Longe Sunday Anthony
Head- Quality Assurance
May & Baker Nigeria Plc.
Pharmacentre, Ota, Nigeria
[email protected]; [email protected] .
Quality Risk Management
(ICH Q9): WHO Model for Sustainable Quality
Medicines
• The Pharmaceutical Industry is constantly being challenged to comply with rigorous regulatory requirements. Therefore the need to ensure that a company’s processes are being operated at a level of control using risk management approach
• Compliance is evolving from a “reactive approach” - Inspection, checks and comprehensive testing to a “Proactive approach” scientific and risk management approach.
• However, compliance is not a one-time event and organizations are redesigning their compliance programs to make them repeatable processes that could be sustained.
Preamble
Challenges
• Rising Standards of Quality
• Rising Regulatory requirements and reporting
mandates- ADR’s, ADE’s etc.
• Competitive sector within a harsh business
environment- Conversion Cost vs Quality
Compliance is not just a regulatory requirement, but a Quality Culture that guarantees good quality product.
Who Governs
cGMP Current Good
Manufacturing Practices
21 CFR Part 211 ( Pharma )
21 CFR Part 820 ( Med devices)
21 CFR Part 110 ( Food )
21 CFR 600 – 680 Biologics
GAMP Good Automated
Manufacturing Practices
GAMP 5(ISPE) Guide
GALP Good Automated Laboratory Practices
EPA Directive 2185 ( 1995 Ed. )
GCP Good Clinical Practices
21 CFR 312 Sub part
GLP Good Laboratory Practices
21 CFR Part 58
40 CFR Part 160 ( EPA )
ICH Guidelines Quality, Efficacy, Safety, CTD / e – CTD
Regulators Speak through
Regulations
Q1A(R2)
Q1B
Q1C Stability Testing
Q1D
Q1E
Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
Q8(R1) Pharmaceutical Development
Q9 Quality Risk Management
Q10 Pharmaceutical Quality System
M4(R3)* Organization of the Common Technical Document for the Registration of
Pharmaceuticals for Human Use
-The assessment of individual risks related to specific
products and starting materials and the recognition of hazards
at specific stages of production or distribution.
- Quality risk management (QRM) is a process that is relevant
to all countries and should provide a rationale to understand
risk and mitigate it through appropriate and robust controls.
- QRM is the overall and continuing process of appropriately
managing risks to product quality throughout the product's
life-cycle in order to optimize its benefit–risk balance.
Concept of Quality Risk Management
ICH Q9 Quality Risk
Management
MA
CH
INE
S (
Eq
uip
me
nt)
ME
TH
OD
S (
Pro
ce
sse
s)
MIL
IEU
(E
nv
iro
nm
en
t)
Road to Compliance
Importance of Vendor Development & Qualification
“Using a pharmaceutical ingredient without a
knowledge of the specific manufacturing site,
Regulatory status, and how it got to you is like
traveling without a definite destination.”
MATERIAL CONTROL
API Manufacturers & Vendors
Are responsible for assuring that ingredients they supply comply with GMP, are not misbranded or contaminated, are packaged/stored appropriately, and adhere to signed Quality Agreement.
FPP (MAH) & Regulators
Are ultimately responsible for the use of appropriate ingredients
and assuring ingredient quality at every stage of the supply chain
and Storage before final conversion.
Pharmaceutical Ingredient Supply
Chain – A Shared Responsibility!
Process Control
CCP
Dispensing
Equipment e.g.
RLAF, Balance, scoops
Cross contamination, inaccurate
quantities,Failure incidence;
Reprocessing/re-work, Overdosing or underdosing, Poor
product quality
Environment e.g. HVAC, Drains, lightings
MAN
Temp/RH/DP
out of control;
contamination
Material Mix-
ups; inaccurate
weighing etc.
•Equipment must be located, designed, constructed, adapted and maintained to suit the operations to be carried out.
•The layout and design of equipment must aim to minimize the risk of errors.
•Permit effective cleaning and maintenance in order to avoid cross-contamination, build-up of dust or dirt, and, in general, any adverse effect on the quality of products.
Equipment Controls
URS
(To specify the
end use requirement)
Design
(By manufacturer to
meet expectations)
Manufacturing of
Equipment
(Easy to handle,
Easy to clean.
Good surface
Finishing)
FAT
(To ensure for
functioning as per
expectation at
manufacturing site)
SAT
(Receive at site
In proper condition)
IQ/OQ
Qualify equipment
as per SOP
PQ
Placebo run
(Matrix approach to
qualify for
intended use)
PM
(Preventive Maintenance
to maintain equipment
as per functionality)
BM
Breakdown
Maintenance
(Trending)
Usage Evaluation
Retirement/ decommissioning
What ?
• A set of operations that establish, under specified conditions, the relationship between the
values of quantities indicated by a measuring instrument or measuring system, or values
represented by a material measure or a reference material, and the corresponding values
realized by its standards.
Why ?
• When process measuring instruments age and experience physical stress or temperature
variations, critical performance gradually declines. This is called drift.
• The slow variation with time of metro logical characteristics of the measuring instruments.
As a result of this, the measurement results become unreliable and ultimately the production
quality can suffer.
• Drift cannot be eliminated, but it can be discovered through calibration.
Calibration
•Risk-based approach. •Conduct appropriate levels of product impact and
critical risk assessment of systems and system functionality early in the planning stage and then throughout the validation life cycle as required.
•Qualification •URS, DQ, FAT, SAT, IQ,OQ, PQ
•Process Validation & Cleaning Validation Process & equipment Design Vs Equipment
performance are critical to process validation and cleaning validation success.
Qualification & Validation
• Calibrated equipment provides confidence that
products/services meet their specifications.
• Calibration:
-Increases production yields, Optimizes resources,
- Assures consistency and ensures measurements
are compatible with those made elsewhere.
• Ensures measurements are appropriate based
on National and International standards and
traceable.
• Avoid wastages due to uncertainties.
“
Calibration Benefits
Concept Stages Outcome
Process
Validation:
General
Principles
and
Practices
WEF: Jan'11
Stage 1- 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: (Ongoing assurance
is gained during routine production
that the process remains in a state
of control). PQR for each year
Robust
manufacturing
process.
Compliance to the
regulatory
requirement.
New FDA guidance on Process Validation
January 2011
Laboratory Controls
• Qualified personnel
• Effective sample management
• Approved specifications and methods
• Appropriate Qualified instruments
• Effective calibration program
• Effective preventive maintenance program
• Adequate SOP for OOS and OOT
• Trending of laboratory failures and CAPA
management.
Glassware
Controls
Quality by Statistical Process Control
Review of historical output of process to
identify the limits of a stable process and
source of error.
Quality by Inspection
Inspect Approve / Reject
Pharmaceutical Quality System
Training
Change Control
Planned Deviation
Incidence Investigation
Market Complaint
CAPA
Internal Quality Audit
Product Quality
Reviews/ Management
reviews
Pharmaceutical Quality System
Complaints Internal
Inspections
Supplier Audits
Regulatory Audits
Non-conforma
nces Deviations
Out of Specification
Out of Specification
Adverse Drug
Reactions
Adverse Events
Incoming Inspections
And others…
CAPA Sources
Road to Compliance
When it comes to ensuring drug product quality
and ultimately Consumer/Patient Safety . . . We
need to think and act globally!