audit Flashcards
1) Objectives of warehouse audit
- Assess that
o All starting material – APIs, packaging materials and finished products have approved specifications, and materials are purchased from approved suppliers.
o Procedures are in place for handling receipt, quarantine, sampling (including availability of Sampling Room), release of materials & for handling rejected materials & products.
o Environment of warehouse (e.g. temperature & RH monitoring and pest control programs) preserves quality of materials & products stored.
2) Objective of weighing room audit
- Assess that
o Calibrated, accurate and reliable weighing balance are used.
o Weighed materials are of correct identity, Quantity and Quality
o Authorized personnel wear appropriate PPE and weighing room ENV controlled to prevent cross-contamination. - Areas covered under audit of weighing room
o Calibration of weighing balance (M)
o Labeing of starting material (M)
o Personnel wear proper gowns & PPE (M)
o SOP for weighing method (M)
o Dust extraction system and housekeeping of weighing room (P)
3) Objectives of auditing production areas
- Assess that:
o Premises are designed to prevent cross-contamination
o Equipment are effectively cleaned and regularly maintained
o Personnel control programs are in place:
Restriced access only to authorized personnel
Authorized personnel wear appropriate gowns and PPE
o Materials of correct identity, quantity and quality are used for production
o Process controls are in place, eg,
Critical processes are validated/Re-evalidated
In-process quality controls are in place
Comprehensive batch processing records are kept.
4) Objectives of auditing packaging room
- Assess that
o There is proper design, construction, maintenance, cleaning and ENV monitoring of packaging rooms to prevent cross-contamination and mix-ups.
o There is regular maintenance, cleaning and status labelling of packaging equipment to prevent corss-contamination and mix-ups.
o Packaging process is validated, line clearances are performed and batch packaging records are kept.
o There is effective control of labels to prevent mix ups and appropriate temperature/RH control to maintain quality of packaed products.
5) Objectives of QC lab audit
- Assess that:
o Properly trained analysts are availabe and there is independent authority for head of QC.
o QC test methods are approved by HSA and are robust, sensitive, accurate and reliable for testing as evident from records of analytical method validation and routine QC test results.
o Procedures are in place for maintenance, calibration, status labeling and assuring integrity of QC test equipment, eg, HPLC, GC, dissolution tester.
o Procedures are in place for receipt, storage, security, record-keeping of test samples, reagents and reference standards.
Other audited areas/activities
- Ancillary premises
o Engineering workshop
o Rest room and wash room
o Corridors - External premises/outsourced activities
o Contract Testing laboratories
ISO 17025 Certification by SPRING singapore is accepted by HAS.
6) Objectives of documentation Audit
- Assess that
o Regulatory commitments to HAS are complied by manufacturer.
Eg composition of finished product and specifications of starting materials
Test methods used
Process validation/stability study reports: protocols and acceptance criteria.
o Conditions of PL (product license) and ML (manufacturing license) and legal requirements under medicines, poisons and health product acts are complied.
o All manufacturing data are authentic – No falsification of Data.
o All manufacturing/QC deviations, annual product reviews, self-inspection findings and complaints and recalls are investigated and close-out.
major steps involved in process validation
- establish tablet quality specification
1) blend homogeneity
2) hardness
3) thickness
4) friability
5) particle size
6) dissolution profile - identify critical processes
1) blending
2) milling
3) compression - Design sampling plan
1) for blending: 10 samples taken from top, middle and bottom of blender
2) for milling: 1 representative sample (~100g) drawn from mill
3) for compression: ~6x20tablets collected at 4 equal intervals from tablet compression machines: 3 compression speeds covered (low, target and high speed) - design testing plan
1) for blend uniformity: assay content of blended samples
2) for compression: test hardness, friability, thickness, potency, dissolution profile of tablets samples. - Set acceptance criteria
eg within 90-110% of labeled amount - perform statistical analysis (intra- and inter Batch)
eg intra-batch analysis: process capability studies
Inter-batch anaysis: variance analysis
HSA GMP Inspection System follows PIC/S Framework
3 Stages:
- Pre‐Audit Planning (1 to several days)
- Conduct of On‐Site Audit (2 to 4 days or 4 to 8 man‐days)
- Post‐Audit Follow Up Activities (Varies)
Pre‐Audit Planning (1 to several days)
Pre‐Audit Planning (1 to several days)
- HSA Forms Audit Team (comprising Lead & Co‐Auditors)
- Confirms Dates of Audit & Send out Pre‐Audit Letter
- Reviews Site Master File (Up to date information nn manufacturing / QC activity etc)
- Reviews Previous Inspection Report
- Reviews Conditions of Manufacturer’s Licence
- Checks Out Past Product Recalls, Complaints or Unresolved Problems
- Obtains Approved Product Specifications from HSA Computer System/Files
- Goes Through Pre‐Audit Check List
- Prepares Audit Agenda & Strategy
Conduct of On‐Site Audit (2 to 4 days or 4 to 8 man‐days)
- Conduct of On‐Site Audit (2 to 4 days or 4 to 8 man‐days)
- Opening Meeting
- Facility Audits (Warehouse, Production & Packaging Areas, QC Labs)
- Debrief/Caucus (Closed Door Discussion Amongst GMP Auditors)
- Closing Meeting (verdict announced)
- Attendance Sheet
- Post‐Audit Follow Up Activities (Varies)
- Post‐Audit Follow Up Activities (Varies)
- Send Post‐Audit Letter & Write Audit Report
- Establish Next Audit Dates & Issue ML & GMP Certificates
- Assess CAPA & Close Out Audit
CAPA = corrective action, preventive action
a) Establishing Next Audit Dates : A Risk‐Based System
- Manufacturers classified into 3 “risk” categories :
o Sterile Products (High Risk)
o Non‐Sterile Oral Products (Medium Risk)
o Non‐Sterile External Products & APIs (Low Risk) - Risk Factors Considered :
o Category of Manufacturer (Sterile, Oral, External)
o GMP Compliance Profile(Acceptable, Unacceptable, Marginal)
o Frequent Changes to Key Personnel & Premises
o History of Product Recalls
o History of Legal & Regulatory Contraventions
o Multiple Products Manufacturer
o Manufacturer of Steroids, Hormones, Penicillins, Cytotoxics, etc - Frequency of Audit <= 24 months, depending on overall risk status of manufacturer & types of products manufactured
Types of GMP Audit
Types of GMP Audit
- Pre‐Approval Audit(New Facility/New Dosage Form)
- Routine Audit(Existing Facility/Existing Dosage Forms)
- Follow‐Up Audit(Subsequent Audit of a New or Existing Facility)
- Investigational/“For Cause” Audit (arising from Complaints, Product Recalls)
- Voluntary Audit (for Granting GMP Certificate)
- Manufacturer Should Know 10 Commandments of SOPs
o SOPs shall :
o be in a consistent standard format
o be simple, clear & unambiguous
o be approved & signed by authorized persons
o comply with legislations & standards
o not be changed without authorization
o be current & be reviewed periodically
o be easily retrieved or traceable
o Be retained, archived, disposed in a defined manner
o Period of retention of SOPs/documents shall be specified
o For electronic or computerized documents :
a system of login ID & password shall be in place
only authorized persons can create or modify data
all entries, changes and deletions shall be recorded
critical data shall be counter-checked independently
audit trails shall be available (for verification)
back-up systems are in place
