process

or facility must be validated before routine pharmaceutical formulation commences

Retrospective validation

• what it purports to do on review and analysis of historical information (Process

control)
Concurrent validation
• process monitoring of critical processing steps and product testing

Revalidation
• This is carried out when there is any change or replacement in formulation, equipment
plant or site location, batch size and in the case of sequential batches
 Various types of validations :

➢Equipment/Instrument validation :
DQ
IQ
OQ
PQ
➢Area Qualification
➢Analytical Method validation
➢Cleaning validation
➢Process Validation
IQ - Verification that the equipment/system is installed in a proper
manner and that all of the devices are placed in an environment
suitable for their intended operations.

OQ - Verification that the equipment performs as expected throughout

the intended range of use.

PQ - Verification that the system is repeatable and consistently

producing a quality product.

DQ - Document verification of the design f equipment and manufacturing

facilities.
 Elements of Validation:

The validation of a process requires the qualification of each of the important

elements of the process. The relative importance of an element may vary from
process to process. Some of the elements commonly considered in a process
validation study are presented below
 Instrument Calibration

Critical support system

Analytical Procedures

Operator Qualification Validated Process Raw & Packaging Materials

Product design
Equipment and Facilities

Mfg. Stages
Thank U
Analytical Method Validation
by using HPLC

Dr.K.Kathiresan,M.Pharm., Ph.D.,M.B.A.,
Associate Professor
Department of Pharmacy
Annamalai University
 Def
For method validation the FDA designated the
specifications and is listed in USP and can be referred to
as the "Eight steps of method validation“.

These terms are referred to as "Analytical performance

parameters", or sometimes as "analytical figures of
merit“

International Conference on Harmonization (ICH) divides

the "validation characteristic" somewhat differently, as
outlined in the table.
The difference in the USP and ICH terminology is for the
most part 1, however, with one notable exception that is
ICH treats systems suitability as a part of method
validation, where as the USP treats in it in a separate
chapter (<621>).

Discussions of definition of analytical performance

parameter are given below
 Accuracy

It is a measure of exactness of an analytical method, or the

closeness of agreement between the value that is
accepted as either a conventional, true value or an
accepted reference value and the value found.
 Recovery percentage

About 25 mg of drug WRS, was weighed accurately, into a 50 ml

volumetric flask, was dissolved in mobile phase and diluted to
volume with the mobile phase (Stock solution).

1.0 ml of stock solution was transferred to 4 different 50 ml

volumetric flasks and 0.0, 0.2, 0.4, and 0.6 ml of stock solution
was added and the volume was made up with the mobile
phase and mixed.

Separately each solution was injected and the percentage

recovery of drug was calculated by recorded chromatogram.
 Precision

It is the measure of the degree of repeatability of an

analytical method under normal operation and is
normally expressed as the percent relative standard
deviation for a statistically significant number of samples.
According to the ICH, precision should be performed at 3
different levels: repeatability, intermediate precision and
reproducibility.
Repeatability is the results of the method operating over a
short time interval under the same condition (inter-assay
precision).

Intermediate precision is the result from within lab

variations due to random events such as different day's
analysts, equipment, etc

Reproducibility refers to the results of collaborative studies

of the laboratories
 Procedure

About 25 mg of drug WRS, was accurately Weighed, into a 50 ml

volumetric flask, dissolved and diluted to volume with the
mobile phase. 1.0 ml of this solution was diluted to 50 ml
with the mobile phase and mixed (10 ppm).

Separately equal volume (about 20 l) of above solution was

injected six times and recorded the chromatogram.
 Specificity

Specificity is the ability to measure accurately and

specifically the analyte of interest in the presence of
other components that may be expected to be present in
the sample matrix.

It is a measure of the degree of interference from such

things as other active ingredients, excipients, impurities,
and degradation products, ensuring that a peak response
is due to a single component into two separate
categories: identification, and assay / impurity tests.
 Procedure

System suitability solution:

About 25 mg of drug (Terbutaline Sulphate) WRS and 7 mg

of 3,5- dihydroxy-w-t-butyl amino acetophenone
hydrochloride was weighed into a 50 ml volumetric flask,
dissolved and diluted to volume with the mobile phase.
 LOD

The limit of detection (LOD) is defined, as the lowest

concentration of an analyte in a sample that can be
detected, not quantitated.

It is a limit test that specifies whether an analyte is above

or below a certain value.

It is expressed as a concentration at specified signals - to -

noise (S/N) ratio, usually two - or three - to - one.
The ICH has recognized the signal to - noise (S/N) ratio
convention, but also lists two other options to determine
LOD: Visual non-instrumental methods and a means of
calculating the LOD.
 Procedure

About 25 mg of drug WRS, was accurately weighed, into a

50 ml volumetric flask, dissolved and diluted to volume
with the mobile phase. 1.0 ml of this solution was diluted
to 50 ml with the mobile phase and mixed. 1.0 ml of this
solution was diluted to 100 ml with the mobile phase and
mixed (0.1 ppm).

Equal volume (about 20 L) of above solution and mobile

phase (Blank) was separately injected and recorded the
chromatogram.
 LOQ

The limit of quantitation (LOQ) is defined as the lowest

concentration of an analyte in a sample that can be
determined with acceptable precision and accuracy
under the stated operations of the method.

The ICH has recognized the 10 - to - 1 signal - to - noise

ratio as typical, and also, like LOD, lists the same two
additional options that can be used to determined LOQ,
visual non - instrumental methods and a means of
calculating the LOQ.
 PROCEDURE

About 25 mg of drug WRS, was accurately Weighed, into a

50 ml volumetric flask, dissolved and diluted to volume
with the mobile phase. 1.0 ml of this solution was diluted
to 50 ml with the mobile phase and mixed. 5.0 ml of this
solution was diluted to 100 ml with the mobile phase and
mixed (0.5 ppm).

Equal volume (about 20 L) of above solution and mobile

phase (Blank) was separately injected and recorded the
chromatogram
 Linearity & Range

Linearity is the ability of the method to elicit test results

that are directly proportional to analyte concentration
with in a given range.

Linearity is generally reported as the variance of the slopes

of the regression line.
Range is the interval between the upper and the lower
levels of analyte that have been demonstrated to be
determined with precision, accuracy and linearity using
the method as written
 Procedure

About 25 mg of Drug WRS, was accurately weighed, into a

50 ml volumetric flask, dissolved and diluted to volume
with the mobile phase (Stock solution).

0.4, 0.6, 0.8, 1.0, 1.2 and 1.4 ml of above stock solution was
transferred to separate six 50 ml of volumetric flasks and
diluted with mobile phase to volume and mixed, so the
resulting solutions contained 4, 6, 8, 10, 12 and 14 ppm
of Drug respectively.

Equal volume (about 20 L) of each solution was injected

separately and recorded the chromatogram.
 Ruggedness

This is a degree of reproducibility of the results obtained

under a variety of conditions, expressed as % Relative
Standard Deviation (RSD).

This condition includes different laboratories, analyst,

instruments, reagents, days etc.

ICH did not address ruggedness specifically instead, it

covered the topic of ruggedness as part of precision
 Procedure

Different analysts carried out the performance of the method,

on different days and on different instruments.
 Robustness

It is a capacity of a method to remain unaffected by small

deliberate variations in method parameters.

Robustness of a method is evaluated by varying method

parameters such as percent organic, pH, ionic strength,
temperature, etc., and determining the effect (if any) on
the results of the method..
As in ICH guidelines, robustness should be considered early
in the development of a method.

In addition, if the results of a method or other

measurements are susceptible to variation in method
parameters, these parameters should be adequately
controlled and a precautionary statement included in the
method documentation
 System Suitability

According to the USP, system suitability tests are an integral

part of chromatographic methods.

These tests are used to verify that the resolution and

reproducibility of the system are adequate for the
analysis to be performed.

System suitability tests are based on the concept that the

equipment, electronics, analytical operations, and
samples constitute an integral system that can be
evaluated as a whole.
System suitability is the checking of a system to ensure system
performance before or during the analysis of unknowns.

Parameters such as Plate count, Tailing factors, Resolution and

Reproducibility are determined and compared against the
specifications set for the method.

These parameters are measured during the analysis of a system

suitability, "Sample" that is a mixture of main components
and expected by-products.
USP chapter 1225 on validation of analytical methods
specifically address terms and definitions, but leaves
protocol and methodology open for interpretation
 Conclusion

A well-defined and documented validation process provides

regulatory agencies with evidence that system and
method is suitable for its intended use.

By approaching method development, optimization and

validation is logical, stepwise fashion, laboratory
resources can be used in a more efficient and productive
manner
Thank U