Qb d agency expectations

This presentation is compiled by “ Drug Regulations” a
non profit organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
8/22/2013 1

 This presentation is compiled by “ Drug
Regulations” from freely available resources
like the FDA on the World wide web.
 “Drug Regulations” is a non profit
organization which provides free online
 Visit http://www.drugregulations.org for
latest information from the world of
Pharmaceuticals.
8/22/2013 2
Drug Regulations : Online
Resource for Latest Information

 Pilot program of the EMA and FDA
 Launched in March 2011
 Aimed at a parallel assessment of certain
quality/CMC sections relevant to QbD :
◦ Development,
◦ Design space and
◦ Real time release testing.
8/22/2013 3

 The objective of the pilot is to ensure
◦ Consistent implementation between EU and US of
ICH Q8, 9, 10, 11 guidelines in the assessment
process and
◦ To facilitate sharing of regulatory decisions on new
regulatory concepts.
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 Voluntary pilot program open to
◦ New Marketing Authorisation Applications (MAAs)
◦ New Drug Applications (NDAs),
◦ Type II Variations/Prior-approval supplements
(sNDA)
◦ Scientific Advice requests/CMC formal meeting
requests that include QbD/Process Analytic
Technology (PAT) elements
8/22/2013 5

 Voluntary pilot program
◦ Submitted to either both agencies at the same time
resulting in a parallel evaluation, or
◦ Either to EMA or FDA in which case the agency
doing the evaluation obtains consultative advice
from the other agency.
8/22/2013 6

 The first EMA-FDA parallel assessment of
QbD elements of an initial marketing
authorisation application finalised.
 Consultative advice procedures finalized
8/22/2013 7

 The EMA and FDA reached agreements on a
wide range of QbD aspects
 Summary of agreements reflected in the Q&A
follow.
 In the future, more lessons learnt resulting
from this EMA-FDA pilot program will be
published.
8/22/2013 8

 Provide prospective description of the quality
characteristics a drug product should achieve
to ensure the desired quality, taking into
account
◦ Safety and
◦ Efficacy of the drug product.
8/22/2013 9

 Specify QTPP only for the finished product.
 Preferably submit the QTPP information in a
tabular format in the application.
8/22/2013 10

 Provide a list of CQAs for drug substance,
finished product, and excipients when
relevant.
 Provide acceptance limits for each CQA
 Provide a rationale for designating these
properties as a CQA.
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 Include a discussion of how the drug
substance and excipient CQAs relate to the
finished product CQAs based on
◦ Prior knowledge
◦ Risk assessment or
◦ Experimental data
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 Devise the control strategy to ensure that the
drug substance and finished product CQAs
are consistently within the specified limits.
 Preferably provide information on CQAs in a
tabular format in the application
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 ICH Q8(R2)
 A critical process parameter has an impact on
a critical quality attribute.
 A critical process parameter should be
monitored or controlled to ensure the
process produces the desired quality.
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 Pilot programme submission included a
three-tier classification for quality attributes
and process parameters:
◦ Critical,
◦ Key and
◦ Non-critical.
8/22/2013 15

 A critical factor was defined as a factor that
led to failure during experimentation.
 A factor that had not led to failure within the
range studied, but still may have an impact
on product quality, was considered as a key
factor.
8/22/2013 16

 Different applicants will use the term “key”
differently.
 The Agencies do not support the use of the
term Key Process Parameters (KPP)
 KPP is not an ICH terminology.
 Agencies recommend not to underestimate
assignment of criticality specially when a
robust proactive control strategy mitigates a
risk of failure.
8/22/2013 17

 This terminology may be used in the
pharmaceutical development section.
 However, classify all parameters that have an
impact on a CQA as critical in the
◦ 3.2.P.3.3 “Description of the Manufacturing Process
and Process Controls” ,
◦ 3.2.P.3.4 “Control of Critical Steps and
◦ Intermediates” sections
8/22/2013 18

 Provide same level of detail in the
manufacturing process description
irrespective of the development approach.
 For US FDA,
◦ A detailed process description can be submitted in
lieu of a Master Production Record for drug product
manufacturing for 505(b)(1) products.
8/22/2013 19

 For US FDA,
◦ However, proposed or actual commercial scale
Master Production Records are required for generic
and 505(b)(2) products.
 For EU,
◦ There is requirement for a full description of the
manufacturing process in all cases.
8/22/2013 20

 Provide comprehensive process descriptions
 Describe process steps in a sequential
manner
 Provide details of batch size(s) and
equipment type.
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 Identify the critical steps and points at which
process controls, intermediate tests or final
product controls are conducted.
 Provide necessary detail in terms of
appropriate process parameters along with
their target values or ranges.
8/22/2013 22

 Do not restrict the process parameters in the
manufacturing process description to the
critical ones.
8/22/2013 23

 Describe all parameters that have been
demonstrated during development as
needing to be controlled or monitored during
the process to ensure that the product is of
the intended quality.
8/22/2013 24

 Industry has applied QbD concepts in the
area of analytical methods based on
◦ Risk assessments
◦ Statistically designed experiments
◦ Analytical Target Profiles (ATP)
◦ Method Operational Design Ranges (MODR)
8/22/2013 25

 The ATP parallels Quality Target Product
Profile (QTPP)
 MODR parallels the Design Space
 No international consensus on the definition
of ATP and MODR.
 Agencies will evaluate applications on a case-
by-case basis
8/22/2013 26

 Analytical process profile acceptable as a
qualifier of the expected method
performance.
 Analytical methods that have different
principles (e.g., HPLC to NIR) will not be
considered equivalent solely on the basis of
conformance with the ATP.
8/22/2013 27

 Do not switch between these two types of
methods without appropriate regulatory
submission and approval.
8/22/2013 28

 Apply principles similar to “Design Space” for
MODRs.
 Data to support an MODR
◦ Appropriately chosen experimental protocols to
support the proposed operating ranges/ conditions;
and
◦ Demonstration of statistical confidence throughout
the MODR.
8/22/2013 29

 More lessons learnt & Agency Expectations will
be published.
◦ Design Space verification
◦ Design Space
◦ Risk assessment level of detail in submissions,
◦ Continuous process verification and
◦ Continuous manufacturing.
◦ Assessment of validation requirements as identified in
ICH Q2(R1) throughout the MODR
◦ Confirmation of system suitability across all areas of the
MODR.
8/22/2013 30

 This presentation is compiled by “ Drug
Regulations” from freely available resources
like the FDA on the World wide web.
 “Drug Regulations” is a non profit
organization which provides free online
 Visit http://www.drugregulations.org for
latest information from the world of
Pharmaceuticals.
8/22/2013 31

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