www.biopharminternational.com March 2020 BioPharm International eBook 7
• Original: Original or source
data are the record, report,
notebook etc. where the data
point was initially recorded.
• Accurate: The data recorded
must be complete, consis-
tent, truthful, and represen-
tative of facts.
• Complete: Information that
is critical to recreating and
understanding an event. This
would include any repeat or
reanalysis performed on a lab-
oratory test sample.
• Consistent: The data are pre-
sented, recorded, dated, or
time-stamped in the expected
and defined sequence.
• E n d u r i n g : T h e d at a o r
information must be main-
tained, intact, and accessible
throughout their defined
retention period.
• Available: The data or infor-
mation must be able to be
accessed at any time during
the defined retention period.
Data integrity has always con-
cerned regulatory authorities, but
it is important to understand what
is prompting the renewed discus-
sion of ALCOA and the introduc-
tion of ALCOA+ when discussing
data integrity issues. Many of the
concepts for ALCOA have been
captured in the regulations as far
back as 1978.
A GROWING INDUSTRY
Since that time, the industry has
changed dramatically. The gener-
ic-drug industry has grown and in
the United States alone accounts
for more than 80% of the prescrip-
tions written today (2). Coupled
with the emergence of biosimi-
lars, virtual companies, contract
m a nu f ac t u r i n g or ga n i z at ion s,
rapid adva nces i n automat ion
and information technology, and
the globalization of the industry
have resulted in reinterpretation
of the attributes associated with
maintaining the integrity of data
throughout the product lifecycle,
whether those data are generated
from electronic, paper-based, or
hybrid systems.
I n add it ion, t here has b een
an increase in citations interna-
tionally by the FDA, European
M e d i c i n e s A g e n c y ( E M A ) ,
Medicines and Healthcare products
Regulatory Agency (MHRA), World
Health Organization (WHO), and
other health authorities. These
changes and increased violations
have brought about a resurgence
and need to reeducate the industry
on the basic principles and con-
cepts regarding the proper control
of data used to support the quality
and safety of medicines.
DATA INTEGRITY REGULATIONS
The A LCOA acrony m has been
used since the 1990s; however, the
requirements governing data ele-
ments have been in regulations
for a much longer period of time.
EudraLex chapter 4 states, "Suitable
controls should be implemented
to ensure the accuracy, integrity,
availability, and legibility of doc-
uments. Instr uction documents
should be free from errors and
available in writing" (3). The US
Code of Federal Regulations (CFR)
refers to these elements in various
sections of the regulations (4–8).
An example for language speak-
ing to the element of attributable
is in 21 CFR 211.194(a)(7), which
states, "The initials or signature
of the person who performs each
test and the date(s) the tests were
performed." Language in 21 CFR
58.130 (e) addresses the elements
of contemporaneous and legible by
stating, "All data generated during
the conduct of a nonclinical labo-
ratory study, except those that are
generated by automated data col-
lection systems, shall be recorded
directly, promptly, and legibly in
ink. All data entries shall be dated
on the date of entry and signed or
initialed by the person entering
the data."
Recent documents issued by WHO
(9) and the PIC/S (1) have added to
the original ALCOA attributes as
indicated above. The PIC/S docu-
ment actually states, "Some key con-
cepts of GDocPs are summarized by
the acronym ALCOA: Attributable,
Legible, Contemporaneous, Original,
and Accurate. The following attri-
butes can be added to the list:
Complete, Consistent, Enduring, and
Available. Together, these expecta-
tions ensure that events are prop-
erly documented and the data can
be used to support informed deci-
sions." WHO refers to ALCOA+ in
the title of Appendix 1 to their 2018
document. The last two documents
also address the concept of quality
culture (10). The impact to an orga-
nization is that the quality culture
must ensure that data supporting the
quality and safety of a product must
now meet the ALCOA+ elements in
order to avoid regulatory citations for
data integrity issues.
REFERENCES
1. PIC/S, Draft Guidance: Good Practices
for Data Management and Integrity
in Regulated GMP/GDP Environments
(PIC/S, August 2016).
2. statista.com 2019.
3. EC, EudraLex,The Rules Governing
Medicinal Products in the European
Union, Volume 4, Good Manufacturing
Practice for Medicinal Products for
Human and Veterinary Use, Chapter 4.
4. 21 CFR 11: Electronic Records;
Electronic Signatures
5. 21 CFR 58: Good Laboratory Practice
for Nonclinical Laboratory Studies
6. 21 CFR 211: Current Good
Manufacturing Practice for Finished
Pharmaceuticals
7. 21 CFR 212.50: Current Good
Manufacturing for Positron Emission
Tomography Drugs
8. 21 CFR 820: Quality System Regulation
9. WHO, Annex 5, Guidance on Good Data
and Record Management Practices
(WHO, June 2016).
10. S. Schniepp, Pharmaceutical Technology
42 (10) 2018.
BP
Regulatory Sourcebook Data Integrity