M.

Pharm Sem -I Presentations

SIX SYSTEM INSPECTION MODEL

SUBMITTED TO
SAVITRIBAI PHULE, PUNE UNIVERSITY , PUNE
FOR
PARTIAL FULFILMENT OF REQUIREMENTS FOR THE AWARD OF
MASTER OF PHARMACY

IN THE SUBJECT

QUALITY MANAGEMENT SYSTEM

IN THE FACULTY OF SCIENCE AND TECHNOLOGY
Presented By- Guided By-
Shalaka Shashikant Dhikale Dr. S. P. Ahirrao Ma’am
( Roll No. 3)
Pratiksha Dnyaneshwar Mandlik
(Roll No. 11) Bhujbal Knowledge City,
MET’s Institute of Pharmacy,
Adgaon, Nashik, 422003.
Maharashtra, India

Academic Year- 2021-22 1

 CONTENTS :
 Introduction
 The Quality system
• Management responsibilities
• Resources
• Manufacturing operation
• Evaluation activities
 Case study
 Production system
 Facilities & Equipment system
 Laboratory Controls system
 Materials system
 Packaging & Labeling system
 Case study

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 INTRODUCTION :
• Six – System Inspection Model is a model that can help
pharmaceutical manufacturers comply with CGMP regulations. The
six systems referred to in this inspection model are : Quality,
Production, Facilities and Equipment, Laboratory Controls,
Material, Packaging & Labeling.

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 I)THE QUALITY SYSTEM MODEL :
A Quality system model is a collection of business processes
focused on meeting customer requirements and enhancing their
satisfaction.
It is expressed as organizational goals and aspirations, policies,
processes, documented information and resources needed to
implement and maintain it.
 WHO guidelines of GMP define quality management as-
“ The aspect of management function that determine and
implement the Quality Policy “
1) An appropriate infrastructure of ‘quality system’ considers
organizational structure, procedure and resources.
2) Systematic action necessary to check product.

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 The model is described according to four major factors:

EVALUATION
ACTIVITIES

MANAGEMENT
RESPONSIBILITIES QMS RESOURCES

MANUFACTURING
OPERATIONS

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 A) Management Responsibilities :
 A quality management system plays a key role in the design,
implementation, and management of the quality system.
 For example, management is responsible for establishing the
quality system structure appropriate for the specific organization.
Management has responsibility to provide the leadership needed
for the successful functioning of a quality system.
 Various roles of management in developing and managing a robust
quality system include:
1. Provide leadership
2. Structure the organization
3. Build your Quality to meet requirement
4. Establish Policies, objectives, and plans
5. Review the system

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 1) PROVIDE LEADERSHIP :
 In a robust, modern quality system, senior management should
demonstrate dedication to building and maintaining their quality
system in a solid, modern quality system.
 To guarantee that the system is a part of the manufacturer’s
mission and quality strategies, quality system plans should be
integrated with strategic plans.
 A staff from the quality system are fully integrated into
manufacturing activities and participate in non conformance
investigations.

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 CONT….
 All levels of management can provide support of the quality
system by:
1)Actively participating in system design, implementation, and
monitoring, including system review.
2)Advocating continual improvement of operations of the quality
system.
3)Committing necessary resources.

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 2) STRUCTURE THE ORGANIZATION :
 Management has the role of structuring the organization and
ensuring that allocated authorities and responsibilities support the
production, quality and management activities required to
generate quality products while developing a comprehensive
quality system.
 It is the obligation of senior management to guarantee that the
organization’s structure is recorded.
 Within the system, all managers are responsible for
communicating employee roles, duties and authorities, as well as
ensuring that interactions are specified and understood.
 An organization also has the responsibility of delegating authority
to the person in charge of the quality system to discover problems
and implement solutions.

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3) BUILD YOUR QUALITY SYSTEM TO MEET
REQUIREMENTS :
 Implementing a strong quality system can assist in meeting CGMP
requirements for drug safety, identity, strength, quality, and purity.
 The agency suggests that top managers use the quality systems
model to ensure that the quality system that is created and
implemented gives clear organizational guidelines and supports
systematic issue review.
 When documenting the implementation of a quality system, for
example, the following should be handled, according to the model:
 The definition of quality
 The quality level that shall be adheres
 The policies of the manufacturer for implementing the quality
system criterion.

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4) ESTABLISH POLICIES, OBJECTIVES, AND
PLANS :
 A modern quality system’s policies, objectives and strategies
enable senior managers to communicate their vision of and
commitment to quality to all levels of business.
 Senior management should include a strong commitment to
quality into the organizational mission under a quality system.
 Senior management should design a quality policy for the
organization that :
 Corresponds with this mission
 Ensure that standards are met while also enhancing the quality
system.
 Provide objectives to meet the quality policy’s requirements.

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 5) REVIEW THE SYSTEM :

 A vital component of every solid quality system is system review,

which ensures the system’s continued suitability, sufficiency and
effectiveness.
 Senior management should examine the performance of the
quality system on a regular basis as part of quality system.
 A typical review involves evaluations of the process, product and
client requirements (here, customer is defined as the recipient of
the product and the product is the goods or services provided).

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CONT….
 Under a quality systems approach, a review should consider at
least the following:
• The appropriateness of the quality policy and objectives.
• Customer feedback, including complaints.
• The analysis of data trending results .
• Any follow-up actions from previous management reviews.
• Any changes in business practices or environment that may
affect the quality system.
• Product characteristics meeting the customer’s needs.

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 B)RESOURCES :
 Appropriate allocation of resources is key to creating a robust
quality system and complying with the CGMP regulations.
1) General Arrangements :
 Under the model, senior management, or a designee, should be
responsible for providing adequate resources for the following:
• For laboratory analysis of the finished drug product, including
collection, storage, and examination of in-process, stability, and
reserve samples.
• There should be proper supply and maintenance of appropriate
facilities and equipment to manufacture a quality product.

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 2)PERSONNEL DEVELOPMENT :

 In a quality system, personnel should be qualified to do the

operations that are assigned to them in accordance with the
nature of, and potential risk of, their operational activities.
 Under a quality system, managers are expected to establish
training programs that include the following:
• Evaluation of training needs
• Provision of training to satisfy these needs
• Evaluation of effectiveness of training
• Documentation of training and/or re-training

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 3) FACILITIES AND EQUIPMENT :

 Under a quality system, the technical experts (e.g., engineers,

development scientists), who have an appreciation of
pharmaceutical science, and manufacturing methods related to
the product, are accountable for defining unique facility and
equipment requirements.
 Under the CGMP regulations, the quality unit ( QU) has the
responsibility of reviewing and approving all preliminary diagram
standards and techniques pertaining to services and tools and any
subsequent changes.

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 4) CONTROL OUTSOURCED OPERATIONS :

 Outsourcing involves hiring a second party under a contract to

perform the operational processes that are part of a
manufacturer’s inherent responsibilities.
 For example, a producer can also appoint some other association
to package deal and label or function CGMP regulatory training.
 Quality systems call for contracts (quality agreements) that
absolutely describe the service, high quality specification
responsibilities.

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 C)MANUFACTURING:
 Significant overlap exists between the factors of a quality system
and the CGMP law requirements for manufacturing operations.
1) Design, Develop, and Document Product and Processes
2) Examine inputs
3) Preform and reveal operation
4) Address Nonconformities

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 D) EVALUATION ACTIVITIES :

1) Analyze Data for Trends : Quality systems call for constantly

monitoring trends and enhancing systems. This can be done via
monitoring and information, figuring out and resolving problems,
and anticipating and stopping problems.
2) Conduct Internal Audits : A fine systems approach calls for audits
to be performed at deliberate intervals to evaluate positive
implementation and products meet established parameters and
specifications.
3) Quality Risk Management : Effective decision-making in a quality
systems environment is based on an informed understanding of
quality issues. Elements of risk should be considered relative to
intended use of a product, and in the case of pharmaceuticals,
patient security and ensuring availability of medically necessary
drug products.

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CONT….
4) Corrective Action : Corrective action is a reactive tool for
improvement to ensure that extensive problems do not recur. Both
quality systems and the CGMP guidelines emphasize corrective
actions.
5) Promote Improvement : The effectiveness and efficiency of a
quality system can be improved through the quality activities
described in this guidance. Management may choose to use other
improvement activities as appropriate.

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 CASE STUDY
Background:
 Firm markets an extended release tablet.
 Production covered manufacture of extended release “beads”
which were blended with excipients and then compressed.
 Operations had to pre-compress combination samples in the lab to
decide running parameters for the tablet press.
 Different blends would require exclusive settings, and the company
had no notion why.

Test for press

parameters

Blending Compression QA testing

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 CASE STUDY
What Happened:

 During a FDA inspection, investigators noticed the pre-

compression practice.

 Investigators also found insufficient launch testing, in particular in

mild of recognized system problems.

 Warning Letter issued for lack of technique validation.

QA testing

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 CASE STUDY
Takeaways:
 Operational parameters must be selected usage of risk-
based, science-based approach.

 Process design/qualification (Stage 1-2) must be completed and

adequate prior to distribution of your product.

 Knowledge received for the duration of scale-up need to be

incorporated into manner design/control strategy.

 Sampling plans for batch launch should be scientifically sound.

QA testing

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 II)PRODUCTION SYSTEM :
 This system includes measures and activities to control the
manufacture of drugs and drug products including
• Batch compounding
• Dosage form production
• In-process sampling and testing
• Process validation
 It also includes establishing, following and documenting perform of
approved manufacturing procedure.
 Inspection is carry out according to the cGMP regulation, 21 CFR
211

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 According to the cGMP :
• Quality and manufacturing process and procedures must be
defined, authorised and controlled.
• Batch numbering and maintaining proper traceability is
required/process validation is require
• Equipment use records, labelling used, personnel, and raw
material are traceable
• Verification of all steps including sign-off are requires for critical
process step.
• All batch must be reviewed and have QA approval before the
product is released

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 OBJECTIVES OF INSPECTION
1. To discover and take away the faulty raw materials before it
undergoes production.
2. To observe the misguided merchandise in production every
time it is detected.
3. To convey statistics to the observe of managers before they
become serious to allow the discover weak point and over the
problem.
4. To prevent recognition for quality and reliability.
5. To promote recognition for quality and reliability.

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 PURPOSE OF INSPECTION
• To distinguish good lots from bad lots
• To distinguish good pieces from bad pieces
• To determine if the process is changing
• To determine if the process is approaching the specification
limits
• To rate the quality of product
• To rate accuracy of inspection
• To measure the precision of the measuring instrument
• To measure process capability

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 III)FACILITIES AND EQUIPMENT SYSTEM :
 This system includes the measures and activities which provide an
appropriate physical environment and resources used in the
production of the drugs or drug product.
 It includes:
• Buildings and facilities along with maintenance
• Equipment qualification(installation and operation), equipment
calibration and preventative maintenance and cleaning and
validation of cleaning tactics as appropriate.
• Process performance qualification will be evaluated as section
of the inspection of the average procedure validation.

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 BUILDING AND FACILITIES
• Design and construction features
• Storage of in-process materials & other materials
• Ventilation, air filtration, air heating and cooling
• Sanitation
• Maintenance
 EQUIPMENT
• Equipment design, size
• Equipment construction
• Equipment cleaning and maintenance
• Automatic, mechanical, and electronic equipment

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 IV. LABORATORY CONTROL SYSTEM

 This system includes measures and activities related to

– Laboratory procedures
– Testing
– Analytical methods development
– Validation or verification
– Stability testing
– Laboratory animals
• Inspection is carry out according to 21 CFR 211.

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 V)MATERIAL SYSTEM :
 This system includes measures and activities to control finished
products, components, including water or gases that are
incorporated into the products, containers and closures.
 It includes :
• Validation of computerized inventory control processes.
• Drug storage
• Distribution controls
• records

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 COMPONENT
• Any ingredient intended for use in the manufacture of a drug
product, including those that may not appear in such drug
product.
• Ex. Excipients, water, gases, etc., even if not in final product

 ACTIVE INGREDIENT
• Any component that is intended to furnish pharmacological
activity or other direct effect in the diagnosis, cure, mitigation,
or to affect the structure or any function of the body of man or
other animal.
 INACTIVE INGREDIENT
• Any component other than an active component

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 CONTROL OF COMPONENTS AND DRUG PRODUCT CONTAINERS
AND CLOSURES
• General requirements
• Receipt and storage of untested components, drug products
containers and closures.
• Testing and approval or rejection of components, drug product
containers and closures.
• Use of approved components, drug product containers and
closures
• Retesting of approved components, drug product containers
and closures.
 HOLDING AND DISTRIBUTION
• Warehousing procedures
• Distribution procedures

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VI)PACKAGING AND LABELING SYSTEM :
 It includes
• Written procedures
• Label examination and usage
• Label storage and issuance
• Packaging and labeling operations controls
• Validation of these operations

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PACKAGING AND LABELING CONTROL

 Materials examination and usage criteria

 Labeling issuance
 Packaging and labeling operations
 Tamper- evident packaging requirements for OTC human drug
product
 Drug product inspection
 Expiration dating

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OBJECTIVE OF INSPECTION

 To detect and remove the faulty raw materials before it undergoes

production.
 To detect the faulty product in production whenever it is detected.
 To bring facts to the notice if managers before they become
serious to enable them discover weaknesses and overcome the
problem.
 To prevent the standards reaching the customer and reducing
complaints
 To promote reputation for quality and reliability of product

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 CASE STUDY :
Background:

 Company manufactures multiple transdermal patch for many years.

 Firm developed a new drug, making the use of equal adhesion

matrix as it did for others.

 1st year on the market – obtained ~5000 complaints involving

efficacy and issue in the use of patch.

 Up to 25% of the drug was sticking to the liner.

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 CASE STUDY

What Happened:

Firm’s investigation indicated a drug/adhesive interaction problem.

Firm argued that since there were no specifications regarding peel force in
their application, a recall wasn’t warranted, and it could continue to distribute.

Firm ultimately recalled.

FDA issued a Warning Letter citing lack of specifications, as well as a failure to

assure proper strength.

Firm established a peel force specification.

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 CASE STUDY
CMC review and the CGMP program:

 21 CFR § 211.180(e)

 "Written documents required with the aid of this phase shall be

maintained so that data therein can be used for evaluating at
least annually, the quality standards of each drug product to
determine the need for changes in drug product specifications or
manufacturing or control procedures. Written procedures shall
be established and followed for such evaluations…”

• Important to use product experience to improve your product

and process in a timely manner.

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 CASE STUDY
Takeaways:

 Don’t except what worked earlier than will work under equal
conditions.

 Evaluate data to determine the need for modification in drug

product specifications

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 Reference
 https://www.fda.gov
 https://www.ivtnetwork.com/sites/default/files/SystemInspection_0
1.pdf
 https://www.researchgate.net/publication/Review_of_FDA_Warnin
g_Letters_to_Pharmaceuticals_Cause_and_Effect_Analysis
 https://www.fda.gov/media/92861
 https://www.nsf.org/newsroom_pdf/Pharma_QualitySystem.pdf

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