Lecture 1 Role of Pharmaceutical Inspector

Question 1

what are counterfeits usually made by

Answer 1

backyard manufacturers

Question 2

medicinal products with false representation have falsified:

Answer 2

1. name of the manufacturer
2. name of market authorisation holder
3. batch number
4. packaging/ labeling
5. identity/ composition
6. manufacturing records/ cert of analysis

Question 3

role of regulator in accessing medicinal products

Answer 3

1. weed out adulterated, counterfeits, and falsified products
2. ensure safe, efficacious, and quality products
3. oversee drug/ API manufacturing and supply chain

Question 4

role of pharmaceutical inspector

Answer 4

inspecting manufacturers compliance to PICS GMP standard

• under Med Act/ HPA, manufacturer license is required
• compliance with PIC/S GMP standard is pre-req for issuance and retention of Manu. license
• GMP compliance assessed through periodic audits by inspectors from HSA

Question 5

conventional manufacturing flow

Answer 5

1. input
2. production and packaging
3. QC testing
4. output

Question 6

input of manufacturing

Answer 6

contains starting materials such as: APIs, excipients, packaging material

Question 7

processes involved in production and packaging of manufacturing

Answer 7

DCC GP/L WM

1. Drying
2. Coating
3. Compression
4. Granulation
5. Packaging/labeling
6. Weighing
7. Mixing

Question 8

where does QC testing usually take place at, and what do they do

Answer 8

where: QC labs (chem/microbio lab)
what: SOP, records, reports, etc

Question 9

outputs of manufacturing

Answer 9

finished dosage forms: tablets, capsules, cream, ointment, liquids, eyedrops, injections

Question 10

the objective of warehouse inspection

Answer 10

1. assess all starting materials have approved specifications, and materials are purchased from approved suppliers
2. assess procedures (SOP) are in place for handling receipts, quarantine, sampling (availability of sampling room), release of materials & for handling rejected materials and products
3. assess environment of warehouse preserves quality of materials and products stored

Question 11

objectives of weighing room inspection

Answer 11

assess that:

1. calibrated, accurate and reliable weighing balances are used
2. weighed materials are of correct identity, quality and quantity
3. authoritised personenel wear appropriate PPE and environment of weighin room controlled to prevent cross contamination

Question 12

what are items covered during audit of weighing room

Answer 12

1. calibration of weighing balances
2. labeling of starting materials
3. personnel wear proper gowns and PPE
4. SOP for weighing methods (& records of weighing)
5. dust extraction system and housekeeping of weighing room

Question 13

objective of inspecting production departments

Answer 13

assess:

1. premises are designed to prevent cross-contamination
2. equipment are effectively cleaned and regularly maintained
3. personnel control programs are in place
4. materials of correct identity, quantity and quality are used for production
5. process controls are in place

Question 14

types of personnel control programmes

Answer 14

1. restricted access only to authorised personnel

2. authorised personnel wear appropriate gowns and PPE

Question 15

types of process controls

Answer 15

1. critical processes are validated/ re-validated
2. in-process quality controls are in place
3. comprehensive batch processing records are kept

Question 16

items/ areas to be covered during inspection of production department (room)

Answer 16

1. (premises):
   - design/construction
   - partition/segregation, air handling and containment
   - connecting pipework (stainless steel), drainage (no backflow)
   - change room (appropriate class and air shower)
   - cleaning/ maintenance and record
   - environmental and microbiological monitoring

Question 17

items/ areas to be covered during inspection of production department (equipment)

Answer 17

2. (machine)
   - design and construction
   - cleaning/maintenance, calibration, and usage records
   - status labeling of equipment

Question 18

items/ areas to be covered during inspection of production department (process)

Answer 18

3. (method)
   - labeling control of weighted starting materials
   - gowning of production personnel
   - batch production records
   - process deviation and investigation
   - process validation, revalidation and change controls

Question 19

items/ areas to be covered during inspection of production department (personnel)

Answer 19

4. (manpower)

- wear appropriate PPE and do not wear cosmetics and jewelry

Question 20

items/ areas to be covered during inspection of the packaging room

Answer 20

1. premises:
   - design and construction
   - cleaning/maintenance and calibration
   - environmental and microbiological monitoring

Question 21

items/ areas to be covered during inspection of the packaging equipment

Answer 21

2. machine
   - cleaning/ maintenance, calibration and usage records
   - status labeling of equipment

Question 22

items/ areas to be covered during inspection of the packaging process

Answer 22

3. method:
   - control of labels and packaging materials, bulk and finished products
   - batch packaging records
   - validation, revalidation and change controls

Question 23

items/ areas to be covered during inspection of the packaging personnel

Answer 23

4. manpower:

- gowns and PPE

Question 24

objectives of inspecting QC departments

Answer 24

assess that:

1. properly trained analysts are available and there is independent authority for head of QC
2. 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
3. procedures are in place for maintenance, calibration, status labeling and assuring integrity of QC test equipment (eg. HPLC, GC, dissolution tester
4. procedures are in place for receipt, storage, security, record-keeping of test samples, reagents and reference standards

Question 25

areas/ items covered under inspection of QC labs

Answer 25

aka chem testing lab:

• test samples
• prep reagents
• ref standards (chemical: primary; secondary)
• retention samples (for stability or regulatory testing)
• test methods (types, calibration of equipment, validation, raw data records and print outs)
• failure (OOS) investigation
• stability studies

Question 26

other areas/ activities inspected

Answer 26

1. ancillary premises:
   - engineering workshop
   - rest room and wash room
   - corridors
2. external premises / outsource activities
   - contract testing labs

Question 27

objective of documentation audits

Answer 27

assess that:

1. legal requirements under med and HP act are complied by manufacturer
2. regulatory commitments to HSA are complied by manufacturers
3. manufacturing SOPs, including those on product quality reviews, handling of complaints and recalls and self inspection, are followed
4. manufacturing records are authentic, no falsification of data

Question 28

types of regulatory commits to HSA does manufacturers need to comply to

Answer 28

1. composition of finished products and specifications of starting materials
2. test methods used
3. process validation/ stability study reports: protocols of starting materials

Question 29

areas/items to cover under documentation audit

Answer 29

1. document control system (SOP on Preparation of SOP, Document Control and Record Control)
2. SOP and records on pest control
3. SOP and records of tempatature/ RH monitoring
4. batch manufacturing records
5. stability testing program
6. process validation program
7. GMP training program
8. SOP & records on Product Quality Review/ Product Compliants and Recalls, Self Inspection IQA Program

Question 30

what should PQR be conducted annually on authorised products about?

Answer 30

1. quality of starting materials
2. quality of finished products and critical in-process controls
3. failed batches of products
4. manufacturing process/QC deviations
5. changes to manufacturing processes and analysis methods
6. changes to market authorisations (product lisences)
7. stability testing program
8. complaints and product recalls- investigations and closed out
9. adequacy of previous CAPAs carried out
10. qualification status of key equipment and utilities (eg. water, HVAC, steam)

Question 31

complaints procedures

Answer 31

• designated person should be responsible for handling complaints and deciding on actions to be taken
• written SOP on handling complaints should be in place
• all complaints shall be recorded, investigated and closed out with decisions taken documented
• all complaint records should be reviewed regularly for any recurring trend
• the competent authority should be notified if manufacturer is considering product recall following serious quality defects, faculty manufacture and evidence of counterfeit products

Question 32

product recalls

Answer 32

• designated person, independent of sales and marketing, should be responsible for coordinating and executing recalls
• written procedure should be in place for product recall
• distribution records should be readily available to the designated person
• competent authorities where the product is distributed, should be notified if manufacturer is considering product recall
• recalled product should be stored securely while awaiting decision on its fate
• progress of recall process should be recorded and final report issued, including a reconciliation between delivered and recovered products
• effectiveness of recall procedure should be evaluated regularly

Question 33

self inspection

Answer 33

• carried out at periodic intervals in accordance with pre-arranged program
• areas covered during self-inspection should include production, QC, premises, equipment, personnel, documentation
• self-inspection should be conducted in an independent and detailed way by designated competent persons from company
• independent audits by external experts are also useful
• all self-inspections should be recorded, covering observations made during inspections and proposed CAPAs
• statements of eventual actions taken should also be recorded