Role of quality system and audits in pharmamaceutical

Role of Quality system and
Audits in pharmamaceutical
mfg environment
Prepared By: Guided By:
Rajpurohit Ganpatsingh Mrs. Avani khristi
Roll No:10 Assistant Professor,
M.Pharm QA,2nd sem, QA Department
PARUL INSTITUTE OF PHARMACY,LIMDA

CONTENTS:
• Introduction
• cGMP Regulations
• Quality Assurance Function
• Quality Systems Approach
• Management Responsibilities
• Resources
• Manufacturing Operations
• Evaluation Activities
• Transitioning to Quality Systems Approach
• Audit Checklist for Drug Industry
• References
11/16/2019 2RAJPUROHIT

Introduction
• This presentation describes outlines and discusses the regulations applicable to
the QA function and unit, structure, function and application of the unit in the
pharmaceutical manufacturing environment. In addition, it discusses additional
quality - related responsibilities that may result when manufacturers move
toward a quality systems approach to quality that incorporates current quality
system models to further improve quality and harmonize with international
quality system requirements.
• The QA audit are also described, including preparation, key items of interest, a
typical checklist of the audit itself, corrective and preventive actions following
the audit, and suggested measures for assuring successful operation of the unit.

c GMP REGULATIONS
• The cGMP regulations for the manufacture of pharmaceutical products
are contained in Parts 210 and 211 of Title 21 of the Code of Federal
Regulations (CFR)
• Part 210 specifies the scope and applicability of the cGMP regulations
and defines terms used in the regulations.
• Part 211 contains specific good manufacturing practice requirements for
finished pharmaceuticals and is divided into Subparts A – K as follows:

CONT…..
A. Scope
B. Organization and Personnel
C. Buildings and Facilities
D. Equipment
E. Control of Components and Drug Product Containers and Closures
F. Production and Process Controls
G. Packaging and Labeling Control
H. Holding and Distribution
I. Laboratory Controls
J. Records and Reports
K. Returned and Salvaged Drug Products

QUALITY ASSURANCE FUNCTION
 QUALITY SYSTEMS APPROACH
• It involves:
• A management commitment to quality that is communicated throughout
the organization
• Identifying quality requirements using risk management and other
methods as appropriate
• Developing a quality policy, plan, objectives
• Establishing an organizational structure with identified responsibilities
and authorities that allows quality objectives to be met.

CONT….
• Providing the resources needed to meet quality objectives
• Developing the required systems and processes
• Establishing methods for the ongoing objective evaluation of the
performance of systems and processes including quality auditing
• Initiating corrective and preventive actions as needed to assure that
quality objectives are consistently and reliably met

MANAGEMENT RESPONSIBILITIES
• Current quality system models assign management a major role in the
deployment and operation of a successful quality system. In such systems,
major management responsibilities include the following:
LEADERSHIP STRUCTURE QUALITY
SYSTEM
QUALITY
POLICY
ACCOUNTABIL
ITY SYSTEM

RESOURCES
• Resources is essential to the success of any endeavor, and this is
particularly critical in a pharmaceutical manufacturing environment.
• Inadequate staffing, training, manufacturing equipment and facilities,
environmental controls, analytical equipment, and other resources can be
sources of variability leading to the production of product that does not
meet specified requirements.
• Management is responsible for identifying resource requirements and
providing resources accordingly, including providing training that is
appropriate to the assigned activities

CONT….
• Under a quality system model, the specification of facility and equipment
requirements may be performed by technical experts (e.g., engineers,
development scientists) who have an understanding of the pharmaceutical
science, manufacturing processes, and risk factors associated with the
product and its manufacture.

MANUFACTURING OPERATIONS
• The FDA has identified four major elements of a QS approach to manufacturing
operations. These are identified and compared to the cGMP requirements which
are :
1. Design and develop product
and processes
2. Examine Inputs
3. Perform and monitor
operations
4. Address nonconformities

CONT….
1. Design and develop product and processes :
• In a modern quality systems manufacturing environment, the
significant characteristics of the product being manufactured should be
defined and verified as meeting requirements from design to delivery, and
control should be exercised over all changes
• The idea of controlling the design of both product and process is
consistent with concepts included in the FDA Pharmaceutical cGMPs for
the 21st Century Initiative to assure product safety that focus on the entire
product life cycle.

CONT….
• Documentation is required and can include the following:
 Resources and facilities used
 Procedures to carry out the process
 Identification of the process owner who will maintain and update the
process as needed
 Identification and control of important variables
 Quality control measures, necessary data collection, monitoring, and
appropriate controls for the product and process
 Any validation activities, including operating ranges and acceptance
criteria
 Effects on related process, functions, or personnel

CONT….
• The PAT guidance document describes a voluntary approach to the
design, analysis, and control of manufacturing processes that involves the
timely (e.g., in -process) measurement of critical quality and performance
attributes of raw and in - process materials and processes, with the goal of
ensuring final product quality.
• In the PAT guidance, the FDA indicates that the desired state for
pharmaceutical manufacturing may be characterized as follows:
Product quality and performance are ensured through the design of
effective and efficient manufacturing processes
Product and process specifications are based on a mechanistic
understanding of how formulation and process factors affect product
performance

CONT….
• Relevant regulatory policies and procedures are tailored to accommodate
the most current level of scientific knowledge.

2.Inputs
• A robust quality system will ensure that all inputs to the manufacturing process
are suitable for use by establishing quality controls for the receipt and acceptance
from qualified vendors, production, storage, and use of all inputs.
• The cGMP regulations require either testing or use of a certificate of analysis
(COA) plus an identity analysis for the release of materials for manufacturing.
PERIODIC AUDITING
OF SUPPLIRS
EXAMINATION
CONDUCT BY SUPPLIES
CHANGE CONTROL

3.Perform and Monitor Operations
• The cGMP regulations require written production and process control
procedures and specify process control activities that must be performed
and documented.
• Current quality system models also require written procedures, process
verification and validation as appropriate, the establishment of
appropriate process control measures and documentation.
• A quality systems approach allows the manufacturer to more efficiently
and effectively validate, perform, and monitor operations and ensure that
the controls are scientifically sound and appropriate.
• One important aspect of the quality systems approach is the ongoing
collection and analysis of quality data to continuously evaluate quality
system effectiveness.

4.Address Nonconformities
• A key component in any quality system is appropriately responding to
nonconformities
• The cGMP regulations require an investigation to be initiated and that the
investigation, conclusion, and follow - up be documented.
• The complete response to nonconformities should be risk based and can include
the following components:
• Assessment of how the nonconformity will affect the quality of the finished
Product
• Determine the cause of the nonconformity.
• Identify any actions needed to correct the cause and to prevent recurrence.
• Document the investigation, findings, and follow - up actions.
• Assess the effectiveness of follow - up actions.
• Repeat the cycle as needed.

EVALUATION ACTIVITIES
• The evaluation component of a QMS is intended to provide objective information and
data that allow the organization to assess the conformity of the product, evaluate the
performance of its quality system, and maintain and improve its effectiveness. The
cGMP regulations similarly require evaluation activities as shown.
11/16/2019RAJPUROHIT 19
TREND ANALYSIS
CONDUCT INTERNAL AUDITS
QUALITY RISK MANAGEMENT
CORRECTIVE AND
PREVENTIVE ACTION
PROMOTE IMPROVEMENT

1.Trend Analysis
• Trend analysis is one statistical tool specifically recommended by the
FDA in its pharmaceutical QS guidance document that can be very
valuable in monitoring processes and quality system performance to
identify emerging problems and to assess the effectiveness of
improvement efforts.
• Traditional statistical process control and other methods also provide
valuable support in the objective and ongoing analysis of quality data and
can be helpful in implementing real - time quality assurance practices as
recommended by the FDA

Conduct Internal Audits
• Current quality system models call for audits to be conducted at planned intervals to
evaluate effective implementation and maintenance of the quality system and to
determine if processes and products meet established parameters and specifications.
• Factors that can be incorporated into a risk - based approach to planning audit
frequency and scope include the following :
• Existing legal requirements (e.g., cGMPs)
• Overall compliance status and history of the company or facility
• Robustness of a company ’ s quality risk management activities
• Complexity of the site
• Complexity of the manufacturing process
• Complexity of the product and its therapeutic signifi cance
• Number and significance of quality defects (e.g., recall)

CONT….
• A top - down approach first evaluates the overall structure of the quality
system and its subsystems. Selected subsystems may be chosen for
review. Systems identified and developed by the FDA in a six - system
inspection model for the inspection of drug manufacturers include the
following:
• Overall quality system
• Facilities and equipment
• Materials system
• Production system
• Packaging and labeling
• Laboratory controls

CONT….
• When using the top - down approach, the auditor will first review each
subsystem to determine if the requirements that apply to that subsystem
(e.g., regulatory requirements, the requirements of the standard) are met
by defining, documenting, and implementing appropriate procedures.
• A bottom - up approach may be used to follow upon a specific quality
problem identified from trend analyses, product nonconformities, adverse
experiences, customer complaints, or other sources of quality data.
• A combination approach may also be used that employs elements of top –
down and bottom - up audits. This allows some level of assessment of the
effectiveness of the overall quality system while evaluating the cause of
specific quality problems.

CONT….
• Initial quality system audits or regularly scheduled audits are likely
candidates for the top - down approach, while audits conducted as part of
a root cause analysis, for example, may best employ a bottom - up
approach
• For cause inspections conducted in response to a specific product issue
such as a recall are more likely to employ a bottom - up approach.
• The QMS models require periodic audits but do not specify audit
frequency. Audit frequency must be determined based on the risk
associated with the matters to be audited and other factors including
results of previous audits and other quality data.

Quality Risk Management
• The FDA has endorsed quality risk management as part of an overall
quality systems approach to compliance with the cGMP regulations and
achieving overall quality system objectives
• Implementation of quality risk management includes assessing the risks,
selecting and implementing risk management controls commensurate
with the level of risk, and evaluating the results of the risk management
efforts

Corrective and Preventive Actions
• A corrective action is initiated to correct the cause of an identified
nonconformity and to prevent it or similar problems from reoccurring. It
may include initial and follow - up actions (e.g., conducted after root
cause analysis).
• Current quality system models and the cGMP regulations emphasize
corrective actions and require that actions be documented. Under current
quality system models, preventive actions include actions taken in
response to quality data to address the cause of potential nonconformities
to prevent their occurrence.

Promote Improvement
• Continual improvement is a requirement of existing quality system
models such as ISO 9001 - 2000 in which the organization is required to
continually improve the effectiveness of the quality management system
through the use of the quality policy, quality objectives, audit results,
analysis of data, corrective and preventive actions, and management
review .

TRANSITIONING TO QUALITY SYSTEMS
APPROACH
• The cGMP regulations assign significant responsibilities to the
organizational unit responsible for quality - related activities.
Organizations implementing a quality system model will be responsible
for additional quality - related activities including, but not necessarily
limited to, conducting quality audits, analysis of quality data, risk
assessment, and preventive actions based on review and analysis of
quality data to prevent the occurrence of product nonconformities.
• Following are some points to consider in planning the transition:
 Create a transition team:
 Train the transition team:

CONT….
Develop a transition plan:
Identify staffing requirements:
Identify other resource needs:
Define roles and responsibilities
Consider benchmarking:
Consult with experts:
Communicate regularly:
 Sell the system:

AUDIT CHECKLIST FOR DRUG INDUSTRY
• Instructions for Using Audit Checklist
• Before starting an on - site audit, plan the audit. Review past audits, note
indications of possible problem areas and items, if any, that were
identified for corrective action in a previous audit.
• If you are not already familiar with this facility, learn the type of product
produced and how it is organized by personnel and function. What does
your “ customer, ” that is, your superior or senior facility management,
expect to learn from this audit ?
1. The checklist is to be used with a notebook into which detailed entries
can be made during the audit.

CONT….
2. While the checklist is to guide the auditor, it is not intended to be a substitute
for knowledge of the GMP regulations.
3. Although a single question may be included about any requirement, the
answer will usually be a multipart one since the auditor should determine the
audit trail for several products that may use many different components. Enter
details in you notebook and cross reference your comments with the questions.
4. At least three production batches should be selected for thorough analysis to
include: (a) traceability of all components or materials used in the subject
batches, (b) documentation of raw material or component, in - process, and
finished goods testing for the subject product batches, and (c) warehousing
and distribution records as they would relate to a possible recall.

CONT….
5. Responses entered on the checklist should be consistent. “ X ” is
recommended for “ No ” ; a checkmark for “ Yes ” ; “ N/A ” for not applicable
to questions that do not apply. An asterisk and notebook page number should
be entered on the checklist to identify where relevant comments or questions
are recorded in your notebook.
6. The notebook used should be a laboratory - type notebook with bound pages.
The notebook should be clearly labeled as to the audit type, date, and
auditor(s). Many auditors prefer to use a notebook for a single audit so it may
be filed with the checklist and the final report.

REFERENCE
• Pharmaceutical manufacturing handbook regulations and
quality by shayne cox gad, a john wiley & sons, inc.,
Publication page no : 201 – 237.

Role of quality system and audits in pharmamaceutical

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