Drug Quality

Module 2 | Slide 1 of 31 2013

 What is Quality?

 A quality product of any kind consistently meets the

expectations of the user.

 Patients expect safe and effective medicine with every

dose they take.

 drug quality relates to consistent delivery of the label

performance and lack of contamination.

Module 2 | Slide 2 of 31 2013

 Quality Definitions

 The suitability of either a drug substance or a drug

product for its intended use. This term includes such
attributes as the identity, strength, and purity

 A product that is fit for use can be defined as one that

meets its established quality attributes and standards and
has been manufactured in accordance with GMP
regulations.

Module 2 | Slide 3 of 31 2013

 Quality Assurance and GMP concept
 Quality must be built in; it cannot be tested in
 Quality Assurance (QA) The sum total of the organized arrangements made with
the object of ensuring that all APIs and FP are of the quality required for their
intended use and that quality systems are maintained.

 Quality assurance (QA) in the pharmaceutical industry is a systematic and

comprehensive approach to ensuring that pharmaceutical products meet
established quality standards, are safe, effective, and consistent in their
performance. The primary goal of quality assurance is to prevent defects, errors,
and deviations in all aspects of pharmaceutical manufacturing, from research
and development to production and distribution.

Module 2 | Slide 4 of 31 2013

 Quality Control (QC) Checking or testing that
specifications are met

 Quality control in the pharmaceutical industry is a

systematic process that involves a set of activities and
procedures designed to ensure that pharmaceutical
products meet specific quality standards, are safe, and
are effective. It is a critical component of the quality
management system in pharmaceutical manufacturing
and is essential to producing high-quality pharmaceutical
products.

Module 2 | Slide 5 of 31 2013

 Good manufacturing practice (GMP) is a system for
ensuring that products are consistently produced and
controlled according to quality standards. It is designed to
minimize the risks involved in any pharmaceutical
production that cannot be eliminated through testing the
final product (contamination, cross-contamination, and
mixed-up)

Module 2 | Slide 6 of 31 2013

 Quality Management

Quality relationships

Quality Management and PQS

Quality Assurance

GMP

Production and Quality Control

Module 2 | Slide 7 of 31 2013

 We have a cascade arrangement:

 Quality management, defining the overall policy of the organization towards quality, is
over everything else.

 Next comes quality assurance, which is the concept that ensures the policy is
achieved.

 GMP is part of quality assurance. It deals with the risks that cannot be tested. It
builds quality into the product.

 Quality control is a part of GMP. It is that part of GMP that is focused on testing of
the environment and facilities, as well as the testing of the materials, components
and product in accordance with the standard.

Module 2 | Slide 8 of 31 2013

 QA and GMP

Module 2 | Slide 9 of 31 2013

 PQS and Quality Management
Comprehensive Pharmaceutical Quality System,
GMP and Quality Risk management:

The manufacturer assumes responsibility. Ensures that

products:
–fit for their intended use
–comply with marketing authorization
–do not place patients at risk due to inadequate safety, quality
or efficacy

1.1. – 1.2.

Module 2 | Slide 10 of 31 2013

 PQS and Quality Management
Pharmaceutical Quality System

Senior management - leadership and active

participation in the PQS is essential. Ensure the support
and commitment of all staff to the PQS.

Senior management has the ultimate responsibility to

ensure:
– effective PQS is in place
– adequately resourced and that roles, responsibilities, and
authorities are defined, communicated and implemented
throughout the organization 1.1. – 1.2.

Module 2 | Slide 11 of 31 2013

 PQS and Quality Management

 PQS should be defined and documented

 Quality manual or equivalent documentation describing

the quality management system including management
responsibilities.

 Periodic management review of the PQS

 Continual improvement of PQS, products and processes

1.6. – 1.7.

Module 2 | Slide 12 of 31 2013

 PQS and Quality Management
QA System should ensure that:

 Products are designed and developed in accordance with

GMP

 Production and control operations are clearly specified in

SOPs

 Managerial responsibilities are clearly specified in job

descriptions
1.5.
 Systems ensure that the correct starting and packaging
materials are used

Module 2 | Slide 13 of 31 2013

 PQS and Quality Management
QA System should ensure:
 Starting materials, intermediate products, bulk products are
controlled

 In-process controls, calibrations, and validations are carried out

 Finished products are correctly processed and checked

 Products are not sold or supplied before release by authorized

persons

 Systems ensure that products are appropriately stored and

distributed 1.5.

Module 2 | Slide 14 of 31 2013

 PQS and Quality Management

QA System should ensure:

 Self-inspection and/or quality audits are done regularly

 Deviations are reported, investigated and recorded

 Changes are controlled

 Systems are followed to verify the consistency of processes

and ensuring continuous improvement

1.5.

Module 2 | Slide 15 of 31 2013

 A Pharmaceutical Quality System (PQS) is a comprehensive and
integrated framework used in the pharmaceutical industry to ensure
that pharmaceutical products are consistently produced to meet
established quality standards, are safe, and are effective.

 The PQS is a fundamental component of pharmaceutical

manufacturing and is aligned with regulatory requirements and
industry standards.

 It encompasses a range of processes, procedures, and practices

designed to manage quality throughout the entire product lifecycle.

 The concept of a Pharmaceutical Quality System is based on the

principles outlined in International Conference on Harmonisation
(ICH) guidelines, particularly ICH Q10, which provides guidance on
pharmaceutical quality systems.

Module 2 | Slide 16 of 31 2013

 Key elements of a Pharmaceutical Quality
System include:
 Quality Management: The PQS places a strong
emphasis on quality management, with a focus on
defining and maintaining high standards for the
production, testing, and distribution of pharmaceutical
products.

 Risk Management: Pharmaceutical companies are

required to identify, assess, and manage risks throughout
the product lifecycle. This includes the identification of
potential risks to product quality and strategies to mitigate
those risks.

Module 2 | Slide 17 of 31 2013

 Document Control: Comprehensive and controlled
documentation is integral to the PQS. This includes the
development and management of documentation related
to product specifications, manufacturing processes,
quality control, and other critical information.

 Change Control: Procedures are in place to assess and

manage any changes to processes, equipment, or
procedures that could affect product quality.

Module 2 | Slide 18 of 31 2013

 Corrective and Preventive Actions (CAPA): When quality issues
or deviations are identified, companies must take corrective actions
to address the immediate problem and implement preventive
actions to prevent its recurrence.

 Training and Personnel Qualifications: The PQS includes

requirements for training programs and qualifications to ensure that
personnel are well-trained and qualified to perform their roles.

 Supplier and Vendor Quality Management: Pharmaceutical

companies must assess and manage the quality of raw materials,
components, and services provided by suppliers and vendors,
which may include conducting audits and quality assessments.

Module 2 | Slide 19 of 31 2013

 Quality Audits and Inspections: Regular audits and
inspections are conducted to ensure compliance with
quality standards. Regulatory agencies may also conduct
inspections to assess compliance with relevant
regulations.

 Continuous Improvement: The PQS promotes a culture

of continuous improvement, where companies continually
evaluate and enhance their processes and systems to
maintain and improve product quality.

Module 2 | Slide 20 of 31 2013

 Product Quality Review
A Product Quality Review (PQR) in the pharmaceutical industry is
a comprehensive and systematic assessment of the quality
and performance of a pharmaceutical product over its entire
lifecycle, from development through manufacturing,
distribution, and post-marketing surveillance. The purpose of a
PQR is to evaluate and document the quality, safety, efficacy,
and regulatory compliance of the product. PQRs are required
by regulatory authorities in many countries, including the U.S.
Food and Drug Administration (FDA), as part of Good
Manufacturing Practices (GMP) and other quality management
systems.
1.10.

Module 2 | Slide 21 of 31 2013

 Key aspects of a Product Quality Review
(PQR) include:
 Scope: The PQR covers a specific pharmaceutical
product, including its active pharmaceutical ingredient
(API) or drug substance, dosage forms, and finished
products. It encompasses all batches and production
sites associated with that product.

 Periodicity: PQRs are typically conducted at regular

intervals, often annually. The specific interval can vary
depending on regulatory requirements and company
policies.

Module 2 | Slide 22 of 31 2013

 Data Collection: The PQR collects and compiles data
from various sources, including production records,
laboratory testing results, quality control data, complaints,
stability data, and any changes made to the product or
manufacturing processes.

 Data Analysis: The collected data is thoroughly analyzed

to assess product quality, consistency, and compliance
with regulatory requirements. Any trends and deviations
are identified and evaluated.

Module 2 | Slide 23 of 31 2013

 Compliance with Specifications: The PQR assesses whether
the product meets all established quality specifications,
including identity, purity, potency, and performance
characteristics.

 Stability Data: Stability data are reviewed to determine whether

the product remains safe and effective throughout its shelf life.
Any potential degradation or changes in quality are evaluated.

 Batch Records and Documentation: The review includes an

assessment of batch records, documentation, and change
control records to ensure that manufacturing processes have
been consistent and well-documented.

Module 2 | Slide 24 of 31 2013

 Complaints and Adverse Events: Information from
customer complaints, product recalls, and adverse event
reports is examined to identify any issues or trends
related to the product.

 Regulatory Compliance: The PQR verifies that the

product and its manufacturing processes are compliant
with relevant regulatory requirements, including GMP and
product-specific regulations.

Module 2 | Slide 25 of 31 2013

 Summary and Conclusions: The PQR summarizes the
findings of the review and provides conclusions regarding
the quality and safety of the product. It may also include
recommendations for corrective and preventive actions
(CAPA) if issues or deviations are identified.

 Continuous Improvement: The PQR process aims to

drive continuous improvement by identifying areas where
product quality, manufacturing processes, or other
aspects of the product's lifecycle can be enhanced

Module 2 | Slide 26 of 31 2013

 Good Manufacturing Practices (GMP)

 That part of QA that ensures that products are consistently

produced and controlled
 Quality standards
 Marketing authorization and product specification

 Aim: Diminishing risks that cannot be controlled by testing of

product
 Contamination and cross-contamination
 Mix-ups (confusion) 2.1

Module 2 | Slide 27 of 31 2013

Contamination in pharmaceutical industry

 Contamination in the pharmaceutical industry refers to the

unintended presence of impurities, foreign substances, or
microorganisms in pharmaceutical products, drug
manufacturing processes, equipment, or facilities.
Contamination can compromise the safety, quality, and
efficacy of pharmaceutical products, posing risks to
patients and violating regulatory standards. There are
several types of contamination in the pharmaceutical
industry:

Module 2 | Slide 28 of 31 2013

 Microbiological Contamination: This involves the presence of
microorganisms, such as bacteria, yeast, molds, or viruses, in
pharmaceutical products, manufacturing processes, or
environments. Microbiological contamination can lead to product
spoilage, reduced efficacy, or even infection risks for patients.

 Chemical Contamination: Chemical contamination occurs

when unwanted chemicals, impurities, or contaminants are
introduced into pharmaceutical products. This can result from
the use of contaminated raw materials, cross-contamination in
equipment, or unintended reactions during the manufacturing
process.

Module 2 | Slide 29 of 31 2013

 Physical Contamination: Physical contamination
involves the presence of foreign particles, such as glass,
metal, rubber, or plastic fragments, in pharmaceutical
products. These particles can be harmful if ingested or
injected and may result in physical harm to patients.

 Environmental Contamination: Contaminants from the

surrounding environment, such as dust, airborne
particles, or even hazardous chemicals, can enter the
manufacturing area and potentially contaminate
pharmaceutical products.

Module 2 | Slide 30 of 31 2013

 Residue Contamination: Residue contamination can
occur when residues from cleaning agents, solvents, or
previous processes remain on equipment or surfaces,
leading to contamination of subsequent products.

Module 2 | Slide 31 of 31 2013

 Cross contamination

 Cross-contamination in the pharmaceutical industry refers

to the unintentional transfer of contaminants, such as
active pharmaceutical ingredients (APIs), chemicals,
microorganisms, or other substances, from one product
or process to another. This contamination can occur
during various stages of pharmaceutical manufacturing,
handling, and packaging. Cross-contamination is a
significant concern in the pharmaceutical industry
because it can lead to safety and quality issues in
pharmaceutical products, potentially harming patients and
violating regulatory standards

Module 2 | Slide 32 of 31 2013

 Sources of Cross-Contamination:

 Cross-contamination can originate from various sources,

such as shared equipment, facilities, personnel, raw
materials, intermediates, or even the air in the
manufacturing environment.

 Equipment and Facilities: Shared manufacturing

equipment, storage areas, and facilities are common
sources of cross-contamination. For example, if the same
equipment is used for multiple products without proper
cleaning and validation, residues from one product can
contaminate another.

Module 2 | Slide 33 of 31 2013

 Personnel: Personnel can inadvertently transfer contaminants if
they do not follow strict hygiene and gowning procedures, leading
to the risk of contaminants being carried from one area to another.

 Raw Materials: Contaminated raw materials or excipients can

introduce impurities into the manufacturing process, leading to
cross-contamination.

 Cleaning and Cleaning Validation: Cleaning processes play a

crucial role in preventing cross-contamination. Pharmaceutical
manufacturers use validated cleaning procedures to ensure that
equipment, surfaces, and facilities are free from residues of
previous products.

Module 2 | Slide 34 of 31 2013

 mixed-up in pharmaceutical industry

 In the pharmaceutical industry, the term "mixed-up"

typically refers to a situation in which products or
components have been mistakenly interchanged or
confused during manufacturing, packaging, labeling, or
distribution processes. Such mix-ups can lead to serious
safety and quality issues in pharmaceutical products.

Module 2 | Slide 35 of 31 2013

 -product Mix-Up: This occurs when two or more different
pharmaceutical products are mistakenly combined or
packaged together. For example, if two different
medications with similar packaging or labeling are mixed up
on the production line, it can result in patients receiving the
wrong medication.

 Labeling Mix-Up: Labeling mix-up happens when the

labels for different pharmaceutical products are placed on
the wrong packaging. This can lead to incorrect dosing or
administration instructions and can pose a significant risk to
patients.

Module 2 | Slide 36 of 31 2013

 Packaging Mix-Up: A packaging mix-up occurs when the
primary or secondary packaging (e.g., blister packs,
bottles, cartons) for one product is used for another. This
can lead to patients receiving the wrong drug or the
wrong strength of a medication.

 Dosage Form Mix-Up: In some cases, different dosage

forms (e.g., tablets, capsules, liquid) of the same
medication can be mixed up, resulting in patients
receiving the wrong form of the drug.

Module 2 | Slide 37 of 31 2013

 Good Manufacturing Practices (GMP)

 These risks can best be controlled by having a properly managed system of

working that takes them into account.

 This means that there must be good design, sound operation, and planned
maintenance of facilities.

 It also means that the quality checking system must be designed with these
risks in mind and set out to find whether any errors have occurred.

 If we do not know what sort of cross contamination we have, then the work
of the analyst is very difficult. The analyst should ideally know what to test
for before commencing testing.

 In other words, if we do not know what the likely cross-contaminant is then

we cannot analyse for it.

Module 2 | Slide 38 of 31 2013

 Basic Requirements for GMP

(a) all manufacturing processes are clearly defined,

systematically reviewed for associated risks in the light of
scientific knowledge and experience, and shown to be
capable of consistently manufacturing pharmaceutical
products of the required quality that comply with their
specifications;

(b) qualification and validation are performed;

Module 2 | Slide 39 of 31 2013

 Qualification

 Qualification is a process that verifies and documents that

equipment, systems, or facilities are installed and operate
according to their design specifications.

 Example:

Installation Qualification (IQ): Confirms that equipment is

installed correctly and according to design specifications

Module 2 | Slide 40 of 31 2013

 Validation:

 validation is a broader and more comprehensive process

that establishes documented evidence demonstrating that
a specific process, system, or facility consistently
produces results or products that meet predefined quality
standards

Module 2 | Slide 41 of 31 2013

 Tyoe of process validation
 Process Validation: This ensures that a specific manufacturing
process consistently produces products that meet predetermined
quality specifications.

 Analytical Method Validation: This confirms that the analytical

methods used to test pharmaceutical products are accurate,
reliable, and suitable for their intended purpose.

 Cleaning Validation: This verifies that cleaning processes

effectively remove residues, contaminants, or cleaning agents from
equipment and surfaces to prevent contamination of subsequent
products.

Module 2 | Slide 42 of 31 2013

 Basic Requirements for GMP

(c) all necessary resources are provided, including:

(i) sufficient and 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;

Module 2 | Slide 43 of 31 2013

 Basic Requirements for GMP

(d) instructions and procedures are written in clear and unambiguous

language, specifically applicable to the facilities provided;

(e) procedures are carried out correctly and personnel are trained to
do so;

(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 with the objective of
determining the root cause and appropriate corrective and preventive
action implemented;

Module 2 | Slide 44 of 31 2013

 Basic Requirements for GMP

(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 and takes account of good distribution practice

(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

Module 2 | Slide 45 of 31 2013