Transcript Quality control of r..

Quality control of raw materials
In-process control
To minimize and eliminate these sources of variation
which can cause product quality variation approaches
such as material control, good manufacturing practice
(GMP), in-process quality control (IPQC) and many
other techniques, such as packaging control, automation
and statistical sampling are employed.
Drug substance control:
 Drug substances must meet the specifications previously
established for it.
 Moreover, the materials used in the manufacture and
processing of drugs shall be identified, stored, examined,
tested, handled and otherwise controlled.
 Drugs generally are not absolutely pure, since they may contain
substances that are by-products of the synthesis of products.
Appropriate records should be maintained as to their origin, receipt,
testing, and disposition and as to the assurance of their
conformance to the appropriate standards of identity, purity,
quality, strength, potency, and freedom of contaminants at time of
use.
 Infact, control of raw materials whether active or inactive and of
packaging and printed materials actually begins before purchase
and is maintained by careful handling procedures throughout the
manufacture of the packaged dosage form.
 The quality control inspector performs appropriate visual
examination of the incoming materials and then follows a
prescribed sampling procedure to provide test material for
laboratory evaluation.
 The testing results submitted by the suppliers are compared and
reviewed with those acquired by the quality control department of
the drug manufacture.
Excipients control:
 Excipients are components of the finished dosage form other
than the therapeutic ingredient.
 Although they are inert, they may influence the quality of a
product owing to interaction with the drug substance affecting the
physical properties of the dosage form or influencing the
production process.
To prevent such effects:
● Excipients should be examined carefully and critically for compliance with
established standards.
● They must be supplied in clean and properly sealed containers.
● They should be inspected prior to laboratory testing.
Labeling should be correct.
The material should be packaged in the correct container.
No obvious damage of the container in transit.
Lot number should be stated.
Quality control procedures include:
● Sampling of raw materials
- All incoming raw materials are initially quarantined and
samples are taken and tested to ensure that the material meets
strict purity guidelines.
- This testing involves both microbiological and chemical
testing, as is laid out in the relevant pharmacopeia (a reference
book on the preparation of pharmaceuticals three are
published British, United States and European).
● In-process checks
The manufacturing staff carry out checks on such things as tablet
weight and size at frequent intervals.
At hourly intervals the quality control staff take samples to check for
contamination and to ensure that composition is as expected.
● Final product checking
Checking similar parameters to those measured during production.
● Monitoring cleaning
When a batch of a certain drugs has been made, all equipment that
has been used must be cleaned.
When the next pharmaceutical to be made on that line is going to be
different, this cleaning must be particularly through to prevent
contamination. In this instance, after cleaning the QC staff take
swabs off each piece of equipment and test them to see if they can
detect the presence of the active previously used.
● The results of all these tests are recorded on the batch records for
the pharmaceutical, as well as the name and batch number of the
pharmaceutical made immediately prior on the same production
line.
 Raw material standardization is the only way for all the drug
manufactures to produce the drugs in same quality and to maintain
the uniformity.
Incoming raw material
Transfer
Store
Samplin
g
Identification
Analyse
d
Equipments
Inspected
Manufacture
Assessed and
control of microbial
contamination
Documented
Purity testing
Finished
products
Representative
samples analysed
The ultimate goals of QC/QA programs are to assure that:
● The drug product contains the labeled amount (s) of the active
ingredient (s), within the accepted tolerance limits.
●The ingredients (active or inactive) were of the acceptable
pharmaceutical purity according to quality specifications as cited
by drug compendia.
● The variation of drug levels between dosage units is
minimized.
● The finished dosage forms should be of the highest possible
purity i.e. no contamination.
● The ingredients in the finished dosage form are stable within
specified time (shelf-time).
● The finished dosage form is therapeutically efficacious i.e.
bioavailability studies or bioequivalency studies have been
carried out properly in the research and development (R&D)
phase.
 Good raw material specifications must be written in precise
terminology and details of test methods, type of instruments and
manner of sampling must be identified.
 Table 27-1 lists general tests, limits and other physical or chemical data for
raw materials related to identity, purity, strength and quality.
 Table 27-2 presents the quality assurance monograph for acetaminophen,
USP, as an example of a specific raw material quality assurance monograph.
 The manufacturer physically inspects and assigns lot numbers
to all raw materials received and quarantines them untill they are
approved for use.
 Each raw material is sampled according to standard sampling
procedures and is sent to the quality control laboratory for testing
according to the written procedures (Table 27-2).
 If acceptable, it is moved to the release storage area, after being
properly stickered to indicate the item number, name of material, lot
number, date of release, reassay date and signature of the quality
assurance inspector.
 It is retested as necessary according to an established schedule
to assure that it still conforms to specifications at time of use.
 Quality assurance personal should keep preservation samples
of active raw materials that consist of at least twice the necessary
quantity to perform all tests required to determine whether the
material meets the established specifications. These preservation
samples should be retained for at least 7 years.
 Approved materials should be rotated so that the oldest stock is used
first.
 Any raw material not meeting specifications must be isolated from
the acceptable materials, stickered as a rejection, and returned to the
supplier or disposed of promptly.