GMP

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GMP Quality Assurance

• B

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Introduction

• GMP ensures that quality is built into the
  organization processes involved in manufacture
• GMP covers all aspects of manufacture including
  collection, transportation, processing, storage,
  QC delivery of the finished product

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GMP

• Part of QA which ensures that products are
  consistently produced controlled to the
  quality standards appropriate to their use.
• GMP is an integral part of QA.

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QA, GMP QC inter-relationship

• QA

It is the sum total of the organized
arrangements with the objective of ensuring that
products will be of the quality required for
their intended use
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QA, GMP QC inter-relationship

• GMP

Is that part of QA aimed at ensuring that
products are consistently manufactured to a
quality appropriate to their intended use
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QA, GMP QC inter-relationship

• QC

Part of GMP concerned with sampling,
specification testing, documentation release
procedures which ensure that the necessary
relevant tests are performed the product is
released for use only after ascertaining its
quality
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QC QA

• Part of GMP which is concerned with sampling,
• specifications, testing and with in the
  organization, documentation and release
  procedures which ensure that the necessary
  relevant tests are carried out

• QA is the sum total of organized arrangements
  made with the object of ensuring that product
  will be of the Quality required by their intended
  use.

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QC QA

• Operational laboratory techniques activities
  used to fulfill the requirement of Quality

• All those planned or systematic actions necessary
  to provide adequate confidence that a product
  will satisfy the requirements for quality

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QC QA

• QC is laboratory
• based

• QA is company
• based

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GMP

• GMP in solid dosage forms
• GMP in semisolid dosage forms
• GMP in Liquid orals
• GMP in Parenterals Production
• GMP in Ayurvedic medicines
• GMP in Biotechnological products
• GMP in Nutraceuticals cosmeceuticals
• GMP in Homeopathic medicines

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GMP

• Good Manufacturing Practice
• Good Management Practice
• Get More Profit
• Give more Production
• GMP Training with out tears

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Ten Principles of GMP

• Design construct the facilities equipments
  properly
• Follow written procedures Instructions
• Document work
• Validate work
• Monitor facilities equipment
• Write step by step operating procedures work
  on instructions
• Design, develop demonstrate job competence
• Protect against contamination
• Control components product related processes
• Conduct planned periodic audits

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Beyond GMP

• Reduce pollution -? Zero discharge
• Adaptation of environment friendly methods
• Consideration for better healthier life
  tomorrow
• Consideration of ethics in life
• One should begin with end in mind otherwise it
  will be the beginning of the end

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Cost of effective GMP

• In fact Cost benefits positive cost benefits of
  GMP/QA
• Good plant lay out, Smooth work flows, Efficient
  documentation systems, well controlled process,
  good stores lay outs and stores records- These
  are Good manufacturing practices
• Reduction in work in process inventory holding
  costs
• Avoidance of cost of Quality failure ( cost of
  waste, of rework, of recall, of consumer
  compensation and of loss of company reputation)

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List of important documents in GMP

• Policies
• SOP
• Specifications
• MFR (Master Formula Record)
• BMR
• Manuals
• Master plans/ files
• Validation protocols
• Forms Formats
• Records

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How do GMPs of different countries compare?

• At a high level, GMPs of various nations are
  very similar most require things like
• Equipment facilities being properly
• designed, maintained, cleaned
• SOPs be written approved
• An independent Quality unit (like QC and/or QA)
• Well trained personnel management

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Basic Requirements of GMP

• All manufacturing processes are clearly defined,
  systematically reviewed, shown to be capable of
  consistently manufacturing medicinal products of
  the required quality complying with
  specifications.
• Critical steps of the process and significant
  changes to the process are validated

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Why GMP is important

• A poor quality medicine may contain toxic
  substances that have been unintentionally added.
• A medicine that contains little or none of the
  claimed ingredient will not have the intended
  therapeutic effect.

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Quality Management
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QUALITY RELATIONSHIP
QA
GMP
QC
Quality Control
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What is Quality Management?

• The aspect of management function that determines
  implements the quality policy
• The overall intention direction regarding
  quality, as formally expressed authorized by
  top management

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BASIC PRINCIPLE OFQUALITY MANAGEMENT (1)

• Manufacturer should ensure the cosmetic products
  comply with the requirements of ASEAN Cosmetic
  Directives (ACD).
• They should also comply with any other applicable
  regulations pertaining to your specific country.
• The attainment of this quality objective should
  be led by the senior management requires the
  participation and commitment by staff, by the
  companys suppliers and distributors.

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BASIC PRINCIPLE OFQUALITY MANAGEMENT (2)

• To achieve the reliable quality objective, there
  should be a comprehensive QA system incorporating
  GMP.
• The QA system should be fully
  documented its effectiveness
  should be monitored.

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QUALITY ASSURANCE

• QA covers all matters which individually or
  collectively influence the quality of a product.
• All parts of QA system should be
  adequately resourced with
• Competent personnel
• Suitable sufficient premises,
  equipment facilities

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Principles of Quality Assurance (QA)

• Wide-ranging concept
• Covers all matters that individually or
  collectively influence the quality of a product
• Totality of the arrangements
• To ensure that the drug is of the right quality
  for the intended use
• QA incorporates GMP
• and also product design
• development which is outside the
• scope of this module

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BASIC REQUIREMENTS OFQA

• Ensure that products are designed and developed
  based on sound scientific rationale and with GMP
  or GLP principles being taken into consideration.
• Ensure that managerial responsibilities are
  clearly specified.
• Ensure that production and control operations are
  clearly specified and GMP is adopted.
• Organize supply use of correct starting
  packaging materials.
• Ensure that finished products are correctly
  processed checked before release.
• Ensure that products are released after review by
  authorized person.
• Provide satisfactory arrangement to ensure
  products are stored, distributed handled
  appropriately.
• Put in place a mechanism for regular self
  inspection / internal quality audit.

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GOOD MANUFACURING PRACTICES

• Part of QA which ensures that products are
  consistently produced and controlled to the
  quality standards appropriate to their intended
  use.
• Minimize risks
• cross contamination
• mix up
• Ensure products/materials are traceable to the
  original source.
• Product testing is not reliable way to assure
  product quality. Should BUILD quality into the
  product!
• Production and quality control functions should
  be independent of each other.
• All manufacturing process are clearly defined and
  systematically reviewed.

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• All necessary facilities/resources for GMP should
  be provided
• adequate, qualified and well-trained personnel
• suitable premises and sufficient space
• suitable location
• good personal hygiene and proper sanitation
• suitable equipment and services

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QUALITY CONTROL

• QC is part of GMP.
• QC is concerned with sampling, specification and
  testing.
• Manufacturer should have a QC department.
• QC should be headed by an appropriately qualified
  and experienced person.
• QC should be independent from production and
  other departments.
• Ensure that the necessary and relevant tests are
  actually carried out.
• Ensure that no materials or products will be
  released for sale or supply, until their quality
  have been evaluated and judged to be
  satisfactory.

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SCOPE OF QC

• Items concerned
• Starting materials
• Packaging materials
• Bulk products
• Intermediate and finished products
• Environmental conditions

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BASIC REQUIREMENTS OFQUALITY CONTROL (1)

• Adequate facilities, trained personnel and
  approved procedures should be available for
  sampling,
• inspecting and testing and, where
  appropriate, environment monitoring.
• Sampling by QC personnel testing by approved
• methods.
• Approved test methods.
• Maintenance of QC records
• failure investigation records.

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BASIC REQUIREMENTS OFQUALITY CONTROL (2)

• Ingredients comply with regulatory specification
  (grade, composition, strength)
• Review and evaluation of production documentation
• Assessment of process deviations
• Release of batches by authorised person
• Sufficient reference samples of starting
  materials and finished products

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OTHER DUTIES OF QC

• Establish QC procedures
• Manage reference standards
• Ensure correct labeling
• Stability testing (if applicable)
• Complaint investigation
• Environmental monitoring

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QUALITY CONTROL ACTIVITIES

• QC should cover the following
• Sampling
• Specification
• Testing
• Release procedures
• Recalls and complaints
• Decision making in all quality matters
• Definition of product quality
• Laboratory operations
• Release authorisation
• Investigation and reporting

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BASIC REQUIREMENTS OFQUALITY CONTROL

• Adequate facilities, trained personnel and
  approved procedures should be available for
  sampling, inspecting and testing and, where
  appropriate, environment monitoring.
• Sampling by QC personnel testing by approved
  methods.
• Approved test methods.
• Maintenance of QC records failure investigation
  records.
• Ingredients comply with regulatory specification
  (grade, composition, strength)
• Review and evaluation of production documentation
• Assessment of process deviations
• Release of batches by authorised person
• Sufficient reference samples of starting
  materials and finished products

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OTHER DUTIES OF QC

• Establish QC procedures
• Manage reference standards
• Ensure correct labeling
• Stability testing (if applicable)
• Complaint investigation
• Environmental monitoring

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Personnel
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PERSONNEL

• Adequate staff with relevant knowledge,
  experience and capabilities in assigned task
• a. Production and QC are headed by different
  persons, neither of whom shall be responsible
  to the other
• b. Responsibilities and authority of key
  personnel are clearly defined
• c. Training on the understanding of procedures,
  work instruction, GMP principles , etc.

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Personnel Qualifications

• Each person engaged in the manufacture,
  processing, packing, or holding of a drug product
  shall have education, training, and experience,
  or any combination thereof, to enable that person
  to perform the assigned functions. Training
  shall be ...

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• There are competent and appropriately qualified
  personnel in sufficient numbers to ensure service
  provision.
• ?? The responsibilities of all staff should be
  clearly understood and recorded.
• ?? All personnel receive initial and continuing
  training relevant to their needs.
• ?? Only staff who have appropriate training are
  authorised to carry out that procedure.
• ?? Training should be structured and continuous.
  Training records based on SOPs are a good means
  of evidencing that staff are able to perform
  tasks.
• ?? Competency Assessments can also be used to
  assess procedural training.

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3 Key Personnel

• The head of production
• The head of QC
• The head of QM (QA)

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The head of production

• The head of production should be a qualified
  pharmacist, adequately trained, possess good
  practical experience in pharmaceutical
  manufacture managerial skill.
• The head of production should have full authority
  responsibility to manage production of
  pharmaceutical products.

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The head of QC

• The head of QC should be a qualified pharmacist,
  have adequate training practical experiences
  which enable him/her to perform him/her function
  personally.
• The head of QC should given full authority
  responsibility in all QC duties.

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The head of QM (QA)

• The head of QM (QA) should be a qualified
  pharmacist, have adequate training practical
  experiences which enable him/her to perform
  him/her function personally.
• The head of QM (QA) should given full authority
  responsibility in all quality system/assurance
  duties.

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Premises
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PREMISES

• Specify the requirements of location, design ,
  constructions and maintenance of manufacturing
  premises with respect to the following
• prevention of contamination from surrounding
  environment and pests
• prevention of mix up of materials and products
• facilities such as toilet, changing rooms,
  sampling areas and QC lab
• defined areas for certain activities
• wall, ceiling, drains , air intake and exhaust,
  lighting and ventilation, pipe work and light
  fitting
• storage areas

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• Suitable location, design , constructions and
  maintenance for manufacturing premises
• defined areas for certain activities (e.g
  material sampling dispensing)
• wall, ceiling, drains , air intake and exhaust,
  lighting and ventilation, pipe work and light
  fitting
• storage areas of adequate space
• Physical separation of toilets and QC lab from
  production

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Building facilities

• Design and construction features.
• Lighting.
• Ventilation, air filtration, air heating and
  cooling.
• Plumbing.
• Sewage and refuse.
• Washing and toilet facilities.
• Sanitation.
• Maintenance.

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Paint Finish

• Not only building paintwork must be considered
  but also equipment

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Building Finishes

• In module 1 we discussed the need for all
  facility components to complement each other.
• Therefore a good air handling system must be
  complemented by a building of good design and
  good finishes.
• On the next slide we will be looking at some of
  the Acceptable and Un-acceptable building
  finishes.

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Building Finishes
Not Acceptable Acceptable
PVA Paint L Epoxy or Enamel paint J
Window sills L Flush glazed windows J
Exposed pipes L Smooth surfaces J
Horizontal pipes services L Concealed services J
Open floor drains L Hygienic drains J
Floor cracks, flaking floor surfaces L Homogonous sealed floors epoxy finish or welded vinyl J
Ceiling cracks joints L Smooth sealed ceilings J
Exposed, open light fittings L Flush light fittings J
Wooden furniture L S/Steel or Melamine furniture J
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Floors / drains
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Design and Construction Features

• Any building or buildings used in the
  manufacture, processing, packing, or holding of a
  drug product shall be of suitable size,
  construction, and location to facilitate
  cleaning, maintenance, and proper operation.

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Product Areas

• Premises should preferably be laid out in such a
  way as
• To allow the production to take place in areas
  connected in a logical order corresponding to the
  sequence of the operations, the requisite
  cleanliness levels,
• To avoid crowding and disorder,
• To allow effective communication and supervision.

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Weighing Area

• The weighing of starting materials and the
  estimation of yield by weighing should be carried
  out in separate weighing areas specially designed
  for that use. Such areas may be part of either
  storage or production areas.

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Storage Areas

• Specify the requirements concerning storage of
  materials/ products with respect to the following
• Space, design, security and cleanliness
• Storage of quarantine stocks
• Storage of hazardous substances
• Conditions of storage area
• (e.g. temperature relative humidity)
• Receiving of incoming materials
• Stock control (e.g. FIFO principle,
• proper labeling on the container)

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Ventilation, Air Filtration, Air Heating and
Cooling

• Equipment for adequate control over air
  pressure, micro-organisms, dust, humidity, and
  temperature shall be provided when appropriate
  for the manufacture, processing, packing, or
  holding of a drug product.
• Air-handling systems for ... penicillin shall be
  completely separate from those for other drug
  products for human use.

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Poor Good Windows
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QC Areas

• QC laboratories should be designed to suit the
  operations to be carried out in them.
• QC laboratories should be separated from
  production areas.
• Areas where biological or radioisotope test
  methods are employed should be separated from
  each other.

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Ancillary Areas

• Rest and refreshment rooms should be separated
  from production QC laboratory areas.
• Facilities for changing clothes and for washing
  and toilet purposes should be easily accessible
  appropriate for the number of users.

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Thank you for Your Kind Attention