Good Documentation Practice and Data Integrity

Question 1

When was the 1st GMP standard created?

Answer 1

1962

Question 2

What is ALCOA

Answer 2

Attributable 
Legible 
Contemporaneous 
Original 
Accurate 
Retention periods

Question 3

Attributable

Answer 3

• Documents should be approved, dated and signed by authorised persons.
• Effective date of a document should be defined.

Question 4

Legible

Answer 4

• Entries should be made in clear, legible, indelible way.

Question 5

Contemporaneous

Answer 5

• Records should be made at the time of action, and be traceable

Question 6

Original

Answer 6

• 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

Question 7

Accurate

Answer 7

• Integrity of records should be ensured throughout retention period

Question 8

Retention periods

Answer 8

• 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

Question 9

What are the types of documents?

Answer 9

• 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

Question 10

What is pharmaceutical data?

Answer 10

• 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

Question 11

What is critical pharmaceutical data?

Answer 11

Critical Pharmaceutical Data are any manufacturing data which affect product quality

Question 12

What is data integrity?

Answer 12

Data Integrity is the degree to which pharmaceutical data are ALCOA

Question 13

What are the differences between raw data and meta data?

Answer 13

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

Question 14

What are computerised systems validation (CSV) and their characteristics?

Answer 14

• 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

Question 15

What are the objectives of CSV?

Answer 15

To ensure:

• Accuracy
• Consistency
• Reliability of the computerized system

Question 16

What are the current regulations and GMP standards in place to ensure DI are adequate?

Answer 16

• 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)

Question 17

What is industry 4.0?

Answer 17

• 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

Question 18

What are falsified medicines and their characteristics?

Answer 18

• 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.

Question 19

_____________ consists of 25% of data integrity violations, __________ constitute the remaining 75%/

Answer 19

international falsification, bad practices

Question 20

Examples of intentional falsification

Answer 20

• 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

Question 21

Good practice in data management should include ______________ by manufacturer.

Answer 21

audit trail review

Question 22

What should an audit trail include?

Answer 22

• 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)

Question 23

Audit trails shall be presented in a __________ and be retained for __________ after batch expiry.

Answer 23

human readable form, at least 1 year

Question 24

How should an audit trail be recorded?

Answer 24

• 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.

Question 25

ALCOA for paper data

Answer 25

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

Question 26

ALCOA for electronic data

Answer 26

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.

Question 27

ALCOA Data is about _________ to GMP/GXP and Good Documentation Practice

Answer 27

Compliance