Good Documentation Practice and Data Integrity Flashcards
When was the 1st GMP standard created?
1962
What is ALCOA
Attributable Legible Contemporaneous Original Accurate Retention periods
Attributable
- Documents should be approved, dated and signed by authorised persons.
- Effective date of a document should be defined.
Legible
- Entries should be made in clear, legible, indelible way.
Contemporaneous
- Records should be made at the time of action, and be traceable
Original
- Alteration of records should permit reading of original information
- Any alteration of records should be signed and dated
- Reason(s) for alteration of records should be captured
Accurate
- Integrity of records should be ensured throughout retention period
Retention periods
- Batch manufacturing records should be kept for 1 year after batch expiry
- For IMPs, batch records should be kept for at least 5 years after clinical trial
What are the types of documents?
- Standard Operating Procedure (SOP)
» A document which describes - Batch manufacturing formula
» A document which describes manufacturing process - Site master file
» A document which describes GMP-related activities of the manufacturer - Records
» Documents that provide evidence of actions taken to demonstrate compliance - Reports
» Documents that capture conduct of studies
What is pharmaceutical data?
- Pharmaceutical data includes all original records (raw data & metadata) generated during a GMP activity, and their transformation for complete reconstruction of GMP activity.
- They cover evidential and instructional documents
What is critical pharmaceutical data?
Critical Pharmaceutical Data are any manufacturing data which affect product quality
What is data integrity?
Data Integrity is the degree to which pharmaceutical data are ALCOA
What are the differences between raw data and meta data?
Raw data:
- Original records retained either in paper or electronic format.
» For (modern) computerized systems, raw data are stored within system as e-records (e.g. chromatogram)
» For (legacy) electronic equipment which do not store electronic data, the print-out may constitute raw data.
Meta data:
- Attributes that describe data
- E.g. unit of weight, date/time of weighing, name of analyst, type and model of weighing balance
What are computerised systems validation (CSV) and their characteristics?
- A computerised system comprises hardware and software components
- Includes associated people
- Includes 3rd party suppliers and service providers
- Collectively, a computerised system fulfills a specific set of manufacturing (e.g. warehousing, production or QC) function
- Increasingly, computerised systems are customised
What are the objectives of CSV?
To ensure:
- Accuracy
- Consistency
- Reliability of the computerized system
What are the current regulations and GMP standards in place to ensure DI are adequate?
- Pharmaceutical Legislations (Health Products Act & Medicines Act) – a legal contravention to supply false information to regulator
- PIC/S GMP Standard: Chapter 4 & Annex 11
- Industry Guidance Notes on Computerized Systems (ISPE GAMP5)
What is industry 4.0?
- Industry 4.0 consists of new products such as embedded technologies (cyber-physical systems) and cloud-based data (cloud computing).
- With cloud-based data, data no longer need to be stored physically in the computer – hacking becomes a real threat
What are falsified medicines and their characteristics?
- Falsified medicines are medicinal products with false representation. This may include false:
» Manufacturer’s name/batch number
» Product composition
» Packaging/Labeling
» Manufacturing records/Certificates of Analysis
» Stability testing and process validation reports - Falsified data will lead to the creation of falsified medicines.
_____________ consists of 25% of data integrity violations, __________ constitute the remaining 75%/
international falsification, bad practices
Examples of intentional falsification
- Tampering with system clock
» Falsifying date/time stamp
» Non-contemporaneous recording of manufacturing/QC activities - Switching off/tampering with audit trails
» Switching off: no evidence of creation, changes, or deletion of original data
» Tampering: falsification of data - Injections & sequences of HPLC system not documented
» Repeat analyses of samples to cherry-pick best results - Chromatograms and analytical records / CoA do not match
» Unauthorized tweaking of chromatogram peaks
Good practice in data management should include ______________ by manufacturer.
audit trail review
What should an audit trail include?
- All original data/records
- Any alteration, addition, deletion or modification of data
- Dates and times of commitment/action of data
- Identity of operator(s) performing such action(s)
Audit trails shall be presented in a __________ and be retained for __________ after batch expiry.
human readable form, at least 1 year
How should an audit trail be recorded?
- Audit trails shall be independently recorded.
- An audit trail is a form of metadata containing information relating to the creation, change or deletion of GMP record.
- It facilitates reconstruction of manufacturing event, including the “who”, “what”, “when” and “why” of the action.
- Review of audit trails should include checks on date/time stamps for evidence of tampering with system clock.
ALCOA for paper data
Attributable: signatures, dates and personal seals should be used as unique identifiers for the creator of records/data
Legible: use of indelible ink, single line cross-outs with dates and signatures, no correction fluid/pencil
Contemporaneous: reports should be entered immediately at Point of Generation, indicating Dates/Times.
Original: correction fluids, pencils/erasers should not be used. Original paper records should be retained in secure areas (only authorized persons can create, modify or delete data).
Accurate:
Accuracy is assured through:
- Process and analytical method validations
- Investigation of process deviations
- Investigation of OOS (failure investigation)
- Keeping comprehensive batch manufacturing records
ALCOA for electronic data
Attributable: personal login IDs and passwords, or biometrics and electronic date/time stamps
Legible: use of computer systems with audit trails
Contemporaneous: computer system with enforced saving of data and date/time stamps should be used.
“Temporary folder” which permit saving of data at a later period should be disabled.
Original: no switching off/tampering with audit trail.
Original e-records should be routinely backed up, with off-site storage in case of disasters.
Accurate:
Accuracy is assured through:
- Process and analytical method validations
- Investigation of process deviations
- Investigation of OOS (failure investigation)
- Keeping comprehensive batch manufacturing records
- And (for Computerized Systems), accuracy is further assured through robust CSV and regular calibration and maintenance programs.
ALCOA Data is about _________ to GMP/GXP and Good Documentation Practice
Compliance
