QUALITY CONTROL AND ASSURANCE IN RELATION

TO PREPARATION OF PHARMACEUTICAL
PRODUCTS:

Prepared by Simbo D. A; B. Pharm

 Learning objectives
By the end of this session students are expected to be able to:
• Define the terms used in quality control and assurance
• Explain the importance of quality in relation to preparation of
pharmaceutical products
• Compare between QC/QA
• List functions of quality control laboratory in relation to preparation of
pharmaceutical products
Definition of Terms used in Quality Control and Assurance

• Quality is a set of inherent properties of a product, system or process

fulfills requirements. (Customer satisfaction).
• Is the ability of a product or service to satisfy the specific customer
needs, achieved by conforming to established requirements and
standards. OR alternatively quality can be defined as; is the attribute or
collection of attributes appropriate for intended use.
• Quality = E2+C,
• EFFECTIVENESS – Meeting Customer Needs
• EFFICIENCY – Quantity of Resources used to meet needs
• COMPLIANCE – Meeting Regulatory Requirements
Cont..
• The typical dictionary definition of quality refers to the ‘‘degree or
grade of excellence’’; in this sense, quality is a relative measure of
goodness. Defining quality as goodness is so general that it offers no
operational content. How do we build an operational definition?
• The answer is, ‘‘Adopt a customer focus.’’ Operationally, a quality
product or service is one that meets or exceeds customer expectations.
In effect, quality is customer satisfaction. But what is meant by
‘‘customer expectations’’? Customer expectations can be described by
quality attributes or by what are often referred to as ‘‘dimensions of
quality. ’Thus, a quality product or service is one that meets or exceeds
customer expectations on the following eight dimensions
Eight dimensions of quality
 Performance
 Aesthetics
 Serviceability
 Features
 Reliability
 Durability
 Quality of conformance
 Fitness for use/perceived quality
Cont..
The first four dimensions describe important quality attributes but are
difficult to measure.
• Performance: refers to how consistently and how well a product
functions. For services, the inseparability principle means that the
service is performed in the presence of the customer. Thus, the
performance dimension for services can be further defined by the
attributes of responsiveness, assurance, and empathy. Responsiveness
is simply the willingness to help customers and provide prompt,
consistent service. Assurance refers to the knowledge and courtesy of
employees and their ability to convey trust and confidence. Empathy
means providing caring, individualized attention to customers
Cont..
• Serviceability: measures the ease of maintaining and/or repairing the
product.
• Features (quality of design) refer to characteristics of a product that
differentiate between functionally similar products. For example, the
function of automobiles is to provide transportation. Yet, one auto may have
a four-cylinder engine, a manual transmission, vinyl seats, room to seat four
passengers comfortably, and front disk brakes; another may have a six-
cylinder engine, an automatic transmission, leather seats, room to seat six
passengers comfortably, and antilock brakes. Similarly, first class air travel
and economy air travel reflect different design qualities. First-class air
travel, for example, offers more leg room and more luxurious seats.
Cont..
• Obviously, in both cases, the product features are different. Higher
design quality is usually reflected in higher manufacturing costs and in
higher selling prices. Quality of design helps a company determine its
market. A market exists for both the four-cylinder and the six-cylinder
cars as well as economy air travel and first-class air travel.
Cont..
• Aesthetics: is concerned with the appearance of tangible products (for
example, style and beauty) as well as the appearance of the facilities,
equipment, personnel, and communication materials associated with
services

• Reliability: is the probability that the product or service will perform

its intended function for a specified length of time.

• Durability: is defined as the length of time a product functions

Cont..
• Quality of conformance: is a measure of how a product meets its
specifications. For example, the specifications for a machined part may be a
drilled hole that is three inches in diameter, plus or minus 1/8 inch. Parts
falling within this range are defined as conforming parts.

• Fitness of use: is the suitability of the product for carrying out its advertised
functions. If there is a fundamental design flaw, the product may fail in the
field even if it conforms to its specifications. Product recalls are frequently
the result of fitness-of-use failures.
cont..
• Improving quality, then, means improving one or more of the
eight quality dimensions while maintaining performance on
the remaining dimensions. Providing a higher-quality product
than a competitor means outperforming the competitor on at
least one dimension while matching performance on the
remaining dimensions.
Cont..
• Although all eight dimensions are important and can affect customer
satisfaction, the quality attributes that are measurable tend to receive more
emphasis. Conformance, in particular, is strongly emphasized. In fact, many
quality experts believe that ‘‘quality is conformance’’ is the best operational
definition. There is some logic to this position.

• Product specifications should explicitly consider such things as reliability,

durability, fitness for use, and performance. Implicitly, a conforming product
is reliable, durable, fit for use, and performs well. The product should be
produced as the design specifies it; specifications should be met.
Conformance is the basis for defining what is meant by a nonconforming, or
defective, product.
Cont..
• A defective product is one that does not conform to specifications. Zero
defects means that all products conform to specifications. But what is
meant by ‘‘conforming to specifications’’? The traditional view of
conformance assumes that there is an acceptable range of values for each
specification or quality characteristic. A target value is defined, and upper
and lower limits are set that describe acceptable product variation for a
given quality characteristic. Any unit that falls within the limits is deemed
non defective. For example, losing or gaining zero minutes per month
may be the target value for a watch, and any watch that keeps time
correctly within a range of plus or minus two minutes per month is
judged acceptable. On the other hand, the robust quality view of
conformance emphasizes fitness of use.
Cont..
• Robustness means hitting the target value every time. There is no
range in which variation is acceptable. A non-defective watch in the
robust setting would be one that does not gain or lose any minutes
during the month. Since evidence exists that product variation can be
costly, the robust quality definition of conformance is superior to the
traditional definition.
Cont..
• Quality Control
• Is defined as that part of Good Manufacturing Practice which is concerned
with sampling, specifications and testing, and with the organization,
documentation and release procedures which ensure that the necessary and
relevant tests are actually carried out and that materials are not released
for use, nor products released for sale or supply, until their quality has
been judged to be satisfactory.
• The GMP requirements concerning with quality are: :
• Adequate facilities, trained personnel and approved procedures are
available for sampling, inspecting and testing starting materials, packaging
materials, intermediate, bulk, and finished products, and where
appropriate for monitoring environmental conditions for GMP purposes
Quality control
It ensures the following:
 necessary and relevant tests are carried out
 materials are not released for use until their quality has
been judged to be satisfactory
 Products are not released for sale or supply, until their
quality has been judged to be satisfactory.
Cont..
• Samples of starting materials, packaging materials, intermediate
products, bulk products and finished products are taken by personnel and
by methods approved by Quality Control;
• Test methods are validated;
• Records are made, manually and/or by recording instruments, which
demonstrate that all the required sampling, inspecting and testing
procedures were actually carried out. Any deviations are fully recorded
and investigated;
• The finished products contain active ingredients complying with the
qualitative and quantitative composition of the marketing authorization,
are of the purity required, and are enclosed within their proper containers
and correctly labeled
Cont..
• Records are made of the results of inspection and that testing of materials,
intermediate, bulk, and finished products is formally assessed against
specification. Product assessment includes a review and evaluation of
relevant production documentation and an assessment of deviations from
specified procedures
• No batch of product is released for sale or supply prior to certification by an
authorized person that it is in accordance with the requirements of the
relevant authorizations;
• Sufficient reference samples of starting materials and products are retained
to permit future examination of the product if necessary and that the product
is retained in its final pack unless exceptionally large packs are produced
Cont..
Quality Assurance
• Is defined as wide-ranging concept, which covers all matters, which
individually or collectively influence the quality of a product
• It is the sum total of the organized arrangements made with the
objective of ensuring that medicinal products are of the quality
required for their intended use.
• Quality Assurance therefore incorporates Good Manufacturing
Practice plus other factors like product design and development
 Cont..
The system of Quality Assurance appropriate for the manufacture of medicinal products
Should ensure that:
• Medicinal products are designed and developed in a way that takes account of the
Requirements of Good Manufacturing Practice;
• Production and control operations are clearly specified and Good Manufacturing Practice
adopted;
• Managerial responsibilities are clearly specified;
• Arrangements are made for the manufacture, supply and use of the correct starting and
packaging materials;
• All necessary controls on intermediate products, and any other in process controls and
Validations are carried out;
• The finished product is correctly processed and checked, according to the defined
Procedures;
Cont..
• Medicinal products are not sold or supplied before an authorized person
has certified that each production batch has been produced and
controlled in accordance with the Requirements of the marketing
authorization and any other regulations relevant to the production,
control and release of medicinal products;
• Satisfactory arrangements exist to ensure, as far as possible, that the
medicinal Products are stored, distributed and subsequently handled so
that quality is maintained throughout their shelf life;
• There is a procedure for self-inspection and/or quality audit, which
regularly appraises the effectiveness and applicability of the quality
assurance system.
 Cont..
• Deviations are reported, investigated and recorded;
• There is a system for approving changes that may have an impact on product
Quality;
• 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
Cont..
• pharmaceutical products are designed and developed in a way that
takes account of the requirements of GMP and other associated codes
such as those of good laboratory practice (GLP) and good clinical
practice (GCP);
• The manufacturer must assume responsibility for the quality of the
pharmaceutical products to ensure that they are fit for their intended
use, comply with the requirements of the marketing authorization and
do not place patients at risk due to inadequate safety, quality or
efficacy.
Cont..
• The attainment of this quality objective is the responsibility of senior
management and requires the participation and commitment of staff in many
different departments and at all levels within the company, the company’s
suppliers, and the distributors.
• To achieve the quality objective reliably there must be a comprehensively
designed and correctly implemented system of quality assurance incorporating
GMP and quality control.
• It should be fully documented and its effectiveness monitored.
• All parts of the quality assurance system should be adequately staffed with
competent personnel, and should have suitable and sufficient premises,
equipment, and facilities.
Importance of Quality in Relation to
Preparation of Pharmaceutical Products
o Helps in describing attributes of a product hence facilitating
contractual or legal agreements. PRODUCT IDENTITY
o Helps in defining the superiority of a product over other similar
products. PRODUCT BEAUTY
o Helps in designing new or advanced product attributes. PRODUCT
NOVELTY. Therefore, when the quality of a product is defined as “the
degree to which a set of inherent properties of a product, system or
process fulfills requirements”, the requirements are those attributes
that reflect the identity, beauty and novelty of the product
Difference between QA & QC
 Quality Assurance Quality Control

Definition QA is a set of activities for ensuring quality in QC is a set of activities for ensuring quality in
the processes by which products are developed. products. The activities focus on identifying
defects in the actual products produced.

Focus on QA aims to prevent defects with a focus on the QC aims to identify (and correct) defects in
process used to make the product. It is a the finished product. Quality control,
proactive quality process. therefore, is a reactive process.

Goal The goal of QA is to improve development and The goal of QC is to identify defects after a
test processes so that defects do not arise when product is developed and before it's
the product is being developed. released.

How Establish a good quality management system Finding & eliminating sources of quality
and the assessment of its adequacy. Periodic problems through tools & equipment so that
conformance audits of the operations of the customer's requirements are continually met.
system.
 Quality Assurance Quality Control

What Prevention of quality problems through The activities or techniques used to achieve
planned and systematic activities including and maintain the product quality, process
documentation. and service.
Responsibility Everyone on the team involved in developing Quality control is usually the responsibility of
the product is responsible for quality a specific team that tests the product for
assurance. defects
Example Verification is an example of QA Validation/Software Testing is an example of
QC
Statistical Statistical Tools & Techniques can be applied When statistical tools & techniques are
Techniques in both QA & QC. When they are applied to applied to finished products (process
processes (process inputs & operational outputs), they are called as Statistical Quality
parameters), they are called Statistical Control (SQC) & comes under QC
Process Control (SPC); & it becomes the part
of QA.
As a tool QA is a managerial tool QC is a corrective tool

Orientation QA is process oriented QC is product oriented

Good Laboratory Practice, Location, Designing, Functions of Quality
Control Laboratory in Relation to Preparation of Pharmaceutical Products

• Good Laboratory Practice (GLP) is a quality system concerned with the

organizational process and the conditions under which tests are
planned, performed, monitored, recorded, archived and reported.
Cont..

• Quality Control Laboratories shall be independent of the production

areas.
• Separate areas shall be provided each for physico-chemical,
biological, microbiological or radio-isotope analysis.
• Separate instrument room with adequate area shall be provided for
sensitive and sophisticated instruments employed for analysis also to
protect sensitive instruments from vibration, electrical interference,
humidity, etc.
Cont..
• Quality Control Laboratories shall be designed appropriately for the
operations to be carried out in them.
• Adequate space shall be provided to avoid mix-ups and cross-
contamination.
• Sufficient and suitable storage space shall be provided for test
samples, retained samples, reference standards, reagents and records.
• The design of the laboratory shall take into account the suitability of
construction materials and ventilation
Cont..
• Special requirements are needed in laboratories handling particular
substances, such as biological or radioactive samples.
• Separate air handling units and other requirements shall be provided
for biological, microbiological and radioisotopes testing areas.
• The laboratory shall be provided with regular supply of water of
appropriate quality for cleaning and testing purpose.
• Quality Control Laboratory shall be divided into separate sections i.e.
for chemical, microbiological and wherever required, biological
testing
Cont..
• These shall have adequate area for basic installation and for ancillary purposes.
• The microbiology section shall have arrangements such as airlocks and laminar
air flow work station, wherever considered necessary.
• Quality control deals with the system which accepts or rejects any activities or
parameters which affects the quality of product and thus prevent quality
deficiency.
• Q.C. is not confined to only laboratory operation but must be involved in all
decisions, concerning with the quality of the product”
• AS PER WHO DEFINITION: Q.C. is the part of GMP concerned with
sampling, specification, and testing and with the organization, documentation
and release procedure which ensure that the necessary and relevant tests are
actually carried out and those materials are not released for use, nor product
released for sale or supply, until their quality has been satisfactory.
Responsibilities of QC
Laboratory
• QC department is responsible for day-to-day control of quality within
the company
• QC plays major role in selection of qualified vendors from whom raw
materials are purchased
• Tests representative samples as required
• Audit vendor’s operations to determine suitability of the vendor and degree of
compliance with GMPs prior to being approved
• QC is responsible for analytical testing of incoming raw materials (e.g.
assay, titrations etc)
Cont..
• QC is responsible for analytical testing and inspection of packaging
components, including labelling (e.g. appearance, spectroscopy, loss on
drying etc)
• QC is responsible for conducting in-process testing when required, perform
environmental monitoring, and inspect operations for compliance
• QC is responsible for conducting required tests on finished products or
dosage forms (e.g. assay, dissolution, content uniformity etc)
• Environmental areas for manufacturing of various dosage forms are tested
and inspected by QC department
• Generally QC is responsible for efficacy, safety, quality and compliance in
pharmaceutical manufacturing
Cont..
Laboratory must have the following managerial and technical personnel:
 Head of laboratory (supervisor)
 Head of central registry
 Analysts
 Technical staff
 Head of central store
 Quality Manager
 Reference material coordinator
Cont..
Quality control Laboratory is divided into the following
sections.
 Instrumentation
 Wet Chemistry
 Microbiology room
 Stability studies
Instrumentation

 Gas Chromatography
 Dissolution Instruments
 High Performance Liquid Chromatography (HPLC)
 UV/VIS visible spectrophotometer
 Viscometer
 Melting point apparatus
 Fourier-Transform Infrared (FTIR machine)
 PH meter
 Hardness tester
 Conductivity meter
 Friability Tester
Wet Chemistry (1)

• Wet lab are laboratories where chemicals, drugs or other biological

matter are tested and analyzed using liquids/ water.
 The unit for preparation of reagent and volumetric solution
standardization.
 Dissolution tester
 Friability Tester
 Refractometer
 Muffle furnace
 Density tester
 Leak Test Apparatus
 Disintegration tester
 Log books
Wet Chemistry (2)

 Reference standard and working standard are to be stored

at 2-8ºC and in a locked cabinet.
 Working standards stock card.
 Equipment usage log
 Eye shower and hood chamber
 Flammable and corrosive reagents and solvents to be
provided with separate storage cabinet installed with
exhaust system
 Microbiology room (1)

• The microbiology laboratory is responsible for microbial limit test and sterility test. It is divided
into instrument room, media preparation room, incubation room and analysis room.
• Microbial limit testing (MLT) must be conducted for every finished products, water and raw
materials including environmental monitoring in the critical areas.
• The laboratory should have separate entry/exit for samples and personnel with air lock door
(self-closing)
• Microbiology labs should contain incubators used separately for Fungal, bacterial growth and E.
Coli monitoring including microbial limit test.
• Deep Freezer 2 – 8ºC dedicated for storage of media and agar,
• Laminar Air Flow (LAF) cabinet
• Steam sterilizer Autoclave for media preparation
• All equipment to be qualified/calibrated and affixed with status labels.
• The sample preparation room is to be kept under positive pressure relative to the surrounding to
control ingress of contaminants
Stability studies (1)
Drug stability is the ability of pharmaceutical dosage form to
maintain the physical, chemical, therapeutic and microbial properties
during the time of storage and usage by the patient.
Drug must retain, within specified limits, and throughout its period of
storage and use (shelf-life), the same properties and characteristics
that it possessed at the time of its manufacturing
Stability studies (2)
• Includes testing attributes of drug substance that are susceptible to
change during storage and are likely to influence quality, safety and
efficacy.
• The variation with time can be due to a variety of environmental
factors
• Essential for shelf -life determination. The Stability chambers to be set
at different conditions
• 25±2°C/60±5%RH
• 30C5/65%5 RH
• 30C5 & 75%5 RH
• Accelerated: 40C5 & 75%5 RH
• Adequate space for placement of samples
 Factors affecting drug stability
• Temperature
• pH
• Moisture / Humidity
• Light
• Oxygen
• Pharmaceutical dosage form
• Concentration
• Drug incompatibility
 SAFETY INSTRUCTIONS
General and specific safety instructions in quality control laboratories
must be
• Available to each staff member and
• Supplemented regularly as appropriate (e.g. written material, poster displays,
audio-visual material, and occasional seminars).
• General rules for safe working in accordance with the national regulation and
SOPs include normally:
• Availability of safety data sheets to staff prior to testing being carried out
• Prohibition of smoking, eating, and drinking in the laboratory
• Familiarity with the use of fire-fighting equipment, including fire
extinguishers, fire blankets, and gas masks
Cont..
• The use of laboratory coats or other protective clothing including eye
protection
• Special handling as required for example for highly potent, infectious, or
volatile substances
• Full labeling of all containers of chemicals, including prominent warnings
(e.g. "Poison", "Flammable", "Radiation", etc.) whenever appropriate
• Adequate insulation and spark-proofing of electrical wiring and equipment,
including refrigerators
• Observation of safety rules in handling cylinders of compressed gases and
familiarity with their color identification codes
• Awareness of avoiding solitary work in the laboratory
• Provision of first-aid materials and instruction in first-aid techniques,
emergency care, and use of antidotes
Key points
• QA is the sum total of organized arrangements made with the object
of ensuring that product will be of the Quality required by their
intended use
• QC is that part of GMP which is concerned with sampling,
specifications, testing and within the organization, documentation, and
release procedures which ensure that the necessary and relevant tests
are carried out
• QC is lab based while QA is company based
• Quality helps in defining the superiority of a product over other
similar products.
Evaluation
• What is quality?
• What is the importance of quality in relation to preparation of
pharmaceutical product?
• What is quality assurance?
• What is quality Control?