Quality of drugs is basically responsibility of manufacturers & GMP guidelines are a means to assure very quality. Draft of GMP regulations was prepared in 1975 which could be finalized & implemented in 1988, in form of amended schedule M. It embraces Rule 71,74,76 & 78 under D & C Rules 1945. To achieve objectives of GMP, licensee shall comply with requirements of GMP as laid down in Schedule M. Part I deals with GMP relating to factory premises, & Part II deals with plant & equipment for manufacture of drugs.

1. GOOD MANUFACTURING PRACTICESGOOD MANUFACTURING PRACTICES
(GMP)(GMP)
(SChEDUlE M)(SChEDUlE M)
ByBy
Tarun tjTarun tj
11

2. 22

3.  Quality of drugs is basically responsibility ofQuality of drugs is basically responsibility of
manufacturers & GMP guidelines are a means tomanufacturers & GMP guidelines are a means to
assure very quality.assure very quality.
 Draft of GMP regulations was prepared in 1975Draft of GMP regulations was prepared in 1975
which could be finalized & implemented in 1988,which could be finalized & implemented in 1988,
in form of amended schedule M.in form of amended schedule M.
 It embraces Rule 71,74,76 & 78 under D & CIt embraces Rule 71,74,76 & 78 under D & C
Rules 1945.Rules 1945.
 To achieve objectives of GMP, licensee shallTo achieve objectives of GMP, licensee shall
comply with requirements of GMP as laid down incomply with requirements of GMP as laid down in
Schedule M.Schedule M.
 Licensee shall evolve methodology & proceduresLicensee shall evolve methodology & procedures
which should be documented & kept forwhich should be documented & kept for 33

4. reference & inspection.reference & inspection.
 Part I deals with GMP relating to factory premises,Part I deals with GMP relating to factory premises,
& Part II deals with plant & equipment for& Part II deals with plant & equipment for
manufacture of drugs.manufacture of drugs.
FACTORY PREMISESFACTORY PREMISES
GENERAl REQUIREMENTS :GENERAl REQUIREMENTS :
 Location of factory & its surroundings shouldLocation of factory & its surroundings should
ensure freedom from contamination due to sewage,ensure freedom from contamination due to sewage,
drain & obnoxious odours or fumes, or largedrain & obnoxious odours or fumes, or large
quantity of soot, dust or smoke.quantity of soot, dust or smoke.
 Factory building should be so constructed as toFactory building should be so constructed as to
ensure production of drugs under hygienicensure production of drugs under hygienic
conditions.conditions. 44

5.  Operations like manufacturing, processing,Operations like manufacturing, processing,
packaging, labelling & testing should be carriedpackaging, labelling & testing should be carried
out in such a way that mix up & crossout in such a way that mix up & cross
contamination are avoided.contamination are avoided.
 Premises should be so constructed & maintained asPremises should be so constructed & maintained as
to prevent entry of insects & rodents.to prevent entry of insects & rodents.
 Interior surface should be smooth & free fromInterior surface should be smooth & free from
cracks & permit easy cleaning & disinfection.cracks & permit easy cleaning & disinfection.
 Adequate lighting, ventilation & humidity must beAdequate lighting, ventilation & humidity must be
maintained.maintained.
 Drainage system should be underground.Drainage system should be underground.
 Sanitary fitting & electrical fixtures inSanitary fitting & electrical fixtures in
manufacturing area should be concealed.manufacturing area should be concealed. 55

6.  Water used in manufacture should be pure & ofWater used in manufacture should be pure & of
a drinkable quality, free from pathogenic micro-a drinkable quality, free from pathogenic micro-
organisms.organisms.
 Waste water should be treated before disposal toWaste water should be treated before disposal to
render it harmless.render it harmless.
STERIlE PRODUCTS :STERIlE PRODUCTS :
 For manufacture of sterile drugs separate enclosedFor manufacture of sterile drugs separate enclosed
areas provided with air locks, dust free, ventilatedareas provided with air locks, dust free, ventilated
with air supply through HEPA filters, arewith air supply through HEPA filters, are
recommended.recommended.
 During manufacturing operation routine microbialDuring manufacturing operation routine microbial
counts of area is necessary.counts of area is necessary. 66

7.  Access to manufacturing areas should be restrictedAccess to manufacturing areas should be restricted
to authorized personnel.to authorized personnel.
 Design of area must preclude possibility of mix upDesign of area must preclude possibility of mix up
between sterile & non-sterile.between sterile & non-sterile.
WORKING SPACE :WORKING SPACE :
 Adequate working space & adequate room forAdequate working space & adequate room for
orderly placement of equipment & materialsorderly placement of equipment & materials
should be provided to eliminate any risk of mixshould be provided to eliminate any risk of mix
up between different drugs, & crossup between different drugs, & cross
contamination.contamination.
 In storage area separate space should be providedIn storage area separate space should be provided
for "under test", "approved" & "rejected" materials.for "under test", "approved" & "rejected" materials.77

8. 88

9. 99

12. HEALTH, CLOTHING & SANITATION OFHEALTH, CLOTHING & SANITATION OF
WORKERSWORKERS
 All personnel coming in direct contact withAll personnel coming in direct contact with
products including raw materials should be freeproducts including raw materials should be free
from contagious or obnoxious diseases & shouldfrom contagious or obnoxious diseases & should
undergo periodic health check up.undergo periodic health check up.
 Just before entry to manufacturing area, changeJust before entry to manufacturing area, change
room with facility for personnel cleanliness shouldroom with facility for personnel cleanliness should
also be provided.also be provided.
MEDICAL SERVICES :MEDICAL SERVICES :
 Manufacturer should provideManufacturer should provide
(i)(i) adequate facilities for first aid.adequate facilities for first aid.
(ii) Medical examination of workers at time of(ii) Medical examination of workers at time of
1212

13.  a year.a year.
(iii) Facility for vaccination.(iii) Facility for vaccination.
 Services of qualified physician forServices of qualified physician for assesingassesing
health status of personnel involved inhealth status of personnel involved in
manufacturing &manufacturing & qualitquality control of drugs shouldy control of drugs should
also be made available.also be made available.
SANITATION IN MANUFACTURINGSANITATION IN MANUFACTURING
PREMISES :PREMISES :
 Manufacturing area should not be utilized for anyManufacturing area should not be utilized for any
other purpose & should be maintained cleanother purpose & should be maintained clean inin anan
orderly manner, free from accumulated waste, dust,orderly manner, free from accumulated waste, dust,
debris etc.debris etc.
 Routine sanitation programme should be drawn upRoutine sanitation programme should be drawn up1313

14. EQUIPMENT :EQUIPMENT :
 Equipment used for manufacture of drugs shouldEquipment used for manufacture of drugs should
Be constructed, designed, installed & maintained toBe constructed, designed, installed & maintained to
(i) Achieve to operational efficiency to attain(i) Achieve to operational efficiency to attain
desired quality;desired quality;
(ii) Prevent physical,(ii) Prevent physical, chemical & physico-chemicalchemical & physico-chemical
change through surface contact;change through surface contact;
(iii) Prevent contact of any substance required for(iii) Prevent contact of any substance required for
operation of equipments like lubricants etc.;operation of equipments like lubricants etc.;
(iv)(iv) Facilitate thorough cleaning wherever necessary;Facilitate thorough cleaning wherever necessary;
(v) Minimize any contamination of drugs & their(v) Minimize any contamination of drugs & their
containers duringcontainers during manmanufacture.ufacture.
1414

15.  Specific written cleaning instructions for allSpecific written cleaning instructions for all
equipments & utensils should be readily availableequipments & utensils should be readily available
& operators must be familiar with them.& operators must be familiar with them.
 Accuracy, precision & performance of allAccuracy, precision & performance of all
equipmentsequipments should be monitored at regularshould be monitored at regular
intervals.intervals.
RAW MATERIALS :RAW MATERIALS :
 All raw materials should beAll raw materials should be
(i) Identified & their containers examined for damage(i) Identified & their containers examined for damage
& assigned control number.& assigned control number.
(ii) Stored(ii) Stored atat optimum temperatures & relativeoptimum temperatures & relative
humidity.humidity.
1515

16. (iii) Conspicuously labelled(iii) Conspicuously labelled indicating name ofindicating name of
materials; control number, name ofmaterials; control number, name of mamanufacturer &nufacturer &
be specifically labelled "under test" or "approved"be specifically labelled "under test" or "approved"
or rejected.or rejected.
(iv) Systematically sampled by QC personnel.(iv) Systematically sampled by QC personnel.
(vi) Tested for compliance with required standards(vi) Tested for compliance with required standards
of quality.of quality.
(vi) Released from quarantine by quality control(vi) Released from quarantine by quality control
personnel through written instructions.personnel through written instructions.
(vii) So organized that stock rotation is on basis of(vii) So organized that stock rotation is on basis of
'first in first out‘'first in first out‘princprinciple in storage areaiple in storage area
1616

17. (viii) so arranged that all rejected materials are(viii) so arranged that all rejected materials are
Conspicuously identified & are destroyed orConspicuously identified & are destroyed or
returned to suppliers as soon as possible & recordsreturned to suppliers as soon as possible & records
maintained thereof.maintained thereof.
MASTER FORMULA RECORDS :MASTER FORMULA RECORDS :
 Licensee should maintain master formula recordsLicensee should maintain master formula records
relating to all manufacturing procedures for eachrelating to all manufacturing procedures for each
product, which should be prepared & endorsed byproduct, which should be prepared & endorsed by
competent technical staff.competent technical staff.
 Master formula record shall giveMaster formula record shall give
(i) Patent or proprietary name of product along with(i) Patent or proprietary name of product along with
generic name, strength & dosagegeneric name, strength & dosage form.form.
1717

18. (ii) Description or identification of final containers,(ii) Description or identification of final containers,
packagingpackaging materials, labels & closures to be used.materials, labels & closures to be used.
(iii) Identity, quantity & quality of each raw(iii) Identity, quantity & quality of each raw
material to be used.material to be used.
(iv) Description of all vessels & equipments & size(iv) Description of all vessels & equipments & size
used in process.used in process.
(v) Manufacturing & control instructions along with(v) Manufacturing & control instructions along with
parameters for critical steps such as mixing,parameters for critical steps such as mixing,
drying, blending, sieving, sterilizing product.drying, blending, sieving, sterilizing product.
1818

19. (vi) Theoretical yield to be expected from(vi) Theoretical yield to be expected from
formulation at different stages of manufacture &formulation at different stages of manufacture &
permissible yield limits.permissible yield limits.
(vii) Detailed instructions on precautions to be(vii) Detailed instructions on precautions to be
taken in manufacture & storage of drugs & oftaken in manufacture & storage of drugs & of
semi finished products & requirements of inprocesssemi finished products & requirements of inprocess
quality control test & analysis to be carried outquality control test & analysis to be carried out
during each stage of manufacture includingduring each stage of manufacture including
designation of persons or departments responsibledesignation of persons or departments responsible
for execution of such tests & analysisfor execution of such tests & analysis
1919

20. BATCH MANUFACTURING RECORDS :BATCH MANUFACTURING RECORDS :
 Licensee shall maintain batch manufacturingLicensee shall maintain batch manufacturing
record as per Schedule U for each batch of drugrecord as per Schedule U for each batch of drug
produced.produced.
 Manufacturing records are required to provide aManufacturing records are required to provide a
complete account of manufacturing history of eachcomplete account of manufacturing history of each
batch of drug showing that it has beenbatch of drug showing that it has been
manufactured, tested & analyzed in accordancemanufactured, tested & analyzed in accordance
with manufacturing procedures & writtenwith manufacturing procedures & written
instructions as per master formula.instructions as per master formula.
MANUFACTURING OPERATIONS &MANUFACTURING OPERATIONS &
CONTROLS :CONTROLS :
 All manufacturing operations should be carried outAll manufacturing operations should be carried out2020

21.  Critical steps in process relating to selection,Critical steps in process relating to selection,
weighing & measuring of raw materials duringweighing & measuring of raw materials during
various stages should be performed under directvarious stages should be performed under direct
personnel supervision of a competent technical staff.personnel supervision of a competent technical staff.
 Even non-sterile products should be free fromEven non-sterile products should be free from
pathogens like Salmonella, E. Colt, etc.pathogens like Salmonella, E. Colt, etc.
 All vessels, containers & mechanicalAll vessels, containers & mechanical
manufacturing equipment should be conspicuouslymanufacturing equipment should be conspicuously
labelled with name of product & batch No.labelled with name of product & batch No.
 licensee should prevent cross contamination oflicensee should prevent cross contamination of
drugs.drugs. 2121

22.  All process controls as required under masterAll process controls as required under master
formula including room temperature, relativeformula including room temperature, relative
humidity, weight variation, disintegration time ,humidity, weight variation, disintegration time ,
mixing time, homogeneity of suspension, volumemixing time, homogeneity of suspension, volume
filled, leakage, clarity shall be checked & recorded.filled, leakage, clarity shall be checked & recorded.
REPROCESSING &RECOVERY:REPROCESSING &RECOVERY:
 If a product batch has to be reprocessed,If a product batch has to be reprocessed,
reprocessing procedure should be authorized &reprocessing procedure should be authorized &
recorded.recorded.
 Recovery of product residue may be carried out byRecovery of product residue may be carried out by
incorporating in subsequent batches of product, ifincorporating in subsequent batches of product, if
permitted in master formula.permitted in master formula. 2222

23. PRODUCT CONTAINERS & CLOSURES:PRODUCT CONTAINERS & CLOSURES:
 All containers & closures should comply withAll containers & closures should comply with
pharmacopoeial requirements.pharmacopoeial requirements.
 Suitable specifications, testSuitable specifications, test methods,methods, cleaningcleaning
procedures & sterilization procedures, whenprocedures & sterilization procedures, when
indicated should be used to assure that containers,indicated should be used to assure that containers,
closures & other component parts of drug packagesclosures & other component parts of drug packages
are suitable & they are not reactive, adsorptive orare suitable & they are not reactive, adsorptive or
leach to an extent that significantly affectsleach to an extent that significantly affects qualitqualityy
or purity of drug.or purity of drug.
 Wherever bottles are being used, written scheduleWherever bottles are being used, written schedule
of cleaning should be laid down & followed.of cleaning should be laid down & followed. 2323

24.  Where bottlesWhere bottles are driedare dried after washing, they shouldafter washing, they should
be rinsed with deionised waterbe rinsed with deionised water or distilledor distilled water.water.
LABELS & OTHER PRINTED MATERIALS :LABELS & OTHER PRINTED MATERIALS :
 Printed labels & packaging materials includingPrinted labels & packaging materials including
leaflets should be stored, handled & accounted inleaflets should be stored, handled & accounted in
such a way as to ensure that batch packagingsuch a way as to ensure that batch packaging
materials & leaflets relating tomaterials & leaflets relating to different productsdifferent products
do not become intermixed.do not become intermixed.
 Prior to issue, all labels for containers, cartons &Prior to issue, all labels for containers, cartons &
boxes & all circulars, inserts & leaflets shouldboxes & all circulars, inserts & leaflets should bebe
examined & released as satisfactory for use byexamined & released as satisfactory for use by
quality controlquality control personnel.personnel. 2424

25.  A known number of labelling & packaging unitsA known number of labelling & packaging units
should beshould be issuedissued against a written signed request.against a written signed request.
 Prior to packaging & labelling ofPrior to packaging & labelling of a givena given batch of abatch of a
drug it must be ensured that batch has been dulydrug it must be ensured that batch has been duly
tested, approved & released by QC personnel.tested, approved & released by QC personnel.
 UponUpon completion of packaging & labellingcompletion of packaging & labelling
operation, a comparison shouldoperation, a comparison should bebe made betweenmade between
number of labelling & packaging units issued &number of labelling & packaging units issued &
numbernumber ofof labelled & packaged.labelled & packaged.
 Unused, coded & spoiled labels &Unused, coded & spoiled labels & packagingpackaging
materials should be destroyed.materials should be destroyed. 2525

26. DISTRIBUTION RECORDS :DISTRIBUTION RECORDS :
 Records for distribution of drug should beRecords for distribution of drug should be
Maintained for distribution of finished batch of aMaintained for distribution of finished batch of a
drug in order to facilitate promptdrug in order to facilitate prompt && complete recallcomplete recall
of batch, if necessary.of batch, if necessary.
RECORDS OF COMPLAINTS & ADVERSERECORDS OF COMPLAINTS & ADVERSE
REACTIONS :REACTIONS :
 Reports of serious adverseReports of serious adverse reactions resulting fromreactions resulting from
use of drug along with comments shall be informeduse of drug along with comments shall be informed
2626

27. 2727

28. QUALITY CONTROL SYSTEM :QUALITY CONTROL SYSTEM :
 Every manufacturing establishment shallEvery manufacturing establishment shall have QChave QC
department supervised by an approved expert staffdepartment supervised by an approved expert staff
directly responsible to management butdirectly responsible to management but
independent of other department.independent of other department.
 QC department shall control all raw materials,QC department shall control all raw materials, or allor all
in process quality checks & control quality &in process quality checks & control quality &
stability of finished products.stability of finished products.
 QC department shall have followingQC department shall have following duties:-duties:-
1. To prepare detailed instructions in writing for1. To prepare detailed instructions in writing for
carrying out eachcarrying out each test & analysis.test & analysis.
2828

29. 2.2. To release or rejectTo release or reject
(i) each batch of raw materials;(i) each batch of raw materials;
( ii)( ii) semi-finished products,semi-finished products,
(iii) packaging & labelling materials & final(iii) packaging & labelling materials & final
containers in which drugs are to be packed;containers in which drugs are to be packed;
(iv) each batch of finished product ready for(iv) each batch of finished product ready for
distribution;distribution;
3. To evaluate adequacy of conditions under which3. To evaluate adequacy of conditions under which
raw materials, semi-finished products & finishedraw materials, semi-finished products & finished
products are stored;products are stored;
4. To evaluate quality & stability of finished4. To evaluate quality & stability of finished
products &products & of raw materials & semi-finishedof raw materials & semi-finished
2929

30. 5.5. To establish & when necessary revise, controlTo establish & when necessary revise, control
procedures &procedures & specifications.specifications.
6. To examine returned products as to whether such6. To examine returned products as to whether such
products should be released, reprocessed orproducts should be released, reprocessed or
destroyed.destroyed.
 In summary, all areas of activities & proceduresIn summary, all areas of activities & procedures
relating to handlingrelating to handling of materials, manufacturing &of materials, manufacturing &
quality control should be well defined, designed,quality control should be well defined, designed,
implemented & documented.implemented & documented.
 Emphasis is on GMP which includes good recordEmphasis is on GMP which includes good record
keeping practice or proper documentation.keeping practice or proper documentation.
3030

31.  It is a means by which manufacturer can fulfil hisIt is a means by which manufacturer can fulfil his
commitment of consumer protection by assuringcommitment of consumer protection by assuring
quality of his drug products.quality of his drug products.
PLANT & EQUIPMENTPLANT & EQUIPMENT
 Part II of Schedule M recommends requirementsPart II of Schedule M recommends requirements
of plant & equipment for manufacture of drugsof plant & equipment for manufacture of drugs
under following sections :under following sections :
(i) Ointments, emulsions, lotions & suspensions.(i) Ointments, emulsions, lotions & suspensions.
(ii) Syrups, elixirs & solutions.(ii) Syrups, elixirs & solutions.
(iii) Pills, compressed tablets & hypodermic tablets.(iii) Pills, compressed tablets & hypodermic tablets.
(iv) Powders.(iv) Powders. 3131

32. (v) Hard gelatin capsules.(v) Hard gelatin capsules.
(vi) Surgical dressings other than absorbent cotton(vi) Surgical dressings other than absorbent cotton
wool.wool.
(vii) Eye ointments, Eye lotions & other(vii) Eye ointments, Eye lotions & other
preparations for external use (manufactured underpreparations for external use (manufactured under
aseptic conditions).aseptic conditions).
(viii) Pessaries & suppositories.(viii) Pessaries & suppositories.
(ix) Inhalers & vitrallae.(ix) Inhalers & vitrallae.
(x) Repacking of drugs, Pharmaceuticals & chemicals.(x) Repacking of drugs, Pharmaceuticals & chemicals.
(xi) Parenterals preparations.(xi) Parenterals preparations.
3232

33.  For most of sections an area of minimum 30 sqFor most of sections an area of minimum 30 sq
metres (60 sq metres for parenteral section) ismetres (60 sq metres for parenteral section) is
recommended for basic installation.recommended for basic installation.
 Recommended requirements do not includeRecommended requirements do not include
requirement of machinery, equipment & premisesrequirement of machinery, equipment & premises
required for preparation of containers & closures forrequired for preparation of containers & closures for
different categories of drugs.different categories of drugs.
 Licensing Authority shall have discretion to relaxLicensing Authority shall have discretion to relax
or alter requirements of Schedule in circumstancesor alter requirements of Schedule in circumstances
of a particular case.of a particular case.
3333

34.  In respect of other categories of drugs not includedIn respect of other categories of drugs not included
in Schedule such as basic drugs, pharmaceuticals,in Schedule such as basic drugs, pharmaceuticals,
chemicals & aids, medicinal gases, empty gelatinchemicals & aids, medicinal gases, empty gelatin
capsules, mechanical contraceptives, new dosagecapsules, mechanical contraceptives, new dosage
forms etc..forms etc..
 Licensing Authority shall have discretion toLicensing Authority shall have discretion to
examine factory premises, space, plant & machineryexamine factory premises, space, plant & machinery
& direct manufacturer to carry out necessary& direct manufacturer to carry out necessary
modifications.modifications.
3434

35.  According to provisions of Schedule M & U ofAccording to provisions of Schedule M & U of
Rules it is obligatoryRules it is obligatory manufacturers to effectivelymanufacturers to effectively
destroy, in their factory premises,destroy, in their factory premises, rejecterejected rawd raw
materials, defective drugs rejected duringmaterials, defective drugs rejected during
manufacturing & rejected packing material e.g.manufacturing & rejected packing material e.g.
labels, cartons & tolabels, cartons & to maintainmaintain records.records.
 This is essential to curb malpractice of recyclingThis is essential to curb malpractice of recycling
such stocks for manufacture of drugs, which issuch stocks for manufacture of drugs, which is
harmful to public health.harmful to public health.
3535