In the last year or so the FDA and the EMA have issued new guidance/ draft guidance on "Process Validation".These align process validation activities with a product lifecycle concept and the International Conference on Harmonisation (ICH) guidances for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System. The earlier guidelines were developed before the elaboration of the new ICH guidelines.With these new guidelines, additional opportunities are available to verify the control of the process by alternative means to the manufacture of traditional process validation batches. The main objective of process validation remains that a process design yields a product meeting its pre-defined quality criteria. ICH Q8, Q9 and Q10 provide a structured way to define product critical quality attributes, design space, the manufacturing process and the control strategy. ICH Q8 refers to an ‘enhanced’ approach to pharmaceutical development which includes an alternative to the traditional process validation.
Continuous process verification [see definition in ICH Q8(R2) glossary] can be utilised in process validation protocols for the initial commercial production and for manufacturing process changes for the continual improvement throughout the remainder of the product lifecycle.
There is now a new paradigm in process validation. This presentation has been prepared from material available from FDA , EMA and ICH for beginners to have an overview of the new paradigm.
2. This presentation is compiled from freely available resources like the
website of FDA & EMA specifically
“Guidance for Industry Process Validation: General Principles and
Practices , Revision 1, 2011” “EU Guidelines for Good Manufacturing
Practice Annex 15: Qualification and Validation” and” EMA Guideline on
process validation for finished products - information and data to be
provided in regulatory submissions”
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3. Effective process validation contributes
significantly to assuring drug quality.
Quality, safety, and efficacy are designed or
built into the product.
Quality cannot be adequately assured merely
by in-process and finished-product
inspection or testing.
www.drugragulations.org 3August 15
4. Process Validation is now defined as the
collection and evaluation of data, from the
process design stage through commercial
production, which establishes scientific evidence
that a process is capable of consistently
delivering quality product. Process validation
involves a series of activities taking place over
the lifecycle of the product and process
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5. Validation is the act of demonstrating and
documenting that a procedure operates
effectively.
Process validation is the means of ensuring and
providing documentary evidence that processes (
within their specified design parameters) are
capable of consistently producing a finished
product of the required quality.
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6. The documented evidence that the process,
operated within established parameters, can
perform effectively and reproducibly to produce a
medicinal product meeting its predetermined
specifications and quality attributes.
www.drugragulations.org 6August 15
7. Stage1:Process Design:
◦ The commercial manufacturing process is defined during this stage based
on knowledge gained through development and scale-up activities.
Stage 2: Process Qualification:
◦ During this stage, the process design is evaluated to determine if the
process is capable of reproducible commercial manufacturing.
Stage 3: Continued Process Verification
◦ Continued Process Verification: Ongoing assurance is gained during
routine production that the process remains in a state of control.
www.drugragulations.org 7August 15
8. Manufacturing process should consistently produce APIs
and drug products meeting quality attributes.
Assurance based on objective information and data from
laboratory-, pilot-, and/or commercial-scale studies.
Information and data should demonstrate that the
commercial manufacturing process is capable of
consistently producing acceptable quality products within
commercial manufacturing conditions.
www.drugragulations.org 8August 15
9. Information and knowledge from product and
process development.
Understanding sources of variation
Detecting the presence and degree of variation
Understanding the impact of variation on the process
and ultimately on product attributes
Controlling the variation in a manner commensurate
with the risk it represents to the process and product.
www.drugragulations.org 9August 15
10. Manufacturer judging whether it has gained sufficient understanding of
the process.
Not focusing exclusively on qualification efforts
Understanding the manufacturing process and associated variations.
Maintaining the process in a state of control over the life of the process,
even as materials, equipment, production environment, personnel, and
manufacturing procedures change.
Collecting and analyzing product and process data to evaluate the state
of control of the process.
www.drugragulations.org 10August 15
11. Life cycle approach
Good project management
Good archiving
An integrated team approach
Studies based on sound scientific principles
Risk based decision making
Criticality as a continuum rather than a binary
state
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12. Evaluate attribute(s) (quality, product, component) &
parameter(s)( process, operating, & equipment) in
terms of their roles in the process and impact on the
product or in-process material.
Reevaluate above as new information becomes
available.
Exercise degree of control on attributes &
parameters commensurate with their risk to the
process and process output
www.drugragulations.org 12August 15
13. cGMP conditions not required at this stage
Follow good documentation practices
Use sound scientific methods and principles
Conduct internal review & document decisions and
justification of the controls
Use knowledge and data from product development
◦ Critical quality attributes
◦ Critical material attributes
◦ Critical process parameters
Consider functionality and limitations of commercial
manufacturing equipment
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14. Consider contributions to variability posed by
◦ Different component lots,
◦ Production operators,
◦ Environmental conditions, and
◦ Measurement systems in the production setting.
Use laboratory or pilot-scale models designed to
be representative of the commercial process
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15. Use DOE to develop process knowledge by
◦ Revealing relationships,
◦ Multivariate interactions, between the variable inputs
(e.g., component characteristics or process parameters)
and the resulting outputs (e.g., in-process material,
intermediates, or the final product).
Use risk analysis tools to screen variables for
DOE
www.drugragulations.org 15August 15
16. Based on the DOE results Establish ranges of
◦ Incoming component quality,
◦ Equipment parameters, and
◦ In-process material quality attributes
FDA does not generally expect manufacturers to develop and test the
process until it fails.
Use lab or pilot scale to predict performance at commercial scale
Use the data to model or simulate a commercial scale process
Understand the degree to which the models represent a commercial
process
www.drugragulations.org 16August 15
17. Process controls should address variability
Design process control to
◦ Reduce Input variation, or
◦ Adjust for input variation during manufacturing or
◦ Combine both approaches
Controls can consist of
◦ Material analysis and
◦ Equipment monitoring at significant processing points
Use risk assessment for type and extent of process controls
www.drugragulations.org 17August 15
18. Use operational limits & in-process monitoring
◦ When the product attribute is not readily measurable due
to limitations of sampling or detectability (e.g., viral
clearance or microbial contamination or
◦ When intermediates and products cannot be highly
characterized and well-defined quality attributes cannot
be identified
Establish these controls in Master production &
controls record
www.drugragulations.org 18August 15
19. Advanced strategies like PAT can be used
Strategies can include timely analysis and control loops to
adjust the processing conditions so that the output
remains constant.
These systems can provide higher degree of process
control than non-PAT systems.
In case of PAT system approach to process validation will
be different
www.drugragulations.org 19August 15
20. Process Qualification
◦ Determines if the process designed is capable of reproducible
commercial manufacture.
◦ Has two elements
Design of the facility and qualification of the equipment and utilities
Process performance qualification
◦ Requires cGMP compliant procedures
◦ Completion of this stage is required before commercial distribution.
◦ Products manufactured during this stage can be released for distribution , if
they are acceptable.
www.drugragulations.org 20August 15
21. Design & commissioning of facilities & utilities precede
process performance qualification ( PPQ).
Qualification refers to demonstration that utilities and
equipment are suitable for their intended use and perform
properly.
www.drugragulations.org 21August 15
22. Qualification of utilities and equipment generally
include
◦ Selection of utilities and equipment construction materials,
operating principles, and performance characteristics.
◦ Verification that utility systems and equipment are built and
installed in compliance with the design specifications.
◦ Verification that utility systems and equipment operate in in all
anticipated operating ranges.
www.drugragulations.org 22August 15
23. Qualification of utilities and equipment generally
include
◦ Challenge to the equipment or system functions while under load
comparable to that expected during routine production.
◦ Performance of interventions, stoppage, and start-up as is
expected during routine production.
◦ Performance for as long as necessary during actual production at
operating ranges
www.drugragulations.org 23August 15
24. Can be preformed under individual plans or part of
overall plan
Use risk assessment for prioritization
Use risk assessment for level of effort in
performance & documentation
www.drugragulations.org 24August 15
25. Plan should identify the
◦ Studies or tests to use,
◦ Criteria appropriate to assess outcomes,
◦ Timing of qualification activities,
◦ Responsibilities of relevant departments and the quality
unit, and
◦ Procedures for documenting and approving the
qualification.
www.drugragulations.org 25August 15
26. Process Performance Qualification Combines following to
produce commercial batches.
◦ Actual facility
◦ Utilities
◦ Equipment (each now qualified)
◦ Trained personnel with
◦ Commercial manufacturing process,
◦ Control procedures
◦ Components
www.drugragulations.org 26August 15
27. Process Performance Qualification
◦ Confirms process design
◦ Demonstrates that the commercial manufacturing
process performs as expected.
Commercial distribution succeeds PPQ
completion
www.drugragulations.org 27August 15
28. Process performance qualification should be based on
◦ Overall level of product and process understanding
◦ Level of demonstrable control
◦ Data from lab, pilot & commercial batches
◦ Effect of scale
◦ Previous credible experience with sufficiently similar products and
processes
◦ Objective measures to achieve adequate assurance
www.drugragulations.org 28August 15
29. Process performance qualification should be based on
◦ Higher level of sampling
◦ Additional testing,
◦ Greater scrutiny of process performance than would be typical of
routine commercial production
◦ Level of monitoring and testing sufficient to confirm uniform product
quality throughout the batch
◦ Not necessary to explore entire operating range at commercial scale
www.drugragulations.org 29August 15
30. Establish levels and frequency of routine sampling
and monitoring based on increased sampling
Base duration of increased sampling on
◦ Volume of production
◦ Process complexity
◦ Level of process understanding
◦ Experience with similar products and processes.
www.drugragulations.org 30August 15
31. Different approach for processes using PAT
PAT process designed to
◦ Measure attributes of in process material
◦ Adjust the process in a control loop
◦ Maintain desired quality of output
The process design and qualification stage should
focus on measurement system and control loop.
www.drugragulations.org 31August 15
32. The protocol should address following:
◦ The manufacturing conditions, including operating
parameters, processing limits, and component (raw
material) inputs
◦ The data to be collected and when and how it will be
evaluated.
◦ The sampling plan, including sampling points, number of
samples, and the frequency of sampling for each unit
operation and attribute.
www.drugragulations.org 32August 15
33. The protocol should address following:
◦ The number of samples should be adequate to provide
sufficient statistical confidence
◦ The confidence level selected can be based on risk analysis
as it relates to the particular attribute under examination
◦ Criteria and process performance indicators that allow for a
science- and risk-based decision about the ability of the
process to consistently produce quality products
www.drugragulations.org 33August 15
34. The protocol should address following:
◦ A description of the statistical methods to be used in analyzing
all collected data
◦ Provision for addressing deviations from expected conditions
and handling of nonconforming data.
◦ Design of facilities and the qualification of utilities and
equipment, personnel training and qualification, and
verification of material sources.
◦ Status of the validation of analytical methods used
◦ Review and approval of the protocol
www.drugragulations.org 34August 15
35. Execution to begin after approval of protocol
Any departures form protocol should follow quality
system
All departures should be justified & approved
Follow commercial manufacturing process &
routine procedures
www.drugragulations.org 35August 15
36. Normal operating conditions should include
the
◦ Utility systems,
◦ Material,
◦ Personnel,
◦ Environment, and
◦ Manufacturing procedures.
www.drugragulations.org 36August 15
37. Report should
Discuss and cross-reference all aspects of the protocol.
Summarize data collected and analyze the data, as specified
by the protocol.
Evaluate any unexpected observations and additional data not
specified in the protocol.
Summarize and discuss all manufacturing nonconformance
Describe in sufficient detail any corrective actions or changes
www.drugragulations.org 37August 15
38. Report should
State a clear conclusion as to whether the data indicates the
process met the conditions established in the protocol and
whether the process is considered to be in a state of control
If not, the report should state what should be accomplished
before such a conclusion can be reached
Review and sign off
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39. Goal to ensure that process remains in a state of
control during commercial manufacture
System to detect unplanned departures from
designed process is essential to achieve the goal
Collect & evaluate data to determine process
variability
Identify problems and implement corrective actions
if required
www.drugragulations.org 39August 15
40. Establish a program to collect & analyze product & process
data
◦ Process trends
◦ Quality of incoming materials or components,
◦ In-process material,
◦ Finished products
Statistically review and trend the data
Use statistical and qualitative tools to detect variation
Scrutinize inter batch and intra batch variation
www.drugragulations.org 40August 15
41. Continue monitoring and sampling of process
parameters and quality attributes at the level
established during the process qualification stage
until sufficient data are available to generate
significant variability estimates.
These estimates can provide the basis for
establishing levels and frequency of routine
sampling and monitoring for the particular product
and process.
www.drugragulations.org 41August 15
42. Monitoring can then be adjusted to a statistically
appropriate and representative level.
Process variability should be periodically assessed
and monitoring adjusted accordingly.
www.drugragulations.org 42August 15
43. Detect variation by assessment of
◦ Defect complaints,
◦ Out-of-specification findings,
◦ Process deviation reports,
◦ Process yield variations,
◦ Batch records,
◦ Incoming raw material records, and
◦ Adverse event reports.
www.drugragulations.org 43August 15
44. Periodic meeting between quality unit and
production staff to
◦ Evaluate data
◦ Discuss possible trends
◦ Undesirable process variation
◦ Co-ordinate any correction or follow-up actions by
production.
www.drugragulations.org 44August 15
45. Improve/optimize the process based on the data by
altering
◦ Operating conditions (ranges and set-points),
◦ Process controls,
◦ Component, or
◦ In-process material characteristics
Document, justify & approve the change as per PQS
Additional process design and process qualification
activities could be warranted
www.drugragulations.org 45August 15
46. Important to maintain facility, utilities, and equipment
Maintain qualification status through routine
monitoring, maintenance, and calibration procedures
and schedules.
Re-assess data periodically to determine the need of
re-qualification
Adjust maintenance and calibration frequency based on
above inputs.
www.drugragulations.org 46August 15
47. Commercial distribution of product only after
◦ Successful completion of PPQ
◦ After obtaining high degree of assurance in process
Under special circumstances PPQ batches can be released
concurrently
FDA expects that concurrent release will be used rarely
Circumstances and rationale for concurrent release should be
fully described in the PPQ protocol
www.drugragulations.org 47August 15
48. Lot released concurrently must comply with all
CGMPs, regulatory approval requirements, and PPQ
protocol lot release criteria
Lot release under a PPQ protocol is based
upon meeting confidence levels appropriate
for each quality attribute of the drug
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49. Appropriate for processes used infrequently for various
reasons
Manufacture drugs for which there is limited demand
◦ Orphan drugs,
◦ Minor use and
◦ Minor species veterinary drugs
Drugs with short half live
◦ Radio pharmaceuticals
◦ Positron emission tomography drugs
Drugs manufactured in co-ordination with agency to alleviate
short supply
www.drugragulations.org 49August 15
50. Document each step for life cycle management
Documentation ensures knowledge gained is accessible
to others
Documentation is dependent on the stage of validation
Documentation requirements are greatest during
Stage 2, process qualification, and Stage 3,
continued process verification
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51. Diagram the process flow for the full-scale
process.
◦ Describe each unit operation,
◦ its placement in the overall process,
◦ monitoring and control points, and
◦ the component, as well as other processing material inputs (e.g.,
processing aids) and
◦ expected outputs (i.e., in-process materials and finished product).
www.drugragulations.org 51August 15
52. Accurate & precise analytical techniques are essential.
Validated methods not required for product/process-
development. However
◦ Sound & reliable methods are required.
◦ Assurance of proper equipment function.
◦ Documented maintenance & calibration procedures.
◦ New analytical technology and modifications to existing technology
can be used to characterize the process or the product.
Methods for commercial batch release must follow cGMP’s
www.drugragulations.org 52August 15
53. Replaces the emphasis on the first few commercial-scale validation
batches with enhanced assurance of product quality in many, or
even all, batches;
Provides the foundation for a robust process performance and
product quality monitoring system, increasing product and process
knowledge and facilitation of continual improvement opportunities
for process and product quality;
Enables earlier detection of manufacturing-related problems and
trends;
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54. Provides immediate feedback of the effect of a change,
thereby facilitating the management of changes;
Provides a higher assurance of an ongoing state of control, as
more data from CPV provide higher statistical confidence for
ongoing monitoring and trending;
Is particularly suited to the evaluation of continuous
manufacturing processes; and
Contributes to the verification of the design space, if used,
throughout the product lifecycle.
www.drugragulations.org 54August 15
55. Irrespective of whether a medicinal product is
developed by a traditional approach or an enhanced
approach, the manufacturing process should be
validated before the product is placed on the market.
In exceptional circumstances concurrent validation
may be accepted.
Please refer to GMP Annex 15 for further guidance or
our presentation on the same. ( Click here )
www.drugragulations.org 55August 15
56. Process validation
◦ Should confirm that the control strategy is adequate to the process design and the
quality of the product.
◦ Should cover all manufactured strengths
◦ Should cover all manufacturing sites used for production of the marketed product.
◦ Data should be generated for all products to demonstrate the adequacy of the
manufacturing process at each site of manufacture.
◦ Should be carried out in accordance with GMP
◦ Data should be held at the manufacturing location and made available for inspection
if not required in the dossier
◦ A bracketing approach may be acceptable for different strengths, batch sizes and
pack sizes.
www.drugragulations.org 56August 15
57. Process validation can be performed in a traditional way,
regardless of the approach to development taken.
Continuous process verification can be implemented if
◦ An enhanced approach to development has been performed or
◦ Where a substantial amount of product and process knowledge and
understanding has been gained through historical data and manufacturing
experience.
www.drugragulations.org 57August 15
58. Traditional process validation is normally
performed when
◦ The pharmaceutical development and/or process
development is concluded, after scale-up to production
scale and prior to marketing of the finished product.
www.drugragulations.org 58August 15
59. As part of the process validation lifecycle, some process validation
studies may be conducted on pilot scale batches if the process has
not yet been scaled up to production scale.
It should be noted that pilot batch size should correspond to at least
10% of the production scale batch (i.e. such that the multiplication
factor for the scale-up does not exceed 10).
For solid oral dosage forms this size should generally be 10% of the
maximum production scale or 100,000 units whichever is the
greater.
www.drugragulations.org 59August 15
60. Where the intended batch size is less than 100,000 units, the
predictive value of the pilot batches may be limited
A justified approach should be followed.
For other dosage forms the pilot batch size should be justified
taking into account risk to the patient of failure of the dosage form.
Since it is not generally considered useful to conduct full validation
studies on pilot scale batches, the process validation scheme
outlined in subsequent slides should be completed for each product
for subsequent execution at production scale;
Bracketing may be acceptable.
www.drugragulations.org 60August 15
61. Where validation data on production scale batches are not provided
with the application and traditional process validation is proposed,
the process validation scheme described below should be submitted
by the applicant.
This should outline the formal process validation studies to be
conducted on production scale batches.
The number of batches used would depend on the variability of the
process, the complexity of the process / product and the experience
of the manufacturer,
However would usually be a minimum of 3 consecutive batches.
www.drugragulations.org 61August 15
62. The information from these studies should be available for
verification post authorization by the supervisory authority.
The process validation scheme should be submitted in the
marketing authorization dossier and should include the following
information as a minimum:
◦ Short description of the process with a summary of the critical
processing steps or critical process parameters to be monitored
during validation;
◦ Finished product release specification (references to the dossier);
details of analytical methods (references to the dossier);
www.drugragulations.org 62August 15
63. The process validation scheme should be submitted in the
marketing authorization dossier and should include the following
information as a minimum:
◦ In-process controls proposed with acceptance criteria;
◦ Additional testing intended to be carried out (e.g. with proposed
acceptance criteria and analytical validation as appropriate);
◦ Sampling plan - where, when and how the samples are taken;
details of methods for recording and evaluation of results;
proposed timeframe
www.drugragulations.org 63August 15
64. Following completion of the scheme, a report containing the
following information and signed by the appropriate authorized
person should be generated and made available for inspection:
◦ Batch analytical data
◦ Certificates of analysis
◦ Batch production records
◦ Report on unusual findings, modifications or changes found
necessary with appropriate rational
◦ Conclusions.
www.drugragulations.org 64August 15
65. It is a science and risk-based real-time
approach to verify and demonstrate that a
process that operates within the predefined
specified parameters produces material which
meets all its Critical Quality Attributes (CQAs)
and control strategy requirements.
www.drugragulations.org 65August 15
66. Again, the focus is put explicitly on extensive
◦ In-line or
◦ At-line controls and
◦ On monitoring process performance and product quality
in a timely manner.
Relevant process quality attributes of incoming
materials or components should be collected.
www.drugragulations.org 66August 15
67. This should include the verification of
◦ Attributes
◦ Parameters
◦ End points
◦ Assessment of CQA and Critical Process Parameter
(CPP) trends.
www.drugragulations.org 67August 15
68. Process analytical technology applications can be
viewed as enablers for continuous process
verification.
◦ NIR spectroscopy with or without feedback loop
End point determination of blend homogeneity
Determination of granules surface area
Determination of content uniformity with large sample size)
Multivariate statistical process control (MSPC)
www.drugragulations.org 68August 15
69. Scope and extent of CPV are influenced by a
number of factors including:
◦ Development and manufacturing knowledge from similar
products and/or processes;
◦ The extent of process understanding gained from
development studies and commercial manufacturing
experience;
◦ The complexity of the product and/or manufacturing
process;
www.drugragulations.org 69August 15
70. ◦ The level of process automation and analytical
technologies used;
◦ With reference to the product lifecycle, process
robustness and manufacturing history since point
of commercialization as appropriate.
The process should be verified on commercial
scale batches prior to marketing.
www.drugragulations.org 70August 15
71. Continuous process verification can be
introduced at any time of the lifecycle of the
product:
It can be used to design
◦ Process validation protocols for the initial
commercial production,
◦ To re-validate as part of process changes or
◦ To support continual improvement throughout the
lifecycle.
www.drugragulations.org 71August 15
72. If a design space has been implemented
continuous process verification may
contribute to ensuring its validity throughout
the product lifecycle.
www.drugragulations.org 72August 15
73. Continuous process verification performance
depends strongly on compliance with GMP, if
necessary complemented by Pharmaceutical quality
systems (PQS) as described in ICH Q10.
GMP matters and PQS should not be included in the
submission.
They are assessed and handled by GMP inspectors.
www.drugragulations.org 73August 15
74. It may be necessary to use either the
traditional process validation or the
continuous process verification approach for
different steps within the manufacturing
process.
A justification for using this hybrid approach
should be presented in the dossier
www.drugragulations.org 74August 15
75. It should be clear which approach to
validation has been taken for which part of
the manufacturing process.
The validation requirements in terms of batch
size and number of batches would depend on
the extent to which continuous process
verification has been used.
www.drugragulations.org 75August 15
76. A design space will normally be developed at laboratory or
pilot scale.
During scale-up the commercial process is generally
conducted and validated in a specific area of the design
space, defined as the target interval or Normal Operating
Range (NOR).
During the product lifecycle, moving from one area to
another within the design space (i.e. change in the NOR)
may represent higher or unknown risks not previously
identified during initial establishment of the design space.
www.drugragulations.org 76August 15
77. For this reason there will be situations where it will be
necessary to confirm the suitability of the design space
and verify that all product quality attributes are still being
met in the new area of operation within the design space.
This is termed ‘design space verification’.
www.drugragulations.org 77August 15
78. Verify Design Space when
◦ The parameters investigated during development of the
design space have not been shown to be scale independent
and
◦ The process has been validated using traditional process
validation
If continuous process verification has been utilized,
this may contribute towards ensuring the validity of
the design space throughout the product lifecycle.
In this case, a design space verification strategy
should be included as part of the continuous
process verification strategy.
www.drugragulations.org 78August 15
79. Depending on the change and the extent of
movement within the design space protocols
for verification may include
Controls of quality attributes (QA’s)
Process parameters (PP’s) not included in the
routine control system
◦ (e.g. monitoring or testing of QA’s and PP’s that are
expected to be scale dependent and when applicable,
equipment dependent).
www.drugragulations.org 79August 15
80. It is not necessary to verify entire areas of the
Design Space or the edge of failure.
In principle more than one area of the design
space should be verified
A stepwise approach taking into consideration
the need to adjust the NOR within the approved
design space during product lifecycle is
acceptable.
www.drugragulations.org 80August 15
81. A discussion on the appropriateness and
feasibility of the CPV strategy should be
included in the development section of the
dossier and should be supported with data
from at least lab or pilot scale batches.
www.drugragulations.org 81August 15
82. A description of the CPV strategy including the
process parameters and material attributes that
will be monitored as well as the analytical
methods that will be employed should be
included (reference to Annex 1), with cross
reference in the validation section of the dossier.
www.drugragulations.org 82August 15
83. Actual CPV data generated at commercial
scale should be held at the site for inspection
The applicant should define the stage at
which the product is considered to be
validated and the basis on which that
decision was made.
www.drugragulations.org 83August 15
84. This rationale should include a justification for
the number of batches used based on the
complexity and expected variability of the
process and existing manufacturing experience
of the company.
www.drugragulations.org 84August 15
85. The objectives of process validation are
unchanged when using ICH Q8, Q9, and Q10.
The main objective of process validation
remains that a process design yields a
product meeting its predefined quality
criteria.
www.drugragulations.org 85August 15
86. ICH Q8, Q9, and Q10 provide a structured way to
define product critical quality attributes, design
space, the manufacturing process, and the
control strategy.
This information can be used to identify the type
and focus of studies to be performed prior to and
on initial commercial production batches.
www.drugragulations.org 86August 15
87. As an alternative to the traditional process
validation, continuous process verification
can be utilized in process validation protocols
for
◦ The initial commercial production and
◦ For manufacturing process changes for the
continual improvement throughout the remainder
of the product lifecycle.
www.drugragulations.org 87August 15
88. For detail of Stage 2 of Process Validation
click on link below for a presentation on :
“ No. of batches required in Stage 2 Process
Performance Qualification”
For Details on stage 3 of Process Validation
click on link below for a presentation on
“ Continued Process Verification”
www.drugragulations.org 88August 15
89. This presentation is compiled from freely available resources like the
website of FDA & EMA specifically
“Guidance for Industry Process Validation: General Principles and
Practices , Revision 1, 2011” “EU Guidelines for Good Manufacturing
Practice Annex 15: Qualification and Validation” and” EMA Guideline on
process validation for finished products - information and data to be
provided in regulatory submissions”
“Drug Regulations” is 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.
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