gmp requirement who

8/8/2019 Gmp Requirement Who

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Sr.No Requirements

1

1 General requirement

2 Ancillary Area

3 Storage area

4 Weighing area

5 Production area

6 Quality control

2 Equipement

3 Material

Premises


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1 Starting material(SM)

2 packing material

3 Intermediate or bulk product

4 Finished product(FP)

5

6 Recalled product

7 Returned goods

8 Reference standard

9 Waste material

Rejected/ reprocessedmaterial


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4 Documentation

5 Quality assurance

6 Sanitation and hygiene

7 Qualification/ Validation


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8 Complaints

9 Product recall

10

11

12 Personnel

Contract production/Analysis

Self inspection and QualityAudit


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13 Training


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WHO

Orderly storage of variuos category of material and product with proper seperation

Premises with Good sanitation,appropriate electrical supply, lightning,humidity,temperature ventillation with Logical flow of material and personnel

Rest & refreshment room , maintainence workshop, washing & toilet area,cloth changingand storing room should be separate from production & storage area.Animal house shouldbe isolated from other area with separate entrance

Separate weighing area for starting material & estimation of yield by weighing withprovisions for dust control

Separate production area for active substances & non- pharmaceutical products.Ifcampaign working is there then neccesary validation (Cleaning validation) should bedone.Production should be in logical order with logical positioning of equipements.Areashould be easy to clean & effectively ventilated.

Sufficient space to avoid mix ups & cross contamination and for storage of samples,reference standards, reagents, solvents& record.Propeperly ventilated with facilities forprevention of fumes.

Designed to provide effective cleaning & maintainance and to avoid cross contamination.Fixed pipework should be clearly labelled to indicate the content.Service pipings should bemarked & provisions for non-interchangeable connections or adaptors for dangerous gases& liquids should be made.Measuring equipment with appropriate Range & Precision should

be made available for production & control operation. production equipement shouldclaened on shceduled basis.Defective equipment should be labelled DEFECTIVE or sholudbe removed.Non dedicated equipment should be cleaned according to validated cleaningprocedure between production of differenet product.Current drawing of criticalequipment & support system should be maintained.


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Should be handelled on receipt similar to Starting material

SM Label in storage area should bear DESIGNATED NAME OF PRODUCT & internalreference code,Batch No.of supplier & on receipt control or batch No. given bymanufacturer to ensure traceability & STATUS of content (i.e on quarantine, on test,released, rejected, returned,recalled ).Expiry date should be given where appropriate.

If SM is made up of different batches then it should be considered seperate for sampling,testing& release.SM relased by QC & SM within their shelf-life should be used.Material

dispensed for each batch of final product should be kept together.

Printed packing material should be stored in secured conditions to prevent unauthorisedaccess.For each batch of printed or primary packing material a specific reference No.orIdentification mark should be given.Outdated or obsolate primary packing material orprinted packing material should be destroyed & disposal should be recorded

FP should be kept in quarantine until release after that stored in usable stock underconditions establishrd by manufacturer.Evaluation and Documentation of FP for release forsale.

Rejected material should be clearly marked & stored seperately in RESTRICTED AREA &should be returned to supplier, reprocessed or destroyed.Reworking/ Recovery permittedonly if quality of Final product is not affected. Introduction of all or part of earlier batchesonly if it conforms to required quality.The need of additional testing should considered byQC dept

Stored in secured area until decision is take & decision about their fate should be taken assoon as possible

Should be destroyed if quality is not satisfactory.If quality is satisfactory then it can beconsidered for labelling or resale or alternative action will be taken if critically assesed byQC

Official reference should be used for the purpose described in appropriatemonograph.Label should bear Name of material,Batch/ lot No. & Control No., Date ofpreparation, Shelf life, Potency and storage condition.In-House reference standard shouldbe standerdized against Official reference standard.

Material awaiting disposal should be stored properly.Toxic substances & flammablematerial should be stored in separate, enclosed cupboard as required by Nationallegislation.Waste material should not be allowed to accumulate, should be collected inreceptacle for removal to collection point outside the building.


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Defines specifications and procedures for all material and method of manufacture andcontrol to ensure all personnel concerned with manufacture know what to do & when to do& having all information to decide whether or not to release the batch of a drug for sale.Documentation is for ensuring existence of documented evidence, traceability & makingdocuments available for audit.

QA incorporate GMP and product design and development. It should be fully documented& its effectiveness should be monitored.

Scope of sanitation and hygiene covers perssonel, premises, equipment and apparatus,production material and containers, products for cleaning and disinfection .

Any aspect of operation including significant changes in premises, facilities, equipment andprocess which may affect quality of product should be qualified and validated.Theprogramme should follow their first review & should be based on annual review.Validationstatus of company should be stated in Quality manual or in Validation mater plan


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Quloified personnel are needed to carry out manufacturing operation

Complaints should be carefully reviewed according to written procedures & correctiveaction should be taken.Written procedures should be there for action to be taken & needfor considering product recall in case if the product is defective. Any complaint of defectiveproduct should be recorded with original details & should be investigated.

Approved person should be responsible for execution & co-ordination of productrecall.Instruction should be included in written procedures for storage of recalled product insegregated area untill their fate is decided.All countries where product has been distributedshould be informed about intention of recalling product.The distribution record containinginformation of wholesaler & directly supplied customers should be easily made available toauthorised person for effective product recall.

Arrangement for contract production/ analysis should be in accordance with Marketingauthorisation of the product.Contract should permit contract giver , to audit facilities ofcontract acceptor.Final approval for release will be given by approved person.Contractacceptor should not pass to third party any work entrusted to him wiyhout prior approval orevaluation from Contract giver.

Should be performwd routinely & for recalled product or rejected product. Procedure forself inspection shpuld be documented and should contain questionnaires onGMP.Frequency should be at least once in a year.Quality audit includes inspection of all orpart of quality system.SUPPLIER'S AUDIT includes supplier of starting material & packingmaterial & suppliers should meet established specifications and if audit is required supplirshould conform with GMP requirement.


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Training should be given to persons involved in manufacturing operation, GMPrequirement.VISITORS orUNTRAINED PERSONS should not be taken in production andQC area.Consultant & Contract staff should be qualified for the service they are providing.


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EUROPE

In premises there should minimum risk of contamination of material or product.Lightning, humidity,temperatureventillation should be appropriate.

Rest and refreshment rooms should be separate from other areas.Maintenance workshops should beseparated from production areas.

sufficient capacity to allow orderly storage of the various categories of materials and products namely startingand packaging materials, intermediate, bulk and finished products, products in quarantine, released,rejected, returned or recalled.

The areas should be connected in a logical order corresponding to the sequence of the operations and to therequisite cleanliness levels.The working and in-process storage space should permit the orderly and logicalpositioning of equipment and materials so as to minimise the risk of confusion between different medicinalproducts or their components, to avoid cross-contamination.Interior surfaces (walls, floors and ceilings) shouldbe smooth, free from cracks and open joints, and should not shed particulate matter and should permit easyand effective cleaning and, if necessary, disinfection.

should be separated from production areas.No entry to unauthorised people.Facilities for changing clothes,and for washing and toilet purposes should beeasily accessible

Repair and maintenance operations should not present any hazard to thequality of the products. Manufacturing equipment should be located & designed so that it can be easily andthoroughly cleaned. It should be cleaned according to detailed and written procedures and stored only in aclean and dry condition.Balances and measuring equipment of an appropriate range and precision should be

available for production and control operations.


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purchased from approved suppliers named in the relevant specification and, where possible, directly from theproducer.The specifications established by the manufacturer for the starting materials be discussed with thesuppliers.There should be appropriate procedures or measures to assure the identity of the contents of eachcontainer of starting material.Each dispensed material and its weight or volume should be independentlychecked and the check recorded.

Printed materials should be stored in adequately secure conditions such as to exclude unauthorisedaccess.Each delivery or batch of printed or primary packaging material should be given a specific referencenumber or identification mark.Outdated or obsolete primary packaging material or printed packaging materialshould be destroyed and this disposal recorded.

Should be kept under appropriate condition & before starting processing operation the working area should bemade free from starting material, product, product residue, documentsA significant deviation in the expectedyield should be recorded

Finished products should be held in quarantine until their final release under conditions established by themanufacturer.The evaluation of finished products and documentation which is necessary before release of product for saleare described in Chapter 6 (Quality Control). After release, finished products should be stored as usable stockunder conditions established by the manufacturer

Rejected materials and products should be clearly marked as such and stored separately in restricted areas.They should either be returned to the suppliers or, where appropriate, reprocessed or destroyed.Thereprocessing of rejected products is permitted if the quality of the final product is not affected.Record shouldbe kept of the reprocessing.

Product returned fropm market which has left the control of the manufacturer should be destroyed if quality ofproduct is not satisfactory. These product can be considered for re-sale, re-labelling or recovery withsubsequent batch if quality is found satisfactory by QC Dept.


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ocuments should be clearly written. Specifications,Manufacturing Formulae and instructions, procedures and records must be free from errors and available inwriting.Documents should be designed, prepared, reviewed and distributed with care. They should comply with therelevant parts of the manufacturing and marketing authorisation dossiers.Documents should be approved, signed and dated by appropriate and

authorised persons. The title, nature and purpose of the the document should be clearly stated.Thereproduction of working documents from master documents must not allow any error to be introduced throughthe reproduction process.When a document has been revised, systems should be operated to preventinadvertent use of superseded documents.. Documents should not be hand-written. Alteration made to theentry on a document should be signed and dated & the reason for the alteration should be recorded.Therecords should be made at the time each action is taken and in such a way that all significant activitiesconcerning the manufacture of medicinal products are traceable. They should be retained for at least one yearafter the expiry date of the finished product.

The system of Quality Assurance for the manufacture of medicinalproducts should ensure that:i. medicinal products are designed and developed in a way that takes account of the requirements of GMP;ii. production and control operations are clearly specified and GMP adopted;

iii. managerial responsibilities are clearly specified;iv. arrangements are made for the manufacture, supply and use of the correct starting and packagingmaterials;v. all necessary controls on intermediate products, and any other inprocess controls and validations are carriedout;vi. finished product is correctly processed and checked, according to the defined procedures;vii. medicinal products are not sold or supplied before an authorised person has certified that each productionbatch has been produced andcontrolled in accordance with the requirements of the marketing authorisation and any other regulationsrelevant to the production,control and release of medicinal products;viii. satisfactory arrangements exist to ensure, as far as possible, that the medicinal products are stored,distributed and subsequently handled so

that quality is maintained throughout their shelf life;ix. there is a procedure for self-inspection and/or quality audit, which regularly appraises the effectiveness andapplicability of the qualityassurance system.

Detailed hygiene programme related to procedure to health, clothing should be adapted. All person shouldreceive medical examination upon recruitment. The person engaged in manufacture should not have anyinfectious disease,open lesions.

Validation should be conducted in accordance with defined procedures. Results and conclusions should berecorded. Significant amendments to the manufacturing process, including any change in equipment ormaterials, which may affect product quality and/or thereproducibility of the process should be validated. Processes and procedures should undergo periodic criticalrevalidation to ensure that they remain capable of achieving the intended results.


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A person should be designated responsible for handling the complaints There should be written proceduresdescribing the action to be taken, including the need to consider a recall, in the case of a complaint concerninga possible product defect.Complaint concerning a product defect should be recorded with all the originaldetails and investigated. The person responsible for Quality Control will be involved in the study of suchproblems.If a product defect is discovered or suspected in a batch, other batches should be checked in orderto determine whether they are also affected.

All the decisions and measures taken as a result of a complaint should be recorded and referenced to thecorresponding batch records.Complaints records should be reviewed regularly .

A person should be designated as responsible for execution and co-ordinationof recalls. written procedures should be established, regularly checked and updatedwhen necessary, in order to organise any recall activity.All Competent Authorities of all countries to whichproducts may have been distributed should be informedThe distribution records should be readily available to the person(s) responsible for recalls, and should containsufficient information on wholesalers and directly supplied customersRecalled products should be identifiedand stored separately in a secure area

while awaiting a decision on their fateThe progress of the recall process should be recorded and a final reportissued.

There must be a written contract between the Contract Giver and the Contract Acceptor which clearlyestablishes the duties of each party.There should be a written contract covering the manufacture and/or analysis arranged under contract and anytechnical arrangements made in connection with it.The Contract Giver is responsible for assessing the competence of the Contract Acceptor.The Contract Givershould provide the Contract Acceptor with all the information necessary to carry out the contracted operationscorrectly in accordance with the marketing authorisation and any other legal requirements. The Contract Givershould ensure that the Contract Acceptor is fully aware of any problems associated with the product or thework which might pose a hazard to his premises, equipment, personnel, other materials or other products.

Self inspections should be conducted in order to monitor the implementation and compliance with GoodManufacturing Practice.Personnel matters, premises, equipment, documentation, production, quality control,distribution of the medicinal products, arrangements for dealing with complaints and recalls, and selfinspection, should be examined at intervals.Self inspections should be conducted in an independent and detailed way by designated competent person(s)from the company. Independent audits by external experts may also be useful.All self inspections should be recorded. Reports should contain all the observations made during theinspections and, where applicable, proposals for corrective measures. Statements on the actionssubsequently taken shouldalso be recorded.

All personnel should receive medical examination upon recruitment.Hygiene programmes should beestablished and adapted to the different needs within the factory.Steps should be taken to ensure that noperson affected by an infectious disease or having open lesions on the exposed surface of the body isengaged in the manufacture of medicinal products.Eating, drinking, chewing or smoking, or the storage offood, drink, smoking materials or personal medication in the production and storage areas should beprohibited. Personnel should be instructed to use the hand-washing facilities


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Training should be given to the personnel involved in the production or control laboratories.Trainingprogramme should be approved by head of production or quality.Training record should be kept & should beperiodically.Visitors or untrainned person should, preferably , not be allowed to production & quality controlarea or information should be given on personnel hygiene & prescribed protective clothing.


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Sr.No Requirements

1

1 General requirement

2 Ancillary Area

3 Storage area

4 Weighing area

5 Production area

6 Quality control

2 Equipement3 Material

1 Starting material(SM)

2 packing material

3 Intermediate or bulk product

4 Finished product(FP)

5 Rejected/ reprocessed material

6 Recalled product

7 Returned goods

8 Reference standard

9 Waste material

4 Documentation

5 Quality assurance

6 Sanitation and hygiene

7 Qualification/ Validation

8 Complaints

9 Product recall

10 Contract production/ Analysis

11 Self inspection and Quality Audit

Premises


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12 Personnel

13 Training


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South africa

Premises should be in an environment with minimumn risk of contamination of material or product and should preventthe entry of insect or animals. Pest and Insect Control programme should be in place at all times.Waste materialsshould be continually removed from the premises & sholud have written sanitation procedures.Adequate lightening &ventillation should be provided with appropriate humidity, pressure and temperatures .

Storage area should have appropriate limits.Special storage areas required should be provided as per materialrequirement

logical layout in order to prevent mix-ups and should have sufficient space to carry out the production in an orderlymanner.Seperate facility should be there for production of potent product.Production area should should be properlyventilated. All pipes, fittings and other services should be designed and sited in such a way that they do not createplaces that are difficult to clean. Floors, wallsand ceilings should be of materials that facilitate cleaning. In-process controls

may be done within the production area provided they do not carry any risk for the production.

Audits may be in house or carried out by local regulatory authorities or the regulatory authorities of countries to which

companies wish to export. Audits should follow apre-arranged programme and include inspection of :(a) organizational matters and responsibilities(b) qualifications and training programmes(c) compliance with hygiene requirements and entry restrictions(d) cleaning and disinfection programmes(e) medical checks on personnel(f) production facilities, premises and equipment, including quality control(g) production operations, procedures and documentation including quality control(h) storage, handling, distribution and materials management(i) quality assurance aspects such as complaints, returned goods and validationj) suppliers of starting and packaging (especially printed) material.


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(k) third party contractors for manufacturing, packaging, analysis and where required distribution of medicines.Auditreports should be made Written records should be maintained so that data can be used for evaluating the qualitystandards of each product to determine the need for changes in product specifications or manufacturing and controlprocedures


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