Lecture 5 Good Documentation Practice

Question 1

how to develop a documentation system that complies with GMP

Answer 1

1. write SOPs based on what you are doing
2. follow your SOP as written
3. keep records to prove that you follow SOPs
4. improve processes continually guided by PICS GMP standards/ quality policy

Question 2

what should documentation be like

Answer 2

1. attributable: approved, dated and signed by authorised persons
2. legible: clear legible indelible way
3. contemporaneous: made at the time of action and traceable
4. original: alteration of records should permit reading of original information; reasons for alterations should be captured
5. accurate: integrity of records should be ensured throughout retention period

Question 3

when are the retention periods for records

Answer 3

1. manufacturing records: 1 year after batch exp

2. IMP: 5years after clnitical trials

Question 4

types of instructional documents

Answer 4

1. standard operarting procedures (SOP): 4w 1h
2. batch manufacturing formula: describe manufacturing process, including amount of starting materials to be added, equipment used, test methods employed, tgt with acceptance criteria for IPQC/final QC and batch release
3. site master file: describes GMP related activities of manufacturer

Question 5

evidential documents

Answer 5

1. records: provide evidence of actions taken to demonstrate compliance
2. reports: capture conduct of studies, projects or investigations together with results, conclusions and recommendation

Question 6

examples of records

Answer 6

1. temp/pH records*
2. cleaning records*
3. pest control records*
4. records of starting materials
5. batch manufacturing records*
6. QC records
7. distribution records

Question 7

examples of reports

Answer 7

1. stability testing reports*
2. process validation reports*
3. IQA reports
4. CAPA reports*

Question 8

pharmaceutical data

Answer 8

include all original records (raw fata and metadata) generated during GMP activity, and their subsequent transformation for complete reconstruction of GMP activity

Question 9

critical pharmaceutical data

Answer 9

• mass of APIs
• volume of solvents
• batch mfg records
• analytical results
• chromatograms
• stability testing reports

Question 10

data integrity

Answer 10

degree to which pharmaceutical data are ALCOA making the set of data accurate, valid, reliable and complete

Question 11

raw data

Answer 11

original records retained either in paper or electronic format

• modern computerised system: stored within systems as e-records (chromatograms)
• legacy electronic equipment: dont store electronic data (older weighing balances and pH meters, print out)

Question 12

meta data

Answer 12

attributes that describe data, and provide the context to a better understanding of the pharmaceutical data
AKA:
- unit of weight, data/time of weighing, name of analyst, type and model of weighing balance

Question 13

computerised system validation (CSV)

Answer 13

• computerised system comprises hardware and software components
• includes associated people
• includes 3rd party suppliers and service providers
• collectively a computerised system fulfils a specific set of manufacturing function
• increasingly, computerised systems are customised

Question 14

objective of CSV is to ensure what of computerised system:

Answer 14

1. consistancy
2. accuracy
3. reliability

Question 15

industry 4.0 and pharmaceutical marketing

Answer 15

1. biotech and biopharm
2. genetic engineering and cell tissue based and ATP
3. nanotech and nanomeds
4. process analytical tech and quality by design
5. integrated computerised system and continuous manufacturing/process validation
6. single use tech & cross contamination control/ flexi manu
7. supply chain integrity of health products, api and excipients
8. pharmaceutical data integrity and control of falsified meds

Question 16

false representation of meds in forms of

Answer 16

1. false manufacturer’s name/batch #
2. false product composition
3. false packaging / labelling
4. false manu records/cert analysis
5. false stability testing and process validation reports

Question 17

ratio of falsification and bad practicises

Answer 17

1. falsification: 25%

2. poor data management or bad pract: 75%

Question 18

example of intentional falsification

Answer 18

1. tampering with systrm clock: falsifying date/time stamp/ non-contemporaneous recording of manu/QC activities
2. switching off/ tampering audit trails: switch off- no evidence of creation, changes or deletion of original data
3. infections and sequence of HPLC system not documented: repeat analyses of samples to cherry pick best results, testing materials until pass
4. chromatograms and analytical records/ CoA not match: unauthorised tweaking of chromatograph peaks

Question 19

what should audit trail include

Answer 19

1. all original data/records
2. any alteration, addition, deletion, or modification of data
3. dates and times of commitment/action of beta
4. identify of operators performing such actions

Question 20

how long should audit trail be presented, kept, and recorded as

Answer 20

1. presented in human readable form
2. retained for at least 1year after batch exp
3. recorded independently not under the control of users

Question 21

actions types in GMP/GXP records

Answer 21

1. create
2. change
3. delete

Question 22

data integrity depends on

Answer 22

1. people:
   - ignorance
   - lack of GMP/ GDP and QMS knowledge
   - bad practices and behavioural traits
   - time pressure
2. system/hardware
   - tampering of system clock/ audit trails
   - sharing login id passwords
   - manipulation of chromatogram peaks
3. organisation culture:
   - cutting corners during economic downturn
   - not regarding mistakes as learning opportunities
   - harsh punishments for mistakes committed

Question 23

ALCOA for paper data

Answer 23

Attributable: signatures, date, personal seals
Legible: use of indelible ink, single line cross outs with dates & signatures, no correction fluid/pencil
Contemporous: records should be entered immediately at point of generation indicating dates/time
Original: only authorised persons can create modify or delete data; correction fluids, pencil/erasers not allowed; retain original paper records in secured areas
Accurate: process and analytical method validations; investigation of process deviations/ OOS; keep comprehensive batch manu records

Question 24

ALCOA for electronic data

Answer 24

Attributable: personal login ID & passwords, biometrics, electronic time/date stamp
Legibility: use of computer systems with audit trails
Contemporaneous: computer system with enforced saving of data and time stamps should be used; temp folder which permit data saving should be disabled
Original: only for authorised persons to create, change or delete; no switching off/ tampering with audit trail; original e-records should be routinely backed up with off-site storage in case of diasters
Accurate: process and analytical method validation; investigations of process deviations and OOS; keeping comprehensive batch manu records