Pharmaceutical Quality System .pdf

Pharmaceutical
quality system
Presented by: MD. ZAKARIA FARUKI
Manager & Head of Quality Assurance
Silva Pharmaceuticals Limited
Date of Training: March 28, 2023
1 of 47
Please Silence Your Cell Phone
PQS

What is Quality?
 Quality is the totality of features and characteristics of a
product or service that bear on its fitness for intended
use & ability to satisfy customers with particular needs.
 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. (ICH Q6A)
 Quality makes sure that a high-class product or service
is being produced. Quality is important for customer
satisfaction that ultimately results in customer loyalty.
Quality management assists an organisation to create
and developing a product or service which is desired by
the customers.
PQS
Training on PQS conducted by Md. Zakaria Faruki 2 of 47

What is Quality Assurance? PQS

Quality Management System
 Quality Management System
(QMS) is defined as a
formalized system that
documents processes,
procedures, and
responsibilities for
achieving quality policies
and objectives.
 QMS is the heart of any
quality and compliance
process.
 It is one of the basic requirement that regulatory inspectors and ISO
auditors consider critical.
 An automated QMS system reduces audit time and findings, and a
decreases risk of product recalls.
 It improves product quality and safety, increases customer
satisfaction, and ensures FDA and ISO compliance.
PQS

What are the elements of QMS?
The important elements of total quality management
are:
(i) Management’s commitment to quality
(ii) Customer satisfaction
(iii) Preventing rather than detecting defects
(iv) Measurement of Quality
(v) Continuous improvement
(vi) Corrective action for root cause
(vii)Training
(viii)Recognition of high quality
(ix) Involvement of Employees and
(x) Benchmarking.
PQS

Pharmaceutical Quality System: ICH Q10
1.1 Principle
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.
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 this quality objective reliably there
must be a comprehensively designed and correctly
implemented pharmaceutical quality system (PQS)
incorporating GMP and QRM.
The pharmaceutical quality system “assures that the desired product
quality is routinely met, suitable process performance is achieved, the
set of controls are appropriate, improvement opportunities are
identified and evaluated, and the body of knowledge is continually
expanded.”
PQS

Pharmaceutical Quality System
1.2 Senior management has the ultimate responsibility to ensure
an effective PQS is in place, is adequately resourced, and that
roles, responsibilities, and authorities are defined,
communicated and implemented throughout the organization.
Senior management’s leadership and active participation in the
PQS is essential. This leadership should ensure the support
and commitment of staff at all levels and sites within the
organization to the PQS.
1.3 Quality management 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
object of ensuring that pharmaceutical products are of the
quality required for their intended use. Quality management,
therefore, incorporates GMP and other factors, including those
outside the scope of this guide, such as product design and
development.
PQS

1.4 GMP applies to the life-cycle stages from the
manufacture of investigational medicinal products,
technology transfer, and commercial manufacturing,
through to product discontinuation. The PQS can extend
to the pharmaceutical development life-cycle stage and
should facilitate innovation and continual improvement
and strengthen the link between pharmaceutical
development and manufacturing activities. All parts of the
PQS should be adequately resourced and maintained,
including being provided with sufficient competent
personnel, suitable premises, equipment and facilities.
1.5 The PQS appropriate to the manufacture of
pharmaceutical products should ensure that:
Pharmaceutical Quality System PQS

a) Product realization is achieved by designing, qualifying,
planning, implementing, maintaining and continuously
improving a system that allows the consistent delivery
of products with appropriate quality attributes;
b) Product and process knowledge is managed throughout
all lifecycle stages;
c) 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);
d) Production and control operations are clearly specified
in a written form and GMP requirements are adopted;
e) Managerial responsibilities are clearly specified in job
descriptions;

f) Arrangements are made for the manufacture, supply and use of
the correct starting and packaging materials, the selection
and monitoring of suppliers and for verifying that each
delivery is the correct material from the approved supply
chain;
g) All necessary controls on starting materials, intermediate
products, and bulk products and other in-process controls,
calibrations and validations are carried out;
h) The finished product is correctly processed and checked,
according to the defined procedures;
i) Pharmaceutical products are not sold or supplied before the
authorized persons (see also sections 9.11 and 9.12) have
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 pharmaceutical
products;

j) Processes are in place to assure the management of
outsourced activities;
k) Satisfactory arrangements exist to ensure, as far as
possible, that the pharmaceutical products are stored,
distributed and subsequently handled so that quality is
maintained throughout their shelf-life;
l) There is a procedure for self-inspection and/or quality
audit that regularly appraises the effectiveness and
applicability of the PQS;
m) Product and processes are monitored and the results
taken into account in batch release, in the investigation
of deviations and, with a view to taking preventive action
to avoid potential deviations occurring in the future;

n) Arrangements are in place for the prospective evaluation
and approval of planned changes and their approval
prior to implementation taking into account regulatory
notification and approval where required. After
implementation of any change, an evaluation is
undertaken to confirm that the quality objectives were
achieved and that there was no unintended adverse
impact on product quality;
o) Regular reviews of the quality of pharmaceutical
products are conducted with the objective of verifying
the consistency of the process and identifying where
there is a need for improvement;
p) A state of control is established and maintained by
developing and using effective monitoring and control
systems for process performance and product quality;

q) Continual improvement is facilitated through the
implementation of quality improvements appropriate to
the current level of process and product knowledge;
r) There is a system for QRM;
s) Deviations, suspected product defects and other
problems are reported, investigated and recorded. An
appropriate level of root cause analysis is applied
during such investigations. The most likely root
cause(s) should be identified and appropriate
corrective actions and/or preventive actions (CAPAs)
should be identified and taken. The effectiveness of
CAPAs should be monitored.

1.6 There should be periodic management reviews, with
the involvement of senior management, of the
operation of the PQS to identify opportunities for
continual improvement of products, processes and
the system itself. Unless otherwise justified, such
reviews should be conducted at least annually.
1.7 The PQS should be defined and documented. A
quality manual or equivalent documentation should
be established and should contain a description of the
quality management system including management
responsibilities.

Quality Risk Management
1.8 Quality Risk Management (QRM) is a systematic
process for the assessment, control,
communication and review of risks to the quality
of the medicinal product. It can be applied both
proactively and retrospectively.
1.9 QRM should ensure that: – the evaluation of the
risk to quality is based on scientific knowledge,
experience with the process and ultimately links
to the protection of the patient; – the level of
effort, formality and documentation of the QRM
process is commensurate with the level of risk.

Product Quality Review
1.10 Regular, periodic or rolling quality reviews of all
pharmaceutical products, including export-only
products, should be conducted with the objective of
verifying the consistency of the existing process and
the appropriateness of current specifications for both
starting materials and finished product, to highlight
any trends and to identify product and process
improvements.
Such reviews should normally be conducted and
documented annually, taking into account previous
reviews, and should include at least:

a) Review of starting materials and packaging materials
used for the product, especially those from new sources
and in particular the review of supply chain traceability of
active substances;
b) A review of critical in-process controls, and finished
product results;
c) A review of all batches that failed to meet established
specification(s) and their investigation;
d) A review of all significant deviations or non-
conformances, the related investigations and the
effectiveness of resultant CAPAs taken;
e) A review of all changes made to the processes or
analytical methods;
f) A review of dossier variations submitted, granted or
refused;

g) A review of the results of the stability monitoring
programme and any adverse trends;
h) A review of all quality-related returns, complaints and
recalls and the investigations performed at the time;
i) A review of adequacy of any other previous corrective
actions on product processes or equipment;
j) Post-marketing commitments for new dossiers and
variations to the dossiers;
k) The qualification status of relevant equipment and
utilities, e.g. heating, ventilation and air-conditioning
(HVAC), water or compressed gases and a review of
the results of monitoring the output of such
equipment and utilities;
l) A review of technical agreements to ensure that they are
up to date.

The manufacturer and, where different, marketing
authorization holder, should evaluate the results of the review
and an assessment should be made as to whether CAPA or
any revalidation should be undertaken, under the PQS. CAPAs
should be completed in a timely and effective manner,
according to documented procedures.
There should be procedures for the ongoing management and
review of these actions, and the effectiveness of these
procedures should be verified during self-inspection.
Quality reviews may be grouped by product type, e.g. solid
dosage forms, liquid dosage forms, or sterile products, where
scientifically justified. Where the marketing authorization
holder is not the manufacturer, there should be a technical
agreement in place between the various parties that defines
their respective responsibilities in producing the quality
review.

The authorized person responsible for final batch certification,
together with the marketing authorization holder, should ensure
that the quality review is performed in a timely manner and is
accurate.
It augments GMPs by
describing specific
quality system
elements...helping
industry and
regulators achieve
harmonization...

What is Risk?
Risk is a combination of the probability of
occurrence to create harm and the severity of
that harm.
The factors that affect the manufacturing of products
are:
a) Manpower
b) Material
c) Machineries
d) Method
e) Measure
f) Environment
PQS

Quality Risk Management (QRM) is the process
of identifying, evaluating, and mitigating recognized risks
connected with medicines and healthcare goods.
Quality risk management is a systematic, risk-based approach
to quality management process for the-
 Assessment
 Control
 Communication and
 Review of risks….
to the quality of the medicinal
product across the product
lifecycle." (ICH Q9)
It is especially critical in the pharmaceutical industry, where
product quality can greatly affect consumer health and safety.
QRM can be applied both proactively & retrospectively…
Quality Risk Management (QRM) PQS

Quality Risk Management (QRM) PQS

"A systematic process of organizing information
to support a risk decision to be made within a risk
management process. It consist of three processes--
A) Risk Identification
 It is the process of finding, listing, and
characterizing hazards or risk.
B) Risk Analysis
 A process for understanding the nature of hazards
and determining the level of risk.
C) Risk Evaluation
 The process of comparing an estimated risk
against given risk criteria to determine the
significance of the risk.
1. Risk Assessment
PQS

2. Risk Control-
It is actions implementing risk evaluation decisions.
Risk control can involve monitoring, re-evaluation, and
compliance with decisions.
Purpose of Risk control are-
A. Risk Reduction
B. Risk Acceptance Level
Output / Result of the Quality Risk Management Process
The key focus of this step is choosing between risk reduction and
risk acceptance. Answer and discuss the guide questions below
with other QRM team members before making a decision:
 Is the risk above an acceptable level?
 What can be done to reduce or eliminate the risk?
 What is the appropriate balance among benefits, risks, and
resources?
 Are new risks introduced as a result of initial risk being controlled?
PQS

3. Risk Communication
Risk communication involves sharing information
on the entire process with stakeholders who are not part of the
QRM team. It also includes documenting the QRM team’s thought
process at each step and the results they were able to achieve after
completing a step.
Industry
operation
- Submissions
- Manufacturing
Regulators
operation
- Reviews
- Inspections
Communication
facilitates trust
and understanding
PQS

A. Review Events
Once risk control has been implemented, establish a system
for monitoring its effectiveness. Quality risk management
should be continuously reviewed, especially when:
 there is new research, experience, knowledge, or data on
specific risks;
 there are events that may have an impact on the original
decision/s; and
 factors influencing the overall risk level have changed.
4. Risk Review
"Review or monitoring of output/results of the risk
management process considering (if appropriate) new
knowledge and experience about the risk." (ICH Q9).
Ensures nothing has changed to affect the QRM
assumptions, output and conclusions Consider during
product review
PQS

 PDCA Cycle (Plan-Do-Check-Act)
 To familiarize oneself with the risk process overview,
the Plan-Do-Check-Act Model (PDCA) is encouraged.
 Plan: Planning the quality risk management
process.
 Do:
Identifying risk, analyzing and evaluating against the
thresholds.
Determining the additional actions needed.
Developing risk responses (mitigation plans) to
reduce the risk with scores above the thresholds to
acceptable level.
 Check & Act: Monitoring and controlling the risk
PQS

The level of effort, formality and
documentation of the QRM process should be
commensurate with the level of risk.
Evaluation of the risk to quality should be
based on scientific knowledge and be
ultimately linked to the protection of the
patient.
PQS

 Materials and ingredients;
 Physical characteristics and composition of the
product;
 Processing procedures;
 Microbial limits, where applicable;
 Premises;
 Equipment;
 Packaging;
 Sanitation and hygiene;
 Personnel – human error;
 Utilities;
 Supply chain.
 Normally, potential risks in relation to the
following should be considered:
PQS

Benefits of QRM Execution
 QRM execution will help organizations meet
regulatory requirements.
 It is also a proactive measure that prepares
organizations to not be reactive by minimizing risk.
 Being prepared, in turn, creates ongoing risk
reduction and helps to reduce overall costs when
more qualified decisions making is in the planning
stages.
 QRM also promotes quality, through increased
efficiency and knowledge transfer, with strong
potential to reduce catch-up work done to mediate
the effects of poor quality.
PQS

QRM should ensure that:
 The evaluation of the risk to quality is
based on scientific knowledge, experience with the process
and ultimately links to the protection of the patient
 The level of effort, formality and documentation of the QRM
process is commensurate with the level of risk.
While following the steps of the quality risk management process
above is sufficient for starting with QRM, certain industries or
companies may need the help of recognized tools to fully deploy
their strategy. Below are 3 quality risk management tools, their
descriptions, and templates to help get you started:
 Failure Mode Effects Analysis (FMEA)
 Hazard Analysis Critical Control Points (HACCP)
 Hazard Operability Analysis (HAZOP)
Quality Risk Management Tools
PQS

Facilitate Continual Improvement
Implement appropriate product quality improvements, process
improvements, variability reduction, innovations and
pharmaceutical quality system enhancements.
PQS
Continuous Improvement –
An integral part of the
Pharmaceutical Quality
System (PQS) 'Continuous
Improvement' or 'Continual
Improvement' within a quality
system can be described as
a process of on going
improvement of products,
services or processes
through incremental and/or
breakthrough improvements

Objectives of PQS PQS
 A robust PQS is critical to assuring drug products are
manufactured to meet the desired quality and
performance attributes. A robust pharmaceutical quality
system ensures-
QS Elements / Framework - ICH Q10
FDA Evaluation – Inspection & Review
Standards& Expectations – Regulations & CGMPs
 PQS is the key system evaluated during FDA inspection,
and is also key in providing FDA confidence that
appropriate (science and risk based) support information
is used to make decisions (e.g., in submissions).
 Therefore the objectives of PQS involves-
Achieve product realization
Establish and maintain a state of control
Facilitate continual improvement
 Facilitate effective knowledge transfer and management

PQS

A single FDA reviewer does not get the “full picture” of
quality based on the submission…
PQS

PQS

Established conditions - the description of the product,
manufacturing process, facilities and equipment, and
elements of the associated control strategy, as defined
in an application, that assure process performance and
quality of an approved product.
…changes after approval…must be managed and
executed in conformance with current good
manufacturing practices (CGMP)
PQS
 Applicants should use knowledge
obtained during transfer, scale up, and
commercial activities to improve the
control strategy.

PQS
During commercial manufacturing, per 21 CFR Part
211, the applicant must assure:
 The desired product quality is routinely met,
 Suitable process performance is achieved,
 The set of controls are appropriate,
 Improvement opportunities are identified and
evaluated and
 The body of knowledge is continually expanded.
 Recommendations for product lifecycle activities
to monitor continual assurance of the validated
state and continual improvement principles
PQS

CGMP: Every batch, Every day!
 “We rely upon the manufacturing controls and
standards to ensure that time and time again, lot after
lot, year after year the same clinical profile will be
delivered because the product will be the same in its
quality…
 We have to think of the primary customers as people
consuming that medicine and we have to think of the
statute and what we are guaranteeing in there, that
the drug will continue to be safe and effective and
perform as described in the label.”
- Janet Woodcock, M.D
If PQS does not meet expectations (cGMP, ICH Q10
etc) this may impact on regulatory strategy.
PQS

PQS

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