FEDERAL ASPECT OF QBD

1. REGULATORY AND INDUSTRY
ASPECT OF QUALITY BY
DESIGN

2. Pharmaceutical development information is submitted in Section P.2
of the CTD. Other information resulting from pharmaceutical
development studies could be accommodated by the CTD format in a
number of different ways and some specific suggestions are provided
below. However, the applicant should clearly indicate where the
different information is located. In addition to what is submitted in
the application, certain aspects (e.g., product lifecycle management,
continual improvement) of this guideline are handled under the
applicant’s pharmaceutical quality system (see ICH Q10).

3. Quality Risk Management and Product and Process Development
Quality risk management can be used at different stages during
product and process development and manufacturing
implementation. The assessments used to guide and justify
development decisions can be included in the relevant sections of
P.2. For example, risk analyses and functional relationships linking
material attributes and process parameters to product CQAs can be
included in P.2.1, P.2.2, and P.2.3. Risk analyses linking the design of
the manufacturing process to product quality can be included in
P.2.3.

4. Design Space As an element of the proposed manufacturing process,
the design space(s) can be described in the section of the application
that includes the description of the manufacturing process and
process controls (P.3.3). If appropriate, additional information can be
provided in the section of the application that addresses the controls
of critical steps and intermediates (P.3.4). The product and
manufacturing process development sections of the application
(P.2.1, P.2.2, and P.2.3) are appropriate places to summarise and
describe product and process development studies that provide the
basis for the design space(s). The relationship of the design space(s)
to the overall control strategy can be discussed in the section of the
application that includes the justification of the drug product
specification (P.5.6).

5. Control Strategy The section of the application that includes the
justification of the drug product specification (P.5.6) is a good place
to summarise the overall drug product control strategy. However,
detailed information about input material controls and process
controls should still be provided in the appropriate CTD format
sections (e.g., drug substance section (S), control of excipients (P.4),
description of manufacturing process and process controls (P.3.3),
controls of critical steps and intermediates (P.3.4)).

6. Drug Substance Related Information If drug substance CQAs have the
potential to affect the CQAs or manufacturing process of the drug
product, some discussion of drug substance CQAs can be appropriate
in the pharmaceutical development section of the application (e.g.,
P.2.1).

7. REGULATORY ASPECTS TO QBD
FDA perspective In 2005 USFDA asked participating firms to submit
chemistry manufacturing control (CMC) information demonstrating
application of QbD as part of New Drug Application. QbD involves
thorough understanding of process; a goal or objective is defined
before actual start of process. Design space and real time release risk
assessment are other parameters for implementation of QbD.
International conference on harmonization in its Q8 pharmaceutical
development, Q9 quality risk assessment and Q10 pharmaceutical
quality system gives stringent requirements regarding quality of
product. FDA also states the importance of quality of pharmaceutical
products by giving Process Analytical Technology (PAT) which is a
Framework for Innovative Pharmaceutical Development,
Manufacturing and Quality Assurance (Patricia, 2007).

8. REGULATORY ASPECTS TO QBD
QbD ultimately helps to implement Q8 and Q9. FDA’s view of QbD is
‘‘QbD is a systematic approach to product and process design and
development’’. This concept was accepted by FDA in 2004 and
detailed description was given in ‘pharmaceutical cGMPs for 21st
century – a risk based approach’. In nutshell, Product quality and
performance can be assured by designing efficient manufacturing
processes. Product and process specifications are based on a
scientific understanding of how process factors affect product
performance. Risk-based regulatory approaches are for scientific
understanding and control related process for product quality and
performance. Related regulatory policies and measures are modified
to accommodate the real time scientific knowledge. Quality assurance
is continuous process.

9. 3.2. ICH guideline and QbD (ICH guideline Q8, 2012; ICH guideline
Q10, 2012; ICH guideline Q9, 2012) The underlying principles of QbD
i.e. science- and risk-based product development, risk assessment,
lifecycle approach and method design are explained in the quality
guidelines of international conference on harmonization i.e. ICH Q8
Pharmaceutical Development, ICHQ9 Quality Risk Management, and
ICH Q10 Pharmaceutical Quality System.

10. Regulatory challenges and inspection According to Anastasia G. Lolas and
Anurag S. Rathore ‘‘In a QbD concept, the regulatory burden is less because
there are wider ranges and limits based on product and process
understanding. Changes within these ranges and limits do not require prior
approval’’. Traditionally, inspections have been conducted using the FDA
system-based approach and in accordance with CDER’s Compliance Program
‘‘Inspection of Licensed Bio-logical Therapeutic Drug Products’’. But now
query arises that how the inspection will take place in the present scenario
where QbD is mandated. During prelicense or preapproval inspections under
a QbD concept, the FDA inspection team will assess the implementation and
effectiveness of the process design as described in the application and
whether knowledge and risk management have been transferred successfully
from development to manufacturing. The inspection will evaluate the quality
system and its effectiveness regarding consistent product quality, change in
control procedures, process improvements, deviation management, and
knowledge and risk management during the product lifecycle. Inspection of
facility and equipment qualification and maintenance as well as raw material
screening and supplier management will be same as it was performed