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ELIZA ARMAN0811012030

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1. Quality ManagementPrinciple

Quality Assurance is the sum total of the organisedarrangements made with the object of assuring that

Active Ingredients are of the quality required for theirintended use.

The assurance of product quality cannot be delegatedto any single organizational unit such as Quality

Control but is the responsibility of every member ofthe company.

This should have been confirmed in a managementpolicy statement.

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Quality assurance

The assurance of product quality is enhanced byensuring that all activities associated with thepurchasing, storage, production, filling, control anddistribution of Active Ingredients are carried out in asystematic and approved manner.

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Quality Control (QC)

QC is that part of GMP which is concerned withsampling, specification and testing, and with theorganization, documentation and release procedureswhich ensure that the necessary and relevant test areactually carried out.

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2. Personnel Principle

The capability and attitude of all staff involved in the

manufacture and control of Active Ingredients has adecisive influence upon the quality of the products.

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Personnel at all levels should be sufficient in numberto carry out their tasks according to the prescribedprocedures.

Personnel involved in the production and controlActive Ingredients should be adequately trained,including training in GMP.

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Training should be carried out at appropriate intervalsand when new processes are being introduced.

Training should be given to other personnel whoseactivities affect critical aspects of production and/orcontrol of Active Ingredients. Records of training

should be maintained

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3. Facilities and Utilities

Principle

Buildings should be of adequate size and should be

located, designed, constructed, adapted andmaintained to suit the operations carried out in them.

Adequate utilities should be available and suitableareas for the manufacture, testing, and storage of A.I.sshould be provided

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4. Equipment Equipment used in the manufacture of Active

Ingredients should be designed, constructed andlocated so as to minimise the risk of contamination or

mix-ups during the manufacture of Active Ingredients

Equipment should be non-reactive with respect to thematerials contained there in Food grade lubricants and

oils should be used whenever there is a risk ofcontamination of Active Ingredients

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Closed equipment should be used when feasible.

When open equipment is used, or equipment isopened, care must be taken to avoid contamination ofthe products within the equipment, particularly whensuch products are pure or final Active Ingredients.

The equipment to be used should be suitable for itsintended purpose and if the reproducible performanceof the equipment is critical for maintaining productquality, the equipment should have been qualified.

Equipment should be clearly labelled and its status

identifiable at all times

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5. Sanitation and Hygeine

Principle:

high level or sanitation and hygiene should be

practiced in every aspect of manufacturingpharmaceutical product.

the scope of sanitation and hygiene covers personnel,

premises, equipment and apparatus, productionmaterials.

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Equipment cleaning and sanitation

Equipment should be cleaned both inside and outsideafter use according to established procedure andshould be kept or stored in a clean condition.

Vacuum or wet cleaning methods are to be preferred.

Written procedures in sufficient detail should beestablished, validated and followed for cleaning and

sanitaizing equipment

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Validation of cleaning sanitation procedures

In all instances, the cleaning , sanitation, and hygieneprocedures should be validated and periodicallyassessed to ensure that the effectiveness of theprocedures meet the requirements.

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Personal hygiene

All personal should receive medical examinationupon recruitment.

All prsonal should practise good personal hygiene. Personel should be use the hand-washing facilities

and wash their hands before entering productionareas.

Every person entering the manufacturing areas shouldwear protective garments appropriate to theoperations to be carried

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6. Production

Priciple:

production operation must follow clearly definedprocedures; they nuat comply with the principle ofGMP in order to provide assurance.

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At every stage of processing, product and

materials should be protect from microbial andother contaminations.

Any deviation from instructions or procedures

should be avoided as far a possible.

Production should be perfomed and

supervised by competent people.

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All incoming materials should be checked to ensurethat the consignment corresponds to the order.

Damaged to containers and any other problemshould be investigated.

All materials and products should be stored underthe appropriate conditions.

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Prevention of cross contamination in production

Production in separate building

Providing appropriate air-locks and air extraction

Minimizing the risk of contamination caused byrecirculation air.

Keeping protective clothing inside production areas.

Using cleaning and decontamination procedures of

known effectiveness. Using self containing system

Testing for residues

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Processing

oAll materials utilized in processing should be checkedbefore used.

o The environment of an area should be monitored and

controlled to the deree required for the operation to beperformed.

oAll equipment employed in processing should bechecked before used.

oAll operation should be performed in accordance withthe written procedures.

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Process Validation

Validation studies should reinforce GMP and beconducted in accordance with defined procedures.

Significant changes in process,equipment or materials

should be accompanied by further validation steps. Processes and procedures should be periodically

revalidation to ensure that they remain capable ofachieving the intended results.

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7. Quality Control Quality Control is one or more organisational

unit(s) with defined responsibilities for

controlling, through checking or testing, thatspecifications are met and quality systems are

maintained.

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8. Self-inspections and Quality

Audit

Principle

Self Inspections should be conducted in order tomonitor the implementation and the compliance withGood Manufacturing Practices and to proposenecessary corrective measures.

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In order to verify the compliance with the GMPprinciples for A.I.s described in these guidelines,manufacturers should designate an expert or team of

experts to conduct regular Self-Inspections.

Self-inspection findings and the corrective action(s),

where necessary, should be recorded.

Management is responsible for implementing thecorrective actions derived from the findings.

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9. Rejection, recovery,

reprocessing and returns

Principle

The treatment of materials not meeting specificationshould be consistent with assuring the quality of theproduct involved together with a responsible use ofnatural resources and protection of the environment.

Recovery and reworking or reprocessing of rejectedmaterials is prefered to disposal to waste.

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Rejection of materials

Materials not meeting specification should beadequately stored to prevent unauthorized use until adecision has been taken as to their use.

It may not always be necessary to reject materials notmeeting specification but if such non-conformingmaterials are used then additional controls may benecessary.

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Use of materials not meeting specification should beapproved by Quality Control.

When a batch of material is rejected, an evaluation asto whether other batches could have been similarly

affected, should be carried out.

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Recovery of materials and solvents

If materials are recovered for further use in an Active

Ingredients process, there should be written evidencethat the subsequent use of such materials will result ina product meeting its specification.

Solvents should be recovered when feasable.

Recovered solvents should meet an approvedspecification appropriate to their subsequent use.

The working-up of mother liquors or similar materialsto obtain further materials or an Active Ingredients if

carried out, should be specifically prescribed inwriting and recorded.

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Reprocessing or reworking of materials

In general there is no objection to occasionallyreprocessing materials not meeting specification by

repeating all or part of the same process, however ifthis becomes a routine procedure, investigationsshould be conducted into the adequacy of the originalprocess.

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If it is necessary to rework materials by a process differingsubstantially from the original process, including the useof different solvents or reactions or purification steps, thenadditional tests should be carried out to verify that theresulting product not only meets the applicablespecifications but also that any new and possibly unknownimpurities have been adequately investigated.

The procedures used to reprocess or rework materials notmeeting specification should be made jointly by thoseresponsible in Production and Quality Control.

.

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The procedure actually used to reprocess or reworkbatches of materials should be documented andincluded as part of the batch records.

Reprocessed or reworked materials should be assigneda new batch number.

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Returned materials

Returned materials should be quarantined until a

decision has been taken as to their use. The decision on how to deal with returned material

should be made by Quality Control taking intoaccount the age, appearance, integrity of the original

closures, storage and transport conditions, (if known)and conformance with specification of the returnedmaterial. If reprocessing or reworking is indicated thisshould be agreed upon between Production and

Quality Control. Additional process steps or tests maythen be required.

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10. Documentation

There should be written procedures which lay downhow long documents should be retained. In generalthis should be at least 6 years unless otherwisejustified

Documents which should fall under the above rulinginclude, but are not limited to are:

- material receipt records,

- material testing and release records,- batch production records for A.I.s,

- batch analytical records for A.I.s,

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- batch release records for A.I.s,

- batch production records for critical intermediates,

- batch analytical records for critical intermediates,

- equipment cleaning records for that equipment usedto manufacture A.I.s

- maintenance and calibration records for equipmentused in the manufacture of change control records,

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- environmental monitoring records, includingtemperature recording for critical areas,as well as

microbiological monitoring records,- packaging records,

- distribution records,

- customer complaint investigation records, - all records associated with any product recalls

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Other documents which should be retained are, forexample

- product development reports,

- specifications and test procedures for materials,

- validation reports of the analytical test procedures,

- equipment layout plans,

- equipment installations reports, (IQ Reports)

- equipment acceptance reports, (OQ Reports)

- the records supporting the validity of the process,(Validation Reports)

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11. Contract manufacture or

analysis

Principle

Production or analysis under contract of those steps ofa A.I. process which fall under GMP should also becarried out at the contractor under GMP

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Contract

There should be a written and approved contractbetween the contract giver and the contract acceptor,which lays down the responsibilities of each party.

In general the recommendations on GMP as described

in these guidelines are also applicable to contractacceptors.

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12. Qualification and Validation

Design qualification

o The first element of the validation of new facilities,systems or equipment could be design qualification(DQ)

o The compliance of the design with GMP should bedemontrated and documented.

Intallation Qualification

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Qualification

Operational Qualifications OQ is performed after IQ has been com pleted,

reviewed and approved. OQ must include : tests that have been developed

from knowledge of prosesses, systems andequipment

Performance Qualificatios PQ must include : tests using production materials,

qualified substitutes or simulated product, that havebeen developed from knowledge of the process andthe facilities, systems or equipment.

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Validation

Validation is a requirement of GMP thatmanufacturers identify what validation work is neededto prove control of critical aspects of their particular

operations. Significant changes to the facilities, the equipment

and the processes, which may affect the quality of theproduct, should be validated.

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Planning for validation

The Validation Master Plan should contain data : Validation policy

Organization structure or validation activities

Summary of facilities, systems and equipment andprocess should be validated

Documentation format

Change control

Reference to existin document

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THANKS