Quality Unit
Roles and
Directive Statement and Scope
The Requirements
What cannot be delegated
Typical responsibilities for QA
Typical responsibilities for QC
Typical responsibilities for Regulatory QA
1. Directive Statement
• There must be in place both Quality Assurance
(QA) and Quality Control (QC) functions in a
defined and approved organizational structure.
• The organization must be independent from
manufacturing and must ensure that the
manufacture and distribution of all products
comply with the requirements of Good
Manufacturing Practices (GMP), Good Distribution
Practices (GDP), regulatory requirements and the
requirements described in Company policies and
1. Directive Statement
• Depending upon the size and complexity of
the site, the Quality Assurance (QA) and
Quality Control (QC) functions may operate
as one unit.
Approved organgrams indicating QA and QC
Independence from manufacturing unit
QA/QC: overall responsibility for quality
QA/QC can operate as one unit
2. Scope
• This training applies to manufacturing sites,
affiliates (including distribution centres) and
• This is a broad scope which encompasses
regulatory requirements and audits
3. Glossary (1)
• Quality Unit : The term used to describe the all encompassing
roles and responsibilities of the Quality Assurance and Quality
Control departments
• Quality Assurance Unit : That portion of the Quality Unit that
sets policies, procedures and specifications, audits, reviews,
assessments, provides training and is responsible for the approval or
rejection of active pharmaceutical ingredients (APIs) and
pharmaceutical (drug) product. It works in concert with, and as a
check on the Quality Control Unit
• Quality Control Unit : That part of the Quality Unit that is
responsible for the ongoing control of quality within the company. It
is responsible for the acceptance, quarantining or rejection of
incoming raw materials and packaging components, conducting inprocess tests, labelling and inspection.
3. Glossary (2)
• Quality Assurance (QA) : A system of activities designed to
ensure that product quality, safety, purity and efficacy is
known and effectively controlled.
• The system includes a continuous evaluation of the adequacy
and effectiveness of the overall Quality program. Corrective
and preventive measures initiated as necessary.
• For a specific product or service, this involves verification
through audits, and the evaluation of the quality factors that
affect the specification, production, inspection and use of the
product or service.
• Quality Control (QC) : That part of GMP, which is
concerned with assessing and measuring specific and predefined Quality attributes
Quality Assurance - Part of the
Quality Unit
4. Responsibilities (1)
Head of Site or Managing Director
• approves the appointment of a Head of Quality at site
• endorses any major change to the site Quality department
Senior Site Management
• is responsible for ensuring that there are systems and
procedures in place to comply with Pharmaceutical Directives
Site Management
• is responsible for implementing the Quality System at the site.
4. Responsibilities (2)
Site Management
• must allow Quality Unit independence and the necessary
objectivity required, to fulfil its responsibilities
The Head of Quality
• ensures that product manufacturing and distribution are
in compliance with GMPs and GDPs; company policies
and procedures; and applicable regulatory requirements
The Site Quality Unit
• defines, implements, manages, and controls all Quality
Responsibilities of the Quality Control
Unit in US according to the CFR 211
• There shall be a QCU that shall have the responsibility and authority
to approve or reject all drug components, APIs, etc
• To review production records that no errors have occurred, or if
errors have occurred, that they have been fully investigated
• Adequate lab facilities for testing and approval shall be available
• The QCU shall have the responsibility for approving or rejecting all
procedures or specifications impacting product quality
• The responsibilities and procedures applicable to the QCU shall be in
writing; such written procedures shall be followed.
5. Requirements (1)
• Head of Quality must report directly to Senior Site
• Head of Quality must report functionally to the
Head of site/Managing Director
• Site Management must ensure that the Quality
Unit is adequately staffed with associates having the
necessary education, training, and experience to
perform the assigned functions.
Clear and defined reporting lines
5. Requirements (2)
• Senior Site Management must provide adequate
laboratory facilities to test the following:
incoming components; inprocess materials;
packaging materials; active pharmaceutical
ingredients (API) or pharmaceutical (drug)
products produced at the site.
• Each Quality Unit must have people or units
responsible for Quality Assurance and Quality
The major responsibilities of each area are outlined
on the next slide.
5. Requirements (3)
• Where the local regulations require that a Qualified
Person (QP) be appointed, this person should be a
part of the Quality Unit.
• When this is not the case, then Quality Assurance
must perform ultimate Batch Release.
The duties of the Qualified Person(s) are
described on the next slide.
Duties of the Qualified Person(s)
• The duties of the Qualified Person(s) are fully described
in Article 51 of Directive 2001/83/EC, and can be
summarised as follows :
 (a) for medicinal products manufactured within the European
Community, a Qualified Person must ensure that each batch has been
produced and tested/checked in accordance with the directives and
the marketing authorisation (2) ;
 (b) for medicinal products manufactured outside the European
Community, a Qualified Person must ensure that each imported batch
has undergone, in the importing country, the testing specified in
paragraph 1 (b) of Article 51 ;
 (c) a Qualified Person must certify in a register or equivalent
document, as operations are carried out and before any release, that
each production batch satisfies the provisions of Article 51.
(From EU GMP Guide Part I, Chapter 2)
5. Requirements (4)
• Site Quality Management must be structured in a way
that the requirements of company policies and procedures are
• The size and complexity of the site will determine how the functions
will be structured within the Quality Unit
• The Quality Unit must be involved in all quality related
But do not forget : Quality should be the
responsibility of all persons involved in
manufacturing !
5. Requirements (5)
• The responsibilities of the Quality Unit must not
be delegated and must include such activities as :
• Final decision on acceptance for use or rejection
of all
materials, Active Pharmaceutical Ingredients (APIs), API Intermediates,
package components, printed packaging materials, in-process materials,
and pharmaceutical products (i.e. drug products)
• Verification of Site compliance
with Good Manufacturing
Practices (GMPs) and Good Distribution Practices (GDPs), as applicable
• Ensure that training programs
at the site are managed
according to company policy and regulatory requirements.
5. Requirements (6)
• Management and monitoring of stability programs for marketed
and distributed products
• Review and approval of master manufacturing and laboratory
control documents to assure adherence to registration, company
Directives, GMPs, GDPs and qualification/validation protocol and
• Review and approval of changes that potentially impact active
pharmaceutical ingredients (APIs), pharmaceutical product and/or
medical device quality (change control management)
• Review and approval of sub-contractor work, (e.g., balance
calibration, HVAC qualification, room qualification, testing
equipment calibration, pest control reports, testing laboratories and
their reports, etc.)
5. Requirements (7)
• Maintenance and management of testing facilities to assure that raw
materials, intermediates, active pharmaceutical ingredients (APIs),
packaging materials, in-process materials and pharmaceutical products
meet their specifications, including approval of all testing
• Conduct internal audits of affiliates, facilities, operations and procedures
to assure conformance with GMPs, GDPs and related regulatory
• Qualification, approval and audit of sub-contractors, contract testing
laboratories and component suppliers to assure they can supply
product or services that meet established requirements
• Quality Management must be aware of, and ensure through audits,
the approved status of suppliers of APIs and other Key Materials
and Components used
• Quality Management is responsible for the approval of Quality
5. Requirements (8)
• Ensuring that deviations are, documented, investigated, resolved and
• Ensuring that effective systems are used for maintaining and calibrating
critical equipment and instrumentation
• Issuing written reports to the appropriate levels of management
documenting instances of non-compliance to standard practices and
requirements such as stability failures, product specifications, GMPs and
• Monitoring progress on quality related corrective and preventive
actions to assure timely compliance
• Working with site operations to identify root causes to problems and
opportunities for quality system improvements.
5. Requirements (9)
• Ensure compliance of products with registration dossier
requirements (“Regulatory Compliance”)
• Ensure that monitoring, reintroduction and distribution of returned nondefective products into the market is managed and controlled
• Preparation, organization and monitoring of Regulatory or Health
Authority inspections
• Additional responsibilities of the Quality Unit organization mandated by
government regulatory agencies include: approval of specifications, product
recalls, product complaint handling, anomaly handling, investigation
management, archive and record retention, and implementation of selfinspections
5.1 Typical Responsibilities of QA (1)
Quality systems and management / continuous improvement
Recalls or stock recovery
Regulatory compliance
Self-Inspection (internal audit)
External audits/GMP and GDP compliance
Management of regulatory audits and inspections
Management of controlled documents, e.g. SOPs, master documentation
Qualification/Validation protocols and reports approval (equipment,
process, cleaning, computerized systems, utilities, environmental,
quality systems)
Management of sub-contractors
Management and monitoring of distribution centres
5.1 Typical Responsibilities of QA (2)
• Complaint investigation and product recall coordination
• Quality Agreement evaluation and approval
• Annual Product Review (APR) for pharmaceutical product (i.e.
drug product) and for finished products of the Chemistry
organization (API’s and intermediates)
• Management of change control evaluation
• Deviations and failure investigations
• Batch rework/ reprocessing approval
• Release or rejection of intermediate materials for external use
• Batch release or rejection for APIs and pharmaceutical products
• Quarantine system
5.1 Typical Responsibilities of QA (3)
• Training programs (e.g. GMP, GDP)
• Supplier or vendor audits, qualification and approval
• Stability program
• Maintenance and calibration program approval
• Master documentation review and approval
• Product or batch documentation review and approval
• Specification approval
• Quality Steering Committee coordination
• Quality communications and regulatory awareness
• Technology transfer approval
5.1 Typical Responsibilities of QA (4)
• Customer country interface for label text control
• Storage and distribution systems
• Implementation of Quality policies and
• Key Performance Indicator (KPI) reporting
• Capital investment and project
recommendations, assessments and reviews for
all quality relevant matters
• Disposition of returned goods
• Record retention and archives
5.2 Typical Responsibilities of QC (1)
• Sampling plans and retained sample management
• Chemical, microbiological, biological, and physical
testing/ batch analysis
• Out of Specification (OOS) result investigations and
• Specification approval
• Release of raw materials, packaging components,
inprocess materials
• Approval of in-process controls
• Calibration verification of QC equipment
5.2 Typical Responsibilities of QC (2)
• Management of reference standards
• Qualification of QC equipment
• Stability program, controls and testing
• Complaint analysis
• Testing of validation samples
• Contribution to raw material supplier approval
• Assistance in audits of contract labs
• Quality Agreement evaluation
5.2 Typical Responsibilities of QC (3)
Annual Product Review (APR) data compilation
Pharmacopoeia reviews
Supplier testing approval
Statistical Process Control (SPC) / Statistical Quality Control (SQC)
Environmental monitoring
Global specification standardization
Analytical Development either as part of QC or separate organizational unit
(e.g. method development, method validation, specification generation,
method transfer, new QC technologies Pharmacopoeia review,
5.3 Site Documentation Review &
Approval (1)
The Quality Unit has responsibility for review and approval of all
documents which have GMP impact. These documents may
need to be reviewed and approved in every instance, as they are produced,
or on a regularly pre-defined (in an SOP) schedule
• There are 2 types of document :
Documents which require review and approval in
every instance
(Examples will be shown on the following slides)
Documents that must be reviewed and approved
on a predefined schedule, or as produced
(Examples will be shown on the following slides)
5.3 Site Documentation Review &
Approval (2)
• Documents which require review and approval
in every instance should include, and are not
restricted to:
• Standard Operating Procedures (SOPs), Analytical methods, inprocess controls and specifications
 Master manufacturing and laboratory control documents
(for example ; Master formulae, Master Batch Records
(MBRs), Analytical records etc.
 Internal and external audit reports, supplier Quality Agreements
 Qualification/validation protocols and reports
5.3 Site Documentation Review &
Approval (3)
• Documents which require review and approval
in every instance (cont) :
 Annual Product Review
 Change control, deviation and failure investigations
o GMP training programs
o Engineering drawings of GMP areas
o Sub-contractor work and reports (for example ; balance
calibration, HVAC qualification, room qualification, pest control
5.3 Site Documentation Review &
Approval (4)
• Documents which require review and
approval in every instance (cont) :
• Final review and approval of completed batch dossier
documents (batch production or manufacturing records,
product control records and batch packaging records, analytical
records) prior to the release of a batch or lot of product and, as
required, to issue Certificates of Analysis (COA).
o For APIs, batch manufacturing records for critical steps
must be reviewed and approved by the Quality unit ;
o Other steps may be delegated to Production for review
and approval.
5.3 Site Documentation Review &
Approval (5)
• Documents that must be reviewed and
approved on a pre-defined schedule, or as
produced, should include, and are not
restricted to:
 Graphs/cycles of any equipment or areas (including,
temperature, humidity records etc.)
 Logbooks and record sheets (Equipment, shift handover, alert
and alarm, pressure differentials, temperature records, cleaning
 Captured computer data of equipment or areas (maintenance,
temperature records, pressure differential records etc.)
5.4 Site Documentation Review &
Approval (6)
Documents that must be reviewed and
approved on a pre-definedschedule, or as
produced: (cont)
 Site Master File
 Preparation of Technical Dossiers [Part 2/ Chemistry
Manufacturing Control (CMC)]
 Registration changes
 CMC change control regulatory evaluation
 Master Certificate of Analysis
 Product license compliance audits
 Technical transfer document interface
Thank You
Any Questions