DFD/ SIP/Nathdwara

GOOD MANUFACTURING PRACTICES FOR PREMISES AND MATERIALS.

Good manufacturing practice (GMP) is that part of quality assurance which
ensures that products are consistently produced and controlled to the quality
standards appropriate to their intended use and as required by the marketing
authorization.
GMP is aimed primarily at diminishing the risks inherent in any pharmaceutical
production, which may broadly be categorized in two groups cross
contamination!mi"#ups and false labelling. $bo%e all, manufacturers must not place
patients at risk due to inadequate safety, quality or e&cacy' for this reason, risk
assessment has come to play an important role in ()* quality assurance
guidelines.
GENERAL REQUIREMENTS
LOCATION AND SURROUNDINGS
+he factory building(s) for manufacture of drugs shall be so situated and shall
ha%e such measures as to a%oid risk of contamination from e"ternal
en%ironmental including open sewage, drain, public la%atory or any factory
which product disagreeable or obno"ious odour, fumes, e"cessi%e soot, dust,
smoke, chemical or biological emissions.
BUILDING AND PREMISES
+he building(s) used for the factory shall be designed, constructed, adapted
and maintained to suit the manufacturing operations so as to permit
production of drugs under hygienic conditions. +hey shall conform to the
conditions laid down in the Factories Act, 19! "#$ o% 19!&
+he premises used for manufacturing, processing, warehousing, packaging
labeling and testing purposes shall be
,ompatible with other drug manufacturing operations that may be carried out
in the same or ad-acent area ! section'
$dequately pro%ided with working space to allow orderly and logical placement of
equipment, materials and mo%ement of personnel so as to
a%oid the risk of mi"#up between di.erent categories of drugs or with raw
materials
a%oid the possibilities of contamination and cross# contamination
/esigned ! constructed ! maintained to pre%ent entry of insects, pests, birds,
%ermins, and rodents
0nterior surface (walls, 1oors and ceilings) shall be smooth and free from cracks, and
permit easy cleaning, painting and disinfection'
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DFD/ SIP/Nathdwara
$ir#,onditioned, where prescribed for the operations and dosage forms under
production
Pro%ided with drainage system, as speci2ed for the %arious categories of
Products, *pen channels shall be a%oided in manufacturing areas and, where
pro%ided, these shall be shallow to facilitate cleaning and disinfection'
'ATER S(STEM
+here shall be %alidated system for treatment of water drawn from own or any
other source to render it potable in accordance with standards s)eci*e+ ,-
t.e B/rea/ o% I0+ia0 Sta0+ar+s or Loca1 M/0ici)a1it-, as the case may
be, so as to produce Puri2ed (ater co0%or2i03 to P.ar2aco)oeia1
s)eci*catio0.
Puri2ed (ater so produced shall only be used for all operations e"cept
washing and cleaning operations where potable water may be used.
(ater shall be stored in tanks, which do not ad%ersely a.ect quality of water
and ensure freedom from microbiological growth.
+he tank shall be cleaned periodically and records maintained by the licensee
in this behalf.
DISPOSAL OF 'ASTE
+he disposal of sewage and e3uents (solid, liquid and gas) from the
manufactory shall be in conformity with the requirements of E04iro02e0t
Po11/tio0 Co0tro1 Boar+.
$ll bio#medical waste shall be destroyed as per the pro%isions of the Bio5
Me+ica1 'aste (Management and )andling) R/1es, 199#.
'ARE6OUSING AREA
$dequate areas shall be designed to allow su&cient and orderly warehousing
of %arious categories of materials and products like starting and packaging
materials, intermediates, bulk and 2nished products, products in quarantine,
released, re-ected, returned or recalled, machine and equipment spare parts
and change items
(arehousing areas shall be designed and adapted to ensure good storage
,onditions
+here shall be a separate sampling area in the warehousing area for acti%e
raw materials and e"cipients
4egregation shall be pro%ided for the storage of re-ected, recalled or returned
materials or products
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DFD/ SIP/Nathdwara
)ighly hazardous, poisonous and e"plosi%e materials such as narcotics,
psychotropic drugs and substances presenting potential risks of abuse, 2re or
e"plosion shall be stored in safe and secure areas.
Printed packaging materials shall be stored in safe, separate and secure areas.
4eparate dispensing areas for 5 (6eta) lactum, 4e" )ormones and ,ytoto"ic
substances or any such special categories of product shall be pro%ided with
proper supply of 2ltered air and suitable measures
4ampling and dispensing of sterile materials shall be conducted under aseptic
conditions
PRODUCTION AREA
+he production area shall be designed to allow the production preferably in
uni#1ow and with logical sequence of operations.
0n order to a%oid the risk of corss#contamination, separate dedicated and self#
contained facilities shall be made a%ailable for the production of sensiti%e
pharmaceutical products like penicillin or biological preparations with li%e
microorganisms
Pipe#work, electrical 2ttings, %entilation openings and similar ser%ices lines
shall be designed, 2"ed and constructed to a%oid creation of recesses
(orking and in#process space shall be adequate to permit orderly and logical
positioning of equipment and materials and mo%ement of personnel to a%oid
cross#contamination
ANCILLAR( AREAS
7est and refreshment rooms shall be separate from other areas. +hese areas
shall not lead directly to the manufacturing and storage areas
8acilities for changing, storing clothes and for washing and toilet purposes
shall be easily accessible and adequate for the number of users
Maintenance workshops shall be separate and away from production areas.
$reas housing animals shall be isolated from other area .(7ule 9:;#,(<) of the
/rugs and ,osmetics 7ules, 9=>:)
QUALIT( CONTROL AREA
?uality ,ontrol @aboratories shall be independent of the production areas.
4eparate areas shall be pro%ided each for physico#chemical, biological,
microbiological or radio#isotope analysis
4eparate instrument room with adequate area shall be pro%ided for sensiti%e
and sophisticated instruments employed for analysis.
$dequate space shall be pro%ided to a%oid mi"#ups and cross#contamination.
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DFD/ SIP/Nathdwara
4u&cient and suitable storage space shall be pro%ided for test samples,
retained samples, reference standards, reagents and records
+he laboratory shall be pro%ided with regular supply of water of appropriate
quality for cleaning and testing purpose
?uality ,ontrol @aboratory shall be di%ided into separate sections i.e. for
chemical, microbiological and where%er required, biological testing
+he microbiology section shall ha%e arrangements such as airlocks and
laminar air 1ow work station, where%er considered necessary
PERSONNEL
+he manufacture shall be conducted under the direct super%ision of
competent technical sta. with prescribed quali2cations and practical
e"perience in the rele%ant dosage and ! or acti%e pharmaceutical products.
Personnel for ?uality $ssurance and ?uality ,ontrol operations shall be
suitably quali2ed and e"perienced.
6EALT6, CLOT6ING AND SANITATION OF 'OR7ERS
$ll personnel shall wear clean body co%erings appropriate to their duties.
4moking, eating, drinking, chewing or keeping plants, food, drink and personal
medicines shall not be permitted in production, laboratory, storage and other
areas
/irect contact shall be a%oided between the unprotected hands of personnel
and raw materials, intermediate or 2nished, unpacked products.
+he personnel handling 6eta#lactum antibiotics shall be tested for Penicillin
sensiti%ity before employment and those handling se" hormones, cytoto"ic
substances and other potent drugs shall be periodically e"amined for ad%erse
e.ects.
$ll personnel, shall undergo medical e"amination including eye e"amination,
and shall be free from +uberculosis, skin and other communicable or
contagious diseases. +hereafter, they should be medically e"amined
periodically, at least once a year
$ll persons prior to and during employment shall be trained in practices which
ensure personnel hygiene
Ao person showing, at any time, apparent illness or open lesions
MANUFACTURING OPERATIONS AND CONTROLS
$ll manufacturing operations shall be carried out under the super%ision of
technical sta. appro%ed by the @icensing $uthority
+he contents of all %essels and containers used in manufacture and storage
during the %arious manufacturing stages shall be conspicuously labeled with
the name of the product, batch number, batch size and stage of manufacture
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Products not prepared under aseptic conditions are required to be free from
pathogens like Salmonella, Escherichia coli, Pyocyanea, etc
Preca/tio0s a3ai0st 2i85/) a0+ cross5co0ta2i0atio0
+he licensee shall pre%ent mi"#up and cross#contamination of drug material
and drug product (from en%ironmental dust) by proper air#handling system,
pressure di.erential, segregation, status labeling and cleaning
+o pre%ent mi"#ups during production stages, materials under process shall be
conspicuously labeled to demonstrate their status. $ll equipment used for
production shall be labeled with their current status.
RA' MATERIALS
+he licensee shall keep an in%entory of all raw materials to be used at any
stage of manufacture of drugs and maintain records as per Sc.e+/1e U
$ll incoming materials shall be 9/ara0ti0e+ i22e+iate1- after receipt or
processing
$ll materials shall be stored under appropriate conditions and in an orderly
fashion to permit batch segregation and stock rotation by a .*rst i0:*rst
e8)ir- ; *rsto/t principle.
$ll incoming materials s.a11 ,e c.ec<e+ to ensure that the consignment
corresponds to the order placed.
Da2a3e+ co0tai0ers s.a11 ,e i+e0ti*e+, recorded and segregated
7aw materials in the storage area shall be appropriately labeled. @abels shall
be clearly marked with the information includes name of the product and the
internal code reference, manufacturerBs name, address and batch number,
status of the contents, manufacturing date, e"piry date and re#test date
+here shall be adequate separate areas for materials ./0+er test., a))ro4e+
a0+ re=ecte+.
EQUIPMENT
Cquipment shall be located, designed, constructed, adapted and maintained to
suit the operations to be carried out
6alances and other measuring equipment of an appropriate range, accuracy
and precision shall be a%ailable in the raw material stores, production and in
process control operations and these shall be calibrated and checked on a
scheduled basis in accordance with 4*P records maintained
+he parts of the production equipment that come into contact with the product
shall not be reacti%e, additi%e or adsorpti%e to an e"tent that would a.ect the
quality of the product
/efecti%e equipment shall be remo%ed from production and ?uality ,ontrol
areas or appropriately labeled
DOCUMENTATION AND RECORDS
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/ocumentation is an essential part of the ?uality assurance system and, as such,
shall be related to all aspects GMP. 0ts aim is to de2ne the speci2cations for all
materials, method of manufacture and control, to ensure that all personnel
concerned with manufacture know the information necessary to decide whether or
not to release a bath of drug for sale and to pro%ide an audit trail that shall permit
in%estigation of the history of any suspected defecti%e batch.
/ocuments designed, prepared, re%iewed and controlled, where%er applicable,
shall comply with these rules.
/ocuments shall be appro%ed, signed and dated by appropriate and
authorized persons.
/ocuments shall specify the title, nature and purpose
/ocuments shall be regularly re%iewed and kept up to date. $ny alteration
made in the entry of a document shall be signed and dated
7ecords and associated 4tandard *perating Procedures (4*P) shall be retained
for at least one year after the e"piry date of the 2nished product.
Master 8ormulae and detailed operating procedures relating to the system in
use shall also be a%ailable in a hard copy to facilitate checking of the accuracy
of the records.
LABELS AND OT6ER PRINTED MATERIALS
@abels are absolutely necessary for identi2cation of the drugs and their use.
+he Printing shall be done in bright colours and in a legible manner. +he label
shall carry all the prescribed details about the product
/i.erent colour coded tablets shall be used to indicate the status of a product
(for e"ample under test, appro%ed, passed, re-ected).
+o a%oid chance mi"#up of printed packaging materials, product lea1ets,
relating to di.erent products, shall be stored separately.
Prior to release, all labels for containers, cartons and bo"es and all circulars,
inserts and lea1ets shall be e"amined by the ?uality ,ontrol /epartment of
the licensee.
7ecords of receipt of all labeling and packaging materials shall be maintained
for each shipment recei%ed indicating receipt, control reference numbers and
whether accepted or re-ected.
Dnused coded and damaged labels and packaging materials shall be
destroyed and recorded.
+he label or accompanying document of reference standards and reference
culture shall indicate concentration, lot number, potency, date on which
containers was 2rst opened and storage conditions, where appropriate.
QUALIT( ASSURANCE
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+he system of quality assurance appropriate to the manufacture of pharmaceutical
products shall ensure that
+he pharmaceutical products are designed and de%eloped in a way that
takes account of the requirement of GMP and other associated codes
such as G@P and G,P
$dequate arrangements are made for manufacture, supply and use of
the correct starting and packaging materials.
$dequate controls on starting materials, intermediate products, and bulk
products and other in#process controls, calibrations, and %alidations are
carried out.
+he 2nished product is correctly processed and checked in accordance
with established procedures'
+he pharmaceutical products are not released for sale or supplied before
authorized persons ha%e certi2ed that each production batch as been
produced and controlled in accordance with the requirements of the
label claim and any other pro%isions rele%ant to production, control and
release of pharmaceutical products.
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