PRODUCTION MANAGEMENT IN GOOD MANUFACTURING PRACTICE : 

PRODUCTION MANAGEMENT IN GOOD MANUFACTURING PRACTICE SUBMITTED BY: K.V.V.S.Narayana

Reddy 1st M.Pharm Dept of Pharmaceutics

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WHY ? WHEN ? GMP CAME IN TO THE FIELD.

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PRODUCTION MANAGEMENT production management,also called operations management, planning

and control of industrial processes to ensure that they move smoothly at the required level. In
manufacturing operations, production management includes responsibility for product and process
design, planning and control issues involving capacity and quality,organization and supervision of the
workforce. GOOD MANUFACTURING PRACTICES AND REQUIREMENTS OF PREMISES, PLANT AND
EQUIPMENT FOR PHARMACEUTICAL PRODUCTS WHO defines Good Manufacturing Practices (GMP) as
“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 covers all aspects of the manufacturing process

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LABELS & OTHER PRINTED MATERIALS QUALITY CONTRIOL AREA ANCILLARY AREA WAREHOUSING AREA
PRODUCTION AREA MANUFACTURING OPERATIONS AND & CONTROLS HEALTH, CLOTHING &
SANITATION OF W0RKERS PERSONNEL e.t.c., QUALITY ASSURANCE DOCUMENTATION & RECORDS
GENERAL REQUIREMENTS EQUIPMENT RAW MATERIALS SANITATION IN THE MANUFACTURING
PREMISES GMP

1. GENERAL REQUIREMENTS : 

1. GENERAL REQUIREMENTS 1.1. Location and surroundings.- The factory building(s) for manufacture of
drugs shall be so situated to avoid risk of contamination from external environmental including open
sewage, drain, public lavatory or any factory which product disagreeable or bad odour, fumes, dust,
smoke, chemical or biological emissions. 1.2. Building and premises.- The 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. The premises used for manufacturing, processing,
warehousing, packaging labeling and testing purposes shall be . (i) compatible with other drug
manufacturing operations that may be carried out in the same or adjacent area / section. (ii) adequately
provided with working space to allow orderly and logical placement of equipment, materials and
movement of personnel so as to: (a) avoid the risk of mix-up between different categories of drugs or
with raw materials, intermediates and in-process material. (b) avoid the possibilities of contamination
and cross- contamination

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(iii) designed / constructed / maintained to prevent entry of insects, pests, birds, and rodents. Interior
surface (walls, floors and ceilings) shall be smooth and free from cracks, and permit easy cleaning,
painting and disinfection. 1.3 Water System. - There shall be validated system for Treatment of water
drawn from own or any other source to render it potable in accordance with standards specified by the
Bureau of Indian Standards or Local Municipality, so as to produce Purified Water conforming to
Pharmacopoeial specification. 1.4. Disposal of waste. - (i) The disposal of sewage and effluents (solid,
liquid and gas) from the manufactory shall be in conformity(compliace) with the requirements of
Environment Pollution Control Board. (ii) All bio-medical waste shall be destroyed as per the provisions
of the Bio-Medical Waste (Management and Handling) Rules, 1996. (iii) Additional precautions shall be
taken for the storage and disposal of rejected drugs. Records shall be maintained for all disposal of
waste. (iv) Hazardous, toxic substances and flammable materials shall be stored in suitably designed and
enclosed areas in conformity with Central and State Legislations.

2. WAREHOUSING AREA : 

2. WAREHOUSING AREA It is a large building where raw materials or manufactured, goods may be
stored. 2.1 Adequate areas shall be designed to allow sufficient and orderly warehousing of various
categories of materials and products like starting and packaging materials, intermediates, bulk and
finished products, products in quarantine, released, rejected, returned or recalled, machine and
equipment spare parts and change items. 2.2 Warehousing areas shall be designed and adapted to
ensure good storage conditions. They shall be clean, dry and maintained with acceptable temperature
limits, where special storage conditions are required (e.g. temperature, humidity), these shall be
provided, monitored and recorded. Proper racks, bins and platforms shall be provided for the storage of
materials.

3. PRODUCTION AREA : 

3. PRODUCTION AREA 3.1. The production area shall be designed to allow the production preferably in
uni-flow and with logical(reasonable) sequence of operations. 3.2. In order to avoid the risk of cross-
contamination, separate dedicated and self-contained facilities shall be made available for the
production of sensitive pharmaceutical products like penicillin or biological preparations with live
microorganisms. 3.3. Pipe-work, electrical fittings, ventilation openings and similar services lines shall be
designed, fixed and constructed to avoid creation of recesses(hallow)spaces. Services lines shall
preferably be identified by colours and the nature of the supply and direction of the flow shall be
marked/indicated.
4. ANCILLARY AREAS : 

4. ANCILLARY AREAS Additional but less important 4.1 Rest and refreshment rooms shall be separate
from other areas. These areas shall not lead directly to the manufacturing and storage areas. 4.2
Facilities for changing, storing clothes and for washing and toilet purposes shall be easily accessible and
adequate for the number of users. 4.3 Maintenance workshops shall be separate and away from
production areas. Whenever spares, changed parts and tools are stored in the production area, these
shall be kept in dedicated rooms or lockers. Tools and spare parts for use in sterile areas shall be
disinfected before these are carried inside the production areas. 4.4. ANIMAL HOUSING AREAS shall be
isolated from other areas. The other requirements regarding animal houses shall be those as prescribed
in Rule 150-C(3) of the Drugs and Cosmetics Rules, 1945 which shall be adopted for production
purposes.

5. QUALITY CONTROL AREA : 

5. QUALITY CONTROL AREA 5.1. Quality Control Laboratories shall be independent of the production
areas. Separate areas shall be provided each for physico-chemical, biological, microbiological or radio-
isotope analysis. Separate instrument room with adequate area shall be provided for sensitive and
sophisticated instruments employed for analysis. 5.2 Quality Control Laboratories shall be designed
appropriately for the operations to be carried out in them. Adequate space shall be provided to avoid
mix-ups and cross-contamination. Sufficient and suitable storage space shall be provided for test
samples, retained samples, reference standards, reagents and records. 5.3. The design of the laboratory
shall take into account the suitability of construction materials and ventilation. 5.4. Quality Control
Laboratory shall be divided into separate sections i.e. for chemical, microbiological and wherever
required, biological testing. These shall have adequate area for basis installation and for ancillary
purposes.

6. PERSONNEL : 

6. PERSONNEL 6.1. The manufacture shall be conducted under the direct supervision of competent
technical staff with prescribed qualifications and practical experience in the relevant dosage and / or
active pharmaceutical products. 6.2 The head of the Quality Control Laboratory shall be independent of
the manufacturing unit. The testing shall be conducted under the direct supervision of competent
technical staff who shall be whole time employees of the licensee. 6.5. Number of personnel employed
shall be adequate and in direct proportion to the workload. 6.6. The licensee shall ensure in accordance
with a written instruction that all personnel in production area or into Quality Control Laboratories shall
receive training appropriate to the duties and responsibility assigned to them. They shall be provided
with regular in-service training.

7. HEALTH, CLOTHING AND SANITATION OF WORKERS : 

7. HEALTH, CLOTHING AND SANITATION OF WORKERS 7.1 The personnel handling Beta-lactum
antibiotics shall be tested for Penicillin sensitivity before employment and those handling sex hormones,
Cytotoxic substances and other potent drugs shall be periodically examined for adverse effects. 7.2 Prior
to employment, all personnel, shall undergo medical examination including eye examination, and shall
be free from Tuberculosis, skin and other communicable diseases. Thereafter, they should be medically
examined periodically, at least once a year. 7.3 All persons prior to and during employment shall be
trained in practices which ensure personnel hygiene. 7.4 No person showing, at any time, apparent
illness or open lesions which may adversely affect the quality of products, shall be allowed to handle
starting materials, packing materials, in-process materials, and drug products until his condition is no
longer judged to be a risk. 7.5 All employees shall be instructed to report about their illness or abnormal
health condition to their immediate supervisor so that appropriate action can be taken.

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7.6 Direct contact shall be avoided between the unprotected hands of personnel and raw materials,
intermediate or finished, unpacked products. 7.7 All personnel shall wear clean body coverings
appropriate to their duties. 7.8 Smoking, eating, drinking, chewing or keeping plants, food, drink and
personal medicines shall not be permitted in production, laboratory, storage and other areas where they
might adversely influence the product quality.

8. MANUFACTURING OPERATIONS AND CONTROLS : 

8. MANUFACTURING OPERATIONS AND CONTROLS 8.1 All manufacturing operations shall be carried out
under the supervision of technical staff approved by the Licensing Authority. Each critical step in the
process relating to the selection, weighing and measuring of raw material addition during various stages
shall be performed by trained personnel under the direct personal supervision of approved technical
staff. The contents of all vessels and containers used in manufacture and storage during the various
manufacturing stages shall be attractively labeled with the name of the product, batch number, batch
size and stage of manufacture. Each label should be dated by the authorized technical staff. Products
not prepared under aseptic conditions are required to be free from pathogens like Salmonella,
Escherichia coli, Pyocyanea, etc.

9. SANITATION IN THE MANUFACTURING PREMISES : 

9. SANITATION IN THE MANUFACTURING PREMISES 9.1 The manufacturing premises shall be cleaned
and maintained in an orderly manner, so that it is free from accumulated waste, dust, debris and other
similar material. A validated cleaning procedure shall be maintained. 9.2 The manufacturing areas shall
not be used for storage of materials, except for the material being processed. 9.3 A routine sanitation
program shall be drawn up and observed, which shall be properly recorded and which shall indicate: (a)
specific areas to be cleaned and cleaning intervals. (b) cleaning procedure to be followed, including
equipment and materials to be used for cleaning; and (c) personnel assigned to and responsible for the
cleaning operation. 9.5 Production areas shall be well lighted, particularly where visual on-line controls
are carried out.
10. RAW MATERIALS : 

10. RAW MATERIALS 10.1 The licensee shall keep an inventory(complete list of items) of all raw
materials to be used at any stage of manufacture of drugs and maintain records as per Schedule U. 10.2
All incoming materials shall be purchased from approved sources under valid purchase vouchers.
Wherever possible, raw materials should be purchased directly from the producers. 10.3 Authorized
staff appointed by the licensee in this behalf, which may include personnel from the Quality Control
Department, shall examine each consignment on receipt and shall check each container for integrity of
package and seal. Damaged containers shall be identified, recorded and segregated(kept a part). 10.4 If
a single delivery of material is made up of different batches, each batch shall be considered as a
separate batch for sampling, testing and release.

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10.5Raw materials in the storage area shall be appropriately labeled. Labels shall be clearly marked with
the following information: (a) designated name of the product and the internal code reference, where
applicable, and analytical reference number; (b) manufacturer.s name, address and batch number; (c)
the status of the contents (e.g. quarantine, under test, released, approved, rejected); and (d) the
manufacturing date, expiry date and re-test date. 10.6 There shall be adequate separate areas for
materials .under test., .approved. and .rejected. with arrangements and equipment to allow dry, clean
and orderly placement of stored materials and products, wherever necessary, under controlled
temperature and humidity. 10.7 Only raw materials which have been released by the Quality Control
Department and which are within their shelf-life shall be used. 10.8 It shall be ensured that all the
containers of raw materials are placed on the raised platforms/racks and not placed directly on the
floor.

11. EQUIPMENT : 

11. EQUIPMENT 11.1 Equipment shall be located, designed, constructed, adapted and maintained to suit
the operations to be carried out.Each equipment shall be provided with a logbook, wherever necessary.
11.2 Balances and other measuring equipment of an appropriate range, accuracy and precision shall be
available 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 Standard Operating Procedures and
records maintained. 11.3 To avoid accidental contamination, wherever possible, non-toxic/edible grade
lubricants shall be used and the equipment shall be maintained in a way that lubricants do not
contaminate the products being produced. 11.4 Defective equipment shall be removed from production
and Quality Control areas.

12. DOCUMENTATION AND RECORDS. : 

12. DOCUMENTATION AND RECORDS. Documentation is an essential part of the Quality assurance
system and as such, shall be related to all aspects Good Manufacturing Practices (GMP). Its aim is to
define the specifications 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.

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12.1 Documents designed, prepared, reviewed and controlled, wherever applicable, shall comply with
these rules. 12.2 Documents shall be approved, signed and dated by appropriate and authorized
persons. 12.3 Documents shall specify the title, nature and purpose. They shall be laid out in an orderly
fashion and be easy to check. 12.4 The records shall be made or completed at the time of each
operation in such a way that all significant activities concerning the manufacture of pharmaceutical
products are traceable. Records and associated SOP’s shall be retained for at least one year after the
expiry date of the finished product. 12.5 Data may be recorded by electronic data processing systems or
other reliable means, but Master Formulae and detailed operating procedures relating to the system in
use shall also be available in a hard copy to facilitate checking of the accuracy of the records. Wherever
documentation is handled by electronic data processing methods, authorized persons shall enter modify
data in the computer.

13. LABELS AND OTHER PRINTED MATERIALS : 

13. LABELS AND OTHER PRINTED MATERIALS Labels are absolutely necessary for identification of the
drugs and their use. The Printing shall be done in bright colours and in a legible manner. The label shall
carry all the prescribed details about the product. 13.1 All containers and equipment shall bear
appropriate labels. Different colour coded tablets shall be used to indicate the status of a product (for
example under test, approved, passed, rejected). 13.2 Prior to release, all labels for containers, cartons
and boxes and all circulars, inserts and leaflets shall be examined by the Quality Control Department of
the licensee. 13.3 Records of receipt of all labeling and packaging materials shall be maintained for each
shipment received indicating receipt, control reference numbers and whether accepted or rejected.

14. QUALITY ASSURANCE. : 

14. QUALITY ASSURANCE. 14.1 The system of quality assurance proper to the manufacture of
pharmaceutical products shall ensure that: - (a) the pharmaceutical products are designed and
developed in such a way that it meets the requirement of Good Manufacturing Practices and other
associated codes such as those of Good Laboratory Practices and Good Clinical Practices. (b) adequate
arrangements are made for manufacture, supply and use of the correct starting and packaging
materials. (d) the finished product is correctly processed and checked in accordance with established
procedures.

15. SELF INSPECTION AND QUALITY AUDIT : 

15. SELF INSPECTION AND QUALITY AUDIT To evaluate the manufacturer's compliance with GMP in all
aspects. The manufacturer shall constitute a team of qualified persons from within or outside the
company. The procedure for self-inspection shall be documented. The team responsible for self-
inspection shall consist of personnel who can evaluate the implementation(completion) of Good
Manufacturing Practice objectively. Written instructions for self-inspection shall be drawn up which shall
include the following: - (a) Premises including personnel facilities. (b) Maintenance of buildings and
equipment. (c) Storage of starting materials and finished products (d) Production and in-process controls
(e) Quality control (f) Documentation e.t.c

16. QUALITY CONTROL SYSTEM. : 

16. QUALITY CONTROL SYSTEM. Every manufacturing establishment shall establish its own quality
control laboratory manner by qualified and experience staff. Quality control shall be concerned with
sampling, specifications, testing, documentation, release procedures. It is not limited to laboratory
operations but shall be involved in all decisions concerning the quality of the product. The area of the
quality control laboratory may be divided into Chemical, Instrumentation, Microbiological and Biological
testing. Adequate area having the required storage conditions shall be provided. SOP’S shall be available
for sampling, inspecting and testing of raw materials, intermediate bulk finished products and packing
materials. All instruments shall be calibrated and testing procedures validated before these are adopted
for routine testing.

17. MASTER FORMULA RECORDS : 

17. MASTER FORMULA RECORDS There shall be Master Formula records relating to all manufacturing
procedures for each product and batch size to be manufactured. The master Formula shall include: - (a)
the name of the product together with product reference code relating to its specifications. (b) the
patent or proprietary name of the product along with the generic name, a description of the dosage
form, strength, composition of the product and batch size. (c) name, quantity, and reference number of
all the starting materials to be used. (e) a statement of the processing location and the principal
equipment to be used. (f) the methods, or reference to the methods, to be used for preparing the
critical equipments including cleaning, assembling, calibrating, sterilizing. (g) detailed stepwise
processing instructions and the time taken for each step. (i) the requirements for storage conditions of
the products, including the container, labeling and special storage conditions where applicable. (j) any
special precautions to be observed and packing details and specimen labels.

18. PACKING RECORDS. : 

18. PACKING RECORDS. There shall be authorized packaging instructions for each product, pack size and
type. These shall include or have a reference to the following: - (a) name of the product. (b) description
of the dosage form, strength and composition. (c) the pack size expressed in terms of the number of
doses, weight or volume. (d) description of the packaging operation, including any significant subsidiary
operations and equipment to be used. (e) details of in-process controls with instructions for sampling.