L5 - GDP & Data Integrity

Question 1

History of GMP & Documentation

Answer 1

Documentation: Integral component of GMP

- Chapter 4 of PICS Guide to GMP for medicinal product covers documentation

Question 2

ALCOA Data

Answer 2

Attributable

• Documents signed by authorised persons
• Effective date of a document defined

Legible
- Entries made in clear, legible, indelible way

Contemporaneous
- Records made @ time of action, traceable

Original

• Original info still retained even w alterations
• Any alterations signed & dated
• Reasons for alteration captured

Accurate

• Integrity of records ensured throughout retention method
• -> Batch manufacturing records kept for 1yr after batch expiry
• -> IMP: Batch records should be kept for >= 5 years after clinical trial

Question 3

Types of Documents & Examples

Answer 3

1) Instructional
- SOP: Describes 4W1H
- Batch manufacturing formula: Forms basis of Batch Manufacturing Record
- Site master file: Describes GMP-related activities

2) Evidential
- Records to provide evidence of actions taken to demonstrate compliance (Temp/RH monitoring records, pest control, cleaning, batch manufacturing records)
- Reports to capture conduct of studies (Stability testings, process validation, CAPA reports)

–> Records & reports of greatest concern to DI bc they are evidence of QC tests conducted/GMP compliance & may be tweaked

Question 4

What is Data Integrity?

Answer 4

Degree to which pharmaceutical data are ALCOA

Question 5

What constitutes Critical Pharmaceutical Data?

Answer 5

Any manufacturing data which will affect product quality
- Mass of API, vol of solvents, batch manufacturing records, analytical results, chromatograms, stability testing reports

Question 6

What is Pharmaceutical Data?

Answer 6

All original records (raw data + metadata) generated during a GMP activity & their subsequent transformation for complete reconstruction of GMP activity
- Covers evidential & instructional documents

Question 7

Raw Data

Answer 7

Original records retained in paper/electronic format

• Modern computerised system: E-records
• Legacy electronic equipment which DO NOT store electronic data: Print out

NOTE: With use of computerised systems today, printouts should not be considered as raw data

Question 8

Meta Data

Answer 8

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

Question 9

[PICS Guide Annex 11] What is Computerised Systems Validation (CSV) & its objective

Answer 9

Hardware & software components + Associated people + 3rd party suppliers + service providers
- Computerised systems fulfils a specific set of manufacturing (eg. warehousing, pdctn or QC) function

Objective: To ensure accuracy, consistency & reliability

Question 10

What are the current regulations & GMP standards in place to assure DI are adequate?

Answer 10

• Pharm legislation (HPA & MA)
• > Legal contravention to supply false info to regulator
• PIC/S GMP Standard (Chapter 4 & 11)
• Industry guidance notes on computerised systems

Question 11

Why are there rising concerns with DI?

Answer 11

Globalisation of pharma industry & increased outsourcing, emergence of Industry 4.0, driven by Big Data & New Technology
- Industry 4.0 expected to transform the world exponentially (business, industry, govt, regulation, people & way of life)

Question 12

What can falsified medicines include?

Answer 12

• Manufacturer’s name/ batch no.
• Product composition
• Packaging/ labelling
• Manufacturing records/ certificates of analysis
• Stability testing & process validation reports

Question 13

What is the extent of intentional data falsification vs Bad Practices

Answer 13

Intentional Falsification: 25%

Poor data management/bad practices: 75%

Question 14

Examples of Intentional Falsification

Answer 14

• Tampering with system clock
• Switching off/tampering with audit trails
• Injections & sequences of HPLC System not documented
• -> Cherry pick best results
• Chromatograms & Analytical Records/CoA do not match
• -> Unauthorised tweaking of chromatogram peaks

Question 15

Requirements of Audit Trail

Answer 15

Should include:

• All original data/records
• Any alteration/+/-/modification to data
• Dates & times of commitment/action of the data
• Identity of operators performing such actions
• -> Audit trails shall be presented in a human readable form & be retained for at least 1yr after batch expiry
• -> Independently recorded

Question 16

Towards data that are ALCOA

Answer 16

Attributable
- needs unique identification of creator of records/data

Legible
- Data needs to be clear, permanent & traceable

Contemporaneous
- Data has to be recorded @ time of generation

Original

• Data has not been tampered during product life cycle
• Only authorised persons can create/modify/delete data

Accurate
- Data is accurate: Correct Complete Valid & Reliable

ALCOA Data us about compliance to GMP/GXP & GDP