1 basic principles of gmp 4. complaints and product recall
TRANSCRIPT
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Basic Principles of GMP4. Complaints and Product
recall
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Product complaint 1
• Ideally, every batch manufacture is a success
• We do not live in an ideal World
• i.e. there will be manufacturing failures
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Product complaint 2
• some of them will not be identified within the company
• i.e., there will be inevitably complaints
• there should be a complaint handling policy…
• …that may cover also recalls
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Complaints
Complaints Handling Principle 1All complaints and other information
concerning potentially defective products must be carefully reviewed according to written procedures
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Complaints
Complaints Handling Principle 2–Handled positively and carefully
reviewed–Must be seen as important work–Managed by a senior staff member–Thorough investigation of the
cause is essential
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Complaints Complaints Handling Principle 3
• All complaints and other information concerning potentially defective products must be carefully reviewed according to written procedures (cont’d)– A major source of information and learning– Enable possible production defects to be
remedied before they lead to a recall.– Necessary actions taken -- even a recall
decision
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Complaints Complaints Procedure - I
• Designated responsible person– May be the authorized person– If not, must advise authorized person of results– Sufficient support staff– Access to records
• Written procedure describing action to be taken• Acknowledge and respond to complainant within
a reasonable period• Record written and verbal comments
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Complaints
Complaints Procedure - II
• Investigate and review
• QA should review complaint
• Appropriate follow up actions
• Review of trends
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Complaints Records of Complaint Investigation
• Name of product• Name of active substance (INN) if
necessary • Strength, dosage form• Batch number• Name of complainant and nature of
complaint (cont’d)
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Complaints Records of Complaint Investigation
• Records, retention sample investigated, other batches reviewed and staff interviewed
• Result of investigation: “Justified” or “Not justified”
• If “justified”, actions taken to prevent reoccurrence
• Sign-off upon completion
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Complaints Decision from a Complaint Investigation
• Complaint justified Actions to prevent reoccurrence
Ongoing observation of process
Recall product may be required
• Complaint not justified Advise customer of findings
Appropriate marketing response
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Complaints
Other issues• Regular review of trends required
–Reoccurring problems
–Potential recall or withdrawal
• Inform competent authority of serious quality problems
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Complaints Classification of Defects
• If complaint is justified, then there has been a failure of the quality system
• Once defect has been identified, company should be dealing with it in an appropriate way, even recall
• The definition of defects is useful
(cont’d)
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Complaints Classification of Defects
• The following system has been found in some countries (but it is not a WHO guideline):
–Critical defects–Major defects–Other defects
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Complaints
Critical Defects
• Those defects which can be life threatening and require the company to take immediate action by all reasonable means, whether in or out of business hours
• Examples (next slide)
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Complaints
Critical Defects
• Examples– Product labelled with incorrect name
or incorrect strength
– Counterfeit or deliberately tampered-with product
– Microbiological contamination of a sterile product
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Complaints
Major Defects
• Those defects which may put the patient at some risk but are not life threatening and will require the batch recall or product withdrawal within a few days
• Examples (next dia)
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Complaints Major Defects
• Examples– Any labelling/leaflet misinformation (or
lack of information) which represents a significant hazard to the patient
– Microbial contamination of non-sterile products with some risk for patients
– Non-compliance to specifications (e.g. active ingredient assay)
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Complaints
Other Defects
• Those defects which present only a minor risk to the patient — batch recall or product withdrawal would normally be initiated within a few days
• Examples (next dia)
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Complaints
Other Defects
• Examples
–Readily visible isolated packaging/closure faults
–Contamination which may cause spoilage or dirt and where there is minimal risk to the patient
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Recalls
Product Recall Principle
“There should be a system to recall from the market promptly and effectively, products known or suspected to be defective.”
(WHO GMP)
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RecallsReasons for Recall
• Customer complaint• Detection of GMP failure after release• Result from the ongoing stability testing• Order of the national authorities• Result of an inspection• Known counterfeiting or tampering• Adverse reaction reporting
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EXAMPLE
„the same” tablets in the same pack
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EXAMPLE: „the same” coated tablets
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EXAMPLE: an ointment if we have a look inside…
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the same ointment, magnified
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Recalls Definition
• RecallRemoval from the market of
specified batches of a product
May refer to one batch or all batches of product
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Recalls
Designated Responsible Recall Person• May be the authorized person• If not, must advise authorized person of
results• Sufficient support staff for urgency of
recall• Independent of sales and marketing• Access to records
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Recalls
SOP for Recall• Established, authorized
• Actions to be taken
• Regularly checked and updated
• Capable of rapid operation to hospital and pharmacy level
• Communication concept to national authorities and internationally
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Recalls
Distribution Records• Available to designated person for recall
purposes• Accurate • Include information on:
– Wholesalers– Direct customers (if any)– Batch numbers– Quantities
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Recalls
Written progress report and reconciliation
–Record progress as procedure followed
–Reconcile delivered with recovered products
–Issue final report
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Recalls
Effectiveness of procedures checked
–Test effectiveness from time to time
Secure segregated storage of returned goods
–Essential to keep returned goods away from other goods
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End of Complaints and Recalls
Do you have any complaint?
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6. Self-Inspection
Basic Principles of GMP
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What is it?
• The manufacturer itself organises regular on-the-spot checks whether the GMP rules are complied with
• „Own” team or hired experts
• Report on deficiencies to the Management
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Self-inspection
• Narrower meaning: Self-GMP inspection of own production and QC
• Broader meaning: also– Quality audit of our own quality system– Suppyers’ audit
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Self-InspectionAim
• Ensures that a company’s operations remain compliant with GMP
• Assists in ensuring continuous quality improvement
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Self-InspectionPrinciple, 1
• Should – cover all aspects of production and
quality control– be designed to detect shortcomings in
the implementation of GMP
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Self-InspectionPrinciple, 2
• Must – recommend corrective action if
shortcomings are observed – set a timetable for corrective action to
be completed
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Self-InspectionPrinciple, 3
Special occasions may demand additional self-inspections. For example
• Recalls• Repeated rejections by QC • GMP inspections announced by the
National Drug Regulatory Authority
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Self-Inspection
Principle, 4• Team consist of personnel who can evaluate
the situation objectively• No conflict of interest• No revenge in mind• Should have experience as observers of a self-
inspection team before becoming team member• Lead self-inspector with experience as team
member
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Self-Inspection types
1. Self-inspection - informal
(daily) Immediate Correction
2. Self-inspection - formal
(quarterly) Improve systems
3. QC - Internal Confirm compliance
(half yearly)
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Self-Inspection Scope of Self-Inspection Programme - I
• Written instructions• Covering all aspects of GMP:
– personnel– premises including personnel facilities– maintenance of buildings and equipment– storage of starting materials and finished products– equipment– production and in-process controls– quality control
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Self-Inspection Scope of Self-Inspection Programme -
II - documentation
– sanitation and hygiene
– validation and revalidation programmes
– calibration of instruments or measurement systems
– recall procedures
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Self-Inspection Scope of Self-Inspection Programme -
III
– complaints management
– labels control
– results of previous self-inspections and any corrective steps taken
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Self-Inspection
The Self-Inspection Team, 1• Team leader needs:
– authority– experience– may be appointed from inside or
outside the company
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Self-InspectionThe Self-Inspection Team, 2
• Team members, including:– local staff who are familiar with the
area– experts in their own field– familiar with GMP– may be appointed from inside or
outside the company
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Self-InspectionCarrying Out a Self-Inspection
• Frequency– May depend on company requirements and the size of the
company
• Report:– results– evaluation– conclusions– recommended corrective measures, if applicable
• Follow-up action– Company management must evaluate both the report and
corrective actions
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Self-Inspection
Quality Audit• GMP Inspectors should encourage Quality Audits• Useful to supplement self-inspection programme
but not mandatory• Examination of all or part of quality system with Examination of all or part of quality system with
specific aim of improving itspecific aim of improving it• Usually conducted by outside experts or team
appointed by management• May extend to suppliers and contractors
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Self-Inspection
Suppliers’ audits, 1• QC department should have
responsibility together with other relevant departments for approving suppliers
• Ensures suppliers can reliably supply materials that meet established specifications
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Self-Inspection
Suppliers’ audits, 1• Avoids trying to test in quality to goods
received from dubious sources• Before suppliers are approved they should be
evaluated• Evaluation does not necessarily mean an audit• Should take into account the supplier’s
history and nature of materials to be supplied
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Self-Inspection
Auditing the Self-Inspection Programme - I
• Check self-inspection programme at end of formal government GMP inspection, not at beginning.
• GMP inspectors should assess:– the SOP – programmes– checklists or “aide memoirs”
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Self-InspectionAuditing the Self-Inspection Programme - II
• The SOP should describe teams, process, and frequency of self inspection
• Company policy may not permit GMP inspector to see actual deficiency reports and corrective actions
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Self-InspectionAuditing the Self-Inspection Programme - III
• GMP Inspectors should be looking for compliance with the self-inspection SOP - not necessarily at actual deficiencies recorded
• Seek objective evidence of reports and action
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Self-Inspection
Auditing the Self-Inspection Programme - IV
• Ensure company is not just doing housekeeping or safety audits
• Check there are “Vertical” as well as normal “Horizontal” audits; both play valuable role in self-inspection
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End of Self-inspection
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5. Contract Production and
Analysis
Basic Principles of GMP
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Contract Production and Analysis
PrincipleContract production and analysis must: • Be correctly defined, agreed, controlled in order to
avoid misunderstandings that could result in inferior product
• Have a written contract clearly establishing each parties’ duties which ...
• Clearly state how the authorized person when exercising his or her full responsibility releases each batch or issues certificate of analysis
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Contract Production and Analysis
General Issues• All arrangements must be in compliance
with marketing authorization• Written contract must cover manufacture,
analysis and any technical arrangements• Should allow audit of contract acceptor• In case of contract analysis, the
authorized person must still give final release for sale
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Contract Production and Analysis
Responsibilities of the Contract Giver, 1
• Must assess competence and compliance of contract accepter with GMP
(cont’d)
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Contract Production and AnalysisResponsibilities of the Contract Giver, 2
• All necessary information must be provided to the contract accepter in order to:– have the operations carried out correctly in
accordance with the manufacturing authorisation and other legal requirements
– be fully aware of any problems with the product, work, tests that might pose a hazard to premises, equipment, personnel, other materials or other products
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Contract Production and Analysis
Responsibilities of the Contract Giver, 3• Authorized person (must be at the
Giver!)
• Batch release in compliance with specifications
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Contract Production and Analysis
Responsibilities of the Contract Accepter, 1
• Competence – must have the necessary facilities, premises and
equipment, both in type and in quantity, to undertake the work.
– must have a manufacturing authorization to do this type of work.
– its staff must have the necessary qualifications, training and experience to be able to do the work
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Contract Production and Analysis
Responsibilities of
the Contract Accepter, 2• No subcontracting without approval
– to accept a 3rd party, contract giver must be able to undertake audits needed to be reassured that the 3rd party is competent.
– All the responsibilities placed upon the contract accepter must be fulfilled by any third party contractor that may be employed
• No conflicting activities
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Contract Production and Analysis
The Contract, 1• Each party’s responsibilities defined• Technical aspects drawn up by competent
persons• Batch release mechanisms; by the
authorized person
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Contract Production and Analysis
The Contract, 2• Materials purchasing, testing and
releasing• Production and in-process QC (IPQC) and
QC • Sampling and analysis;
– who takes the sample? – and where?
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Contract Production and Analysis
The Contract, 3• Reference standards and retention samples
– who keeps them?– where and under what conditions are they
stored?• Records:
– manufacturing– analysis– distribution
should be kept by or made available to the contract giver
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Contract Production and Analysis
The Contract, 4• Rejection management needs to be
described for:– starting materials– intermediate and bulk product– finished product
• = What would happen to materials that are rejected!
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End of Contract Production and Analysis
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Exam topics
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Complaints and recalls in GMP
• Principles of complaint handling
• What to do and to record?
• Which are the possible decisions?
• Defect classification (3)
• How to perform recalls and why?
• Why distribution records are essential?
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Self-inspection in GMP
• Meanings
• Aims, principles
• Types
• Scope
• The Self Inspection Team
• Speak about the different audits
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Contract production and analysis in GMP
• Define them. Why they may be needed?
• Tasks of the Contract Giver
• Tasks of the Contract Accepter
• What kind of expertise is needed to formulate a manufacturing contract?
• Batch release responsibility
• Subcontracting rules