SARI MARDATILLAH
0811012052
PRINCIPLE
The basic elements of the quality management are :
—Quality Assurance
—Organizational structure,
—procedures
Quality assurance . . .
Q.A → a wide ranging concept which covers all matters which individually or collectively influence the quality of product
The system of quality assurance should ensure . . .
—Pharmaceutical product are designed and developed in a way that takes account of the requirment of GMP
—Production n control operation are clearly
—Managerial responsibilities
—All necessary controls on intermediate product and in-process controls n validation
—Documentation
—Regular evaluations of the quality
—etc
The basic requirments of GMP
—All manufacturing processes are clearly n systematically
—All necessary facilities
—Operator are trained to carry out procedures correctly
—A system is available to recall any batch of product
—Records of manufacture
—Critical steps of manufacturing
Necessary Facilities
KEY PERSONNEL
—The head of production
—The head of quality control
—The head of quality management
The basic requirments
—Skill
—Experience
—Qualification
—Knowledge
—Training
Principle
—Premises must be located, designed, adapted and maintained to facilitate proper operations.
—Their layout and design must airn to minimize risk or confusion, and other error.
General
—Premises should be carrefully maintained.
—They should be cleaned and disinfected according to detailed written procedures.
—Lectrical supply, lightng, temperature, humidity, and ventilation shoud be appropriate.
Safe and secure areas
Principle..
Design and construction...
—Equipment surfaces coming into contact with any starting material, intermediate, bulk or finished product shouldnot be reactive, additive, or absorptive
—Equipment shouldnot adversely affect the product
—Equipment should be designed so that it can be easily and thoroughly cleaned
—Balances and measuring equipment of an appropriate range and precision should be available for production and control operations.
Installation and location
—maintenance
—Equipment should be maintained at appropriate intervals to prevent malfunctions or contaminations which could alter the identity, quality, or purity of the product.
—Written procedures should be established and followed for maintenance of equipment.
The scope of sanitation
—PERSONNEL
—PREMISES
—EQUIPMENT
—PRODUCTION MATERIALS & CONTAINERS
PERSONAL HYGIENE
—In manufacturing areas should wear protective garments appropriate to the operations to be carried out.
—They should wear clean body-coverings appropriate to the duties they perform.
}Detailed hygiene programmes should be established.
}All personnel should receive medical examination upon recruitment.
}They should be trained in the practices of personal hygiene.
Premises sanitation
—Adequate employee’s washing and well ventilatedtoilet facilitiesshould be provided
—Waste material should not be allowed to accumulate.
—There should be written procedures for use of suitable rodenticides, fungicides, clening, and sanitazing agents.
Equipment cleaning and sanitation
—Equipmet should be cleaned both inside and ouside after use according to established procedure and should be kept in a clean condition.
—Vacuum or wet cleaning methods are to be preferred.
—Record of cleaning, sanitazing, sterilization and inspection prior to use should be kept properly.
Principle
production operations must follow clearly defined procedures (GMP)
General...
—Production should be performed and supervised by competent people.
—All incoming materials should be checked .
—All materials and products should be stored under the appropriate condition established by the manufacturer.
—Labels applied to containers, equipment or premises should be clear, umambiguous.
Prevention of cross-contamination in production
—Production in separate building (penicillin, sex hormones, certain cytotoxic, live vaccines, live bacterial preparation, etc)
—Poviding appropriate air-locks and air extraction
—Keeping protective clothing
—Using cleaning and decontamination procedures
—Using self contained system
Production in separate building
Processing....
—All materals utilized in processing should be checked before use.
—All operations should be prformed in accordance with the written procedures.
—Any deviation should be justified and reported.
—Containers and closures used should be clean
—All required in-process controls should be accurately.
In-process control...
—All parameter attributes, product fill or count should be cheked
—Finished packages should be checked
—Results of in process test/inspection should be recorded and those documents should become a part of the batchrecord.
Rejected, recovered and returned materials
—Rejected materials and products should be clearly marked as such and stored separately in restricted areas.
—Products returned from the market and which have left the control of the manufacturer should be destroyed.
—Any action taken should be appropriately recorded.
Process validation
—When any master processing procedure is adopted, steps should be taken to demonstrate that it is suitable for routine operation.
—Processes and procedures should undergoperiodic critical revalidation.
Stability study
—Return...
—All starting materials, packaging materials, intermediate and bulk product returned to storage areas should be properly documented and reconciled.
Quality control is..
An essential part of Good Manufacturing Practices to provide assurance that the products will be consistently of a quality appropriate to their intended use.
General.....
—Each holder of a manufacturing authorization should have a quality control department.
—Quality control should involve all analytical functions conducted in the laboratory, including sampling, inspecting and testing of starting material, intermediate, bulk, and finished products.
Principal duties....
—To establish and revise control procedures and spesifications.
—To prepared detailed written instructions for carrying out each inspection,test and analysis.
—To establish written sampling plans and sampling procedures.
—To ensure the correct labelling of containers of materials and products.
—To release or reject each batch or starting material intermediate, bulk, or finished products.
—To take part or assist in validation program
—To prepare secondary reference standars
—To maintain analytical records of the tests of all samples taken.
Good Quality Control Laboratory practices
Ø PREMISES
ØProvisions should be made for the proper and safe storage of waste materials awaiting disposal.
ØThe laboratories should be physiccaly separated from the production rooms.
ØBiological, microbiological, and chemical laboratories should be segregated from each other.
ØPERSONNEL
ØShould have proper education,trining and experienceor comination thereof, to enable the individualto perform the assigned functions.
ØEQUIPMENT
ØControl laboratory aquipment and instruments should be suitable to the testing rpocedures undertaken.
DOCUMENTATION
STABILTY STUDY
The written program should be followed and include ;
—Sample size, test interval
—Storage conditions
—Reliable, meaningful, and spesific test method
—Testing of the product for reconstitution before and after it has been reconstituted.
List for self inspection....
¡Personalia
¡Premises
¡Maintenance of buliding n equipment
¡Storage of starting materials, packaging materials, and finished products
¡Equipment
¡Productions ana in- process control
¡Quality control
¡Documentation
¡Sanitation n hygiene
—Management should appoint a team of self inspection consisting af at least three members who are experts in their own fields and familiar with GMP
¡Self inspection report
QUALITY AUDIT
—A list of approved suppliers of starting n packaging materials should be established n reviewed.
—Before suppliers are approved n included in the approved suppliers list or specifications, they shoud be evaluated.
A product recall is ....
→ instituted following discovery of a quality defect or if there is a raport of serious adverse reaction of a pharmaceutical product which may cause health risk.
A returned pharmaceutical products is
→ a finished product which is already in distribution and returned to the manufacturer due to complain of damage , expiration or other reasons such as the condition of the container or package which may cast doubt on the product identity, quality, quantity, and safety.
Each complaint and report should be thoroughly investigated n evaluated
including :
—The Action
—Recall of the batch or all the finished products
—Other appropriate action
—Corrective action where applicable
RECALL
—There should be established written procedures, regularly checked and updated when necessary, in order to organise any recall activity.
—A product recall should be instituted immediately after discovery of a quality defect or receiving report of adverse reaction of the product.
Decision for recall a product
—May be initiated by the manufacturing or under instruction of the government authority
—From the head of Quality Management n the company management
—May result in suspension or discontinuation of manufacturing of the products
—Documents should have unambiguous contents, title, nature n purpose should be clearly stated
—Reproduced document should be clear and legible
—Any alteration made to the entry on a document should be signed and dated , the alteration should permit the reading of the originil the information.
Documents Required
—Specification
PROCEDURES AND RECORDS
—RECEIPT
¡The name of material on the delivery nnote and containers
¡Code of material
¡Date of receipt
¡Supplier’s name
¡Manufacturer’s batch
¡Total quantity and number of containers receivedthe batch number assigned after receipt
¡OTHERS....
11. CONTRACT MANUFACTURE & ANALYSIS
—CONTRACT MANUFACTURE & ANALYSIS
—There must be written contract between the contract giver and the contract acceptor which clearly establishes the duties of each party.
—There should be a written contract covering the manufacture and/or analysis arranged under contract and any technical arrangements made in connection with it.
The Contract Giver
Should provide the contract acceptor with all the information necessary to carry out the contracted operations correctly in accordance with the marketing authorization and any other legal requirements.
The contract acceptor
—The contract acceptor should refrain from any activity which may adversely affect the quality of the product manufactured and/or analyzed for the contract giver.
The contract acceptor must have....
THE CONTRACT
—A contract should drawn up between the contract giver and the contract acceptor which specifies their respective responsibilities relating to the manufacture and control of the products.
—The contract should describe the handling of stating materials, intermediate and bulk products and finished products if they are rejected.
12. QUALIFICATION AND VALIDATION
—Definition
Validation
—Action of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, activity or system actually leads to the expected results
Qualification
—Action of proving that any premises, systems and items of equipment work correctly and actually lead to the expected results
(Validation usually incorporates the concept of qualification)
Principle
lEssential part of GMP
lManufacturer to identify what qualification and validation work is required
lProve that critical aspects of work are controlled
lKey elements of qualification and validation defined and documented
Scope
—Design Qualification (DQ)
—Installation Qualification (IQ)
—Operational Qualification (OQ)
—Performance Qualification (PQ)
—Process Validation (PV)
Scope
Qualification and validation:
lApplicable to any aspect of operation which may affect the quality of the product
äDirectly or indirectly
lIncludes premises, facilities (utilities), equipment, processes
lIncludes significant changes
Principle
lQualification and validation should be done in accordance with an ongoing programme
äInitial qualification and validation
äAnnual review
lMaintain continued validation status
lPolicy described in relevant documentation, e.g. quality manual, or Validation Master Plan
Types of Documentation
lValidation Master Plan (VMP)
lValidation protocols
lValidation reports
lStandard Operating Procedures (SOPs)
Documentation
lClearly defines responsibility of performing validation
lConducted in accordance with predefined, approved validation protocols
lRecorded results and conclusions presented in written validation reports – prepared and stored
lProcesses and procedures should be established on the basis of these results
Importance
lPremises, utilities, equipment and processes
lCritical importance and particular attention paid to validation of:
äAnalytical test methods
äAutomated systems
äCleaning procedures
Example of priorities for process validation
Type of process Requirement
lNew Every new process before approval for routine
lExisting:
äSterile products All processes affecting the sterility, and
manufacturing environment including
sterilization stage
äNon-sterile Low dose tablets and capsules: mixing and
granulation; content uniformity (and other
parameters)
Other tablets and capsules: uniformity of mass
(and other parameters)
The Validation Master Plan may contain elements (and policy) such as:
äApproval page and table of contents
äIntroduction and objectives
äFacility and process description
äPersonnel, planning and scheduling
äResponsibilities of validation team members
äProcess control aspects
äEquipment, apparatus, processes and systems qualified, validated – and to be qualified or validated
äAcceptance criteria
äDocumentation, e.g.validation protocols and reports
äSOPs
äTraining requirements and other elements…
A qualification or validation protocol may contain:
äObjectives of the validation and qualification study
äSite of the study
äResponsible personnel
äDescription of the equipment
äSOPs
äStandards
äCriteria for the relevant products and processes
A qualification or validation report should reflect the elements of the protocol, and may contain elements such as:
äTitle
äObjective of the study
äReference to the protocol
äDetails of materials, equipment, instruments, personnel
äProgrammes and cycles used
äDetails of procedure and test methods
… etc.
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