1. Roles and Responsibilities
Quality Unit
Roles and Responsibilities

2. Overview Directive Statement and Scope Glossary Responsibilities
The Requirements
What cannot be delegated
Typical responsibilities for QA
Typical responsibilities for QC
Typical responsibilities for Regulatory QA (RQA)

3. 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 procedures.

4. 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

5. 2. Scope
This training applies to manufacturing sites, affiliates (including distribution centres) and subcontractors
This is a broad scope which encompasses regulatory requirements and audits

6. 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 in-process tests, labelling and inspection.

7. 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 pre-defined Quality attributes

8. Quality Assurance - Part of the Quality Unit
Quality Control

9. 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 organization
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.

10. 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 systems.

11. 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.

12. 5. Requirements (1)
Head of Quality must report directly to Senior Site Management
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

13. 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 Control.
The major responsibilities of each area are outlined on the next slide.

14. 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.

15. 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)

16. 5. Requirements (4)
Site Quality Management must be structured in a way
that the requirements of company policies and procedures are satisfied.
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 matters.
But do not forget : Quality should be the responsibility of all persons involved in manufacturing !

17. 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.

18. 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 reports
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.)

19. 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
methods
Conduct internal audits of affiliates, facilities, operations and procedures to assure conformance with GMPs, GDPs and related regulatory requirements
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 Agreements.

20. 5. Requirements (8)
Ensuring that deviations are, documented, investigated, resolved and trended
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 GDPs
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.

21. 5. Requirements (9)
Ensure compliance of products with registration dossier requirements (“Regulatory Compliance”)
Ensure that monitoring, reintroduction and distribution of returned non-defective 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 self-inspections

22. 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

23. 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

24. 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

25. 5.1 Typical Responsibilities of QA (4)
Customer country interface for label text control
Storage and distribution systems
Implementation of Quality policies and procedures
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

26. 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 trending
Specification approval
Release of raw materials, packaging components, inprocess materials
Approval of in-process controls
Calibration verification of QC equipment

27. 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

28. 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, troubleshooting)

29. 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

30. 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, in-process 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

31. 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
GMP training programs
Engineering drawings of GMP areas
Sub-contractor work and reports (for example ; balance calibration, HVAC qualification, room qualification, pest control reports

32. 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).
For APIs, batch manufacturing records for critical steps must be reviewed and approved by the Quality unit ;
Other steps may be delegated to Production for review and approval.

33. 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 etc.)
Captured computer data of equipment or areas (maintenance, temperature records, pressure differential records etc.)

34. 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

35. Thank You
Any Questions