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GMP (SCHEDULE-M)

BYDr. Suman PattanayakAssociate ProfessorDepartment of Pharma Analysis & QA.

Vijaya Institute of Pharmaceutical Sciences for Women

B. Pharm IV year/ II SemDRA, IPR & Patents

Definition That part of QA which ensures that products

are consistently produced and controlled to the quality standards as per the specifications.

The Early Beginnings 1900’s- house-calls Home remedies, ointments and “miracle

elixirs”No regulations until 1902

Public Involvement1905 - The Jungle by Upton SinclairExposure of unsanitary Meat packing plants.Increased Public awareness And involvementPure Food and Drug ActFalse labeling became illegal

A Time line of GMP 1902 - Development of the Biologic Control Act1906 - Development of the Pure Food and Drug Act1938 - Federal Food, Drug and Cosmetic Act1941 - Initiation of GMP1944 - Development of Public Health Services Act1962 - Kefauver-Harris Drug Amendments released1963 - Establishment of GMPs for Drugs 1975 - CGMPs for Blood and Components Final Rule1976 - Medical Device Amendments1978 - cGMPs for Drugs and Medical Devices 1979 - GLPs Final Rule1980 - Infant Formula Act is passed

1941 Initiation of GMPSulfathiaziole tablets contaminated with phenobarbital1941 - 300 people died/injured FDA to enforce and revise manufacturing and quality control

requirements1941 - GMP is born Thalidomide tragedyThousands of children born with birth defects due to adverse

drug reactions of morning sickness pill taken by mothersStrengthen FDA’s regulations regarding experimentation on

humans and proposed new way how drugs are approved and regulated

“Proof of efficacy” law

Guidelines

Areas to be Covered

General considerationsPersonnelPremisesEquipmentSanitationSOP’sRaw MaterialsSelf Inspection And AuditMaster Formula RecordsBatch Manufacturing Records

Areas to be Covered(cont..)Warehousing AreaReference SamplesValidation and process validationLabels And Other Printed MaterialsQA

General considerations

Compliance with GMPConsistent uniform batchesLocation And surroundingsWater systemDisposal Of Waste

PERSONNEL

PERSONNELQualified Personnel a)Experienced b)Sufficient Number

Written job descriptionTrainedHealth a)Diseases b)Open Lesions

Premises

Premises Points to be Consider

LocationDesignConstruction

Premises LocationGeography, climate,and economic factorsNeighbours a) What do they do? Premises must be located to minimize risks of cross-

contamination, e.g. not located next to a malting factory with high airborne

levels of yeast

Pollution/effluent control

Premises Location(cont..)

Premises DesignMinimize risks of errorsPermit effective cleaningPermit effective maintenanceAvoid cross-contamination, build-up of dirt and

dustMaximum protection against entry of insects, birds

and animalsSeparate facilities for other products such as some

antibiotics, hormones, cytotoxic substances

Premises Design(cont..)Maximum protection against entry of insects, birds and animals Specific Areas 1) Production areas 2) Quality control areas 3) Weighing areas 4) Storage areas 5) Ancillary areas

PremisesHygieneEating,Drinking,Smoking Should not be

allowed in the Production area.

Premises ConstructionMeasures should be taken to prevent cross-

contaminationDust control measures (including extraction of

dust and air)No areas for dust accumulationEasily cleanable surfacesProper air supplyUse of HEPA filter’s

Premises Finishing floors,walls,and Ceilings Should be smooth, impervious, hard-wearing,

easy to clean

Equipments

EquipmentsEquipment shall be

located,designed,construcetd,adapted and maintained to suit the operation to be carried out.

Should be made of non reactive material,such as High grade of steel(316,302)

Equipment should be- a) Caliberated b)Checked c)labelled d)Sterilized

SanitationWritten procedures• hygiene, health and clothing practices• waste disposalImplementation and training

SanitationPractices not permitted a)eating, smoking b) unhygienic practices

Standard Operating Procedure

Standard Operating ProcedureThere shall be written Standard Operating

Procedure for each operationIt include- a)For Eqipments b)For sampling c)For Testing d)For Process f)For Packaging

Raw Materials

Raw Materials An Inventory should be maintained for Raw

materials to be used at any stage of manufacture

Records should be maintain as per Schedule UShould be purchased from approved sourcesMust be checked by QC department on recipt Should be labeled.

Self Inspection And AuditRegular independent inspection is necessary

to evaluate the manufacturer’s compliance with GMP in all aspects of manufacturing

Procedure for self inspection shall be documented indicating

a)Evaluation b)Conclusion c)Recommendations for Corrective action

Master Formula RecordsThere shall be MFR relating to all manufacturing procedures

for each product and batch size to be manufactureIt should include- i)The name of the product ii)Quantity,of all starting materials to be used iii)A statement of the expected final yield with acceptable

limits. iv) Principal equipment to be used v) Detaild stepwise processing instructions and the time

taken for each step vi)Any special precations vii)Packing details and Specimen labels

Batch Manufacturing RecordsThere shall be Batch processing record for each

product.During Manufacturing or Processing the following

information shall be recordedIt include-The name of the productThe number of Batch being manufacturedDates and time of commencement of batch and

completionInitials of operatorAmount of Product obtained

Warehousing Area

Warehousing Area

Warehousing area should be designed and adapted to ensure good storage conditions.

Should be Clean,dry and maintained with acceptable temperature limits.

Should have appropriate house-keeping and rodents,pests and vermin control.

Seprate sampling area for active raw material and excipients.

Every Material stored should be labeld properly.Fire Prevention

Reference Samples

Reference SamplesShould be taken in sufficient quantity from

each lot of active ingridient to carry out all the tests

These samples should be retained for a period of 3 months after the date of expiry of the last batch produced from that active ingridient

Samples of raw material should be stored in suitable container(plastic or glass) as mentioned in the SOP

Reference SamplesSamples of finished formulations shall be

stored in the same containers in which the drug has been actually marketed

Reference Samples

Validation and process validation Essential part of GMPNecessary to achieve the intended resultsA written record is prepared summarizing recorded result and

conclusions shall be prepared ,documented and maintainedShould be necessary when- a)Any new new master formula or method of prepration is adopted b)For critical process c)any changes in the equipment,or when using a new equipment,it is first validated to demonstrate its consistentency of required quality

Labels And Other Printed Materials

Labels And Other Printed MaterialsAll containers and equipment should bear

labelsDifferent colour coded labels should be used

to indicate the status of a product(for example under test,approved,passed,rejected)

Labels And Other Printed Materials(cont..)The Printing should be done in bright coloursThe label should contain all the prescribed

details about the product.

Quality Assurance

Quality AssuranceThe main objective of the quality assurance is to

ensure the products are of the quality required for their intended use

Functions-i)Adequates are made for manufacuring,supply and

the use of correct starting and packing materialii)Adequate control on starting

material,intermediate,and bulk products.Iii)Process validation in accordance with established

procedures

References Blackwell, John. 1906: Rumble Over ‘The Jungle’. 31 Aug.

2008. http://www.capitalcentury.com/1906.html FDA Food and Drug Administration. GMP Combination

Handbooks. 31 Aug. 2008. http://images.google.com WHO Technical Report Series, No. 929, 2005