Computer System Validation (CSV)

Comparisons between (GMP VS cGMP, GLP VS GCP, 21 CFR PART 11 VS EU 11)

 GMP VS cGMP :-

At the most basic level, GMP stands for Good Manufacturing

Practice and cGMP stands for current Good Manufacturing Practice.

cGMP:-

The cGMP acronym originated in the USA, where the US Food and Drug
Administration (FDA) wanted to impress upon drug manufacturers the need
for continuous improvement in their approach to product quality. The FDA
cautioned against a ‘set and forget’ approach to compliance to the GMP
guidelines, wanting manufacturers to ensure that product quality became a
core driver within their organizations.

Why we go cGMP

GMP regulations take a long time to change. The regulators typically respond
to disasters, regulating to prevent a re-occurrence. They aren’t changing the
regulations to enforce best practices and new technologies and even if they
do, it’s years after they’ve become common place.
You may be considering implementing new technologies as part of the
Industry 4.0
or Pharma 4.0 approach. Technologies that regulators haven’t fully
considered yet.
It could be additive manufacturing e.g. 3D printing of medical devices, or rapid
microbial methods or voice recognition in manufacturing processes to create
paperless batch sheets. The key is to make sure you can prove to an auditor that you
understand your process and you’ve built quality into that systems and processes
(and have the evidence to prove that it works). If you take this approach then you can
advance beyond the GMPs and not be always chasing compliance with the next
version of GMP guidelines to be released by the regulators. Plus, you get all the
advantages those technologies offer, earlier than your competitors.

GMP vs cGMP vs Pharma 4.0

If you are considering implementing Industry 4.0 or Pharma 4.0 approaches, it is
essential to have proactive discussions with your local regulator to get the benefit of
their experience. They often see these technologies frequently used in the Australian
operations of international organisations but slow adoption by Australian-owned
organisations. The technologies and processes included in the Pharma 4.0
revolution won’t be reflected in GMP regulations for years to come, so don’t want for
them to be regulated in, get the advantages now

 GLP VS GCP

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Comparisons between (GMP VS cGMP, GLP VS GCP, 21 CFR PART 11 VS EU 11)

Good Laboratory Practice (GLP)

As part of Investigational New Drug (IND) documentation, a toxicity report of a drug
in laboratory animals must be attached along with several other documents. These
lab studies and tests must be controlled and carried out as per the FDA defined
GLPs. Some of them include:

 Ensure all applicable GLP are followed throughout the laboratory processes
 Establish a competent quality control / quality assurance (QA/QC) unit in a testing
facility to maintain the master schedule and master testing schedule, and monitor
the study, phase-wise
 Conduct nonclinical laboratory studies as per established protocol
 Ensure every individual engaged in the nonclinical laboratory study has the
education, training and experience of performing the assigned function

Good Clinical Practice (GCP)

All clinical studies for a drug / biological medicine must be conducted in line with
GCP regulations failing to do which (both intentional and unintentional) will lead to
serious consequences for the clinical investigators. The essential GCPs includes:

 Ensure adequate application of informed consent procedures to protect the clinical

subject
 Ensure thorough personal conduct or supervision of the principal investigator
while delegating the tasks part of the clinical trial
 Secure and maintain, accurate and adequate case histories
 Ensure adequate monitoring of the study by the QA/QC unit
 Report unexpected clinical reactions to the Institutional Review Board (IRB) and
the sponsor

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Comparisons between (GMP VS cGMP, GLP VS GCP, 21 CFR PART 11 VS EU 11)

 21 CFR Part 11 VS EU Annex 11:-

Introduction:-

The relationship between FDA’s Part 11 (21 CFR Part 11) and the European
Union’s Annex 11 (EUDRALEX Rules Governing Medicinal Products in the
European Union, Volume 4, Good Manufacturing Practice, Medicinal
Products for Human and Veterinary Use) diverges in philosophy. Both
documents cover
the same topic, the use of computerized systems in regulated activities.
However, the approach of Part 11 is to make clear there are requirements to
be met in order to conform to regulations. The emphasis is on activities and
reporting.

In contrast, the approach of Annex 11 is to make clear how to conform to its

rules. Annex 11 is a detailed guide to the areas of compliance that need
documentation. A significant difference is the approach to risk management.
Annex 11 points to risk assessment as the start of compliance activities.
Part 11 differentiates security for open and closed systems, with extra
security measures for open systems but without reference to risk or
criticality. The aggregate of these differences is represented visually with
the point-to-point comparison matrix shown below.

Table 1: High Level Comparison of Annex 11 and Part 11

Annex 11 Part 11

Computerized systems as part of GMP

Electronic records and electronic
regulated activities.
Scope/Principle signatures as used for all FDA
Application should be validated.
regulated activities.
IT infrastructure should be qualified.

Using electronic records and

Risk- based quality management of
Focus signatures in open and closed
computerized systems.
computer systems.

Using a computerized system should Electronic records and signatures

ensure the same product quality and should be as trustworthy and reliable
Objective
quality assurance as manual systems as paper records and handwritten
with no increase in the overall risk. signatures.

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Conclusions

Annex 11 for computerized systems impacts manufacturers who export to

the EU and those who manufacture products in the EU. Close scrutiny of
the parallel FDA and EU rules shows the authorities share a mutual intent
to have safe, validated computer systems and qualified networks for drug
and device manufacturing.

Limited areas of Part 11 are dissimilar to Annex 11; these, for the most part,
are limited to the verification of identity and accountability of actions by
authorized individuals, as well as to the reporting to authorities. Part 11
applies to e-submissions to the FDA. Annex 11 is different from Part 11 in that
it takes a risk management approach to criticality and emphasises a systems
approach to periodic evaluations. Annex 11 is ‘how to’ while Part 11 is ‘thou
shalt’ in tone. Together they form a robust and usable guide for computer
validation professionals leading their companies and clients to compliance.

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