You are on page 1of 23

Sr.

No Requirements
1 Premises
1 General requirement

2 Ancillary Area

3 Storage area

4 Weighing area

5 Production area

6 Quality control

2 Equipement

3 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

12 Personnel
13 Training
WHO

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 changing
and storing room should be separate from production & storage area.Animal house should
be isolated from other area with separate entrance

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

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

Separate production area for active substances & non- pharmaceutical products.If
campaign working is there then neccesary validation (Cleaning validation) should be
done.Production should be in logical order with logical positioning of equipements.Area
should 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 for
prevention 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 be
marked & 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 should
claened on shceduled basis.Defective equipment should be labelled DEFECTIVE or sholud
be removed.Non dedicated equipment should be cleaned according to validated cleaning
procedure between production of differenet product.Current drawing of critical
equipment & support system should be maintained.
SM Label in storage area should bear DESIGNATED NAME OF PRODUCT & internal
reference code,Batch No.of supplier & on receipt control or batch No. given by
manufacturer 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 unauthorised


access.For each batch of printed or primary packing material a specific reference No.or
Identification mark should be given.Outdated or obsolate primary packing material or
printed packing material should be destroyed & disposal should be recorded

Should be handelled on receipt similar to Starting material

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

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

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

Should be destroyed if quality is not satisfactory.If quality is satisfactory then it can be


considered for labelling or resale or alternative action will be taken if critically assesed by
QC

Official reference should be used for the purpose described in appropriate


monograph.Label should bear Name of material,Batch/ lot No. & Control No., Date of
preparation, Shelf life, Potency and storage condition.In-House reference standard should
be standerdized against Official reference standard.

Material awaiting disposal should be stored properly.Toxic substances & flammable


material should be stored in separate, enclosed cupboard as required by National
legislation.Waste material should not be allowed to accumulate, should be collected in
receptacle for removal to collection point outside the building.
Defines specifications and procedures for all material and method of manufacture and
control 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 & making
documents 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 and
process which may affect quality of product should be qualified and validated.The
programme should follow their first review & should be based on annual review.Validation
status of company should be stated in Quality manual or in Validation mater plan
Complaints should be carefully reviewed according to written procedures & corrective
action should be taken.Written procedures should be there for action to be taken & need
for considering product recall in case if the product is defective. Any complaint of defective
product should be recorded with original details & should be investigated.

Approved person should be responsible for execution & co-ordination of product


recall.Instruction should be included in written procedures for storage of recalled product in
segregated area untill their fate is decided.All countries where product has been distributed
should be informed about intention of recalling product.The distribution record containing
information of wholesaler & directly supplied customers should be easily made available to
authorised person for effective product recall.

Arrangement for contract production/ analysis should be in accordance with Marketing


authorisation of the product.Contract should permit contract giver , to audit facilities of
contract acceptor.Final approval for release will be given by approved person.Contract
acceptor should not pass to third party any work entrusted to him wiyhout prior approval or
evaluation from Contract giver.

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

Quloified personnel are needed to carry out manufacturing operation


Training should be given to persons involved in manufacturing operation, GMP
requirement.VISITORS or UNTRAINED PERSONS should not be taken in production and
QC area.Consultant & Contract staff should be qualified for the service they are providing.
EUROPE

In premises there should minimum risk of contamination of material or product.Lightning, humidity,temperature


ventillation should be appropriate.

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

sufficient capacity to allow orderly storage of the various categories of materials and products namely starting
and 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 the
requisite cleanliness levels.The working and in-process storage space should permit the orderly and logical
positioning of equipment and materials so as to minimise the risk of confusion between different medicinal
products or their components, to avoid cross-contamination.Interior surfaces (walls, floors and ceilings) should
be smooth, free from cracks and open joints, and should not shed particulate matter and should permit easy
and 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 be
easily accessible

Repair and maintenance operations should not present any hazard to the
quality of the products. Manufacturing equipment should be located & designed so that it can be easily and
thoroughly cleaned. It should be cleaned according to detailed and written procedures and stored only in a
clean and dry condition.Balances and measuring equipment of an appropriate range and precision should be
available for production and control operations.
purchased from approved suppliers named in the relevant specification and, where possible, directly from the
producer.The specifications established by the manufacturer for the starting materials be discussed with the
suppliers.There should be appropriate procedures or measures to assure the identity of the contents of each
container of starting material.Each dispensed material and its weight or volume should be independently
checked and the check recorded.

Printed materials should be stored in adequately secure conditions such as to exclude unauthorised
access.Each delivery or batch of printed or primary packaging material should be given a specific reference
number or identification mark.
Outdated or obsolete primary packaging material or printed packaging material
should be destroyed and this disposal recorded.
Should be kept under appropriate condition & before starting processing operation the working area should be
made free from starting material, product, product residue, documentsA significant deviation in the expected
yield should be recorded

Finished products should be held in quarantine until their final release under conditions established by the
manufacturer.
The evaluation of finished products and documentation which is necessary before release of product for sale
are described in Chapter 6 (Quality Control). After release, finished products should be stored as usable stock
under 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.The
reprocessing of rejected products is permitted if the quality of the final product is not affected.Record should
be kept of the reprocessing.

Product returned fropm market which has left the control of the manufacturer should be destroyed if quality of
product is not satisfactory. These product can be considered for re-sale, re-labelling or recovery with
subsequent batch if quality is found satisfactory by QC Dept.
ocuments should be clearly written. Specifications,
Manufacturing Formulae and instructions, procedures and records must be free from errors and available in
writing.
Documents should be designed, prepared, reviewed and distributed with care. They should comply with the
relevant 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.The
reproduction of working documents from master documents must not allow any error to be introduced through
the reproduction process.When a document has been revised, systems should be operated to prevent
inadvertent use of superseded documents.. Documents should not be hand-written. Alteration made to the
entry on a document should be signed and dated & the reason for the alteration should be recorded.The
records should be made at the time each action is taken and in such a way that all significant activities
concerning the manufacture of medicinal products are traceable. They should be retained for at least one year
after the expiry date of the finished product.

The system of Quality Assurance for the manufacture of medicinal


products 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 packaging
materials;
v. all necessary controls on intermediate products, and any other inprocess controls and validations are carried
out;
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 production
batch has been produced and
controlled in accordance with the requirements of the marketing authorisation and any other regulations
relevant 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 and
applicability of the quality
assurance system.

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

Validation should be conducted in accordance with defined procedures. Results and conclusions should be
recorded. Significant amendments to the manufacturing process, including any change in equipment or
materials, which may affect product quality and/or the
reproducibility of the process should be validated. Processes and procedures should undergo periodic critical
revalidation to ensure that they remain capable of achieving the intended results.
A person should be designated responsible for handling the complaints There should be written procedures
describing the action to be taken, including the need to consider a recall, in the case of a complaint concerning
a possible product defect.Complaint concerning a product defect should be recorded with all the original
details and investigated. The person responsible for Quality Control will be involved in the study of such
problems.If a product defect is discovered or suspected in a batch, other batches should be checked in order
to determine whether they are also affected.
All the decisions and measures taken as a result of a complaint should be recorded and referenced to the
corresponding batch records.Complaints records should be reviewed regularly .

A person should be designated as responsible for execution and co-ordination


of recalls. written procedures should be established, regularly checked and updated
when necessary, in order to organise any recall activity.All Competent Authorities of all countries to which
products may have been distributed should be informed
The distribution records should be readily available to the person(s) responsible for recalls, and should contain
sufficient information on wholesalers and directly supplied customersRecalled products should be identified
and stored separately in a secure area
while awaiting a decision on their fateThe progress of the recall process should be recorded and a final report
issued.

There must be a written contract between the Contract Giver and the Contract Acceptor which clearly
establishes the duties of each party.
There should be a written contract covering the manufacture and/or analysis arranged under contract and any
technical arrangements made in connection with it.
The Contract Giver is responsible for assessing the competence of the Contract Acceptor.The Contract Giver
should provide the Contract Acceptor with all the information necessary to carry out the contracted operations
correctly in accordance with the marketing authorisation and any other legal requirements. The Contract Giver
should ensure that the Contract Acceptor is fully aware of any problems associated with the product or the
work 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 Good
Manufacturing Practice.Personnel matters, premises, equipment, documentation, production, quality control,
distribution of the medicinal products, arrangements for dealing with complaints and recalls, and self
inspection, 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 the
inspections and, where applicable, proposals for corrective measures. Statements on the actions
subsequently taken should
also be recorded.

All personnel should receive medical examination upon recruitment.Hygiene programmes should be
established and adapted to the different needs within the factory.Steps should be taken to ensure that no
person affected by an infectious disease or having open lesions on the exposed surface of the body is
engaged in the manufacture of medicinal products.Eating, drinking, chewing or smoking, or the storage of
food, drink, smoking materials or personal medication in the production and storage areas should be
prohibited. Personnel should be instructed to use the hand-washing facilities
Training should be given to the personnel involved in the production or control laboratories.Training
programme should be approved by head of production or quality.Training record should be kept & should be
periodically.Visitors or untrainned person should, preferably , not be allowed to production & quality control
area or information should be given on personnel hygiene & prescribed protective clothing.
Sr.No Requirements
1 Premises
1 General requirement

2 Ancillary Area
3 Storage area

4 Weighing area
5 Production area

6 Quality control

2 Equipement
3 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
12 Personnel
13 Training
South africa

Premises should be in an environment with minimumn risk of contamination of material or product and should prevent
the entry of insect or animals. Pest and Insect Control programme should be in place at all times.Waste materials
should 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 material
requirement

logical layout in order to prevent mix-ups and should have sufficient space to carry out the production in an orderly
manner.Seperate facility should be there for production of potent product.Production area should should be properly
ventilated. All pipes, fittings and other services should be designed and sited in such a way that they do not create
places that are difficult to clean. Floors, walls
and 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 a
pre-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 validation
j) suppliers of starting and packaging (especially printed) material.
(k) third party contractors for manufacturing, packaging, analysis and where required distribution of medicines.Audit
reports should be made Written records should be maintained so that data can be used for evaluating the quality
standards of each product to determine the need for changes in product specifications or manufacturing and control
procedures