Factory and Hospital Hygiene

Manufacturing:
• Manufacture is the complete cycle of production of a medical product.
• This cycle includes the acquisition of all raw materials, their processing into a final
product, and its subsequent packaging and distribution.
Quality assurance (QA)
• This term refers to the sum total of the arrangements made to ensure that the final
product is of the quality required for its intended purpose.
• It consists of good manufacturing practice plus factors such as original product design
and development.
Quality control (QC)
Quality control refers to the part of GMP that ensures that
1. At each stage of manufacture the necessary tests are conducted.
2. The product is not released until it has passed these tests.

In - process control
1. This comprises any test on a product, the environment or the equipment that
is used during the manufacturing process.
2. An example of this is testing that an autoclave is functioning correctly.
Good manufacturing practice (GMP)
Good manufacturing practice (GMP) comprises that part of quality assurance that is aimed at
ensuring the product is consistently manufactured to a quality appropriate for its intended use.
GMP requires that:
(i) the manufacturing process is fully defined before it is commenced; and
(ii) the necessary facilities are provided.
In practice, this means that:
1. Personnel must be adequately trained
2. Suitable premises and equipment employed
3. Correct materials used
4. Approved procedures adopted
5. Suitable storage and transport facilities available
6. Appropriate records made.
Good Manufacturing Practice (GMP):
• A system for ensuring that products are consistently produced and controlled according to
quality standards.
• It is designed to minimize the risks involved in any pharmaceutical production that cannot be
eliminated through testing the final product.
1. GMP covers all aspects of production from the starting materials, premises, and equipment
to the training and personal hygiene of staff.
2. Detailed written procedures are essential for each process that could affect the quality of
the finished product.
3. There must be systems to provide documented proof that correct procedures are
consistently followed at each step in the manufacturing process - every time a product is
made.
Regulation for GMP/cGMP
1. FDA ensures the quality of drug products by carefully monitoring drug manufacturers'
compliance with its Current Good Manufacturing Practice (CGMP) regulations.
2. The cGMP regulations for drugs contain minimum requirements for the methods,
facilities, and controls used in manufacturing, processing, and packing of a drug
product.
3. The regulations make sure that a product is safe for use, and that it has the ingredients
and strength it claims to have.
4. The approval process for new and generic drug marketing applications includes a
review of the manufacturer's compliance with the cGMPs.
5. FDA assessors and inspectors determine whether the firm has the necessary
facilities, equipment, and ability to manufacture the drug it intends to market.
Factory Hygiene

• Plants which are involved in the production of the microbiological

products are at high risk of the microbe born disease
• Also other pharmaceutical manufacturing facilities have large
opportunities for the microorganisms to grow and spread
Steps to avoid contamination
1. Working area should be kept clean, dry and tidy.
2. Cracks must be eliminated as it provide surface for microbes to grow.
3. Coving(bendings) should be used at junctions of walls and wall to the roof.
4. All services point i.e. pipes, air vents and lighting fixtures should be such
positioned that they could be easily cleaned.
5. Proper disinfection policy to remove any chance of contamination.
6. Equipments must be easy to dismantle and clean.
7. Checking of equipments to determine presence of any viable strain must be
performed periodically.
Steps to avoid contamination
1. Entry of clean and purified air into the facility so that there is no chance of
air borne microorganisms
2. High standards of personal cleanness, adequate hand washing and hand
disinfecting with proper solvent
3. Operatives should be cleaned and free from any communicable disease and
open lesions
Manufacturing of sterile pharmaceutical
products
1. Sterile pharmaceutical products are free from all viable microorganisms and
must be apyrogenic.
2. All these products must be terminally sterilized.
3. Terminally sterilized means product must be sterilized after filling into its final
container.
4. Vaccines, consisting of live attenuated microbes should be filled in separate
sterile area.
5. If same area is used then complete killing or removal of microorganism must
be validated before other product run.
Aseptic area

1. Aseptic area(free from any contaminants) should be separate from other area and kept
safe with organized workflow
2. All surfaces in this area must be smooth and impervious(not allowing fluid to pass
through) in order to prevent dust accumulation and easy cleanliness
3. No cracks and open joints – as they may facilitate microbes to grow
4. Laminar/ Unidirectional air flow
5. Fixtures(equipment’s, furniture) kept at minimum so to avoid turbulence in air flow
6. Equipments must be easy to dismantle, clean and could be sterilized when needed
Aseptic area
• Properly illuminated with lights fixed in ceiling
• Electrical switches must be outside the area
• Sinks and drains must be excluded from aseptic area
• Filtered air at positive pressure is provided continuously
• Air inlet point is equipped with HEPA filters and placed in ceiling
• Displacement of air may be vertical or horizontal and must be unidirectional
• Clothing of the sterile area is made up of polyesters
• Clean suits are provided on daily basis while head, foot and mouth covers are
changed for each sessions
Cleaning and disinfection
1. A strict and proper cleaning and disinfection policy is maintained round the clock
2. Floors are cleaned by alkaline detergents and ionic and non ionic surfactants
3. Working surfaces are cleaned by alcohols or chlorine based agents i.e.
hypochlorites
4. Skin is disinfected by the cetrimide or chlorhexidine formulated in 70% isopropyl
alcohol
5. Disinfectants must also be sterile and made in water for injection
Operations
1. Numbers of peoples involved in sterile area must be kept minimum
2. More people results in turbulence(irregular motion of air) and shedding of
particles
3. Activities are also kept minimum
4. Containers made up of fibers like paper, cardboard may easily be contaminated
so it is avoided to bring in sterile area
5. Ingredients must be put into the proper container before taking into the sterile
area
Environmental monitoring
1. Air is monitored for particles and microorganisms
2. Settle plate technique is used to determined the presence of microbe in the air
3. Plates are exposed for four hours and then incubated
4. Surface may be monitored by swabbing or by contact plate method
5. Glove prints are also taken on agar plate to determine adequate cleanliness of the
gloves
Eliminating human intervention
• Movement of staff can increase particle shading
• Isolator both is used to separate the products form the direct contact of the operator
• Restricted access barrier systems (RABS) provide a level of control intermediate
between an isolator and a cleanroom
Guide to GMP
1. Compliance with the GMP is one of the major factors considered by the licensing
authorities when examining an application for license
2. Between 1971 to 1983 essential features of the GMP was covered by the “Orange guide”
prepared and published by the UK
3. In 1989, it was replaced with the “Guide to good manufacturing practice for Medicinal
products” and published by the MHRA(Medicines and Healthcare products
Regulatory Agency)
4. FDA has published “FDA requirement for cGMP compliance (2007)”
5. Sharp in 2000 published “Quality in the manufacture of medicines and other health
care products” as guideline to GMP
6. Beaney in 2005 published “Quality assurance of aseptic preparation services” as
guideline to GMP
Hospital hygiene
• The hospital environment can be contaminated with pathogens. Salmonella or
Shigella spp., Escherichia coli, or other pathogens may be present in the food and
cause an outbreak of disease just as they can in a community outside the hospital
• If the water distribution system breaks down, waterborne infections may develop.
• In more sophisticated premises the water cooling system of air conditioning
equipment may become contaminated with Legionella pneumophilia.
The route of transmission
• Microorganisms can be transmitted from their source to a new host through direct
or indirect contact, in the air, or by vectors
• Vector-borne transmission is typical of countries in which insects, arthropods, and
other parasites are widespread
• Airborne transmission occurs only with microorganisms that are dispersed into the air
and that are characterized by a low minimal infective dose. Only a few bacteria and
viruses are present in expired air, and these are dispersed in large numbers only as a
result of sneezing or coughing.
• Direct contact between patients does not usually occur in health-care facilities, but an
infected health-care worker can touch a patient and directly transmit a large number of
microorganisms to the new host.
• The most frequent route of transmission, however, is indirect contact.

• The infected patient touches and contaminates an object, an instrument, or a surface

Subsequent contact between that item and another patient is likely to contaminate the
second individual who may then develop an infection.

• During general care and/or medical treatment, the hands of health-care workers often come
into close contact with patients. The hands of the clinical personnel are thus the most
frequent vehicles for nosocomial infections. Transmission by this route is much more common
than vector borne or airborne transmission or other forms of direct or indirect contact.
Prevention
• Prevention of disease causing microbes in hospital setup is based on two principles:
• Separate the infection source from the rest of the hospital
• Cut off any route of transmission
• This is achieved through:
1. Isolation of infected patients and standard precautions
2. Standard Cleaning operations in hospitals
3. Sterilization of all equipments i.e. Surgical equipments
4. Disinfection of all surfaces, floors, trolleys etc.
5. Hand hygiene of patients and all staff
Reference
• Hugo and Russell’s Pharmaceutical Microbiology, 8th edition, chapter 23,
page no. 402-415