UNIT TWO
QUALITY CONTROL IN
PHARMACEUTICAL
COMPOUNDING
BY:Yasin U.
Cont…
2
Objectives: At the end of this chapter you will be
able to:
Define Quality Assurance, Good compounding
practice and Quality control
Discuss quality assurance principles
Recognize the essential elements of current good
compounding practice
Perform QC checks for extemporaneous
preparations
BY:Yasin U.
2.1. Introduction
3
Quality control and assurance is designed to
achieve the utmost quality, purity, effectiveness,
and safety concerning drug products.
The Food and Drug Administration (FDA) has
issued many guidelines overseeing specific
dosage forms and operations that include aseptic
manufacturing, stability testing, and validation.
BY:Yasin U.
Cont…
4
Quality system inspections are a regular part of
regulatory preapproval programs for new drugs
Quality control and assurance is designed to
achieve the utmost quality, purity, effectiveness,
and safety concerning drug products.
BY:Yasin U.
Cont…
5
Inadequate quality control practices may lead
to contamination of pharmaceuticals as well as
medication errors.
The pharmacy professional is responsible for
the storage of all pharmaceuticals, for
monitoring expiration dates, and for
monitoring the temperature of refrigerators
and freezers used to store pharmaceuticals.
BY:Yasin U.
Definitions
6
Quality Assurance: is all system which ensures
activities involving planning, quality control,
quality assessment, reporting and quality
improvement to ensure that a product or service
meets defined standards of quality with a stated
level of confidence.
Quality control (QC): is overall system of
activities concerned with sampling, specification
and testing and organization, documentation and
release of procedure to ensure the quality of the
product.
BY:Yasin U.
Cont…
7
GMP (Good Manufacturing Practice): is part of
quality assurance that ensures products are
consistently produced and controlled to the quality
standard appropriate to their intended use
BY:Yasin U.
2.2.Relationships of QA, QC & GMP
8
GMP is a component of quality assurance and QC
is a component of GMP. Or GMP and QC are
components of quality assurance
BY:Yasin U.
2.3. Quality assurance principles Principle:
9
“Quality assurance” is a wide-ranging concept
covering all matters that individually or
collectively influence the quality of a product. It
is the totality of the arrangements made with the
objective of ensuring that pharmaceutical
products are of the quality required for their
intended use.
BY:Yasin U.
Cont…
10
Quality assurance therefore incorporates
GMP/GCP, QC and other factors, including those
outside the scope of this guide such as product
design and development.
BY:Yasin U.
Cont…
11
The system of quality assurance appropriate to
the compounding/manufacture of pharmaceutical
products should ensure that:
a. Pharmaceutical products are designed and
developed in a way that takes account of the
requirements of GMP/GCP and other associated
codes such as those of good laboratory practice
(GLP)
BY:Yasin U.
Cont…
12
b. Production and control operations are clearly
specified in a written form and GMP/GCP
requirements are adopted
c. Managerial responsibilities are clearly specified in
job descriptions
BY:Yasin U.
Cont…
13
d. Arrangements are made for the manufacture,
supply and use of the correct starting and
packaging materials
e. All necessary controls on starting materials,
intermediate products, and bulk products and
other in-process controls, calibrations, and
validations are carried out
BY:Yasin U.
Cont…
14
f. The finished product is correctly processed and
checked, according to the defined procedures
g. Pharmaceutical products are not sold or supplied
before the authorized persons have certified that
each production batch has been produced and
controlled in accordance with the requirements of
the marketing authorization and any other
regulations.
BY:Yasin U.
Cont…
15
h.Satisfactory arrangements exist to ensure, as far as
possible, that the pharmaceutical products are stored by
the manufacturer, distributed, and subsequently handled
so that quality is maintained throughout their shelf-life
There is a procedure for self-inspection and/or quality
audit that regularly appraises the effectiveness and
applicability of the quality assurance system
i. Deviations are reported, investigated and recorded
BY:Yasin U.
Cont…
16
j. There is a system for approving changes that
may have an impact on product quality
k. Regular evaluations of the quality of
pharmaceutical products should be conducted with
the objective of verifying the consistency of the
process and ensuring its continuous improvement
BY:Yasin U.
2.4. Good compounding/manufacturing practices
(GCP/GMP
17
Good Compounding or manufacturing Practices
for pharmaceutical products is that part of
quality assurance which ensures that products
are consistently produced and controlled to the
quality standards appropriate to their intended
use.
GCP/GMP is aimed primarily at diminishing the
risks inherent in any pharmaceutical production.
BY:Yasin U.
Cont…
18
Such risks are essentially of two types: cross
contamination (in particular of unexpected
contaminants) and mix-ups (confusion) caused by,
for example, false labels being put on containers.
BY:Yasin U.
Under GCP/GMP:
19
a. All compounding or manufacturing processes are
clearly defined, systematically reviewed in the light
of experience, and shown to be capable of
consistently compounding/ manufacturing
pharmaceutical products of the required quality
that comply with their specifications
b. Qualification and validation are performed
BY:Yasin U.
Cont…
20
c. All necessary resources are provided, including:
i. Appropriately qualified and trained personnel;
ii. Adequate premises and space;
iii. Suitable equipment and services;
iv. Appropriate materials, containers and labels;
v. Approved procedures and instructions;
vi. Suitable storage and transport;
vii. Adequate personnel, laboratories and equipment for in-
process controls;
BY:Yasin U.
Cont…
21
d. Instructions and procedures are written in clear
and unambiguous language, specifically applicable
to the facilities provided;
e. Operators are trained to carry out procedures
correctly;
BY:Yasin U.
Cont…
22
f. Records are made (manually and/or by recording
instruments) during manufacture to show that all
the steps required by the defined procedures and
instructions have in fact been taken and that the
quantity and quality of the product are as expected;
any significant deviations are fully recorded and
investigated;
BY:Yasin U.
Cont…
23
g. Records covering manufacture and distribution,
which enable the complete history of a batch to be
traced, are retained in a comprehensible and
accessible form;
h. The proper storage and distribution of the
products minimizes any risk to their quality;
BY:Yasin U.
Cont…
24
i. A system is available to recall any batch of
product from sale or supply
j. Complaints about marketed products are
examined; the causes of quality defects
investigated, and appropriate measures taken in
respect of the defective products to prevent
recurrence
BY:Yasin U.
2.5. Continuous quality improvement
25
Before dispensing the prescription to the patient,
the pharmacist should ensure the accuracy and
completeness of the compounded preparation by
reviewing each step in the preparatory,
compounding, final check, and sign-off phases.
BY:Yasin U.
Cont…
26
Aspects to be reviewed in quality control include
the following:
Appropriate ingredients, adjuvants, and equipment
were selected for the specific preparation.
Calculations are correct
Measurements were performed accurately with
properly functioning equipment
The formulation is appropriate for the intended use and
stability limits of the preparation
BY:Yasin U.
Cont…
27
The review of the final check phase should be
comprehensive. It is intended to verify the following:
The calculated yield is consistent with the actual yield.
The tolerance for individual dose weight variation has
been met by a sampling technique when appropriate (e.g.,
capsule weight).
The physical characteristics (clarity, color, and odor) of the
preparation are consistent with those predicted for the
preparation.
BY:Yasin U.
Cont…
28
Physical tests have been performed when
appropriate, and the preparation meets the test
limits.
The preparation is suitably labeled, and the
contents have been verified with the prescription
order.
All legal requirements have been imprinted on
the label and in the compounding record.
BY:Yasin U.
Cont…
29
The preparation is suitably packaged for patient
use, and the container that is selected will
protect the preparation from undue
environmental exposure until at least the discard-
after or beyond-use date.
Documentation is appropriate
BY:Yasin U.
Cont…
30
The patient or caregiver has been adequately
informed about ways to identify obvious evidence
of instability in the compounded preparation.
The preparation is labeled with explicit storage
and administration instructions.
BY:Yasin U.
Cont…
31
The compounder may also decide to submit samples of
compounded preparations to an analytical testing
laboratory or test it within the pharmacy.
Such analytical testing could include dissolution rates
and concentrations of compounded medications.
Additional tests, assays, or visual observations of
samples of the preparation may be performed to ensure
the content, stability, pH, sterility, and non pyrogenicity.
BY:Yasin U.
