Pharmaceutical Development
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disintegration testing, or other means to assure drug release, and the development
and suitability of the chosen test, could be provided in this section. See also ICH Q6A
Specifications: Test Procedures And Acceptance Criteria For New Drug Substances
And New Drug Products: Chemical Substances; Decision Tree #4 (Part 3) and Decision
Tree #7 (Part 1) or ICH Q6B Specifications: Test Procedures and Acceptance Criteria
for Biotechnology/Biological Products. The discussion should cross-reference any
relevant stability data in 3.2.P.8.3.
2.3 Manufacturing Process Development
The selection, the control, and any improvement of the manufacturing process
described in 3.2.P.3.3 (i.e., intended for commercial production batches) should be
explained. It is important to consider the critical formulation attributes, together with
the available manufacturing process options, in order to address the selection of the
manufacturing process and confirm the appropriateness of the components.
Appropriateness of the equipment used for the intended products should be discussed.
Process development studies should provide the basis for process improvement,
process validation, continuous process verification
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(where applicable), and any
process control requirements. Where appropriate, such studies should address
microbiological as well as physical and chemical attributes. The knowledge gained
from process development studies can be used, as appropriate, to justify the drug
product specification (3.2.P.5.6).
The manufacturing process development programme or process improvement
programme should identify any critical process parameters that should be monitored
or controlled (e.g., granulation end point) to ensure that the product is of the desired
quality.
For those products intended to be sterile an appropriate method of sterilization for the
drug product and primary packaging material should be chosen and the choice
justified.
Significant differences between the manufacturing processes used to produce batches
for pivotal clinical trials (safety, efficacy, bioavailability, bioequivalence) or primary
stability studies and the process described in 3.2.P.3.3 should be discussed. The
discussion should summarise the influence of the differences on the performance,
manufacturability and quality of the product. The information should be presented in
a way that facilitates comparison of the processes and the corresponding batch
analyses information (3.2.P.5.4). The information should include, for example, (1) the
identity (e.g., batch number) and use of the batches produced (e.g., bioequivalence
study batch number), (2) the manufacturing site, (3) the batch size, and (4) any
significant equipment differences (e.g., different design, operating principle, size).
In order to provide flexibility for future process improvement, when describing the
development of the manufacturing process, it is useful to describe measurement
systems that allow monitoring of critical attributes or process end-points. Collection of
process monitoring data during the development of the manufacturing process can
provide useful information to enhance process understanding. The process control
strategies that provide process adjustment capabilities to ensure control of all critical
attributes should be described.
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See Glossary for definition