Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5482_Библиотеки_им_академика_М_И_Перельмана.pdf
275
Dosage Forms
Rabies Antiserum
It is prepared from horses by giving a course of dead rabies
virus to horses followed by a course of living virus. Then the
blood is collected and the gamma-globulin fraction containing
the antiviral antibodies separated.
This antiserum is highly effective in preventing rabies if
administered within 24 hours of bitten by the animal. It is given
along with rabies vaccine for preventing rabies if the person is
bitten in a sensitive area like head and neck and specially if the
animal is suspected to be rabies.
Measles Serum
For the preparation of measles serum human serum is used
and not the animal serum. Three types of human immune
serum have been introduced for the prevention and treatment
of measles which are as follows:
1. Convalescent measles serum
2. Adult measles serum
3. Placental extracts.
1. Convalescent measles serum: Convalescent measles serum
is prepared from the blood of children who are recently
recovered from measles because at this time the blood
contains a large number of antibodies. Serum is collected
from children because they are more susceptible to measles
than adults.
2. Adult measles serum: It is prepared from the blood of healthy
adults who had suffered from measles in the past or in their
childhood. This serum is less effective than convalescent
serum.
3. Placental extracts: Newborn babies are immune to a number
of infectious diseases like diphtheria, scarlet fever and
measles due to the presence of large number of antibodies
received from the mother through the placental blood.
These antibodies can be separated from placental blood by
different methods; which are used as measles serum and
they are as potent as that of convalescent serum.
Introduction to Pharmaceutics
276
Storage of Immunological Products
Immunological products lose their potency on storage due to
denaturation of antigens or antibodies by chemical reactions
which are largely influenced by storage temperature. Higher
the temperature larger will be deterioration and vice versa,
therefore these products must be stored at a low temperature
and they should be protected from sunlight as sunlight also
leads to decomposition of immunological products.
Most of the bacterial vaccines, antitoxins and antisera
should be stored in a refrigerator at temperatures between
2°C and 10°C. freezing should be avoided. A number of viral
vaccines, e.g. smallpox vaccine and poliomyelitis vaccine
should be stored at or below their freezing points because they
remain stable at this temperature. Antisera should be protected
from light. Freeze-dried vaccines, e.g. smallpox vaccines and
yellow fever vaccines must be stored at a temperature of 10°C
and 0°C respectively.
The recommended storage conditions and expiry dates of
the immunological products are always printed on tbe label
of the containers and these instructions must be carefully
followed.
6
UNIT
Basic Structure, Layout, Sections,
and Activities of Pharmaceutical
Manufacturing Plants
Premises refers to the buildings and facilities where pharma-
ceutical processing is done. These places must comply with
cGMP requirements. In any pharmaceutical plant, manu-
facturing operations must be carried out under clean and
hygienic conditions. Both the external and internal environ-
ments must be geared to be conducive to maintain the quality
and safety of drug products. Special care must also be taken
to prevent contamination of the products and therefore,
the location, design, construction and layout of premises
is a vital part of the Good Manufacturing Practices (GMP)
regulations.
DESIGN AND CONSTRUCTION
The building utilized for drug production must be designed,
constructed, and maintained to ensure hygienic conditions. It
should be suitable for the specific operations performed and
have a layout that minimizes the risk of errors, prevents dirt
accumulation, and avoids cross-contamination that could
impact drug product quality. The walls, ceilings, and floors
of the building should be smooth, free from cracks, and easily
cleanable and disinfectable. The surfaces should not shed
particles, maintaining smoothness and lacking open joints that
can accumulate dust.
Introduction to Pharmaceutics
278
LAYOUT
Utilities
The building should have good lighting, water supply, power
supply, and ventilation. It should also have systems in place
to control the temperature and humidity levels in different
areas. Measures should be taken to prevent pests, insects, and
rodents from entering the building. The design of fittings,
ducts, pipes, and ventilation points should be such that they
are easy to clean. All areas should receive filtered air, and
the filtration and air change rate should be set to achieve the
desired cleanliness level. Adequate lighting should be provided
in different areas, such as bright lighting for inspection areas
and specific lighting for light-sensitive drug manufacturing.
The water system should meet the quality requirements for
the drug product. Water storage tanks should be designed to
maintain water quality and prevent the growth of microbes
(Fig. 6.1).
Fig. 6.1: Plant layout.
279
Basic Structure, Layout, Sections, and Activities of Pharmaceutical
PRINCIPLE AREAS OF PREMISES
Ancillary Areas
Ancillary areas include the following:
Rest and refreshment rooms
Toilets and washrooms
Clothes storage areas
Changing rooms for employees
The important considerations for ancillary areas are as follows:
Rest and refreshment rooms should be separate from other
areas to provide a dedicated space for employees to relax
and recharge.
Facilities for toilets should not have direct communication
with production or storage areas to maintain hygiene and
prevent potential contamination.
Areas designated for changing rooms, clothes storage,
washing, and toilet purposes should be easily accessible
and appropriately sized to accommodate the number of
users.
Warehousing Areas
Storage areas should have adequate capacity to ensure
organized storage of different categories of materials and
products, including:
Raw materials
Packaging materials
Intermediates
Bulk and finished products
Products in quarantine
Released, returned, rejected, and recalled products
Design considerations for storage areas include meeting the
required environmental conditions such as temperature and
humidity, with records maintained for monitoring these condi-
tions. Separate sampling areas should be provided for active
and raw materials, designed appropriately with cleaning,
drying, and storage facilities for sampling tools.
For the sampling of liquid materials, solvents, flammable
substances, toxic or potent materials, separate areas should
Introduction to Pharmaceutics
280
be designated, taking all necessary safety precautions for the
well-being of individuals and materials.
Returned, rejected, and recalled materials must be
stored securely, using lock and key measures and necessary
precautions.
Printed packaging materials, critical to ensuring conformity
to labeling, should receive special attention in terms of safe
and secure storage. Dispensing areas should be separate for
active and raw materials to prevent cross-contamination and
maintain control over the dispensing process.
Production Areas
To ensure efficient and compliant manufacturing processes,
the following considerations should be taken into account for
production areas:
General category products, excluding antibiotics, cytotoxic
drugs, and hormones, should be manufactured in separate
facilities to prevent cross-contamination.
Highly potent, sensitive, or live micro-organisms require
dedicated areas to minimize the risk of cross-contamination.
Premises should be designed to facilitate a logical flow of
materials, well-organized layout of plant and machinery,
and ease of cleaning for both equipment and the facility.
Adequate space should be provided based on the volume
of materials being handled to avoid mix-ups and facilitate
smooth operations.
Production areas should have effective ventilation
systems, including HVAC (heating, ventilation, and air
conditioning), designed to suit the specific products being
handled and the operations performed, while considering
external environ mental factors.
Regular monitoring of production areas, both during
production and non-production periods, is essential to
ensure compliance with design specifications.
Premises for pharmaceutical packaging should be speci-
fically designed to prevent mix-ups and cross-contamination,
maintaining strict controls over the packaging process.
281
Basic Structure, Layout, Sections, and Activities of Pharmaceutical
By incorporating these considerations into the design and
operation of production areas, pharmaceutical manu-
facturers can maintain product quality, minimize risks, and
ensure regulatory compliance.
Quality Control Areas
To ensure accurate and reliable testing and analysis, the
following considerations should be taken into account for
quality control (QC) areas:
QC laboratories should be physically separated from pro-
duction areas to prevent contamination and maintain the
integrity of testing processes.
Areas dedicated to specific test methods involving
biological, microbiological, or radioisotope analyses should
be separate from each other to prevent cross-contamination
and ensure accurate results.
QC laboratories should be designed to provide suitable
facilities for various types of analyses, including chemical
analysis, instrumental analysis, microbiological and
biological analysis, etc.
Adequate storage space should be available within the
QC laboratories for control samples, glassware, chemicals,
microbiological media, books, documents, and other
necessary materials.
Highly sensitive instruments should be housed in a sepa-
rate room or designated area to protect them from electrical
interference, vibrations, excessive moisture, and other
external factors that could affect their performance.
By implementing these considerations, QC areas can
operate efficiently, maintain the integrity of testing processes,
and ensure accurate and reliable results for quality control
purposes.
Drainage System
Potable water shall be supplied under continuous pressure in a
plumbing system free of defects that could contribute contami-
nation to any drug product. Water not meeting such standards
Introduction to Pharmaceutics
282
of regulatory guidelines shall not be permitted in the potable
water system. Drains shall be of adequate size.
Drainage should be connected directly to the sewer and
it should be provided with an air break or other mechanical
devices to prevent back spoilage. Drainage system maintenance
in the manufacturing facilities is very critical from the point of
view of cleaning and sanitation of the facilities.
A detailed SOP should be there, for cleaning and sanitation
of drains and their records should be maintained and reviewed
periodically.
Sanitation
All parts of the building should be cleaned regularly, and
records of the cleaning should be kept. The drains should be the
right size and designed to prevent anything from flowing back.
If possible, the drains should be closed, but if open channels
are necessary, they should be shallow so that they can be easily
cleaned and disinfected. Waste from the manufacturing area
should be disposed of according to the regulations of the
Environment Pollution Control Board (EPCB). If there are any
wastes that are flammable, hazardous or toxic, they should be
stored separately until they can be disposed of properly. Bio-
medical waste should be disposed of following the regulations
of the Bio-Medical Waste (Management and Handling) Rules,
1996. Drugs that have been rejected should be stored separately
and destroyed according to the regulations. Animal testing
laboratories should also be isolated from these areas, with a
separate entrance and dedicated air-handling systems.
Sanitation of Sterile Areas
Clean and sterile areas should be cleaned and sanitized
frequently following an approved cleaning procedure. It
is important to use more than one type of disinfectant to
effectively kill bacteria. Regular monitoring of clean rooms
should be done to check for any harmful microorganisms.
The cleaning methods should be tested to make sure that
the disinfectant residue is detected and removed during the
cleaning process.
283
Basic Structure, Layout, Sections, and Activities of Pharmaceutical
Environmental Control
The temperature and relative humidity of the premises must be
controlled in order to ensure the area complies with material
and product requirements, as well as regulatory requirements.
Airlocks must be built to separate low-humidity areas from
higher humidity areas; this prevents the migration of moisture
that would otherwise overload the heating ventilation
and air conditioning (HVAC) system. The systems used for
humidity control must be designed to avoid introducing any
contaminants.
Dust and vapours must be extracted at source and not allowed
to travel elsewhere. The dust extraction system must have
adequate transfer velocity in order to make sure that the dust is
truly carried away and does not merely settle into the ducting of the
system. General direction of airflow in a room must be
designed to remove vapours and dust generated in the area.
It must also consider the location of the operator to make
sure he/she does not contribute to contamination. It is often
preferred to introduce air into the room using ceiling diffusers,
and extract the room air through vents at low heights on the
wall to provide a flushing effect as the air moves out of the
room. In case of processes that generate a vapor that is lighter
than air, the extraction grilles will need to be positioned at
higher level.
Storage Areas
Storage areas must have sufficient space for the materials to
be stored in a systematic and organized manner according
to their categories such as starting materials, intermediates,
bulk product, finished products, packaging materials, released
products, quarantined products, rejected products, recalled
products and returned products. These areas must be clean,
well-lit, dry, and be maintained at specified temperatures.
In case of special storage conditions (for example, cold
conditions), the conditions must be monitored and controlled.
Receiving bays must allow cleaning of incoming material if
necessary. The received material must be kept in quarantine
until sampling, testing and approval. Entry to this area must
Introduction to Pharmaceutics
284
be restricted. Materials that have been rejected or returned or
recalled must be physically separated from other materials.
Separate storage areas must exist for holding.
PHARMACEUTICAL QUALITY ASSURANCE
PREMISES—DESIGN AND CONSTRUCTION
Materials that are dangerous or highly active (for example,
narco tics, highly inflammable solvents, radioactive materials,
poisons, etc.). Sampling areas for starting materials must
be sufficiently separated to avoid contamination or cross
contamination.
Production Areas
Products that are highly active (such as hormones, antibiotics,
cytotoxic drugs) or highly sensitizing (e.g., penicillin) must be
manufactured in dedicated facilities that are self-contained.
Other products must not be manufactured here. In facilities
where multiple product batches are being simultaneously
manufactured, there must be measures in place to prevent
cross-contamination. Besides, there must be sufficient
in-process storage space to prevent the occurrence of mix-ups.
Quality Control (QC) Laboratory Areas
QC laboratories must be located in an area separate from
pro duction. In the laboratories, separate areas must exist for
biological, microbiological, and radioisotope testing and these
areas must have dedicated air handling units. Sufficient space
must be provided for storing samples, solvents, reference
standards and laboratory records with no chances of mix-ups
between different samples drawn for testing. Air supply to QC
laboratories must be separate from the unit supplying air to
production areas. Instruments that are sensitive to temperature
and humidity must be housed in separate rooms. Care must
be taken to prevent vibrations and electrical interference
from reaching them. Pharmaceutical companies pay lot of
attention to setting up quality management systems and
validation studies in order to ensure regulatory compliance.