Quality Control of Injectables
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ScribdTranslationsQuality Control of Injectables
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ScribdTranslationsCompounded injectables: when the process and quality control
they make the difference
Maria E. Posternak
The quality of the product is not based on the final control but on everything.
Process of making the injectable.
In November 2007, the National Guarantee Program for Care was incorporated.
Medical resolution 1547 that includes pharmacies with laboratories of
injectables to include in their procedure with the sterilization process. The
The quality of the product is not based on the final inspection but on the whole process of
preparation of the injectable (Table 1). The building requirements are detailed in Table 2,
with the entire process being periodically verified by authorized companies for its
validation.
Table 1: Process for the preparation of an injectable formulation
.Sterile
.Exceptional purity
.Perfect Asepsis
.Free of particles
.Free from pyrogens
.Rigorous preparation and control
Table 2: Building Requirements
Standardized isolation:
Double insulation with unclassified areas
Restricted rooms among themselves and with the outside.
Air classification
Laminar flow (ISO5)
Turbulent flow (ISO 7)
Clean area: environmental control of particles and microbial contamination, built and
isolated to reduce the introduction, generation, and retention of pollution
in the area. HEPA filters are used. Calibrated air supply and return for
renew the air 20 times/hour.
Double locks: maintain air cleanliness through differential pressure between
compartments using manometers inside and outside each compartment.
Continuous supervision and daily recording of
Gate pressure of the room
HEPA filter saturation
Temperature of each area
Humidity of each area
The active ingredient must have high quality and purity parameters, otherwise
there could be a decrease or alteration of the pharmacological action or effects
harmful side effects.
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The vehicle (liquids that contain the active ingredient) is mostly water that must be
be purely bacteriological and chemically, biodistilled, sterile and apyrogenic. The same
specifications apply to non-aqueous diluents that are miscible in water such as the
ethanol, propylene glycol, glycerin, and polyethylene glycol.
The depyrogenation process of the vials requires careful washing with water.
distilled in an ultrasonic cleaner, whose high-frequency waves facilitate the
penetration of the cleaning agent into small cavities unreachable with washing
manual or mechanical. Subsequently, a rinse with sterile pyrogen-free water is performed.
ensuring the removal of the cleaning solution. And finally, the depyrogenation in
oven; this procedure takes a total of three hours at a temperature of 240ºC with
which eliminate pyrogenic agents (products of microbial metabolism capable
to cause fever). The sterilization oven at 180ºC does not eliminate pyrogenic agents.
Given that the rooms are isolated from each other, the solution is passed through the method.
from the preparation room to the filtration and filling room.
Filtration is carried out under class 100 laminar flow (ISO 5), using this method the
air moves in parallel sheets without mixing, providing ultra-clean air and
allows for self-cleaning of the air. For this, HEPA filters are used; a system of
high-efficiency air particles. Filtration is done through sterile membranes,
and the choice of the membrane depends on the solution to be filtered. Before closing, it
perform a magnifying glass inspection of each of the butyl plugs used for the
close and discard those with lint or particles.
Then, aluminum capsules are stapled and bags are assembled for
sterilization with medical grade paper (ANMAT) that allows the entry and exit of
vapor during sterilization; and labeling is done with test tape for steam
(ANMAT) with process indicator (turning of stripes, watch out for brown). The material is
load in the autoclave, placing a witness bottle, with the same amount of liquid as
the rest of the vials and a charging probe inside. When it reaches 121ºC, the process begins
sterilization time count. In the sterilization process, controls are performed.
of load with biological indicators that detect the elimination of microbial spores
the chemical indicators that monitor that the sterilant has penetrated properly
inside the package. The autoclave also has chemical indicators of the
operation of the sterilizer and visually distinguish the processed packages without
need to open them. All temperature, pressure, time controls, records and
witnesses are stored for each batch in the Control Book.
Once sterilization is complete, the vials are visually inspected against a black background and
white, in two consecutive positions observing the inside of the road and the finish of the
product and products with imperfections are rejected (Table 3). To verify the
perfect closure uses methylene blue.
Then labeling is carried out.
Table 3: Product rejection criteria
Strange particles
Integrity defects
Inaccurate filling volume
Absence of uniformity in the totality of the batch roadways
Defect in the closure (poor quality of the aluminum capsule, wet bottle neck)
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Hygiene and sanitization processes (Table 4) are permanently reminded
through an appropriate signaling system. We have also drafted Manuals of
Preparation, Hygiene, and Sanitization Procedures that are currently
employed by the Ministry of Public Health for those pharmacies that need to be licensed
your laboratory of magistral injectables.
Table 4: Disinfection of clean areas
.Daily cleaning with special cloths
.Disinfectants
.Daily preparation respecting dilutions
.Periodic alternation (avoids resistance)
.Records
.UV (sanitizing support, reduces microbial load)
The staff wears sterilizable polyamide clothing or carbon fiber.
sterilizable, lint-free, dissipates static and maintains thermal comfort of
user. Prevents particles of 1 micron size from passing through the clothing. The
staff is especially trained and qualified with permanent supervision of the
Standards of Good Practices for the preparation of compounding formulations that in turn
is supervised by the team of pharmaceutical professionals. We work six
permanent plant pharmacists, and five permanent external accessories.
I can proudly say that by complying with these practices, the Faculty of Pharmacy and
Biochemistry has chosen us for the students of the degree to take the subject of
Professional practice in our facilities
The preparation of injectables, in my opinion, is a pharmaceutical specialty and as such
It must be supported by knowledge, experience, and technical equipment.
according to the processes and quality control necessary to offer a product of
excellence to the intervening physician.
