validation of raw material

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VALIDATION OF RAW MATERIAL

Mardiyati Hasanah

1111013018Kelas B


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DEFINITION OF RAW MATERIAL

RAW MATERIAL: It is a term used to denotestarting materials, reagents and solventsintended for use in the production ofintermediates or active pharmaceuticalingredient(API).

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Validation of raw material

Validation begins with the raw materials,active pharmaceutical ingredients excipients

Raw materials, major causes of productvariation or deviation from specification

Most uncontrollable component in thecomplete product/process validation schemebecause morphology particle size/surface areanot be completely defined this early


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It includes validation of both activeingredients & excipients

Characteristics - particle size, surface area,color, density.

Chemical characteristics- water contentresidue on ignition & heavy metals

Variables : Flow, blend uniformity, granulationsolution/binder uptake compressibility,lubricant efficiency.


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RAW MATERIALS & ITS IMPORTANCE

Chemical characteristics : Drug impurities canaffect the stability.

Physical properties : Drug morphology, solubility

& particle size/surface area may affects drugavailability. The particle size, shape , and density can affect

material flow and blend uniformity. The hygroscopic drug caring in handling the

material and the reproducibility of themanufacturing process.


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STEPS FOR RAW MATERIALSVALIDATION

1. Each raw material validated by testing at least 3batches from primary & alternate supplier ;representing the ranges, both high and low.

2. Depending on the susceptibility aging, physical,

chemical, and/or microbiological stability should beassessed.3. If under acceptable range, especially for materials

sensitive to small changes; then appropriate to useseveral lots of raw material with low and high ends ofthe specification.

4. The final step of raw material validation shouldinvolve an on- site inspection of the vendors to reviewthe manufacturing operations, controlling &

conforming to


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RAW MATERIAL VALIDATION

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

(1) LIST ALL THE RAW MATERIALS NEEDED TOPREPARE A PRODUCT BATCH.

The list should include the materials used in production and testingActive ingredientsExcipients Processing aids ChemicalsOfficial standardsLaboratory materials

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(2) IDENTIFY AT LEAST TWO SUPPLIERS FOR EACHRAW MATERIAL.

After we have complete list of all raw materials needed, wemust 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 thesupplier s capacity) (5)Determine whether our supplier is a manufacturer ordistributor?

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(6) Cost of the raw material.(7) Reputation and reliability of the supplier.

NOTE: He must use written standard operating procedures andestablish proper raw material storage conditions and distribution

procedures.PrecautionsJoint agreementsAttention

Investigation

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

It is important to establish a good relationship with asupplier.

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 identificationThe use of laboratory notebooksThe size of the laboratory area and staffThe use of up to date laboratory instrumentation and

production equipment.

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(4) OBTAIN SAMPLES AND SUPPLIERS CERTIFICATES

OF ANALYSIS

To determine the characteristics of the raw material.

The certificates of analysis and samples the extent ofvariation 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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(5) 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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(6) 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 thatare published literature.

Documentation of so developed test procedures should be paidattention.

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(7) 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 asThe 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 processvalidation.

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(8) ESTABLISH OPTIMUM STORAGE CONDITIONS

Raw material containers must be handled and stored under prescribed conditions in order to protect their stability over thestated shelf life.

The chemistry of each raw material should be reviewed andaspects concerning hygroscopity, sensitivity to light,sensitivity tohigh and low temperature extremes, ability to support microbialgrowth,reactivity with any container or closure system, andoxidising capability are checked.

Once we have established the factors that critically affect a raw

material, we can conduct stability studies that will indicate theoptimum storage conditions and establish a shelf life for the rawmaterial.

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(9) ESTABLISH SHELF LIFE

Shelf life or expiry dating of a raw material is the time periodwithin 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 overtime in the containers and closures to be used, after storage under

the anticipated optimum conditions, and also under adverseconditions.

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(10) CHALLENGE OF THE RAW MATERIALS.

The last step required to validate a raw material is theoperation in which the information that has been establishedconcerning the raw material is challenged, to assure that is

scientifically sound and meaningful.

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To build up quality in the final product a thorough control overeach 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 theyshould be validated by opting an systematic approach.

CONCLUSION

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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.orgGuide 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 PharmacopeiaConvention,Inc.,1995.

A Seminar on Validation of Solid Dosage Forms by Naincy GuptaM.Pharm (IInd Sem) Pharmaceutics.

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validation of raw material

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