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BNT162b2
3.2.S.2.4 Control of Critical Steps and Intermediates
Manufacturing Process
PFIZER CONFIDENTIAL
Page 13.2.S.2.4. MANUFACTURING PROCES S
3.2.S.2.4.1. Introduction
This section provides a description of the controls of critical process steps employ ed during
manufacture of BNT162b2 drug substance to ensure that product quality is maintained.
Process parameters and tests that are used to control the process and drug substance qualit y
are provided in this section.
Process parameters discussed in this section include all critical proces s parameters (CPP s). In
addition to CPPs, the risk assessment process is also used to identify relevant non -CPPs that
have an impact on quality attributes. As described in Section 3.2.S.2.6 Process Development
and Characterization , CPPs were conservativel ydefined after the Cause and Effect ( C&E )
risk assessment by evaluating the parameters which had a strong functional relationship to a
quality attribute (high C&E scores). These relationships were supported by established
scientific rationale ,platform kno wledge or confirmed data available from the process
characterization studies . For this program, no non -CPPs having an impact on quality
attributes were identified.
Assessment of the methodology for the determination of CPPs is provided in
Section 3.2.S .2.6 Process Risk Asses sment Strategy . The ICH guidelines define a critical
process parameter as “A process parameter whose variability has an impact on a critical
quality attribute and therefore should be monitored or controlled to ensure the process
produces the desired quality. ”
The I CH guidelines define critical qualit y attribute ( CQA ) as “ a physical, chemical,
biological, or microbiological property or characteristic that should be within an
appropriate limit, range, or distribution to ensure the desired product quality. The
assignment of criticality to a quality attribute is based upon the potential of the quality
attribute to impact patient safety or efficacy .” CQAs are distinguished from QA by an
iterative process of quality risk management and expe rimentation that assesses the extent to
which their variation can have an impact on the quality of the drug product.
For assessment of the drug substance manufacturing process, the assignment of parameter
criticality was expanded for all applicable quality attributes.
In-process test for control (I PT-C) and in -process test for monitor ing(IPT-M) are used
throughout the process to ensure consistent manufacturing. IP T-Cs are in -process tests used
to control a quality attribute within a specified range so tha t it meets the desired DS/DP
quality . The IPT-Cs have an associated acceptance criterion . These I PT-Cs are tabulated in
this section with their associated acceptance criterion and described in Section 3. 2.S.2.4
In-Process Test Methods [Andover]
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BNT162b2
3.2.S.2.4 Control of Critical Steps and Intermediates
Manufacturing Process
PFIZER CONFIDENTIAL
Page 2IPT-Ms are in- process tests used to monitor a quality attribute to either ensure that it is
consistent with respect to previous process history or for forward processing. The monitoring
tests may have action limits. These I PT-Ms are described in Section 3. 2.S.2.4 I n-Process Test
Methods [Andover] .
3.2.S.2.4.2. Manufacturing Process Controls
As described ab ove, Table 3.2.S.2.4-1 provides a list of in -process controls ( critical process
parameters and IPT -Cs) with their acceptable ranges/acceptance criteria for the drug
substance manufacturing process.
Table 3.2.S.2.4-1. Process Controls
Unit
OperationProcess Control Acceptable Range/
Acceptance CriteriaCategory
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(b) (4)
(b) (4)
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