QMS Training

BRFT, GDOCP, Data Integrity

Oct 2022
List of Content
1. Introduction & Background Data Integrity, GDOCP
2. Purpose, type of documentation
3. Data integrity (ALCOA+) explanation & examples
4. Challenges & Risk, Data governance
5. BRFT, Definition & purpose
6. Batch review flow process
7. Example non BRFT documentation
8. Example improvement
Data Integrity, GDocP
 There are many inspection findings, warning
letter related to Data Integrity issue.

• A Regulator does not distinguish between human error and data falsifications when
assessing the impact of a data integrity failure !!
• Product Assurance is reflected from Data.
Background
US FDA Warning
Canada 2 Letters Citing Data Integrity by China
Year 2018
+ HK 12

South Korea 5
All EUROPE 4
USA 20
Japan 3 Category:

•Review of audit trails

•Access controls to electronic
India 7
systems
•Data back-up
Australia 1 •Failure to include complete data
•Audit trail, data control, and
Others 3 sharing password

57 India, 7

China + HK , 11
warning
letter USA; 20
Warning Letters a live example
Findings Related to Documentation (BPOM, 2022)
• Prosedur pengolahan telah dilakukan, namun belum dilakukan
pencatatan pada dokumen catatan bets (Butir 1.8f)
• Pada catatan pengolahan bets telah dilakukan pencatatan hasil
pengamatan parameter kritis, namun demikian tahapan proses
produksi tersebut belum dilakukan. (Butir 1.8f)
• Pencatatan dilakukan menggunakan pensil (Butir 10.7).
• Perubahan yang dilakukan terhadap pencatatan menyebabkan
ketidakterbacaan dari informasi semula (Butir 10.8)
• Tidak tersedia batasan akses terhadap penggunaan sistem oleh
personil yang tidak berwenang (Aneks 7 Butir 12.1)
• Sistem komputerisasi tidak dilengkapi dengan sistem audit trail
(Aneks 7 butir 9)

Dra. Togi J. Hutadjulu, Apt. MHA

Plt. Direktur Pengawasan Produksi Obat, Narkotika, Psikotropika dan Prekursor Badan POM.
 Definition & Purpose

Data
Document Documentation All original records & true
copies of original records,
Anything that is written Any recording towards
including source data, meta
or printed that use as activity that is data and all subsequent
activity evidence conducted transformations & reports.
(Source KBBI) TRS WHO no. 996 Annex 5

Evidence that the activity is Avoiding misunderstanding, As a information source if

conducted misperception, mistakes needed in the future
Achieve consistent result from time to (problem or complaint occur)
time
Paper records such as Electronic records, Photographs, Instruction/ Static
worksheets and audit trails microfilm, audio, Procedures Dynamic
logbooks video files Records
 • If it isn’t written down, it never happened.
• In GOD we trust, all others bring data
FDA

Self If it doesn’t written/record properly, than it

is not done correctly.
Reminder
Quality Means doing right when no one
is looking
Henry Ford

Kerjakan apa yang ditulis dan Tulis apa

yang dikerjakan.
Data Integrity
Data integrity is the degree to which data are complete, consistent, accurate, trustworthy
and reliable and that these characteristics of the data are maintained throughout the data
life cycle.

Data integrity principles:

+
A
Attributable
L
Legible
C
Contemporaneous
OOriginal
A
Accurate
(Complete,
Consistent,
Enduring,
Available)
Log in using self unique ID
specified for each personnel
NEVER give/share
password to anybody
 Attribution of actions in paper records should occur as appropriate
through the use of initial, full handwritten signature, date and time.
Signage
Signature, Initial, Date How to record Date
3 digit month
10 Jun 2020 10 2020
Jun
ABC 2 digit date 4 digit year

How to record Time

Signature Initial
(unique & standardize) 09.05 Atau 09:05
Using time format 24 hours, time should be written completely (hour,
Date minute and second if necessary)

ATTRIBUTABLE 09.05‘10‘‘ or 9 hours 5 minutes 10 seconds orusing smallest time unit.

14
 ATTRIBUTABLE
If there is delegation process, it should be clear
documented in the document.

Use of stored digital images of a person’s

handwritten signature
Additional data/ print outs data which added to records
to sign a document is not acceptable
should be completed by signature, initial and date by half-
half method.
If there is repeated area to be filled with the same information/data, ATTRIBUTABLE
it is not allowed using ditto (“) or other similar marking.

16
 ATTRIBUTABLE
No empty columns !!

Streak the empy column, give “NA”,

Give “NA” in empty column
signage, date & initial.

17
Legible, traceable and permanent refer to the requirements
that data are readable, understandable, and allow a clear
picture of the sequencing of steps or events in the record so
that all GXP activities conducted can be fully reconstructed
by the people reviewing these records at any point during
the records retention period set by the applicable GXP.
 Manual recording should be clearly written, readable and permanent.

It is not allowed to use Tip-Ex, etc

No pencil
Manual writing should be
using good quality and
permanent ink.

Unacceptable correction
LEGIBLE
20
 Overwritten

LEGIBLE
Document or Data should be clearly written, readable and permanent.
21
 CONTEMPORANEOUS
12
Record the data at the time it
11 1

2
is conducted.
10

9 3

8 4

7 5
6

NEVER change date

and time, timezone
on computer

23
Original data include the first or source capture of data or
information and all subsequent data required to fully reconstruct the
conduct of the GXP activity. The GXP requirements for original data
include the following:
■ original data should be reviewed;
■ original data and/or true and verified copies that preserve the content
and meaning of the original data should be retained;
■ as such, original records should be complete, enduring and readily
retrievable and readable throughout the records retention period.

NEVER do data manipulation: adding, reduce, delete,

replace data
 ORIGINAL
Data should be original or true copy of the original

Data is written based on

original data in print out.
25
 ORIGINAL
How to do correction:
Steps to do correction on document:
1. Make a single streak on the correction part.
2. Write the correction
3. Give reason for the correction (can be full information or using abbreviation) Example for abbreviation
4. Give signage, initial and date of the correction that commonly use :
1
ST = Salah Tulis
SH = Salah Hitung
koreksi 2 SI = Salah Isi
Alasan korksi 3 SU = Salah Unit
TK = Tambah Keterangan
4 TD = Tidak Diperlukan.
10 Jun 2020

26
 If the column is to small for the correction
notes, use * symbol and write the note in other
space of the document.

* 54.2

Give * in the data which need to be corrected.

Information for the correct data and reason can
* 54.2 salah tulis 05 Nov 2018
be note in other space of the document.
 ACCURATE

Weighing print out derived from

calibrate balance

30
Rounding Rules
31

General Chapter 7.20. Rounding Rules

Ketentuan dan Persyaratan Umum 7.2 Aturan Pembulatan

Observed/calculated values shall be rounded off to the number of decimal

places that is in agreement with the limit expression.

Numbers should not be rounded until the final calculations for the reportable
value have been completed. Intermediate calculation (e.g. slope for linearity)
may be rounded for reporting purposes, but the original (not rounded) value
should be used for any additional required calculations.

Consider only one digit in the decimal place to the right of the last place in the
limit expression. It smaller than 5, it is eliminated and the preceding digit is
unchanged. If equal to or greater than 5, it is eliminated and the preceding digit
is increased by 1.
Rounding Rules
Compendial Requirement Unrounded Value Rounded Result Conforms
Assay limit > 98.0% 97.96% 98.0% Yes

97.92% 97.9% No

97.95% 98.0% Yes

Assay limit < 101.5% 101.55% 101.6% No

101.46% 101.5% Yes

101.45% 101.5% Yes

Limit test < 0.02% 0.025% 0.03% No

0.015% 0.02% Yes

0.027% 0.03% No

Limit test < 3 ppm 3.5 ppm 4 ppm No

3.4 ppm 3 ppm Yes

2.5 ppm 3 ppm Yes

Other Examples

01
Never do backdating

02
Never delete/discard any raw
data, such as : print outs from
balance, machine, computer file,
etc

03
Never use post it, uncontrolled
paper, unnumbered document to
record data.

04
Never delete/discard any
data/records, except already
exceeded it’s retention period.

05
Never modify or change original
data.
Challenges of implementation
Risk from
Data Integrity
Implementation
Failure
1. Data is not complete, not accurate
2. Work result is not reliable
3. Warning letter from regulatory
4. Product failure, reject, recall
5. Temporary cessation of activity
6. License withrawal

35
LESSONS LEARNED
1. Documentation is a crucial, essential part in pharmacy industry, the reliance and
assurance of product lies in data (documentation process).
2. Procedure for creating, controlling, storing, and destruction of document should be
well established.
3. ALCOA principles should be implemented in all documentation process.
4. Good Documentation Practice give big impact to Data Integrity.

48
 BRFT
Batch Right First Time
Definition
1. BR (Batch Record)
a written record that documents the entire manufacturing process and the
history of a product batch. In other words, it tells you how to produce a
product and records the way that happens.

2. BRFT (Batch Right First Time)

Performance of manufacturing process, whether there is deviation/not,
calculated from all the process starting from weighing to final packaging
process.
No batch deviation, OOS, No administrative mistakes.
Purpose
As KPI Quality Compliance KPI Quality towards vendor
(Quality Indicators KCQM.FM.1.07) • Deviation
• BRFT
• Customer complaint rate
• Validation (process, CV, AMV) Formula for Quality Aspects

• Change control management

• CAPA Management
• Recall, Reject
• Batch Right First Time
• etc
Formula
BRFT (%) : Number of batch produced without deviation divided to
Total of batch produced which released.

Requirement : min 97.5%

note: Exemption batch validation/supervision

• BRFT documentation calculated for Production, PPIC (site, toll out), Logistic, QC.
Process Flow for Batch Record Review
Document Receiving REVIEW
Batch record from Prod, Documents are reviewed by
analytical record from QC QA Inpector, input checklist
received by QA & disposition form

DISPOSITION VERIFICATION
Batch disposition by
QA Manager
Documents are
verified by QA
Supervisor
 1 Batch record received & reviewed by Kalbe.

2 Findings (documentation mistake, deviation, etc).

3 Confirmation to toller

4 Correction/additional notes on batch record.

5 Batch disposition

Impact if there is non BRFT → documentation correction, other additional

activity needed (testing, sampling, etc) → Released process will be delayed.
Blank Column
 BN 21484
Data is not match

BN 214841

BN 214841

mix up Non Dispense Label

Deviation
Wrong HET, Reg No on IPC records of
Primary Packaging Coding Process

Requirement : Written at IPC at 13.00 :

HET : Rp. 5773 HET : Rp. 2464
Reg No. : DKL0800514910A1 Reg No : GKL0608513110A1

Impact :
Sampling and verification process for products which
coded started from 13.00 – finish (additional process &
cost)
Disintegration time data for IPC
process is not filled

Requirement :
IPC is conducted at the beginning, middle and end of
process
Actual :
IPC data for middle process is not written on Batch
Record

Impact :
Sampling and verification process for disintegration time
(additional process & cost)
Others examples
Improvements
1. BRFT Campaign
2. Define target
3. Regular monitoring
4. Batch record simplification
5. KPI sharing among departments
6. E-BR
Grafik Pencapaian BRFT Administrasi
BRFT ADM Site
Total PPI tanpa
100,00% 100,00% Line Pengembalian % BRFT
Datang Pengembalian
98,31% 98,15% 99,00%
97,94% 98,03% 98,01%
98,00% 97,64%
Target : 97.50% 98,00%
1 61 60 1 98.36%
97,00%
96,00% 2 78 75 3 96.15%
94,76% 96,00%
May 3 82 81 1 98.78%
94,00% 95,00% 2022
94,00% 4 74 72 2 97.30%
92,00%
93,00% 5 64 63 1 98.44%
92,00%
90,00% 89,47% 6 123 122 1 99.19%
91,00%
7 4 4 0 100.00%
88,00% 90,00%
2020 2021 Jan Feb Mar Apr May YTD 2022 486 477 9 98.15%

Average BRFT Administration Achievement per May 2022 is increased by 3,25 % from the previous year
% BRFT Per Departemen May 2022
PPIC LOGISTIK
1 Pengembalian
100%

99.79%

98.56%
99.79%

PRODUKSI
QC
7 Pengembalian 1 Pengembalian
 BRFT ADM ALL DEPT
NOV 2021
Pengembalian Produksi
NOV 2021 : 11 Kasus

BRFT ADM
PROD
Nov 2021
98.61%
Monitored weekly, monthly on WAG All Dept, All Personnel in Site
THANK YOU