GMP and Quality Assurance

Kelas B
GROUP : 7th
VALIDATION ROW
DEFINITION OF MATERIALS
DEFINITION OF RAW
VALIDATION MATERIAL
WHY TO VALIDATE STEPS INVOLVED IN RAW
MATERIAL VALIDATION
CONCLUSION
FDA DEFINITION OF
VALIDATION
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.
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.

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 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).

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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.
(II) IDENTIFY AT LEAST TWO SUPPLIERS FOR EACH
RAW MATERIAL.
(III) IF A SUPPLIER IS NEW, VISIT HIS FACILITY.
(IV) OBTAIN SAMPLES AND SUPPLIERS
CERTIFICATES OF ANALYSIS
(V) ESTABLISH SPECIFICATIONS FOR EACH RAW
MATERIAL
(VI) ESTABLISH TEST PROCEDURES
(VII) ESTABLISH SAMPLING PROCEDURES.
(VIII) ESTABLISH OPTIMUM STORAGE
CONDITIONS
(IX) ESTABLISH SHELF LIFE
(X) CHALLENGE OF THE RAW MATERIALS.
(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

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 (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

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(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.

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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 staff
The use of up to date laboratory instrumentation
and production equipment.

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(IV) OBTAIN SAMPLES AND SUPPLIERS
CERTIFICATES OF ANALYSIS

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
different lots from the same supplier and then the
variation between suppliers.

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(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

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(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.
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(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.

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(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
affect a raw material, we can conduct stability studies
that will indicate the optimum storage conditions and
establish a shelf life for the raw material.
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(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.

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(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.

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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.
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REFERENCES
Berry, I.R.,and Daniel harpaz, validation of active
pharmaceutical ingredients.
Guide to Inspections Validation of Processes. Washington
DC:use Food and Drug Administration.
http:/www.fda.gov/ora/inspect_ref/igs/valid.html.
P.P.sharma, how to practice GMPS.
Robert A. Nash, Pharmaceutical Process Validation.
Validation in API manufacturing plants.Brussels:active
pharmaceutical ingredients committee.
http://www.apic.ecfic.org
Validation of compendia Methods.The United States
Pharmacopeia Convention,Inc.,1995.
Kumar, S.Rajesh. Seminar On : Validation Of Raw 20
Materials. Department of Industrial pharmacy