cgmp

1. A Seminar on
Regulatory Requirements of
Pharma Facilities with
reference to cGMP
Miss. Snehal K. Dhobale.
M-pharmacy- 2nd semester,
Dept. of Pharmaceutics
Padm. Dr.D.Y.Patil college of Pharmacy, Akurdi
Under the guidance of
Prof. Dr. P.H.Sharma
QAT Dept.

2. INTRODUCTION
• In design of pharmaceutical plant we need to follow and
understand basic regulatory requirement for the construction of
pharmaceutical plant .
These requirements are mainly divided in two categories
Requirements related to good manufacturing practices currently
followed in pharmaceutical industry
Requirements related to factories Acts and Rules, which is a
central act and the rules described separately by each state in India.
IN ADDITION TO THESE REQUIREMENTS, THE OTHER
RULES AND REGULATIONS ARE:
1. Regulation related to water and air pollution
2.Regulation related to handling and storage of inflammable

3. Difference between GMP and
cGMP
GMP cGMP
1)Good Manufacturing Practice
Without validation terminology its a
GMP.
1)Good Manufacturing Practice
With validation terminology its a
cGMP.
2)GMP refers to Goods
Manufacturing Practices that are
guidelines followed by over 100
countries
2)cGMP is current goods
manufacturing practices that need
to be adhered to by participating
countries.
3)GMP applies to pharmaceutical
and healthcare products and help
to maintain high standards in
these products.
3) cGMP is to remind accepting
countries that all guidelines must
be followed with latest and current
production processes.

4. Site map of the Location

5. Basic cGMPs
• Remember, QUALITY is the responsibility of everyone
• Don’t just make the product or do your job and leave it
up to Quality Assurance fix the problems
1) Current = dynamic
Standards evolve over time
2) Good practices
Minimal standards
Not “best practices”
 Unless “best” is, in fact, current minimal
3) Feasible and valuable
No threshold for “percentage” in practice
 Doesn’t have to be “predominant”
Enforceable even if nobody is doing it
 Stronger case if someone is doing

6. 4 ‘ P ’s essential Element to represent CGMP
1.Personnels:
The people system and manpower required to carry out the
various tasks within the manufacturing and control function.
2. Parts:
The raw material and components used in connection with the
manufacture and packaging of the drug product as well as the
material used in association with the control.
3. Process:
The building, facilities, equipments instrumentation and support
systems (heat, air, vacuum, water, & lighting ) used in connection
with the manufacturing process and the control.
4. Procedure:
the paper work, documentation of records used in connection
with the manufacturing process and its control
6

7. The Regulations
• Always improving and changing (that is why they are
called “current”)
• Regulations are a minimum that must be met
• cGMPs are listed in the CFR (Code of Federal
Regulations) Part 210 and 211
I. Part 210 - definitions
II. Part 211 - basic instructionscGMP stands for “current
Good Manufacturing Practices”
III. Part 11 - electronic data

8. cGMP requirements are described in
the following categories
1)
• Requirements related to surroundings
2)
• General requirements for pharmaceutical plants
3)
• Requirements related to various departmental
areas in the plant
4)
• Requirements related to special products. eg.
sterile products

9. 1) Requirements Related to
surroundings of the plant
• Schedule M of Drug and Cosmetic Act- 1940 states “The factory
buildings for manufacture of drugs shall be so situated and shall have
such measures as to avoid risk of contamination from external
environment including open sewage, drain ,public lavatory or any
factory which produces disagreeable or oboxious odour, fumes
excessive soot,dust smoke chemicals or biological emission.
• Only Indian cGMP guidelines specifically talk about “surroundings” of
pharmaceutical plant. All other international guidelines talk in terms of
“General Requirements” and “different plant areas.”
• Nowadays many countries have industrial zone concept ie particular
type of industry planned by design in a particular part of country.
Eg. information technology industry is coming up in
Hyderabad,Banglore and Pune.

10. 1) Requirements Related to
surroundings of the plant
• Some of the major points to be considered in case
of surroundings are:
1.Land cost
2.water source
3.Supply of electric power
4.extremes of climate like –heavy rain. Extremes
of temperature, earthquake,
5.transport facilities for material and men
6.Availability of trained and skilled man power,
7.Labour and industrial legislation
8.cost of living etc

11. 2) General Requirements for
pharmaceutical plants
1.They should be easy to clean, maintain and operate. These factors
must be taken in to account while designing the plant layout.
2. Zigzag movements of men and materials should be avoided as far as
possible.
3.Avoiding cross contamination and mix-ups is the main idea in designing
the pharma plant.
4.Mnufacturing plants must be situated in such an environment which
protect all the manufacturing process by minimizing the risk of
contamination of raw material, Packaging material, intermediate and
finish products.
5.Protecting manufacturing processes in plant from contamination
involves control on the environment. A careful planning of HVAC system
must be done to avoid contamination.

12. 2) General Requirements for
pharmaceutical plants (conti..)
6.Manufacturing plants should be so constructed that they can always be kept
in clean and sanitized condition.
7.The vacuum cleaning lines laid down in plants with connections at suitable
points may be a fast and easy method of cleaning.
8. Suitable trash collection system may also be planned and each trash
collection point may have recycled plastic bags put in suitable wire meshed
container.
9.Sanitization SOP and records must be in place and followed.
10.Sanitization SOPs should be clearly described for different area eg
corridors, change room, linen rooms, non sterile processing areas .
11. Aseptic operations areas must have vacuum cleaners made up of at least
S.S.304 and fitted with additional HEPA filters.
12.Well experienced and suitably qualified people should be put in charge of

13. General Requirements for
pharmaceutical plants (conti..)
13. Manufacturing plants should always be kept in a good state of repair. It should be so
designed so that maintenance operation can be carried out without affecting the product
quality .
14.SOPs and records should be kept for cleaning, maintenance, disinfection and
sanitization.
15.Plants should be maintained in order with reference to electric supply ,Lighting,
Temperature, Humidity, HVAC.
16.The maintenance activities should cover following points
a. Wall and ceiling surfaces. No peel off of paint is permissible and such situation must
be immediately repaired this may be main source of contamination.
b. Broken tiles or surfacess can result in accumulation of dust and dirt and also source
of physical accidents.
c. Routine painting of the facility is a must to maintain facility always production worthy.

14. Organization and Personnel
• Shall have a Quality Unit with responsibility to reject or
approve all material, procedures and specifications
• Everyone will have sufficient training, knowledge and
experience to do their job
 Wear clean clothing
 Wear protective apparel to prevent contamination
 Practice good sanitation
 If you are sick or have open lesions that would
impact the drug, then you will be excluded from
direct contact with the product

15. Buildings and Facilities
• Building will be adequately sized for proper storage of
equipment and material
• Operations will be performed in specific areas
• Raw materials received will be placed in quarantine until
tested
• Rejected material will be separated
• There will be adequate lighting
• There will be adequate environmental controls
• There will be air breaks on drain

16. Equipment
• Will be maintained in a good state of
repair
– written schedule of maintenance
• will be cleaned
– written schedule of cleaning
– clean after each batch
• approved cleaning agents
– will not affect product
• ID number on equipment

17. 3) Regulatory Related To Various
Departmental Area
The regulatory guidelines cover requirements
related to the following departments.
Production
areas
Storage and
weighing
areas
Q.C areas
Sterile-
products
areas
Ancillary
areas
Rest, refreshment room
Maintenance workshops
Animal houses.
Change room, toilets
and washrooms.

18. I. Storage and Weighing Areas
• Storage area should be of sufficient capacity to allow orderly
storage of the various categories of materials and products.
• Starting and packaging material, intermediates, bulk and
finished products, products in quarantine and released, rejected
or recalled products.
• Storage area should be designed or adapted to ensure good
storage conditions.
• In particular, they should be clean and dry and maintained
within acceptable temperature limits.
• The weighing should be usually carried out in separate
weighing area.
• Separate suitable and sufficient storage area for
returned,recalled and rejected products.

19. I. Storage and Weighing Areas (CONTI.)
The storage capacity should be calculated based on following points
a.Types of formulation being handled and their volumes per day,week, month
b.Inventory to be carried out of R.M.,P.M.and finish goods at the plant.
c. Specific large volume inventory items eg. Bottles sugar othe formulation solvent
d.Special products to be stored eg sterile drug powders of antibiotics and other similar
products.
e. Active and other substances which are required to be stored in special condition such
as low temp and low humidity
f. Primary packaging materials
g.Printed packaging material
In particular, they should be clean and dry and maintained within acceptable
temperature limits.
The weighing should be usually carried out in separate weighing area.
Separate suitable and sufficient storage area for returned,recalled and rejected
products.

20. II. Production Area
• In order to minimize the risk of a serious medical hazard
due to cross contamination.
• Dedicated and self contained facilities must be available
for the production of particular pharmaceutical products,
such as highly sensitizing materials.eg., penicillin
• Premises should be designed to have logical flow of
materials, well organised layout of plant and machinery
and ease of cleaning, both equipment and facility.
• Production area must be separate in the same building
if we plan to handle sensitive products .

21. II. Production and Process Control
• There will be written procedures
• Document activities
– batch record
– log books
• Control contamination
• Cleanliness
– tanks, paddles, piping, probes, etc.
• Keep organized
• Reconciliation to be done
• Make sure areas are cleared of other lot information
(packaging, labeling, etc.) prior to working with another lot
• Double checks

22. III. Ancillary Area
Rest, Refreshment Room :-
• Rest and refreshment room should be separate from other areas.
Change Rooms and Storing of Linen:-
• Facilities for changing and storing of clothes and for washing and toilet purposes
should be easily accessible and appropriate for the number of users.
• Toilets should not communicate directly with production or storage area. These
areas should be well ventilated.
Maintenance Work Shops
• Maintenance work shops if possible should be separated from production areas.
• Whenever parts and tools are stored in the production area these should be kept
in rooms or lockers reserved for that use
Animal House
. Animal houses should be well isolated from other areas, with
separate entrance and air handling facilities.

23. IV. Sterile Products Area
• All premises should as far as possible designed to
avoid the unnecessary entry of supervisory or
personnel.
• In clean areas all exposed surface should be smooth,
impervious and unbroken in order to minimize the
shedding or accumulation of particle or micro-
organisms and to permit the repeated application of
cleaning agents and disinfectants used.
• Doors should be carefully designed to avoid
uncleanable recesses, sliding doors are undesirable
for this reason.
• False ceiling should be sealed to prevent
contamination from space above them.

24. IV. Sterile Products Area (conti..)
• Pipes and duct should be installed so that they do
not create recesses that are difficult to clean.
• Hand washing facilities should be provided only in
the first stage of changing rooms, not in areas
where aseptic work is done.
• A warning system should be provided to indicate
failure in the air supply.
• Clean areas should be maintained to an
appropriate cleanliness standard and supplied with
air which has passed through filters of an
appropriate efficiency.

25. V. Quality Control Areas
• QC laboratories should be separated from
production areas.
• There should be adequate suitable storage space for
sample, reference standards and records.
• The design of the laboratories should take into
account the suitability of construction materials,
prevention of fumes, and ventilation.
• Separate air handling unit and other provisions are
needed for biological, micro-biological and
radioisotope laboratories.

26. V. Quality Control Areas (conti..)
• A separate room may be needed for instrument to
protect them against electrical interference,
vibrations, excessive moisture.
• All methods used by Q.C. say for sampling, testing,
and other activities, must be validated.
• Validation of testing method is particularly very
important.
• In documentation including, the MPCR (Master
production and control record), BPCR (Batch
production and control record),S.O.P.(Standard
operating procedure), Site Master File.

27. Requirements related to various
departmental areas in the plant
• The factory buildings for manufacture of drugs shall be so situated that it
avoid risk of contamination from external environmental including open
sewage, drain, public lavatory.
Location and
surroundings
• The premises used for manufacturing, processing, warehousing,
packaging labeling and testing purposes shall be .
• (i)compatible with other drug manufacturing operations.
• (ii) adequately working space to avoid the risk of mix-up between
different possibilities of contamination and cross contamination.
• (iii) designed / constructed / maintained to prevent entry of insects,
pests, birds, and rodents.
• (iv) well lighted, effectively ventilated, with proper Air Handling Units.
Building and
premises
• i)There shall be validated system for treatment of water in accordance with
standards specified by the Bureau of Indian Standards or Local Municipality
or Pharmacopoeial specification.
• (ii)Water shall be stored in tanks, which do not adversely affect quality of
water and ensure freedom from microbiological growth.
• (iii) The tank shall be cleaned periodically and records maintained by the
licensee in this behalf.
Water System

28. Requirements related to various
departmental areas in the plant
• The disposal of sewage and effluents (solid, liquid and gas) be
in conformity 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.
Disposal of waste
• Qualifications and practical experience in the relevant field.
• (ii) Written duties of technical and Quality Control personnel
shall be laid and follow strictly.
• (iii) They must have ability to perform the given task at given
level.
Personnel
• Equipment shall be located, designed, constructed, adapted to
suit the operations and logbook is maintained.
• (ii) Equipment shall be calibrated and checked on a scheduled
basis in accordance to SOP and maintain records.
Equipment
• ) Keeping an inventory of all raw materials to be used and
maintain records as per Schedule U.(Particulars to be shown in
manufacturing and analytical records of the drugs.)
• (ii) Authorized staff who examine each consignment for its
integrity.
Raw Materials

29. REFERENCES
1) Overview of cGMP requirements • cGMP Regulations – 21
CFR 211
2) CGMP for Phase 1 INDs Laurie P. Norwood. Deputy Director.
Division of Manufacturing and Product Quality. Office of
Compliance and Biologics Quality
3) How to write Standard Operating Procedures and work
Instructions”. David N.Muchemu, Creatspace, October 2010
4) A primer Good laboratory practice and current good
manufacturing practice Ludwig Huber Agilent Technologies.
5) FDA Food and Drug Administration. GMP Combination
Handbooks. 31 Aug. 2008
6) The Center for Professional Advancement. Good
Manufacturing Practice. 2008. 1 Sep. 2008.
http://www.cfpa.com/gmp-training