RC Sibulo, RPh MBA Nov 2013 - Philippine Association of ... Quality Review slides.pdf · RC Sibulo,...
Transcript of RC Sibulo, RPh MBA Nov 2013 - Philippine Association of ... Quality Review slides.pdf · RC Sibulo,...
RC Sibulo, RPh MBA
Nov 2013
Outline Introduction
PQR as a pillar of quality management
What is Product Quality Review (PQR)?
The rationales behind PQR
What are the Regulatory Guidelines for conducting PQR?
Pre-requisites
Industry Practices
PQR Strategy
PQR tactical
The Pharmacist’s role in PQR
Pharmacy profession and PQR
Pharmacy
Community HospitalManufacturing
Regulatory R&D QA Production
QCPQR QRMGMP
Aspects of Quality Management PIC/S
Quality Management ensure that they (medicinal products) are fit for their
intended use
comply with the requirements of the Marketing Authorization
do not place patients at risk due to inadequate safety, quality or efficacy
“SUM TOTAL of all organized arrangements with the objective of ensuring that medicinal products are of the quality required for their intended use”
Quality AssuranceM
anag
emen
t (i
ncl
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ing
Sel
f-in
spec
tio
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Design and development
Production and control
operations
Starting and Packaging materials
Intermediates, in-process controls and validations
Finished product processing
Batch release
Storage, handling and distribution
Good Manufacturing Practices “..CONSISTENTLY PRODUCED & CONTROLLED to
the quality standards appropriate to their intended use and as required by the marketing authorisation or product specification."
Man
agem
ent
(in
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g S
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)
Design and development
Production and control
operations
Starting and Packaging materials
Intermediates, in-process controls and validations
Finished product processing
Batch release
Storage, handling and distribution GXPs
Quality Control “..part of GMP..”
“..sampling, specifications and testing, and with the organisation, documentation and release procedures..”
“..quality has been judged to be satisfactory."
Facilities
Sampling
Test methods
Records
Label content
Retention
QC
Quality Risk Management “..systematic process for the assessment, control,
communication and review of risks..”
“..can be..proactive..or retro..”
ICH Q9: US FDA guide
What is PQR? PIC/S: GUIDE TO GOOD MANUFACTURING
PRACTICE FOR MEDICINAL PRODUCTS PART I section 1.4, Jan 2013
“Regular periodic or rolling quality reviews of all licensed medicinal products..”
What is PQR?“..verifying the consistency of the existing process, the
appropriateness of current specifications for both starting materials and finished product to highlight
any trends and to identify product and process improvements.”
Man
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Man
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Man
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Man
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on
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Man
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(in
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Design and development
Production and control
operations
Starting and Packaging materials
Intermediates, in-process controls and validations
Finished product processing
Batch release
Storage, handling and distribution
What is PQR? Singapore HSA: GUIDANCE NOTES ON PRODUCT
QUALITY REVIEW , Jan 2013
“..a natural progression of GMP quality system implementation..”
Basic Product (R&D) Lifecycle
Literature review
Pre-formulation
Clinical trial
Pilot production
Process Validation
Routine Production
PQR rationale (benefits) Risk reduction – product complaints, product recall,
Out-of-specifications (OOS) results, manufacturing and testing errors
Increase in productivity via:
Process improvements (manufacturing and testing)
Non-critical test parameter reduction
Reduced down-time from calibration and maintenance (required intervals can be reduced)
Optimization of yield limits
Verification of validation status
Regulatory Guidelines PIC/S: GUIDE TO GOOD MANUFACTURING
PRACTICE FOR MEDICINAL PRODUCTS PART I section 1.4, Jan 2013
US FDA 211.180 (e)
Regulatory GuidelinesParameter US FDA PIC/S
Appropriateness of specs Product Product and Starting materials
Appropriateness of processes
Manufacturing procedure and in-process control
Not specified; only consistency with existing process >> re-validation
Grouping/Matrixing Not allowed Allowed
Trend evaluation (including previous reviews)
For corrective actions For corrective actions and process improvements
Pre-requisites Established Quality Systems
Validation
Non-process validation
Utility systems
Equipment qualification
Process validation
Analytical method validation
QA documentation
Change control
Deviation reporting
OOS investigation
Quality risk management
Established Engineering systems
Equipment calibration
Routine preventive maintenance
How to perform PQR What to include:
Relevant Regulatory issuances in the period covered
Routine (and related Changes) > impact on Finished Product
Parameter Routine Changes
Materials Lot to lot variation Material specs change > Material qualification
Equipment and Processes
Equipment setting/PM status, visual endpoint variations
Critical process/equipmentchanges > Process re-validation
Test methods Reagent, analytical equipment settings/PM status
Compendial revisions > verification or re-validation
How to perform PQR - Materials
95
96
97
98
99
100
101
Para006 Para007 Para008 Para009 Para010
API Potency
92.0
94.0
96.0
98.0
100.0
102.0
104.0
Para006 Para007 Para008 Para009 Para010
Product Assay
How to perform PQR – Equipment/Processes
0.02000.04000.06000.08000.0
10000.012000.014000.0
Viscosity
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
Mixing time (min)
How to perform PQR Stability and retention data
Stability data – from critical changes and routine (e.g. annual stability loading)
Retention data – from retention samples analysis, if applicable
QA
Recalls, complaints, adverse events, returns, deviations, OOS investigations, and related CAPA
How to Perform PQR QC data
Identify critical QC parameters (e.g. assay) and product performance indicators (e.g. viscosity)
Perform statistical analysis (assumption: normal distribution)
Parameter Formula Specifications
RSD (SD/mean) x 100 NMT 3.0 – 6.0%
Cp (USL – LSL)/6σ NLT 1.33
CpK min [(USL-mean)/3σ, (LSL-mean)/3σ)
NLT 1.06 sigma: NLT 2.0
How to Perform PQR - Cp
B
USLLSL
target
C DAA B CBD
Cp Type
C P A
> C P B
00> C P0 C
0.67>C P D
How good does the deviation lie between the specified limits?
How to perform PQR - CpK
10 11 12 13 14 15 16 17 18
LSL
10 11 12 13 14 15 16 17 18
LSL USLnominal
X
USLnominal
X
= 1 = 1
Process mean and deviation compared to pre-specified mean and limits
Industry Practice - Strategy Frequency Approach
Periodic
e.g. Annual
By volume
Rolling
Real-time/on-line
Batch documents copy
Release control
•Process Assignment•For products owned by manufacturers
•Internal PQR•Third party review
•Toll manufactured products•Toll manufacturer review•Review by product owner•Third party review
Industry Practice - Strategy Matrixing
Formulation-based
Similar dosage forms
Similar API
Similar Packaging material and closure system
Process and equipment-based
For low risk formulations
Approach should be documented in the SOP
Industry Practice - Tactical Rolling
Routine provision of batch data (process and QC) from production to QA (internal or third party)
e.g. as part of release requirement
Periodic provision of data (monthly or quarterly)
Periodic
Depending on volume of products (annual, semi-annual or quarterly)
Data management
Hard copies, soft copies (pdf files)
Scan on-site or hard copies via courier
PQR and the Pharmacy profession Why a qualified Pharmacist should perform PQR?
Understand impact of PQR parameters on patient therapy
Up-to-date with FDA regulations and requirements
Systematic approach to managing quality
Thank you for your kind attention