This document discusses good manufacturing practices for manufacturing operations and controls in the pharmaceutical industry. It covers several key topics: 1. Sanitation of manufacturing premises is important to ensure good hygiene of facilities, equipment, processes, and personnel. Cleaning and validation procedures should be established and records maintained. 2. Proper controls must be established to prevent mix-ups and cross-contamination during production. This includes separation of products, labeling, cleaning procedures, and qualified personnel. 3. Waste and scrap from manufacturing must be properly handled, collected, stored, and disposed of according to established guidelines. Hazardous and pharmaceutical wastes require special treatment and disposal.

1. Manufacturing Operations And
Controls
Presented By :- Guided By:-
Jitendra K. Sonawane Dr.G.B.Patil
M.Pharm (QA)
H. R. Patel Institute of Pharmaceutical Education and
Research, Shirpur
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2. Contents
 Introduction.
 Sanitation of manufacturing premises.
 Mix-ups and it’s prevention.
 Cross-contamination and it’s prevention.
 Handling of waste & scrap disposal.
 References
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3. Introduction
 Good manufacturing practices which are currently
acceptable should be followed during carrying out all
manufacturing operations and their control.
 All manufacturing operations shall be carried out
under the supervision of technical staff approved by
the Licensing Authority.
 The operators and workers who actually carry out
various operations should be trained enough to carry
out the activities assigned to them.
 They should have appropriate knowledge and skills to
carry out their responsibility.
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4. 4
• All activities should be carried out as per approved
SOPs and records maintained.

5. Sanitation of manufacturing
premises
Scope :-
Review measures to ensure good sanitation in :-
Premises & personnel
Equipment & apparatus
Processes, materials & containers.
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6. Guidelines by Schedule M of D and C Act
Premises –
 The manufacturing premises shall be cleaned and
maintained in an orderly manner.
 Cleaning all these premises with detergent.
 Premises again wash with disinfectant.
 Premises shall be suitably designed and constructed
to facilitate good sanitation.
 A validated cleaning procedure shall be maintained.
 Sanitization maintain the manufacturing area free
from Dust, Insect, Debris. 6

7. Ex. In Tablet Manufacturing :
1. Powder clean with best napkins
2. After completion clean with disinfectant solution
i.e 1% glycol solution (cleaning sol.)
Glass material :
1. Glass material and residue collected in wastage.
2. All glasses are clean by 70% isopropyl alcohol.
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8. Manufacturing area :–
 The manufacturing area shall not be used for storage of
materials except for the materials being processed. It shall not be
used as a general thorough fare.
 Certain locations in each area should be marked in each
processing area for collection of dust, debris and waste materials.
 All areas must be cleaned using suitable detergents and methods
of cleaning at pre-decided time intervals. The concentration of
detergent used, cleaning method and frequency of cleaning must
be monitored.
 After cleaning activity is over the area should be disinfected by
suitable method. A detailed SOP must be followed.
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9. Equipment and apparatus:-
 Equipment should be cleaned both inside and outside after use
according to established procedure and should be kept or stored
in a clean condition.
 Vacuum or wet cleaning methods are to be preferred.
 Cleaning and storing of mobile equipment and storing of
cleaning materials in rooms separated from processing area.
 Written procedure in sufficient details should be established,
validated and followed.
 Records of cleaning, sanitizing, sterilization and inspection prior
to use should be kept properly.
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10. Personnel –
 Every person entering the manufacturing area should wear
protective garments. Detailed hygiene programmes should be
established and adapted.
 The personnel assigned to and responsible for cleaning operations
must have proper attitude and knowledge towards sanitation and
hygiene.
 Direct contact should be avoided between the operator’s hands and
the exposed starting materials, intermediate and bulk products.
 Their working should be well monitored.
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11. Validation of cleaning and sanitation
procedures:-
 Validation studies should reinforce GMP and be conducted in
accordance with defined procedures.
The reproducibility of the process should be validated
Processes and procedures should undergo periodic critical re-
validation to ensure that they remain capable of achieving the
intended result.
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12. Mix-ups :-
Definition –
It is defined as presence of undesired materials
into desired materials which can be visibly seen.
Ex :- Paracetamol mix with Diclofenac.
Tablets of one product with another product which have
different size, shape, colour, etc.
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13. Sources of mix-ups:–
1. The close proximity or location of similar items.
2. Items having same colour or combination of colours
kept nearby.
3. Improper storage of sterile and non sterile products.
4. Multiple products handled at the same time.
5. Manual packaging and repackaging.
6. Failure of processing equipment.
7. Lack of proper validation.
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14. Contamination:-
Contamination may be define as the presence of the undesired
material, it should be not visible.
The undesired introduction of impurities of chemical or
microbiological nature or foreign matter in to starting material or
intermediate during production, sampling, repackaging, storage or
transport.
Cross-contamination:-
Contamination of starting material or intermediates or finished
product by another material or product during the production is called
as cross-contamination.
Ex:- Fine dust of one product into another product
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15. Sources–
Contaminated clothing and/or equipment.
Contaminated or faulty HVAC system.
Contaminated premises.
People in the working area.
Processing operations.
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16. Precaution against mix-up & cross-
contamination.
1. The drug material and drug product (from
environmental dust) by proper air handling system.
2. The processing of sensitive drugs like BetaLactum
antibiotics, sex hormones and cytotoxic substances is
isolated in production ares.
3. The Manufacturing environment shall be maintained at
the required levels of temp., humidity and cleanliness.
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17. Controlling of mix-ups and cross-
contamination
 Where dry materials and products are used in production, special
precaution should be taken to prevent the generation and
dissemination of dust.
 All the procedure regarding materials and products, regarding
their sampling, storage, cleaning, labelling, quarantine and
dispensing should be in accordance with written procedure.
 Production in segregated areas should be conducted or at different
timings followed by appropriate cleaning.
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18.  Wearing protective clothing in areas where products
with special risk of cross-contamination are processed .
 At each step in processing the materials should be
labelled with their indication, batch number and
strength.
 Appropriate written procedure shall be established and
followed.
 Production area should undergo periodic microbiological
monitoring.
 Non-medical products should not be produced in places
where the pharmaceutical products are produced.
 Using “closed systems” of production.
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19. Documents required:-
SOPs on-
1. Handling materials in processing area.
2. Line clearance and its record thereof.
3. Machine and equipment cleaning.
4. Collection and disposal of waste.
5. Internal labeling of material.
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20. Handling of waste and scrap disposal:-
Scope:
This part provides an overview regarding the generation of
rejects/scrap, its collection and accounting, and recommends guidelines
for dealing with rejects/scrap and their disposal.
Responsibility:
The responsibility may depend on the following of the people in
the Pharma industry:-
 Employees in the production unit
 Representative of QA
 Housekeeping staff
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21. Scrap:
Materials like rejected foils, bottles, cans, and tins etc. which
have a resale value.
The scraps are generated at various stages of manufacturing-
1)During compression encapsulation coating & packing stages.
2)In-process check.
3)Rejected printing packing materials.
4) From floor sweeping
5) Expired or damaged goods.
6) Excess sample in QC after test.
7) Product sample from R&D at development stage
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22. Pharmaceutical Waste :
Pharmaceutical waste is potentially generated thorough a wide
variety of activities health care facility general compounding
partially used vials syringes, and IV preparation discontinued &
unused preparations unused unit dose repacks patients personal
medications
Trash:
This material is to be discarded or disposed by suitable means
and don’t have a resale value. E.g. dust, unsalable materials and
outdated pharmaceuticals.
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23. Types of Health Care Wastes :
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Sr.no. Type of waste Example
1 Communal waste Cardboard boxes, paper, food waste, plastic and glass bottles
2 Biomedical wastes Cultures, tissues
3 Anatomical waste Recognizable body parts
4 Sharps Needles, scalpels, blades, broken glass
5 Pharmaceutical waste Expired or no longer needed medicines or pharmaceuticals
6 Genotoxic waste Wastes containing genotoxic drugs and chemicals
7 Chemical waste Laboratory reagents, solvents, expired disinfectants, organic
chemical wastes
8 Pressurized containers Aerosol cans, gas cylinders

24. Steps for a Health Care Waste Management:-
1. Raise awareness
2. Define a policy.
3. Set up a strategy.
4. Conduct an assessment of the current situation.
5. Draft a HCWM plan.
6. Consolidate the legal & regulatory frameworks.
7. Standardise HCWM practices.
8. Strengthen the institutional capacities.
9. Set up waste management plans
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25. Waste Disposal Methods
 Waste management is the collection, transport, processing, recycling or
disposal of waste materials.
 The term usually relates to materials produced by human activity, and is
generally undertaken to reduce their effect on health, the environment or
aesthetics.
 Waste management can involve solid, liquid, gaseous or radioactive
substances, with different methods and fields of expertise for each.
Methods of disposal/ treatment:-
1. Rotary kiln
2. Pyrolytic incineration
3. Single chamber incineration Solid waste
4. Drum incineration
5. Chemical treatment Liquid waste
6. Biological treatment
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26. Solid Waste Treatment:
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27. Liquid Waste Treatment:
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29. Storage Of Waste:
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30. Schedule M Guidelines:
 All biomedical waste shall be destroyed as per provisions of Bio-
medical Waste (Manufacturing and Handling) Rules, 1996.
 Additional precautions shall be taken for storage and disposal of
rejected drugs.
 Hazardous toxic substance and flammable materials shall be stored in
suitably designed and segregated enclosed areas in conformity with
central and state legislation.
 Provision shall be made for proper and safe storage of waste
materials. Records shall be maintained for all disposal of waste.
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31. WHO Guidelines:
 Provision should be made for proper and safe storage of waste
materials awaiting disposal.
 Toxic substance and flammable materials should be stored in
suitably designed, separate, enclosed cupboards as required by
national legislation.
 Waste materials should not be allowed to accumulate.
 It should be collected in suitable receptacles for removal to
collection points outside the building.
 Disposed of safely and in a sanitary manner at regular and
frequent interval.
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32. References:-
1. Manohar .A. Potdar, “Pharmaceutical Quality Assurance”,
Nirali Prakashan, 2nd edition,2007, pg.no. 6.1-6.5
2. Cole Graham C. ‘‘Pharmaceutical Production Facilities”,
CRC Press, 2nd Edition, pg-199.
3. Willing H. S, Stoker R J, “Good Manufacturing Practices For
Pharmaceuticals” Fourth Edition, 47-48.
4. www.pharmaguideline.com
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33. manufacturing operation and control Tanisha.N.Agrawal 33