how to develop a documentation system that complies with GMP
- write SOPs based on what you are doing
- follow your SOP as written
- keep records to prove that you follow SOPs
- improve processes continually guided by PICS GMP standards/ quality policy
what should documentation be like
- attributable: approved, dated and signed by authorised persons
- legible: clear legible indelible way
- contemporaneous: made at the time of action and traceable
- original: alteration of records should permit reading of original information; reasons for alterations should be captured
- accurate: integrity of records should be ensured throughout retention period
when are the retention periods for records
- manufacturing records: 1 year after batch exp
2. IMP: 5years after clnitical trials
types of instructional documents
- standard operarting procedures (SOP): 4w 1h
- 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
- site master file: describes GMP related activities of manufacturer
evidential documents
- records: provide evidence of actions taken to demonstrate compliance
- reports: capture conduct of studies, projects or investigations together with results, conclusions and recommendation
examples of records
- temp/pH records*
- cleaning records*
- pest control records*
- records of starting materials
- batch manufacturing records*
- QC records
- distribution records
examples of reports
- stability testing reports*
- process validation reports*
- IQA reports
- CAPA reports*
pharmaceutical data
include all original records (raw fata and metadata) generated during GMP activity, and their subsequent transformation for complete reconstruction of GMP activity
critical pharmaceutical data
- mass of APIs
- volume of solvents
- batch mfg records
- analytical results
- chromatograms
- stability testing reports
data integrity
degree to which pharmaceutical data are ALCOA making the set of data accurate, valid, reliable and complete
raw data
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)
meta data
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
computerised system validation (CSV)
- 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
objective of CSV is to ensure what of computerised system:
- consistancy
- accuracy
- reliability
industry 4.0 and pharmaceutical marketing
- biotech and biopharm
- genetic engineering and cell tissue based and ATP
- nanotech and nanomeds
- process analytical tech and quality by design
- integrated computerised system and continuous manufacturing/process validation
- single use tech & cross contamination control/ flexi manu
- supply chain integrity of health products, api and excipients
- pharmaceutical data integrity and control of falsified meds
false representation of meds in forms of
- false manufacturer’s name/batch #
- false product composition
- false packaging / labelling
- false manu records/cert analysis
- false stability testing and process validation reports
ratio of falsification and bad practicises
- falsification: 25%
2. poor data management or bad pract: 75%
example of intentional falsification
- tampering with systrm clock: falsifying date/time stamp/ non-contemporaneous recording of manu/QC activities
- switching off/ tampering audit trails: switch off- no evidence of creation, changes or deletion of original data
- infections and sequence of HPLC system not documented: repeat analyses of samples to cherry pick best results, testing materials until pass
- chromatograms and analytical records/ CoA not match: unauthorised tweaking of chromatograph peaks
what should audit trail include
- all original data/records
- any alteration, addition, deletion, or modification of data
- dates and times of commitment/action of beta
- identify of operators performing such actions
how long should audit trail be presented, kept, and recorded as
- presented in human readable form
- retained for at least 1year after batch exp
- recorded independently not under the control of users
actions types in GMP/GXP records
- create
- change
- delete
data integrity depends on
- people:
- ignorance
- lack of GMP/ GDP and QMS knowledge
- bad practices and behavioural traits
- time pressure - system/hardware
- tampering of system clock/ audit trails
- sharing login id passwords
- manipulation of chromatogram peaks - organisation culture:
- cutting corners during economic downturn
- not regarding mistakes as learning opportunities
- harsh punishments for mistakes committed
ALCOA for paper data
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
ALCOA for electronic data
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
