Good documentation practice and data integrity

Question 1

Steps in a documentation system complying with GMP

Answer 1

1. Document what you do
2. Do what you document
3. Keep records to prove that the SOPs are followed
4. Improve the process continually guided by PIC/S GMP standard/quality policy

Question 2

What does ALCOA stand for?

Answer 2

A: Attributable 
L: Legible 
C: Contemporaneous 
O: Original
A: Accurate

Question 3

How long should records be kept/retained?

Answer 3

Batch manufacturing records: 1 year after batch expiry

Investigational medicinal products: 5 years after clinical trial

Question 4

What is an SOP in an instructional document?

Answer 4

Document describing the 5Ws and 1H of procedures

Question 5

What is a record in evidential document?

Answer 5

Document providing evidence of actions taken to demonstrate compliance such as:

• Temperature/RH monitoring records
• Pest Control Records
• Cleaning Records
• Batch Manufacturing records
• Others such as records of QC, starting materials and distribution

Question 6

What is a report in evidential documents, and what are some of its components?

Answer 6

Document capturing conduct of studies, projects or investigations together with results, conclusions and recommendations, such as:

• Stability testing reports
• Process Validation reports
• OOS reports
• IQA reports
• CAPA reports

Question 7

What is pharmaceutical data integrity?

Answer 7

Degree to which pharmaceutical data are ALCOA

Question 8

What is pharmaceutical data?

Answer 8

Include all original records (raw and metadata) generated during GMP activity and subsequent transformation for complete reconstruction of GMP activity, covers evidential and instructional documents

Question 9

What is critical pharmaceutical data?

Answer 9

Mass of APIs, volume of solvents, batch manufacturing records, analytical results, chromatograms, stability testing reports

Question 10

What is raw data?

Answer 10

Original records retained either in paper or electronic format

Question 11

What is meta data?

Answer 11

Attributes describing data and providing context to better understand pharmaceutical data

Question 12

What comprises a computerised system?

Answer 12

• Hardware and software
• Includes associated people, 3rd party suppliers and service providers
• Customised computerised systems (MRPS, LIMS)

Question 13

Objectives of computerised systems validation:

Answer 13

It ensure:

• Accuracy
• Consistency
• Reliability

of the Computerised system

Question 14

What are some examples of intentional falsification?

Answer 14

• Tampering with system clock
• Switching off/tampering with audit trails
• Injections and sequences of HPLC system not documented
• Chromatograms and analytical record/CoA do not match

Question 15

What are the requirements in periodic audit trail review by manufacturer?

Answer 15

1. All Original data and records
2. Any modification of data
3. Date and time stamps of all actions
4. Identify of operators performing such actions

Question 16

What is an audit trail?

Answer 16

• Form of meta data containing information relating to creation, change or deletion of GMP/GXP record
• Date/time stamp of audit trails should be computer generated –> defined international time zones and date standards

Question 17

Which chapter of GMP is documentation under?

Answer 17

4

Question 18

Which annex is computerised systems under?

Answer 18

11

Question 19

What are the two types of documents involved in pharmaceutical data documentation?

Answer 19

1. Instructional documents

2. Evidential documents

Question 20

What are the components that make up the instructional documents?

Answer 20

1. SOP that describes 4W1H
2. Batch manufacturing formula which describes manufacturing process (e.g. amount of starting materials, equipment, etc.)
3. Site Master file: describes GMP-related activities of manufacturer

Question 21

What are the components that make up the evidential documents?

Answer 21

1. Records: provides evidence of action taken to demonstrate compliance
2. Reports: Capture conduct of studies, projects or investigations with results, conclusion and recommendations

Question 22

During an inspection, the manufacturer hands you a print out of a chromatogram from a HPLC. Would you consider the print out to be raw data?

Answer 22

No. With the use of computerised systems, printouts are NOT considered as raw data, as the electronic data could have been tampered with before printing

Question 23

The content of a data include the model of weighing balance that the manufacturer is using. What type of data is this?

Answer 23

Meta-Data

Question 24

What are some of the current regulations and GMP standards to assure adequate DI?

Answer 24

1. Contraventions to falsifications
2. PIC/S GMP Standard Chapter 4 and Annex 11
3. industry guidance notes on Computerised systems (E.g. ISPE, GAMP5)

Question 25

What are falsified medicines?

Answer 25

Medicinal products with FALSE REPRESENTATION

Question 26

What are some information about falsified medicines may be false?

Answer 26

1. Manufacturer's Name/Batch Number 2. Product Composition 3. Packaging/Labels 4. Manufacturing records and certs of analysis 5. Stability testing & Process validation reports

Question 27

An original chromatogram is stored inside a computer. What type of data is that chromatogram?

Answer 27

Raw Data

Question 28

How long should an audit trail be retained?

Answer 28

At least 1 year after batch expiry