Genral premises on GOOD MANUFACTURING PRACTICE

1. Presented By
Mr. Jagadeesh Tekkali
M.Pharmacy 1st year
15AC1S0414
VIGNAN INSTITUTE OF PHARMACEUTICAL TECHNOLOGY
An ISO 9001:2008, 14001:2004, OHSAS 18001:2007 Certified Institution
Beside VSEZ, kapujaggarajupeta, Duvvada,VISAKHAPATNAM-530046
(Approved by A.I.C.T.E & PCI and affliated to JNTUK)

2.  Location
 Design
 Construction
 Maintenance
 Plant layout
 Sanitations
 Environmental control
 Sterile areas
 Contamination control

3. Principle
Important aspects to be kept in mind to ensure the
Quality product several operations to be carried out for
different dosage forms and product range:

Location
 Design
 Construction
 Adaptation
 Maintenance

4. Location
 Geography, climate, noise and economic factors
 Neighbours
 What do they do?
 What impact can they have on the
business?
 Pollution/effluent control
 Minimum risk for contamination of products and
materials

5. Principle
 Premises must be
located to minimize
risks of cross-
contamination, e.g.
not located next to a
malting factory with
high airborne levels
of yeast

6. Plant layout
The plant layout and design should aim to:
 Minimize risks of errors
 Permit effective cleaning
 Permit effective maintenance
 Avoid cross-contamination, build-up of dirt
and dust
 Avoid any adverse effect on the quality of
products

7. Design Principles
Keep in mind:
 Material flow
 People flow
 Process flow
 Ensure logical flow

8. Design
 Suitable design and construction to facilitate good
sanitation
 Cleaning and disinfecting according to detailed
written procedures – records maintained
 Maximum protection against entry of insects, birds
and animals
 Procedure for rodent and pest control

9. Construction
 Suitable materials
 Electrical supply
 Suitable lighting (especially for visual on-line checks)
 Temperature and relative humidity control
 Appropriate and effective ventilation
These may affect products during manufacture or
storage as well as functioning of equipment

10.  The temperature and
relative humidity should
be controlled, monitored
in accordance with an
SOP, and the results
recorded. The limits
should be appropriate
according to the materials
stored and product
processed

11. Construction
 Dust generating operations
 e.g. during sampling, weighing, mixing,
packing of powders, etc.)
 Measures should be taken to prevent cross-
contamination
 Measures to facilitate cleaning

12. Maintenance
 Careful maintenance done
 Repairs and maintenance should not present any
hazard to the quality of the products

14. some recommendations for specific areas
 Ancillary areas
 Storage areas
 Weighing areas
 Production areas
 Quality control areas
Control of contamination maintain few specific
areas such as

15. Ancillary Areas
 Rest and refreshment rooms separate from
manufacturing and quality control areas
 Changing, washing and toilet areas accessible and
appropriate numbers
 Maintenance workshops separated from
production - if not possible – tools in reserved
areas
 Animal houses well isolated – separate air
handling and entrance

17. Cleaning of incoming
containers
 Cleaning with a cloth, or
duster
 Cleaning by using a
vacuum cleaner
 Use of air curtains and
air tunnels

18. Storage areas
 Storage areas of sufficient capacity
 Orderly storage of categories of materials and
products
 Separate and segregated areas: starting materials,
packaging materials, intermediates, bulk, finished
products, quarantined, released, rejected,
returned and recalled products and materials

20. Storage areas
 Appropriate temperature and relative humidity
conditions within defined limits
Provided, controlled, monitored and recorded
 Good storage conditions: clean, dry and
appropriate lights

21. Storage areas
 Quarantine area: clearly marked and access
restricted
 A separate sampling area is the norm: no risk for
contamination or cross-contamination
 Segregated areas for rejected, recalled and
returned materials and products
 Safe and secure areas for highly active,
radioactive materials, narcotics and other
materials (risk of abuse, fire, explosion)

23.  QC laboratories should be separate from
production areas
 Separate areas for biological,
microbiological and radioisotope methods
 Suitable design with sufficient space to
avoid mix-ups and cross-contamination
 Suitable space for storage samples,
reference standards, solvents, reagents
and records
Quality Control areas

24. Quality Control areas
 Suitable construction materials
 Prevention of fumes
 Ventilation
 Separate air supply (production and QC)
 Separate rooms for some instruments to protect
them from interference (e.g. electrical, vibration,
moisture, etc.)
See supplementary training on QC laboratories

25. Health, clothing ,sanitation of workers –
 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. These personnel should
be moved out of these sections (except in dedicated facilities), by rotation, as a health
safeguard.
 Prior to employment, all personnel, shall undergo medical examination including eye
examination, and shall be free from Tuberculosis, skin and other communicable or contagious
diseases. Thereafter, they should be medically examined periodically, at least once a year.
Records shall be maintained thereof. The licensee shall provide the services of a qualified
physician for assessing the health status of personnel involved in different activities.
 All persons, prior to and during employment, shall be trained in practices which
ensure personnel hygiene. A high level of personal hygiene shall be observed by all those
engaged in the manufacturing processes. Instructions to this effect shall be displayed in
change-rooms and other strategic locations.

27.  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, packaging
materials, in-process materials, and drug products until his
condition is no longer judged to be a risk.
 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.
 Direct contact shall be avoided between the unprotected
hands of personnel and raw materials, intermediate or
finished, unpacked products

28. Environmental Monitoring –
All environmental parameters shall be verified and established at the
time of installation and thereafter monitored at periodic intervals.
The recommended frequencies of periodic monitoring shall be as
follows:
( a ) Particulate monitoring in air – 6 Monthly
(b) HEPA filter integrity testing (smoke testing) – Yearly
(c) Air change rates – 6 monthly
(d) Air pressure differentials – Daily
(e) Temperature and humidity – Daily
(f) Microbiological monitoring by settle plates and/or swabs in aseptic

29.  Class 100 Area - parentrals
 Class 1000 Area- manufactring,production
 Class 10000 Area-filling,sealing.
 Class 100000 Area-packaging,labeling.

30. Terminally Sterilized Products –
 Preparation of primary packaging material such as glass bottles, ampoules and
rubber stoppers shall be done in at least Grade D environment. Where there is
unusual risk to the product from microbial contamination, the above operation
shall be done in Grade C environment. All the processes used for component
preparation shall be validated.
 Filling of products requiring terminal sterilization shall be done under Grade
A environment with a Grade C background.
 Preparation of solutions, which are to be sterilized by filtration, shall be done
in Grade C environment, and if not to be filtered, the preparation of materials
and products shall be in a Grade A environment with Grade B in background.
 Filtration ( Membrane )—
( i ) Solutions for Large Volume Parenterals shall be filtered through a nonfiber
releasing, sterilizing grade cartridge/membrane filter of nominal pore
size of 0.22 μ for aseptic filling whereas 0.45 μ porosity shall be used for
terminally sterilized products

31. ii ) A second filtration using another 0.22 μ sterilizing grade
cartridge/membrane filter shall be performed immediately prior to
filling. Process specifications shall indicate the maximum time during
which a filtration system may be used with a view to precluding
microbial build-up to levels that may affect the microbiological quality
of the Large Volume Parenterals.
( iii ) The integrity of the sterilized filter shall be verified and confirmed
immediately after use by an appropriate method such as Bubble Point,
Diffusive Flow or Pressure Hold Test.