QUALITY ASSURANCE

Roles & Challenges

1
 Outline of the Presentation
• Introduction, Definitions and
Quality Assurance
• Role of Quality Assurance in CMS
• Primary Functions of Quality
Assurance in CMS
• Challenges
• Conclusion

2
 Quality Assurance
• A process, not an end-point
• Must be independent of financial & other
pressures
• Must ensure that quality policies are
followed
• Must have final authority in product
acceptance, rejection and release to public
• Integral to operations, not an add-on
• Responsible for day-to-day operations and
for longer term goal settings
• Quantitative discipline with specified
parameters 3
 DEFINITIONS

• QUALITY
• The totality of features and
characteristics of a medicinal product and
its ability to satisfy stated and/or implied
needs
• QUALITY ASSURANCE
• The sum total of the organized
arrangements made with the object of
ensuring that medicinal products are of
the quality required for their intended
use. 4
 DEFINITIONS

• GOOD MANUFACTURING
PRACTICE (GMP)
• That part of QA which ensures that
products are consistently produced
and controlled to the quality
standards appropriate to their
intended use.
• QUALITY CONTROL
• That part of GMP which is concerned
with sampling, specifications and
testing. 5
Quality relationships

QA
GMP
QC

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Quality relationships

Quality Management

Quality Assurance

GMP

Quality Control
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 Role of Quality Assurance in CMS
LEGISLATIVE
FRAMEWORK- PROCUREMENT
POLICIES, REGULATIONS RECIEPT
& DIRECTIVES

HUMAN
QC ANALYSIS BY
RESOURCES- NDQCL
PROFESSIONALS & NON
PROFESSIONALS

Quality
POSTMARKET
Assurance WAREHOUSING
SURVILENCE

DISTRIBUTION
TRANSPORTATION DISPATCH

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 Quality Assurance
Primary Functions
• Providing Product Specifications
• Registration & Prequalification of Suppliers
• Tender Evaluation
• Inspection of Received Goods
• Monitoring of Storage Conditions
• Monitoring of Expiry Statistics
• Handling of Quality Complaints
• Preparation & Implementation of Quality
Management System and SOP’s

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 Quality Must Be Designed
Into A Product
• Quality is not an add-on: it begins with
research and development
• Product quality criteria must be
established
• Detailed specifications provide
quantitative parameters for measurement
• Written procedures document how quality
is attained and maintained
• Continuous monitoring (sampling, testing)
to confirm quality is being built-into
product 10
A Guiding Philosophy for Quality
Assurance in the Pharmaceutical
Industry
Poor Quality Medicines:
• Are a health hazard
• Waste money for governments and consumers
• May contain toxic substances that have
unpredictable, unintended consequences
• Will not have a desired therapeutic effect
• Does not save anyone any money in the long term
• Hurt everyone – patients, health care workers,
policy makers, regulators, manufacturers 11
 CONSEQUENCES OF QA
BREACHES

• Poor Treatment outcomes

• High Health Bills
• Treatment Failures & Deaths
• Loss of Confidence in the Health
Services
• Enormous Economic Losses
• National Security Issue
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 Providing Product
Specifications
• Assists in providing or updating technical
information or specifications for products
included in the ordering list.
• A complete description of the product may
include but not limited to:
 Generic or international nonproprietary name
 Strength
 Dosage form
 Pack size
 Any other specialized formulation such as EC, FC,
CR, etc.

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 Product Selection Issues
• Unique nature of medicines heightens
need for effective quality assurance
• All medicines used must be safe,
effective, and of consistent quality
• Failure to select proper products will
lead to treatment failure, drug
resistance, wasted resources and
human suffering
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 Suppliers/Manufacturers

“Many reliable manufacturers, both

innovator and generic companies,
can offer quality products…the
aim…is sustained, consistent and
acceptable quality rather than high
or better quality, terms that are
impossible to quantify”
Battling HIV/AIDS, World Bank 2004

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 Sources of Pharmaceutical
Products
Multi-source
Well-established products, long history of use, no
longer subject to patent protection (e.g.
Rifampin)
Single source
Newer products still subject to patent protection
in many countries (e.g. Saquinavir)
Limited source
More than single source/supply possible (e.g.
AZT); may be difficult to manufacture (e.g.
amphotericin); may be unprofitable drug with
limited market potential 16
 Comparison of Sources
Multi-source Single/limited source

# of manufacturers Many Innovator manufacturer

World-wide Limited local generic

Public information Available Not available

C ompendia In-house specifications

Public experience Long-standing Very limited

Well-documented Not documented
Accessible Not easily accessible

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Identifying Product Suppliers
Systematic Approach
• Pre-qualification of suppliers and products
• Specifying supplier conditions in tender
documents & contract
• Monitoring quality of product and
processes
• Continuous evaluation of supplier
performance and product performance in
clinical practice
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Identifying Product Suppliers

Specify Conditions

Evaluate Monitor

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Selecting and Sourcing Multi-
Source Products
• Innovator vs. generic issues
• Prequalification systems
• Technical evaluation of the products
tendered for.

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Procedures for Prequalification of
Suppliers
Rationale
More meaningful, effective, efficient and
less expensive to eliminate sub-standard
manufacturers and products at the opening
of bidding/tendering than during the
process
Purpose
To ensure that products are manufactured
in compliance with GMP and products meet
established quality standards
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Procedures for Prequalification
of Manufacturers
• Suppliers submit prequalification application form
along with requisite documents for evaluation.

• Evaluation of application for prequalification by

technical expertise.

• Random testing of samples

• Verification of compliance with cGMP
• Role of national drug regulatory organizations (in
compliance with WHO standards)

22
Prequalification: Evaluation of Product
& Product Information

• Specifications in WHO guidelines

• Must include details regarding:
- Regulatory status
- Pharmaceutically active ingredient(s)
- Manufacturing processes
- Finished product specifications (stability,
bioavailability, interchangeability etc.)
- Packaging/labeling/storage details
- Product/patient information

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Prequalification: Evaluation of
Product& Product Information –
Single/Limited Source Products

• Include specifications of in-house

quality-control and quality management
practices in sufficient detail to allow
replication by another laboratory
• Validation of in-house methods must be
provided by manufacturer
• Quality assessment of products to be
undertaken by external laboratory
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 Prequalification:
Random Testing of Samples
• Undertaken to verify compliance with
standards and references provided in
the document
• Test samples should be from both pre-
supplies as well as supply batches
• On-going random sampling and quality
control analysis of post-supply

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 Prequalification Verifications
Compliance with GMP
• Inspections and certification of facilities
or reliance on national regulatory
authorities
Compliance with good distribution
practices
• Quality assurance methods for selection
of raw material suppliers, storage of
products, transportation delivery of final
product, etc. 26
Summary of Prequalification
Processes: CMS Perspective
Issue
Guidelines &
Requirements Receive
Submissions

Evaluate
Submissions
Perform
Inspections
Communicate
Decision

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 Tender Evaluation

• Specifying general conditions &

evaluation criteria in the tender
documents
• Requesting for samples of each product
tendered by the supplier.
• Evaluation of tender documents for
technical information.

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 Tender Evaluation (Cont.)
• Evaluation of the sample submitted:
• Visual evaluation of all the samples for
packaging, labeling & defects – at CMS
• Laboratory analysis of the
pharmaceuticals – at NDQCL
• Evaluation of non-pharmaceuticals – by
users at hospitals

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 Tender Evaluation (Cont.)
• Compilation of evaluation reports and
making recommendations
• Presentation of recommendations to
CMS evaluation committee for approval

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Inspection of Received Goods
Inspection involves
 Ascertaining the product ordered for
by checking GPO as well as the
retention sample provided by the
supplier
 Visual inspection for packaging,
labeling & defects

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Inspection of Received Goods
(Cont.)
To ensure the maintenance of
temperature (cold chain) during
transportation by the supplier
To ensure that the product
supplied has stipulated (>80% of
total shelf life) remaining shelf life
upon receipt
Sampling for analysis by NDQCL

32
Monitoring of Storage Condition

To prevent damage during storage

To ensure stability
To maintain hygiene & to prevent
contamination
Easy accessibility, traceability &
accountability

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 Monitoring of Expiry Statistics

 CMS warehouse computer

automated
 Stock is rotated on FEFO or FIFO
basis
 Expiries are monitored on a monthly
basis
 Decisions are taken on expired drugs
& drugs nearing expiry dates.

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 Monitoring of Expiry Statistics
(Cont.)

 Information on Shelf life of all products

procured & supplier’s return policies
are compiled

 Identifying the major cause for expiry

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 Preparation Implementation of
Quality Management System

Preparation & updating of Quality Manual

Preparation, review & validation of SOP’s
Training the CMS Staff on Quality
Management System

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 Post Market Surveillance

• Attending to all product quality

complaints from customers
• Carrying out Investigations
• Advising the complainant on the
outcome of the investigation

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Ideal v/s Reality - Challenges
• Capacity
– Manpower
– Infrastructure
 Lack of office & Storage space
 Inadequate Testing capacity by NDQCL

• Autonomy
– lack of authority to take decisions
• Suppliers
– Capacity
– Reliability
– Competency

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 Challenges (Cont.)

• Regulations & Directives

– PPADB
– CAB Memos

• Communication
– Lack of information from various health
program administrators
– Lack of information from the health facilities

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 Challenges (Cont.)
• Miscellaneous
– Inadequate support from health facilities,
especially on resolution of quality
complaints & product recalls-unable to meet
the deadline
– Inadequate storage conditions at health
facilities
– Lack of source of information to update the
newer developments
– Less scope for continuing education
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