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QUANTITATIVE AND QUALITATIVE LAYOUTS OF PARENTERAL

MANUFACTURING

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

Parenterals :- are Sterile, Pyrogen free preparations


injected through skin or mucous membrane into
internal body compartment.
Parenteral products
A. IV Admixtures consist of one or more sterile drug
products added to an IV fluid. Used for
Drugs intended for continuous infusion
For drugs that may cause irritation or toxicity when given
by direct IV injection.
B. IV fluids
These fluids have multiple uses,
Vehicles in IV admixtures
Provide means for reconstituting sterile powders
Serve as the basis for correcting body fluids and electrolyte
disturbances
For administering parenteral nutrition
Dr. Tushar Gohil, S.L.P.T.P.M.C.,
Amreli

Dextrose : Generally, a solution of 5% dextrose in water


pH of 5% dextrose ranges from 3.5-6.5. Instability may result if it
is combined with an acid sensitive drug.
In higher conc. (e.g. 10% solution in water), dextrose provides a
source of carbohydrate in parenteral nutrition solutions.
Should used cautiously in patients with diabetes mellitus.
C. Electrolyte preparation
D. Dialysate
Used in patients with disorder as renal failure, poisoning, and
electrolyte disturbances.
In peritoneal dialysis,
E. Irrigating solutions
Not intended for infusion into the venous system.

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

GMP Requirements for Sterile Products


Specific points relating to minimizing risks of contamination.
Microbiological
Particulate matter
Pyrogen

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

General Requirements
Production in clean areas
Airlocks for entry
Personnel entry.
Material entry
Separate areas for operations
Component preparation
Product preparation
Filling
Sealing etc
Level of cleanliness
Filtered air
Air classification: Grade A, B, C and D.
Laminar air flow:
Air speed (horizontal versus vertical flow)
Number of air changes
Air samples
Conformity to standards
Work station and environment
Barrier technology and automated systems
Dr. Tushar Gohil, S.L.P.T.P.M.C.,
Amreli

Planning & Scheduling

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

Types of sterile products processing


1 Terminally sterilised prepared, filled and sterilised
2 Sterilised by filtration
3 Aseptic preparation

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

Manufacture of sterile preparations


1. Terminally sterilised:Usually involves filling and sealing product containers under highquality environmental conditions. Products are filled and sealed in
this type of environment to minimize the microbial and particulate
content of the in-process product and to help ensure that the
subsequent sterilization process is successful. In most cases, the
product, container, and closure have low bio-burden, but they are
not sterile. The product in its final container is then subjected to a
sterilization process such as heat or irradiation.
Dr. Tushar Gohil, S.L.P.T.P.M.C.,
Amreli

2. Sterilisation by Filtration:o Previously sterilized container are taken.


o Filters having nominal pore size 0.22 m or less are used for
filtration
o Remove bacteria and moulds but Not viruses & Mycoplasmas
o Double filter layer or second filtration
o No fibre shedding or asbestos filters
o Filter integrity testing

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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3. Aseptic Preparation :- In an aseptic process,


The drug product, container, and closure are first subjected to
sterilization methods separately, as appropriate, and then
brought together.
Note:- In area occupied by personal, the air must be exchanged with the
frequent intervals. Fresh outside or recycled air must be first filtered to
remove particulate matter and than HEPA filters are used to get
CLASS-100 air systems.

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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SPECIFIC REQUIREMENTS FOR MANUFACTURE OF PARENTERAL


PREPARATIONS

(SMALL

VOLUME INJECTABLES AND LARGE

VOLUME PARENTERALS) As per schedule M .


[1] General :- Sterile products, being very critical and sensitive
in nature a very high degree of precautions, prevention are
needed for its preparation. Dampness, dirt and darkness are
to be avoided to ensure aseptic conditions in all there shall be
strict compliance in the prescribed standards especially in the
matter of supply of water, air, active materials and in the
maintenance of hygienic environment.

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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[2] Building and Civil Works:


The building-built on proper foundation with standardized materials
Location of services like water, steam, gases etc. shall be such that
their servicing or repair shall not pose any threat to the integrity of the
facility. Water lines shall not pose any threat of leakage to any of the
manufacturing area.
The manufacturing areas- clearly separated into support areas &
preparation areas. Operations like removal of outer

cardboard

wrappings of primary packaging materials shall be done in the decartoning areas which are segregated from the washing areas.
Wooden pallets, fiberboard drugs, cardboard and other particle
shedding materials shall not be taken inside the preparation areas.

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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General points to be in consideration for ASEPTIC Areas


Walls, floors and ceiling-impervious, non-shedding, non-flaking
and non-cracking.
Flooring-unbroken, provided with a cove both at the junction
between the wall and the floor & wall and ceiling. Epoxy should
done in aseptic area, Walls-shall be flat.
Light-fittings and air-grills-shall flush with the walls and not hanging
from ceiling.
Doors & Windows-made of non-shedding material preferably
Aluminium or Steel material. Doors shall open towards the higherpressure area so that they close automatically due to air pressure.
The furniture-smooth, washable and made of stainless steel or any
other appropriate material

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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[3] Garments
The garments-made of non-shedding and tight weave material, single
piece with fastenings at cuffs, neck and at legs to ensure close fit.
Trouser legs shall be tucked inside the cover boots. Design-include a
hood (head-cover) or a separate hood which can be tucked inside the
over-all. Zips (if any) shall be of plastic material.
Gloves-made of latex or other suitable plastic materials & long
enough to cover wrists completely and allow the over-all cuff to be
tucked in.
footwear- of suitable plastic or rubber material, daily cleaned with a
bactericide. Garment changing procedures shall be documented and
operators trained in this respect.

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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[4] Area planning: Depends on


1). Type of production
A. Batch operations
Advantages:
1.Product quality, consistency, and homogeneity are relatively easily
controlled. 2. Production documentation is easy.
Disadvantages:
1.Economically undesirable because it is labor intensive and does not
exploit the economies of volume.
B. Continuous operations: it is suited to very high volume
production
Advantages:
1. Minimizes shortcoming of batch operations; labor, production time,
and environmental exposure of the product.
2. Since the intermediate material handling steps are eliminated, the
potential for product contamination during those steps no longer exists.
Disadvantages:
1. Product quality assurance is difficult.
2. It is very difficult to document the ingredients or process cycle for a
product produced in a continuous process.
Dr. Tushar Gohil, S.L.P.T.P.M.C.,
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2). Container size


SVPs

and

LVPs

obviously

requires

different

space

considerations.
All the production equipment has container size limitations- large
container requires large equipments and more space.

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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3). Environment control needs

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Amreli

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Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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4). Product characteristics


Liquids are probably the easiest product to handle.
Emulsion may require compounding areas close to filling
lines to ease transfer problems. Pumping systems will be very
critical.
Suspension

will

require

means

of

maintaining

homogenous mixture prior to filling.


To minimize the time the suspension resides in piping, reservoir, and
pump system, filling rate should be kept high and the distance from
compounding to filling should be minimized.

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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5). Space requirements


[QUANTITATIVE LAYOUT OF PARENTERAL MANUFACTURING ]

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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6). Personnel Movement


The movement of personnel should be planned during the design
of individual plant areas.
Discontinuous and crowded flow patterns can decrease
production efficiency, increase security problems, and increase
the problems of maintaining a clean environment.
Personnel flow path from zone to zone must be such that
access to higher level of cleanliness is only through change
rooms, gowning rooms, locker rooms, or other areas as may be
required to prepare the personnel for the cleaner area.
In a parenteral plant degree of access should be restricted.
Planning for visitors and nonproduction employees in
advance

can

prevent

or

lessen

many

future

problems,

particularly in critical area.


A glassed mezzanine or balcony provides absolute isolation,
Tusharof
Gohil,
S.L.P.T.P.M.C.,
yet may give excellent Dr.
view
process.
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Amreli

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Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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Grade A corresponds with Class 100 or M 3.5 or ISO Class 5;


Grade B with Class 1000 or M 4.5 ISO Class 6;
Grade C with Class 10,000 or M 5.5 or ISO Class 7;
Grade D with Class 100,000 or M 6.5 or ISO Class 8.

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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Amreli

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Amreli

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Amreli

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Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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CLEAN ROOM An area with defined environmental control of


particulate and microbial contamination, constructed and used
in
such a way as to reduce the introduction, generation and retention of
contaminants within the area

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Amreli

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Amreli

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REFERENCES
www.GMP.online.coms
Pharmaceutical dosage forms (Parenteral Preparation) by Kenneth
Avis, Leon Lachman, Vol-1.
Pharmaceutical dosage forms (Parenteral Preparation) by Kenneth
Avis, Leon Lachman, Vol-2
Drugs & Cosmetics Act 1940.
www.ispc.org
www.whqlibdoc.who.org
The theory and Industrial pharmacy by Leon Lachman, Third
edition
Aseptic Pharmaceutical Manufacturing by M.J.Groves
Pharmaceutical science by Remington, 20th edition
Pharmaceutical process Validation by Loftus & Nash: 29-90.
Sterile Pharmaceutical Manufacturing by Groves Gisan.
www.fda.gov.
American Journal of Hospital Pharmacy, Vol. 38, Issue 8, 11441147
Dispensing for pharmaceutical students; 10 th edition; by:-S J
Carton
www.dwscientific.co.uk
www.pharmamachines.com
www.bascotech.com
S.L.P.T.P.M.C.,
www.getthatmag.com Dr. Tushar Gohil,
Amreli
www.fabtecheng.com

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Thank You

Dr. Tushar Gohil, S.L.P.T.P.M.C.,


Amreli

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