Documentation & Data Integrity

Question 1

Chapter __ in the PIC/S Guide to Medicinal Products covers documentation

Answer 1

4

Question 2

What is included in Chapter 4

Answer 2

1) Good documentation practice
2) Generation and control of documentation
3) Retention of documentation
4) Types of documents (SOPs, specifications, batch manufacturing records etc.)
5) Comprises of 32 clauses

Question 3

What does ALCOA stand for

Answer 3

Attributable
Legible
Contemporaneous 
Original
Accurate

Question 4

Clause 4.3 - Attributable

Answer 4

Documents should be approved, dated and signed by authorized persons
Effective date of document should be defined

Question 5

Clause 4.7 - Legible

Answer 5

Entries should be made in clear, indelible, legible way

Should be permanent, not easily removed

Question 6

Clause 4.8 - Contemporaneous

Answer 6

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

Question 7

Clause 4.9 - Original

Answer 7

Any alterations to document should:

1) Permit reading of original information
2) Signed and dated
3) Capture reason(s) for alteration

Question 8

Clause 4.10 - Accurate

Answer 8

Integrity of records should be ensured throughout retention period
Accurate: Reliable, valid, correct data

Question 9

Clause 4.11 & 4.12 - Retention periods

Answer 9

Batch manufacturing records should be kept 1 year after batch expiry
For investigational medicinal products, batch records should be kept 5 years after clinical trials

Question 10

Types of documents

Answer 10

1) Instructional documents

2) Evidential documents

Question 11

Types of instructional documents

Answer 11

1) Standard operating procedures (SOPs)
2) Batch manufacturing formula
3) Site master file

Question 12

What do SOPs document

Answer 12

Describes who, what, when, where & how

Question 13

What does batch manufacturing formula document

Answer 13

Describes manufacturing process
Includes amount of starting materials, equipment used, test methods used, acceptance criteria for IPQC/final QC, batch release

Question 14

What does site master file document

Answer 14

Describes GMP-related activities of manufacturer

Question 15

Types of evidential documents

Answer 15

1) Records

2) Reports

Question 16

What are records

Answer 16

Documents that provide evidence of actions taken to demonstrate compliance

Question 17

Types of records

Answer 17

1) Records of starting materials
2) Cleaning records
3) Pest control records
4) Temperature & RH monitoring records
5) QC testing records
6) Batch manufacturing records
7) Distribution records

Question 18

What are reports

Answer 18

Documents capturing studies, investigations or projects, including results, conclusions and recommendations

Question 19

Types of reports

Answer 19

1) Stability testing records
2) Process validation records
3) Process deviations / OOS reports
4) Internal quality audit (IQA) reports
5) CAPA reports

Question 20

What is pharmaceutical data

Answer 20

All original records (raw data & metadata) generated during GMP activity, and their subsequent transformation for complete reconstruction of GMP activity
Includes both evidential and instructional documents

Question 21

What is critical pharmaceutical data

Answer 21

Any manufacturing data which affects product quality

Question 22

What is raw data

Answer 22

Original records

Question 23

Raw data can be presented in the form of

Answer 23

1) E-records (modern computerized systems)

2) Print-outs (legacy electronic equipment)

Question 24

With the use of modern computerized systems today, ____ are NOT considered raw data

Answer 24

Print-outs

Question 25

Limitation of electronic data

Answer 25

May be tweaked/falsified without the knowledge of manufacturer / regulator / stakeholders, who do not have commensurate understanding

Question 26

What is metadata

Answer 26

Attributes that describe data to provide context for a better understanding of the pharmaceutical data

Question 27

Types of metadata

Answer 27

1) Units of measurement 2) Date/Time of measurement 3) Name of analyst 4) Type and model of equipment used

Question 28

PIC/S Guide to GMP Annex __ provides information on computerized systems

Answer 28

11

Question 29

Objective of computerized system validation (CSV) | CSV includes ___

Answer 29

Ensures accuracy, reliability and consistency of computerized system Includes associated people (operators, system owners, process owners) Includes 3rd party suppliers and service providers

Question 30

What is data integrity

Answer 30

Degree to which pharmaceutical data are ALCOA, making them reliable, accurate, valid and complete

Question 31

Current regulations & GMP standards to ensure DI are adequate

Answer 31

1) Pharmaceutical legislations (Health Products Act, Medicines Act) 2) PIC/S GMP Standard Chapter 4 & Annex 11 3) Industry guidance notes on computerized systems (e.g. ISPE GAMP5)

Question 32

DI issues and challenges

Answer 32

1) Globalization of pharmaceutical industry and increased outsourcing 2) Industry 4.0 (Pharma 4.0), driven by big data and new technology

Question 33

Falsified medicines: Medicines with ____, which may include false:

Answer 33

False representation 1) Manufacturer's name / Batch no. 2) Composition of product 3) Packaging/Labelling 4) Batch manufacturing records 5) Certificate of analysis (CoA) 6) Stability testing reports / Process validation reports

Question 34

Types of data integrity violations

Answer 34

1) Intentional falsification | 2) Bad practices / Poor data management

Question 35

__% of data integrity violations is due to bad practices/poor data mangagement, while __% is due to intentional falsification

Answer 35

75 | 25

Question 36

Bad practices/Poor data management can be reduced with ____

Answer 36

Education

Question 37

Examples of intentional falsifications

Answer 37

1) Tamper with system clock - Falsify date/time stamp - Non-contemporaneous recording of manufacturing / QC activities 2) Switching off / Tampering with audit trails 3) Injections and sequences of HPLC system not documented - Can carry out repeat analyses of samples to cherry pick best results 4) Chromatograms and CoA/analytical records do not match (due to unauthorized tweaking of chromatogram peaks)

Question 38

What is an audit trail

Answer 38

Metadata containing information on addition / deletion / change to GMP/GXP records Used to reconstruct manufacturing event, including who, what, where, when of action

Question 39

Requirements of audit trail

Answer 39

1) Should be presented in human readable form 2) Retained at least 1 year after batch expiry 3) Independently recorded

Question 40

Audit trail must include:

Answer 40

1) All original data/records 2) Any modifications/additions/deletions to data 3) Date and time of commitment/action of the data 4) Identity of operator(s) performing action

Question 41

All data should be ____

Answer 41

ALCOA

Question 42

Attributable data

Answer 42

Must have unique identification of creator of data/records Paper data: Signature, date, personal seal Electronic data: Personal login password & ID / Biometrics, electronic date and time

Question 43

Legible data

Answer 43

Data must be clear, permanent, traceable Paper data: Use of indelible ink, single-line cross-outs with signature & date, no correction fluid/pencil Electronic data: Use of computer systems with audit trails

Question 44

Contemporaneous data

Answer 44

Data must be recorded at time of generation Paper data: Records entered immediately at time of generation, with date & time Electronic data: Use computer systems with enforced saving of data, date & time stamps, 'temporary folder' should be disabled

Question 45

Original data

Answer 45

Data should not be tempered with throughout product life-cycle Only authorized personnel allowed to modify/create/delete data Paper data: No correction fluid/pencil/eraser, original paper records should be retained in secure area Electronic data: No switching off/tampering with audit trail, original e-records should be routinely backed up with off-site storage in case of disasters

Question 46

Accuracy

Answer 46

Data must be accurate i.e. correct, complete, valid, reliable Accuracy can be assured through: 1) Process and analytical methods validation 2) Investigation of process deviations / OOS 3) Keeping comprehensive batch manufacturing records 4) Robust CSV, calibration & maintenance programs