Traditional approach of formulating a new drug product is an exhaustive task and involves a number of resources like man, money, time and experimental efforts. While, using this Quality by Design (QBD) approach one can get the pharmaceutical product of desired (best) quality with minimizing above resources as well as knowing the influence of one factor over the desired associated process. Hence aim of this study is the understanding of QBD approach to design product and manufacturing process to get desired pharmaceutical product. QBD follows the concepts of ICH guidelines (Q8, Q9 & Q10) which are essential for processing a pharmaceutical process. In this presentation we are going to focus upon QBD for immediate release dosage forms.

1. QBD for Immediate-
Release Dosage Forms
Anamika Dey
MPH/10009/19

2. INTRODUCTION
Traditional approach of formulating a new drug product is an
exhaustive task and involves a number of resources like man,
money, time and experimental efforts. While, using this Quality by
Design (QBD) approach one can get the pharmaceutical product of
desired (best) quality with minimizing above resources as well as
knowing the influence of one factor over the desired associated
process. Hence aim of this study is the understanding of QBD
approach to design product and manufacturing process to get
desired pharmaceutical product. QBD follows the concepts of ICH
guidelines (Q8, Q9 & Q10) which are essential for processing a
pharmaceutical process. In this presentation we are going to focus
upon QBD for immediate release dosage forms.

3. Overview of QBD
Product Design
& Understanding
Process Design &
Understanding
Control
Strategy
Continuous
Improvement
Target
Product
Profile

4. Elements of QBD
 Quality target product profile (QTPP)
 Define CQA (Critical Quality Attribute)
 Perform Risk Management
 Link raw materials attributes & process
parameter to CQAs
 Design and implement of a control strategy

5. Quality target product profile(QTPP) for ANDA
Products
 QTPP is a prospective summary of the quality characteristics of a
drug product that ideally will be achieved to ensure the desired
quality, talking into account safety and efficacy of the drug
product.
 The QTPP is an essential element of QBD approach and forms
the basis of design of generic product.
 For ANDA’s, the target should be defines early in the development
based on the properties of the drug substances, characterization
of the product and intended patient population.
 The QTPP includes all product attributes that are needed to
ensure equivalent safety and efficiency.
 Based on the clinical and pharmacokinetic (PK) characteristics as
well as invitro dissolution and physicochemical characteristics of
the product, a QTPP is defined.

6. QTPP Components for IR tablets
QTPP Elements Target Justification
Dosage form Tablet Pharmaceutical equivalence
requirement: same dosage
form
Dosage design Immediate release tablet
without a score or coating
Immediate release design
needed to meet label claims
Route of administration Oral Pharmaceutical equivalence
requirement: same route of
administration
Dosage strength 20 mg Pharmaceutical equivalence
requirement: same strength
Pharmacokinetics Immediate release enabling
Tmax in 2.5 hours or less;
Bioequivalent to RLD
Bioequivalence requirement
Needed to ensure rapid onset
and efficacy
Stability At least 24-month shelf-life
at room temperature
Equivalent to or better than
RLD shelf-life

7. QTPP Elements Target Justification
Drug
product
quality
attributes
Physical
Attributes
Pharmaceutical equivalence requirement: Must
meet the same compendial or other applicable
(quality) standards (i.e., identity, assay, purity,
and quality).
Identification
Assay
Content
Uniformity
Dissolution
Degradation
Products
Residual
Solvents
Water Content
Microbial
Limits
Container closure system
Container closure
system qualified as
suitable for this drug
product
Needed to achieve the
target shelf-life and to
ensure tablet integrity
during shipping
Contd…

8. Critical Quality Attributes (CQA)
A critical quality attribute (CQA) is a “physical, chemical, biological
or microbiological property or characteristics that should be within
an appropriate limit, range or distribution to ensure desired product
quality.
 CQA for IR tablets:
• Assay,
• Content uniformity,
• Dissolution,
• Disintegration of products,
• Residual solvents,
• Water content,
• Microbial limits.

9. CQA components for IR tablets

10. • A risk management of the drug substance attributes is
performed to evaluate the impact that each attribute could have
on the drug product CQA’s.
• The two primary principles that should be considered when
implementing quality risk management are-
I. The evaluation of the risk to quality should be based on
scientific knowledge and ultimately linked to the protection of
the patient.
II. The level of effort, formality and documentation of the quality
risk management process should be commensurate with the
level of risk.
• Based upon the physicochemical and biological properties of the
drug substances, the initial risk assessment of drug substance
attributes on drug product CQAs should be done.
Risk Assessment of Drug Substances Attribute

11. Justification for the initial risk assessment of
the drug substance attributes

12. Contd…

14. Control Strategy
The control strategy is a planned set of controls derived from current
products and process understanding, that assures process performances
and product quality.
 Control Strategy for raw material attributes:
The drug substance particle size distribution limits arise from a
combination of its impact on binding and invivo performance.
 Control Strategy for roller compaction & integrated milling:
The intent of control strategy for roller compaction is to maintain ribbon
density with required range to ensure drug product CQAs are met. For
milling, the mill screen orifice size is specified to ensure that the granule
size distribution remains within the acceptable range.
 Control Strategy for blending and lubrication:
The control strategy for blending the granules with the talc is to
maintain the targeted number of revolutions. For granule lubrications
with Mg stearate, the control strategy is to adjust the number of
revolutions based on the blender capacity used and the volume of
blender.

15. Contd…
 Control Strategy for tablet compression:
The control strategy for tablet compression is to maintain the in
process tablet attributes of weight, hardness, thickness, friability
and disintegration within the required ranges.
The target compression force required to produce tablets with
desired hardness, and ultimate friability and disintegration is
established at the beginning of each run.
After tablets with target weight and hardness are obtained during
the tablet press set up, the upper punch penetration depth and the
fill depth are fixed.
The compression force is continuously measured throughout the
run for each tablet and compared to the target compression force.

16. Product Lifecycle Management & Continual
Improvement
Upon approval, the manufacturing process for IR tablets will be validated
using the lifecycle approach that employs risk based decision making
throughout the drug product lifecycle as defined in the FDA process
validation guidance.
 There are 3 stages in Product lifecycle management:
The commercial manufacturing process was defined baaed on knowledge
gained through development and scale up activities.
The goal of stage 2 is to evaluate if the process is capable of reproducible
commercial manufacturing facility will be designed according to cGMP
regulations.
Throughout the product lifecycle, the manufacturing process performance
will be monitored to ensure that it is working as anticipated to deliver the
product with desired quality attributes, process stability and process
capability will be measured and evaluated if any unexpected process
variability is detected, appropriate action will be taken to correct, anticipate
and prevent future problems so that the process remain in control as part of
the continual improvement of the drug product.

17. Thank You