Seminar On

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Seminar On

• Quality Assurance and
• its Importance
• Presented By Dabhi Ajay S.
• M. Pharm
• L. M. C. P. Ahmedabad
• Dept. of Pharmaceutics and Pharmaceutical
  Technology

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List of Contents Quality - Reasons and
characteristic of quality - 5Ms of quality and
factors influencing quality Quality Assurance -
Components and Elements of QA - QA systems -
Fundamental features and benefits of QA system -
TQM - QA in pharmaceutical manufacturing -
Process deviations and failures - Change
controls - QA in RD - Concept of SQC -
Sampling and sampling plans

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Quality??

• Quality represents both function and process.
• Function there are operational groups whose
  major responsibilities are to assure quality
  creation and maintenance (QA) and to monitor the
  specifications established to control activities
  (QC)
• Process set of activities and operations which
  determine whether a pharmaceutical product has
  quality.
• Quality is spelled in terms of specifications
  which are in language easy to understand and have
  methods for measuring, determining or assessing
  and also for verification

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• Reasons for quality consciousness in society
• Increasing consumer awareness Expectations are
  growing in
• consumers
• Liberalization of economy Competition is
  growing
• Globalization of market (shrinking world)
• International standards (ISO 9000)
• Quality tag

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• Characteristic of quality
• IDENTITY
• PURITY
• POTENCY
• STRENGTH
• UNIFORMITY
• SAFETY
• EFFICACY
• STABILITY

• A drug product should comply with such
  requirements within the permitted tolerance limit
  and that up to designated or expected shelf life
  period of the drug in question. It should also
  comply with legal and professional standards.

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• Quality is affected during the process of
  manufacturing on handling and therefore required
  to conform with specified quality form the
  beginning till they are consumed
• Quality cannot be merely justified by the end
  product testing and nor by manufacturing and
  quality control assessment
• Quality is the end product of a thoroughly
  understood, properly designed, implemented and
  controlled manufacturing processes.
• Customary sample size alone cannot verify that
  the various factors in the system intended to
  assure quality within and between batches of
  product are functioning as they were designed to
  function.

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The 5Ms of Quality

• Man
• Material
• Machinery
• Manuals/Methodology ( SOP)
• Motivation

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Factors influencing quality
Pre analytical Analytical Post analytical
Right specimen Laboratory professionals Recording
Right collection Reagents Interpretation
Right labeling Equipment Turnaround time
Right quantity Selection of test - SOP Report to right user
Right transport Records
Right storage Bio-Safety
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Quality Assurance Assurance Guarantee or
promise given to inspire confidence Quality
Assurance is sum total of the organized
arrangements made with the objectives of ensuring
that product will be of quality required by their
intended use. QA is the activity of providing to
all, concerned the evidence needed to establish
confidence that quality function is being
performed adequately. Aim of QA To ensure
that each batch of a medicinal product complies
with its specifications and is fit for its
intended use in terms of safety, efficacy, and
acceptability.
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Quality assurance
Definition It is the sum total of all lab
activities that are undertaken to ensure
generation of accurate and reliable
results. What is the Objective? To ensure
credibility of the lab and generate confidence in
lab results
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Components of Quality assurance

• Internal Quality control IQC
• Nature Concurrent
• performed by lab staff
• Objective Reliable results on a daily basis
• External quality assessment EQA
• Nature Retrospective to evaluate IQC
• Performed by Independent agency
• Objective Ensure inter laboratory comparability

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• Elements of QA
• Quality System Planning A management
  responsibility include strong management,
  facilities, equipments, personnel, control etc.
• Product development
• Vendor control
• Validation Validation of process, Analytical
  method, facilities, equipments, personnel, raw
  materials, product, environment etc.
• Documentation
• Quality Audit Periodic reviews and evaluation
  of manufacture and quality control.

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• Quality Assurance System
• A quality assurance system is constructed by
  merging a series of actions. These actions
  collectively ensure product quality. The QA
  system must
• establish specific activities before production
• control factors during production
• 3) evaluate results following production

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Quality systems

• Objectives
• To prevent risks
• To detect deviations
• To correct errors
• To improve efficiency
• To reduce costs
• How
• By establishing a quality manual defining
• Organizational structure Staff
• Responsibilities
• Procedures and processes
• Resources
• Documentation

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• Fundamental features of quality system
• a quality policy which defines the purpose and
  objectives of the pharmaceutical manufacturing
  facility, it also outlines the ways in which
  these objectives will be achieved.
• resources which include materials, equipments
  and personnel
• documentations which includes procedures and
  standards
• an audit process to provide assurance that
  procedures have been compiled with this process
  can also be used to improve the quality system.

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• In pharmaceutical production process, with
  assurance is involved in the following
  activities
• Purchasing Dispatching
• Warehousing Operational protocols
• Manufacturing Training
• Quality control Validation
• Packaging
• The system for each the listed activities must
  provide
• assurance that materials, product labeling and
  storage have conformed to an established
  programme of operations.
• Monitoring to ensure that the system is
  completed with or updated.

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• Benefits of QA system
• Higher standards of production
• Compliance with regulatory requirements
• Reduce waste
• Less risk of product defects
• Quality System
• Ensure quality
• Provide evidence
• Generate confidence

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• Total Quality Management
• Quality function is part of a team composed of
  research, production Marketing/sales, and
  customer service.
• It requires total commitment of senior-level
  management and
• supervision of all departments, operators,
  suppliers and customers.
• Raw materials must be characterized and then
  purchased
• Facilities must be designed, constructed and
  controlled
• Equipment must be selected
• Personnel must be trained
• Distribution department is responsible for
  controlling the shipping and handling of
  products, using inventory control system based on
  FIFO.
• Marketing department should be sensitive to
  customer needs and be responsive to complaints.

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QA in Pharmaceutical Manufacturing
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• GMPs
• QA is ubiquitous in production
• Quality unit is responsible for ensuring that
  controls are
• implemented during manufacturing operations which
  assures drug product quality.
• - The quality model that these regulations
  establish consists of a sequence of events of
• Qualification
• Validation
• Specifications
• Monitoring
• End of process testing
• Written instructions
• Documentation and monitoring review
• Decision (to approve or reject)

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• Qualification includes essentially activities
  performed to prove that a system does what it
  purpots to do
• Design qualification
• Installation qualification
• Operational qualification
• Performance qualification
• - should establish and provide documentary
  evidence that the premises, the supporting
  utilities, the equipment and the processes will
  consistently produce a product meeting its
  pre-determined specifications and quality
  attributes.
• - PQ should include, but not be limited to
  the following
• tests, using production materials, qualified
  substitutes or simulated product, that have been
  developed from knowledge of the process and the
  facilities, systems or equipment tests to
  include a condition or set of conditions
  encompassing upper and lower operating limits.

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Qualification life cycle
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Specifications

• Results of the validation and qualification
  exercises are specifications
• They should be derived form previous acceptable
  process average
• process variability estimates where possible
• It separates acceptability and unacceptability

Monitoring
- Whether specifications are being met is the
process of monitoring
Documentation

• Procedure, master production and control records
• Data recording documentation
• Review of records, retention of records and
  follow-up of problems
• arising after production

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Technology Transfer

• Technology transfer includes quality involvement
• So QA oversights, review and approves (rejects)
  the transfer

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Facilities and Equipments

• QA role can be review of
• Layouts and floor plans with regard to material,
  personnel, waste
• flow, and the potential for cross contamination
• Materials of construction and design of all
  areas
• Suitability of utilities, services, and the
  systems (adherence to
• GMPs and generally acceptable practices) for
  water, HVAC, gases
• etc.
• Suitability of equipments (design, capacity,
  materials of
• construction, compatibility with process
  materials and conditions,
• ability to be cleaned and/or sterilized)
• Qualification and validation of facilities,
  equipments, utilities etc.

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Materials

• To test them to ensure that they have necessary
  quality attributes
• To segregate acceptable from unaccepted
• To maintain the quality of materials during their
  presence in the
• plant and in their processing

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Documentation control
-Documents are specific for the process, product,
equipment etc. -QA issues, retrieves, reviews,
and stores the documents -SOPs and batch
records must be authorized by a sign off
procedure that includes group responsible for the
procedure, all the groups directly impacted by
the procedure, and QA. -QA may be responsible
for assigning batch numbers and expiration dates
as a part of issuance of batch record. -For
SOPs, calibration logs, and the like standard
distribution lists are necessary to ensure that
all who need to use procedures receive updates at
the same time with instructions as to the
effective date of the new document as to the
destruction or return of the old.
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• review of documents after the completion of the
  process and testing. The batch record should be
  reviewed for completeness, proper sequencing,
  appropriate dates, acceptable yields, meeting of
  all in-process specifications, and explained and
  unexplained deviations.
• Final test results must be reviewed to ascertain
  whether all the specifications are met. If any
  results are not within specifications, the SOP to
  handle this must be implemented.
• - After all these QA decides the releasibility
  of the final product.

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Equipments Facilities Process Containers, Closures, Labeling, Raw materials Staff Product
Purchase order Diagrams and drawings Batch records Purchase orders CVs Inventories
Diagram manuals Floor plans Reconciliations Monitoring Receiving records Inventories Job descriptions Training Sampling, testing Release documents
Use logs Qualifications and validations In process tests Sampling, testing Regulatory Master specificartion sheet
Calibration logs Logs Results Release Documents Procedural Testing methods and procedures
Maintenance logs SOPs SOPs SOPs Technical COA
Cleaning logs Monitoring records Control charts Reconciliations and accountability Distribution
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In process Items control

• Quality Assurance before start up
• Environmental and microbiological control and
  sanitation
• Manufacturing working formula procedures
• Raw materials
• Manufacturing equipments
• Quality assurance at start up
• Raw material processing
• Compounding
• Packing materials control
• Label controls
• Finished product control

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• Quality Events
• Things didnt go as planned
• Events affecting quality should be investigated
  in a timely manner
• under the auspices of QA.
• Technical service dept. is responsible for
  performing the studies
• but QA must access the impact upon the affected
  batches and other
• potentially affected batches
• - Annual review of products

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Process Validation Deviations and Failures

• It is foolhardy to begin process validation
  without an assurance that the process is under
  control
• Recognize validation failure
• well documented investigations for less clear
  deviations
• The following steps should be performed as soon
  as possible after the problem is discovered
• Document clearly what occurred and when it
  occurred.
• Interview personnel as soon as possible (before
  memories can get clouded) and document the
  interview.
• Collect any additional data (as is relevant).
• Describe a sequence of events of when and what
  happened, review batch records, and corroborate
  events through data and records.

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Process Materials Finished products
Process deviations Specification deviations Product complaints
Process condition deviation Unapproved vendors Adverse events
In-process specification deviations Stability problems Specification deviation
Environmental excursions Water, gases, etc. deviations SQC trends
SPC trends Stability problems, recalls, reworks, returns
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• Document any and all remedial actions that may
  have been taken.
• List all possible causes for the event.
• After investigating, eliminate causes that do
  not fit the data.
• Establish a cause or most probable cause based
  upon the data.
• List corrective actions that need to be
  implemented.
• Only events that are not process-related could
  be written off as not negatively affecting the
  validation (e.g., power failures, natural
  disasters, human error, etc.).
• Even if a process validation failed and the cause
  was not process-related, the validation should be
  replaced with a fresh run.

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Change control

• A basic change control system should cover
• Planned changes change in equipment, facilities,
  utilities, and computer systems, temporary
  changes or emergency changes against permanent
  ones, changes in batch records and SOPs, changes
  in analytical test methods, specifications and
  raw materials.
• -planned changes are intentional and pre-approved
  and can be either permanent or temporary.
• Unplanned changes They are actually deviations
• A change control SOP defining terms, levels of
  justification and approval needed, and the
  specific responsibility of approvers, must be
  written approved and followed.
• -There should be a documented change control
  system

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• A technical review by qualified personnel should
  review the - adequacy of the justification
• - whether validation or revalidation is needed
• - the adequacy, accuracy, and usefulness of any
  requested drawings
• - the potential risk(s) (including cost and
  downtime), and whether those risks are
  adequately addressed.
• QA normally reviews proposed changes for the
• - adequacy of the rationale for the decision to
  make the change
• - compliance to the change control policy
• - assurance that adequate documentation of the
  change is present
• - the impact on internal or external customers
  or GMPs, and the required changes to other
  procedures, specifications, batch records,
  and so on.
• - A Financial review

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• Follow up
• Emergency changes
• Emergency or quick changes still require
  writing the change down and getting the approval
  of one technical area manager (such as
  Development) and QA.
• How to do change control?
• 1. Keep it simple use an approved from and SOP
• 2. Hold regular change control meetings
• 3. Distribute proposed changes electronically
• 4. Train your employees
• 5. Follow up
• 6. Publish a report on outstanding change request
  forms
• 7. Be careful how you agree to handle temporary
  changes
• 8. Enlist a powerful ally and assign
  responsibility for
• tracking/monitoring changes to one individual
  / department.

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Monitoring

• Process and environmental monitoring
• testing and issuance of results
• Imp results of testing is reviewed by QA. Thus
  QA must receive all
• notices of deviations and monitoring excursions
  on an on-going
• basis in such a way that it can make
  determinations as to product
• quality and what steps may need to be take.

Inspection Control
- These are online QA staff responsible for
container and label accountability, online
statistical process control of critical
processing steps, online checking of labels lines
for expiration dates, batch no., and proper
labels as well as line clearance before and after
labeling run, filled vial inspections for
particulates, tablet weight variation and other
functions.
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Training
- Necessary in 3 areas of all plant personnel
regulatory, procedural, and technical.
Auditing

• The essence of audit is comparison. The essential
  question of any audit are
• Has the system been established?
• Is the system reasonable and appropriate?
• If so, is it being followed?
• Manufacturing audit program should include
• Vendors and contractors
• Plant inspection
• Procedures
• Batch records
• Submissions (pre-approval)
• Quality systems

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Formulate the question
Draw Conclusions
QA and QC
Reporting and Interpretation
Select or develop analytical procedure
Conduct analysis Sampling Sampling
preparation Analysis
Optimize procedure
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QA in Research and Development

• Goals of RD
• Effective drugs
• data should be real, accurate, complete,
  consistent and reasonable
• results of attendant analyses are the basis for
  companies and
• regulatory agencies decisions, must be unbiased,
  inclusive of all
• appropriate data, and in correct with the
  predetermined protocols
• and/or analytical plans.
• assess the acceptability of and minimize the
  errors in products
• of RD, thats submission and individual reports.

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GLPs

• Detailed, documented evidences of the appropriate
  functioning
• of the controls and assurance function is
  necessary to prove that
• the studies have quality and integrity.

Preclinical QA

• The quality aspects relate to the establishment
  of
• The design of studies
• Investigational materials
• Test subjects
• Data that result from all tests
• Observations
• Gross postmortem pathology and histopathology
  and
• Preparation of report

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• Audits
• Protocol Audits
• Procedure audits
• - Study specific
• - System oriented
• 3. Documentation audits
• 4. Report audits
• 5. Facilities audits

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SQC

• Monitoring of quality by application of
  statistical methods in all stages of production
• Used for estimating parameters, for performing
  test of significance, for determining the
  relationship between factors, and for making
  meaningful decisions on the basis of experimental
  evidence
• SQC has been used to serve
• as a basis for improved evaluation of materials
  through more representative sampling techniques
  and
• as a means of achieving sharper controls in
  certain manufacturing process
• Objective determine whether the major source of
  observed variation is due to chance variation
  which is inevitable during the manufacturing
  process, or to assignable cause which is usually
  detected and corrected

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• For this normal frequency distribution curves and
  quality control charts have been used
• Sampling and sampling plans
• Process of removing an appropriate number of
  items form a population in order to make
  inferences to the entire population
• proper methods of sampling and adequate number
  and size of samples are needed for an effective
  QA program, as judgment of accept or reject lies
  in it
• the number of unacceptable units are controlled
  to rigid standards by the stringency of the
  sampling plan
• Sampling plans based on data from measurement of
  attributes or variables may be constructed
• Govt. sampling plans such as MIL-STD-414 for
  variable sampling and MIL-STD-105D for attribute
  sampling is used
• Acceptability of a batch is determined by the use
  of sampling plans associated with the designated
  acceptable quality level

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• A sampling plan indicates the no, of units of
  product form each
• batch to be inspected and the criteria for
  determining the
• acceptability of the batch
• Inspection level determines the relationship
  between the batch size
• and the sample size
• Single sampling specified sample is selected
• Double sampling a second sample for inspection
  is permitted if
• The first fails, and two acceptance numbers are
  used- the first
• Applying to the observed number of defectives for
  the first sample,
• And the second applying to the observed number of
  defectives for
• First and second samples combined
• Statistical sampling plan requires that four
  basic quality standards
• Be specified
• An acceptable quality level (AQL)
• An unacceptable quality level (UQL)
• Risk or error (producers risk) probability of
  rejecting a good batch
• Risk or error (consumers risk) probability of
  accepting a bad batch

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Thank You