ALCOA

Question 1

Data integrity definition

Answer 1

“Data integrity is the assurance that data records are accurate, complete, intact and maintained within their original context, including their relationship to other data records. This definition applies to data recorded in electronic and paper formats or a hybrid of both”

Question 2

Examples of Data integrity violations

Answer 2

….

Question 3

Data integrity history

1989

Answer 3

Generic Drug Scandal “several manufacturers had falsified data submitted in seeking FDA authorization to market certain generic drugs”

Question 4

Data integrity history

1993

Answer 4

The Barr Decision “The reported problems include misplaced records, test data recorded on scrap paper, failure to control manufacturing steps such as those governing products’ physical properties, release of products not meeting their specifications, inadequate investigation of failed products, and failure to validate test methods and manufacturing processes, including cleaning processes.”

Question 5

Data integrity history

1990-2003

Answer 5

Issuance of Consent Decrees “Of the more than 25 consent decrees issued between 1990 and 2003, only one or two firms have been removed from their decrees.”

Question 6

Data integrity history

2005

Answer 6

The Case of Able Labs “Able Laboratories recalled all of its prescription drugs in one of the USAs largest drug recalls.” & “…failed to tell regulators when drugs failed quality tests and sometimes substituted failing with passing results.” & “The substitutions involved “cutting and pasting” computer records and were done by supervisors and lab analysts, the report says.”

Question 7

Data integrity history

2013

Answer 7

Ranbaxy “The fraud, investigated over eight years by US authorities, was brought to light by a whistle-blowing ex-employee, who said Ranbaxy created ‘a complicated trail of falsified records and dangerous manufacturing practices.’ ”

Question 8

Data integrity history

2019

Answer 8

AveXis 483 “It was alleged that two senior executives altered or instructed others to alter small amount of raw data…” Response: “…ensure a robust culture of quality

Question 9

ALCOA principles

Answer 9

ALCOA is an acronym for the original five principles of data integrity. Those principles are:
Attributable
Legible
Contemporaneous
Original
Accurate

Question 10

Legible

Answer 10

All data recorded must be legible (readable) and permanent. Ensuring records are readable and permanent assists with its accessibility throughout the data lifecycle. This includes the storage of human-readable metadata that may be recorded to support an electronic record.

Question 11

Example of legible

Answer 11

GDP will always promote the use of indelible ink when completing records.

When making corrections to a record, ensure a single line is used to strike out the old record. This ensures the record is still legible.

Controlling your paper records/forms and formatting them such that there is ample room for the information to be recorded.

Question 12

Contemporaneous

Answer 12

Contemporaneous means to record the result, measurement or data at the time the work is performed. Date and time stamps should flow in order of execution for the data to be credible. Data should never be back dated.

Question 13

Contemporaneous Example

Answer 13

If executing a validation protocol, tests should be performed and their results recorded as they happen on the approved protocol.

Data that is logged, or testing that is performed electronically, should have a date/time stamp attached to the record.

Ensure electronic systems that log data have their system clocks synchronised.

Consider the use of a master clock system that synchronises to the IT network so wall clocks within labs and processing areas are synchronised

Question 14

Original

Answer 14

Original data, sometimes referred to as source data or primary data, is the medium in which the data point is recorded for the first time. This could be a database, an approved protocol or form, or a dedicated notebook. It is important to understand where your original data will be generated so that its content and meaning are preserved.

Question 15

Original Example

Answer 15

Ensure validation test results are recorded on the approved protocol. Recording results in a notebook for transcription later can introduce errors.

¡If your original data is hand written and needs to be stored electronically, ensure a “true copy” is generated, the copy is verified for completeness and then migrated into the electronic system.

Question 16

Accurate

Answer 16

For data and records to be accurate, they should be free from errors, complete, truthful and reflective of the observation. Editing should not be performed without documenting and annotating the amendments.

Question 17

Accurate Example

Answer 17

¡Use a witness check for critical record collection to confirm accuracy of data.

¡Consider how to capture data electronically and verify its accuracy. Build accuracy checks into the design of the electronic system.

Place controls/verification on manual data entry, for example, temperature results can only be entered within a predefined range of 0-100°C.

Question 18

Attributable

Answer 18

All data generated or collected must be attributable to the person generating the data. This should include who performed an action and when. This can be recorded manually by initialling and dating a paper record or by audit trail in an electronic system.
Note:It is important to ensure a signature log is maintained to identify the signatures, initials and/or aliases of people completing paper records.

Question 19

Attributable Example

Answer 19

¡During a validation exercise, test results should be initialled and dated by the person executing the test.

¡Adjustment of a setpoint on a process or monitoring system should be made by an authorised user and the details of the change logged in an audit trail.

¡A correction on a lab record should be initialled and dated to show when and who made the adjustment.

Question 20

ALCOA+:

Complete

Answer 20

Complete

All recorded data requires an audit trail to show nothing has been deleted or lost.

Question 21

ALCOA+

Available

Answer 21

This point follows on from the last point, i.e. data must not only exist, it must be accessible. The most efficient way of achieving this is normally by recording data electronically.

Question 22

ALCOA+:

Enduring

Answer 22

While this is touched on in a previous principle, this principle of ALCOA+ places specific emphasis on ensuring data is available long after it is recorded – decades in some situations.

Question 23

ALCOA+:

Consistent

Answer 23

This primarily means ensuring data is chronological, i.e. has a date and time stamp that is in the expected sequence.