Good Manufacturing Process and Quality Assurance

VALIDATION OF RAW MATERIALS

Oleh:
Kelompok 2
Kelas A
Yuliana Puspita Sari 1211011008
Adek Saputra Amri 1211011009
Azizah Fitri 1211011010
Hasanatul Khairiyah 1211011012
Sylvi Istiqhamah 1211011013
CONTENTS
INTRODUCTION TO VALIDATION
DEFINITION OF VALIDATION
QUALITY ATTRIBUTES
WHY TO VALIDATE
WHEN TO VALIDATE
DEFINITION OF RAW MATERIAL
STEPS INVOLVED IN RAW MATERIAL VALIDATION
CONCLUSION
REFERENCES
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.

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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.

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Quality Attributes
Identity
Safety
Potency
Purity
Stability
Efficacy

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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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WHEN A PROCESS SHOULD BE
VALIDATED

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

A B C
Is Process Is Verification Verify &
YES YES
Output Sufficient & Control
Verifiable Cost Effective the Process

NO NO

E
D Redesign Product
Validate and/or
Process

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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.
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.
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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
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.
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