VALIDATION OF RAW

MATERIAL
PRIMA RAMADHANI
1111011003
CLASS A

CONTENTS

INTRODUCTION TO VALIDATION
DEFINITION OF VALIDATION
QUALITY ATTRIBUTES
WHY TO VALIDATE
WHEN TO VALIDATE
DEFINITION OF RAW MATERIAL
STEPS
INVOLVED
IN
RAW
VALIDATION
CONCLUSION
REFERENCES

MATERIAL

VALIDATION
Validation is the scientific study of
a system

To
prove
that
the
facility/system/equipment/method is
consistently doing what it is supposed to do
(i.e., that the process is under control).
We want to make decisions based on good
science and not hunches and assumptions!
To determine the process variables and
acceptable limits for these variables, and to
set-up appropriate in-process controls.

FDA DEFINITION OF VALIDATION

Validation
is
a
process
of
demonstrating,
through
documented evidence, that a
process, procedure, method, piece
of equipment, or facility will
consistently produce a product or
result that meets predetermined
specifications
and
quality
attributes.
2

Quality Attributes
Identity
Safety
Potency
Purity
Stability
Efficacy

Why validate?
It is required by the current good
manufacturing
practice(CGMP)
regulations promulgated by the
US FDA.
It should be performed because it
is in accord with good business
judgment.

WHEN A
VALIDATED

PROCESS

SHOULD

BE

The following model may be useful in determining whether or not a process should validated:

A
Is Process
Output
Verifiable

NO

D
Validate

YES

B
Is Verification
Sufficient &
Cost Effective

YES

C
Verify &
Control
the Process

NO

E
Redesign Product
and/or
Process

DEFINITION OF RAW MATERIAL

RAW MATERIAL: It is a term used to
denote starting materials, reagents
and solvents intended for use in the
production of intermediates or active
pharmaceutical ingredient(API).

RAW MATERIAL VALIDATION

Several steps are required to validate a raw material.
They are as follows:

(I) LIST ALL THE RAW MATERIALS NEEDED TO

PREPARE A PRODUCT BATCH.
The list should include the materials used in
production and testing
Active ingredients
Excipients
Processing aids
Chemicals
Official standards
Laboratory materials

(II) IDENTIFY AT LEAST TWO SUPPLIERS FOR EACH

RAW MATERIAL.
After we have complete list of all raw materials
needed, we must locate sources of these materials.
It is always advisable to locate and validate at
least two suppliers.
EVALUATION FOR SELECTING A SUPPLIER:
(1)Provide the raw material that we need
(2)Must be capable of providing the grade that we
want
(3)Providing the quantity that we require
(4)To provide increased quantities quickly (to
evaluate the supplier s capacity)
(5)Determine
whether
our
supplier
is
a
manufacturer or distributor?

(6) Cost of the raw material.

(7) Reputation and reliability of the supplier.
NOTE: He must use written standard operating
procedures and establish proper raw material
storage conditions and distribution procedures.
Precautions
Joint agreements
Attention
Investigation

(III) IF A SUPPLIER IS NEW, VISIT HIS FACILITY.

It is important to establish a good relationship

with a
supplier.

To meet representatives personally.

Inspect his facility.

During the visit, it is also important to observe..

housekeeping and sanitation practiced
The use of written procedures and logs
proper segregation and batch identification
The use of laboratory notebooks
The size of the laboratory area and staf
The use of up to date laboratory instrumentation
and production equipment.

(IV)
OBTAIN
SAMPLES
CERTIFICATES OF ANALYSIS

AND

SUPPLIERS

To determine the characteristics of the raw

material.

The certificates of analysis and samples the

extent of variation from lot to lot on specific tests.
It is important to measure this variation between
diferent lots from the same supplier and then the
variation between suppliers.

(V) ESTABLISH SPECIFICATIONS FOR EACH RAW

MATERIAL
List of parameters.
For each parameter listed, an acceptable ,
measurable range of activity should be
established.
Compendial raw materials
And non- compendial raw materials

(VI) ESTABLISH TEST PROCEDURES.

A test procedure must be established for each
specification.
For raw materials that are compendial, test
procedures are denoted along with their
respective specifications.
For raw materials that are not listed in official
compendia,we
embark
into
methods
development.
This work calls on compendial methods that
exist for similar compounds, which can be
modified. It also calls for methods that are
published literature.
Documentation of so developed test procedures
should be paid attention.

(VII) ESTABLISH SAMPLING PROCEDURES.

Documentation of raw material sampling is
developed.
This procedure includes general requirements that
may apply to any raw material received in the plant,
such as
The number of containers to sample(sample size).
Method of sampling.
Individual raw materials may have certain
sampling requirements based on their stability
and/or intended use.
Before these individual sampling procedures are
instituted in routine practice, they should be
evaluated as part of process validation.

(VIII) ESTABLISH OPTIMUM STORAGE CONDITIONS

Raw material containers must be handled and
stored under prescribed conditions in order to
protect their stability over the stated shelf life.
The chemistry of each raw material should be
reviewed and aspects concerning hygroscopity,
sensitivity to light,sensitivity to high and low
temperature extremes, ability to support microbial
growth,reactivity with any container or closure
system, and oxidising capability are checked.
Once we have established the factors that
critically afect a raw material, we can conduct
stability studies that will indicate the optimum
storage conditions and establish a shelf life for the
raw material.

(IX) ESTABLISH SHELF LIFE

Shelf life or expiry dating of a raw material is
the time period within which it must be used.
Some times we assign an expiry date that is
shorter than our data indicate, so that we will
always use fresh raw materials.
The shelf life of a raw material is established by
testing over time in the containers and closures
to be used, after storage under the anticipated
optimum conditions, and also under adverse
conditions.

(X) CHALLENGE OF THE RAW MATERIALS.

The last step required to validate a raw material
is the operation in which the information that has
been established concerning the raw material is
challenged, to assure that is scientifically sound and
meaningful.

CONCLUSION
To build up quality in the final product a thorough
control over
each step of the process is
required.
This makes it essential to establish a documented
evidence
to
be
developed
by
thorough
experimentation.
So the raw materials are not an exception to this
and they should be validated by opting an
systematic approach.

REFERENCES
Robert

A.

Nash,

pharmaceutical

process

validation.
Berry, I.R.,and Daniel harpaz, validation of
active pharmaceutical ingredients.
P.P.sharma, how to practice GMPS.
Validation
in
API
manufacturing
plants.Brussels:active
pharmaceutical
ingredients committee. http://www.apic.ecfic.org
Guide to Inspections Validation of Processes.
Washington
DC:use
Food
and
Drug
Administration.
http:/www.fda.gov/ora/inspect_ref/igs/valid.html.
Validation of compendia Methods.The United
States Pharmacopeia Convention,Inc.,1995.