Data Integrity, ALCOA+, Common Issue of Data Integrity and How to minimize the risk of Data Integrity, Procedure for correction of Data Integrity issues
Data integrity is one of the most serious issues
that most pharmaceutical companies are facing. Here, we are going to discuss
what is data integrity, the common issue of data integrity, how to minimize the
risk of data integrity.
1. What is data?
Data is facts, figures, and statistics recorded or
generated (collected) during the GXP activity. Data includes all original
records, true copies, source data, metadata, reports which are record during
the GXP activity. Data should follow the ALCOA+ principle
i.e Attributable, Legible, Contemporaneous, Original, Accurate,
Available, Enduring, Complete, Consistent.
Refer guideline Data integrity and compliance with cGMP
2. Type of data:
2.1 Raw data –
It is the original record which captured the first
time either electronically or recorded on paper (manually). In the case of
balance, pH meter instrument data do not store electronically they provide
printed data output that time printed data consider as raw data.
Refer Guideline GXP data integrity guidance and
definitions
Complete record in the form
of laboratory worksheet, records, notes, memoranda,
microfilms, photographs, computer printouts, magnetic media, dictated
observation, recorded data from automated instruments also consider raw data.
Refer guideline Data integrity and compliance with
cGMP
2.2 Source data -
This terminology is used for clinical investigation
purposes. Source data is the same as raw data (laboratory investigation purpose).
Source data include original records of clinical observation and investigation.
Source data review by both sponsor and FDA for safety, quality, and integrity (ALCOA+).
Refer guideline Guidance for electronic source data in a clinical study
2.3 Metadata -
Data which indicates
attributes (Specialty) of other data and gives reference and meaning of that
other data. Contextual information required to understand
data. Metadata described as data about data. The audit trail is
considered as metadata. Data that automatically generated by the original data
source also consider as metadata.
Refer Guideline GXP data integrity guidance and
definitions
Refer guideline Data integrity and compliance with
cGMP
2.3.1 Audit trial –
Form of metadata having
information about creation, alteration, or deletion of GXP record. This secure
recording of product details during the manufacturing life cycle. This is the
medium includes who, what, when, why chronologically the action performed. The
computerized system responsible for the generation of raw data always links
with an audit trail to identify the alteration, deletion, or any changes in
data by retaining both altered data and original data. An audit trail is
secure, computer-generated data The audit trail should always switch on. Only
administrators having the right to switch off audit trail and the record
retains of that activity. Audit trial should review as relevant data if any
abnormality found during reviewing audit trial, an investigation is required.
Refer Guideline GXP data integrity guidance and
definitions
Refer guideline Data integrity and compliance with cGMP
 |
Raw
data, Source data, Metadata |
3. List of Data Generated in pharma industry but not be limited
3.1 Batch Manufacturing Record (BMR) / Batch
Processing Cleaning Record (BPCR)
3.2 Batch Packing Record
3.3 Training Record
3.4 Laboratory test report (In process/Finished
Product)
3.5 Out of Specification (OOS)
3.6 Out of Trend (OOT)
3.7 Deviation
3.8 Change Control
3.9 Market Complaint
3.10 Product Recall
3.11 Validation (Analytical/Process/Equipment
/Cleaning)
3.12 Stability record
3.13 Logbooks
3.14 Returned good
3.15 Job description of the employee
3.16 Attendance of employee
3.17 Health checkup
3.18 Work orders
3.19 Preventive maintenance
3.20 Internal / External Audit
3.21 Audit compliance
3.22 Annual Product Quality Review (APQR) / Annual
Product Review (APR)
3.23 Approved vendor documents.
4. What is Data Integrity?
Completeness, consistency, and accuracy of data is
data integrity. Data must follow the ALCOA+ principle i.e Attributable,
Legible, Contemporaneous, Original, Accurate, Available, Enduring, Complete,
Consistent.
Refer guideline Data integrity and compliance with cGMP
Data are complete, consistent, accurate, legible, reliable, prompt and data maintained throughout the lifecycle. The ALCOA+ principle i.e Attributable, Legible, Contemporaneous, Original, Accurate, Available, Enduring, Complete, Consistent. Data integrity directly indicates quality. Follow good documentation practices (GDP) for better data quality.
Refer Guideline GXP data integrity guidance and
definitions
5. Why ALCOA+ (plus) / ALCOA+ Principle :
ALCOA+ acronym is used for data integrity purposes.
ALCOA represents the terms Attributable, Legible, Contemporaneous, Original,
Accurate. But now, ALCOA is outdated and ALCOA+ is the updated concept. This
"+" represents Available, Enduring, Complete, Consistent.
6. The Common Issues of Data Integrity:
6.1 Share Username and Password:
Employee shares their username and password so
difficult to identify who did the activity or alter the record. Not follow the attributable of ALCOA+.
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients Point 5.4
6.2 No Computer system control:
In some organizations, it found that the user has
the right to change or modify the method which is not acceptable. Not follow
original, accurate of ALCOA+.
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients Point 5.4
6.3 Data Manipulation:
Manipulation of data is a common issue found in most industries. Alter the original data to pass the sample. Not follow the original, accurate of ALCOA+.
6.4 Destruction without recording:
Torn documents are found in dustbin or scrap with
the sign of employee without recording and justification. Indicates data
falsification.
6.5 Backdated documentation:
Filling document backdated or run the sample by
changing the date in the system there is no control over the computer system.
Not follow the contemporaneous of ALCOA+.
6.6 Incomplete data:
The record is not completed. Record found unfilled which is a question mark on the quality of the product. Not follow the Good documentation practices (GDP), Complete, accuracy of ALCOA+.
6.7 Audit trail turn off:
The laboratory has turned off the audit-trail
functionality within the system without justification.
Refer Guideline GXP data integrity guidance and definitions
Refer guideline Data integrity and compliance with cGMP
6.8 Lack of Knowledge:
People involved in the activity having a lack of
knowledge. Just doing the activity but don't know why, how, when. Due to
inadequate training person using the wrong technique. Don't follow the written
procedure.
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients point 3.1
6.9 Cybersecurity:
Inadequate cybersecurity available so, the chance
of losing data after a cyber attack.
Refer USFDA 21 CFR 212.110 (b)
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients Point 5.4
6.10 Improper data backup system :
The system fails to take a backup of data and
protect records from loss. The auto backup system not available.
Refer USFDA 21 CFR 212.110 (b)
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients Point 5.4
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7. How to minimize the risk of Data
Integrity
7.1
Management promotes Integrity:
Several
risks of data, integrity reduces by promoting integrity by management. Each and
every employee be honest about work. Management responsible to generate
culture, provide awareness programs, quarterly meetings, discussion on warning
letters, form 483, etc is helpful for understanding what mistakes are they
doing while practicing or working activity. Explain the management strategy for
a site with corrective and preventive action (CAPA) plan.
7.2.
Trustworthy Audit Trail:
An
audit trail is helping to minimize the risk of data integrity risk. Audit
trails are capture all data including original data, modified data. Data secure
and recorded throughout the different stages of its lifecycle, including where
it came from and alteration in data.
7.3.
Consultant:
FDA
recommends third party consultant having a good experience, known about
regulatory expectation, evaluate data integrity, suggest a remediation plan.
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients point 3.3
7.4.
Comprehensive evaluation:
In-depth
evaluation of the procedure for finding the problem, root cause. FDA expects a
detailed and complete description/procedure to find the scope of the problem.
FDA evaluates this comprehensive evaluation by interviewing people and system
that breaks data integrity.
7.5.
Corrective and preventive action (CAPA):
FDA
expects proper analysis of finding. The procedure is available for monitoring
the plan. This action is helpful to detect and eliminate cause to prevent
occurrence. CAPA system procedure should be defined and documented. CAPA
procedure is able to identify, analyzed, and correct the data existing source
of the problem. Investigate and prevent the potential cause of the problem.
Verify this preventive action are appropriate
7.6 Good
Documentation Practices (GDP):
This is one of the best method to minimize the risk of data integrity. Good documentation Practice (GDP) applies while recording all quality-related data. This tool is helpful to maintain consistency, legibility, the accuracy of documents. So, the documents are trustworthy.
Overwriting
is the most common mistake found during audit/inspection. Overwriting is
consider as false data, inaccurate, alteration of data. If any mistake
happens while reporting data such entry correct without alteration of original
entry. Draw a single horizontal line on the wrong entry
rewrite the original entry (true value) with sign and date.
7.7 Ensure all computer systems are regulatory
compliant:
Computer hardware and software should
demonstrate competency with proper installation and operational qualification.
The computer system is reliable, accurate, and consistent. Data for the protection system is available.
ICH Q7 guideline Good manufacturing practice for
Active Pharmaceutical Ingredients Point 5.4
7.8. Validate computer systems:
Computer system
validation is a high degree of assurance that computer software producing
results are consistent with the predetermined rate. Validation is depending on
the complexity, the criticality of the computer system application.
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients Point 5.4
7.9. Limited system access:
All systems should
require a control login system to prevent unauthorized access so minimize the
chances of change or any modification. All data captured that who made the
change and when.
Refer USFDA 21 CFR part 11 subpart B sec.11.10 (d)
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients Point 5.4
7.10 Backup and recovery procedures available:
A backup and recovery strategy is necessary for the unexpected event of permanent data loss
and errors. This procedure is helpful in the reconstruction of data in any
major event.
Refer USFDA 21 CFR 212.110 (b)
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients Point 5.4
7.11 Design a Quality Management System with SOPs
and logical controls:
All pharma manufacturers should establish and
implement an effective system for quality management. Management actively
involved in this quality management system. Quality Assurance (QA), Quality
Control (QC), Production, QA, QC is part of the quality management
system. QA and QC are independent of the production department.
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients Point 2
7.12 Vendor qualification:
The vendor defines as a supplier of the product,
service to another business. The manufacturer also acts as a vendor or supplier
if the manufacturer directly supplies service or product to another
business. Vendor supply raw material (RM), packing material (PM),
personal protective equipment (PPE) like gloves, masks, etc. to the
pharmaceutical industry. The vendor should fulfill all quality-related issues.
The pharmaceutical industry qualifies the vendor depends on their quality, cGMP
compliance. Quality agreement plays a very important role to solve the quality-related conflict between the pharmaceutical industry to vendor.
7.13 Employee training and maintain training records:
An adequate number
of persons should be qualified, train-related to employee function. GMP related
training is mandatory for all persons. Documented training records provide this
proof.
Guideline ICH Q7 Good manufacturing practice for Active Pharmaceutical Ingredients Point 3.1
7.14 Conduct Internal Audits to evaluate controls
and procedures:
Prevention is
always better than cure this phrase is applicable in case of internal audit /
self-inspection. Prevent our self before any serious issue. Internal
audits / Self-inspection ensures that all procedures,
the system is in accordance with cGMP. Internal audits / Self-inspection is
best to identify the gaps between the system and the regulatory requirements.
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients Point 2.4
7.15 Annual
product review (APR) / Periodic product Review (PPR) /
Annual
Product Quality Review (APQR):
This is a bunch of
data that we produced in one year. It includes all data of each
product
manufactured in one year. Its lifecycle history of the product till starting
material to the finished product. The statistical trend of annual
product quality review (APQR) helpful to identify the process capability of our
product. Product process improvement based on the conclusion of APQR/APR/PQR/PPR.
ICH Q7 guideline Good manufacturing practice for Active Pharmaceutical Ingredients Point 2.4
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8. Why necessary to
minimize data integrity / FDA basic requirement:
8.1 Reconstruct the
manufacturing process -
Regulator and industry to be able to reconstruct
the manufacturing process to record.
8.2 To avoid falsification -
There is no false, omission, hiding, and
substitution of data. Regulatory bodies take serious action on such an issue.
8.3 To avoid regulatory action –
Regulatory bodies like USFDA, MHRA, TGA, etc. take
serious action if they are not satisfied with your data handling procedure,
product mix up, cross-contamination, cleaning the procedure, manufacturing
procedure, etc. They consider its serious cGMP violation.
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