My recent interest in the Pharmaceutical Industry has allowed me to explore learn a great deal about the manufacturing processes and regulatory guidelines in different countries. I would like to share what i have learned about Good Manufacturing Practices(GMP) in the Pharmaceutical Industry.
Good Manufacturing Practices (GMP)
Guidelines and standards are
important in any industry you work in but nowhere does it get updated and
changed more so than in the Pharmaceutical Industry. Designing a modern,
compliant pharmaceutical facility is difficult enough within a demanding and
competitive industry but constantly changing standards and increasing
complexity of regulations make it even tougher1.
Overview
According to the World Health
Organisation(WHO): “GMP or good manufacturing practice is a part of quality
assurance which ensures that products are consistently produced and controlled
to the quality standards appropriate to the intended use as required by
the marketing authorisation.” The general guiding principle behind GMP is that
quality should built into the product and not just into a finished
product. So the product not only meets the final specification but has been
made using the same procedures under the same conditions under the same
conditions each and every time. There is a term for ensuring quality is built
into the design of pharmaceutical products, Quality by Design (QbD), which is
probably the hottest topic in the industry now since GSK has successfully
demonstrated a continuous production process. I will have to talk more on QbD
on another article and place the link here**.
This would mean that we have to
control the quality of the starting materials, the facility and its systems
should be top notch as well as maintaining quality of production at all stages.
Apart from these, quality should be ensured during testing of the product and
all materials must have adequate storage facilities.
GMP covers all aspects of
manufacturing process and I am going to list out below what GMP inspectors are
typically looking for:
1.
A well-defined manufacturing process
2.
Validated critical manufacturing steps
3.
Suitable premises for storage and transport of materials
4. Qualified
and trained production, quality control personnel
4.
Adequate laboratory facilities
5.
Approved written procedures and instructions
6.
Records all steps taken
7.
Full traceability of product
8.
Systems for recall and investigation of
complaints
If we look at a typical
project stages in the Pharmaceutical industry, we can locate the stages in
which certain guidelines and regulations kick in. For example see the figure
below for an overview:
Regulatory driven manufacturing
requirements cover various issues including facilities design, product delivery
and validation issues.
Regulatory Issues
Although different countries have their own regulatory bodies, the most widely used (accepted) are the FDA, EU and Japan regulations because these regions house major pharmaceutical manufacturers and represent the largest proportion of the market combined. While FDA’s current GMPs provide minimal guidance by outlining facility requirements and requirements for documentation of manufacturing procedures, the FDA also issues regulations in the code of federal register (CFR) 21. These regulations are summarised in the table below:|
No.
|
CFR Regulations
|
|
21 CFR
210
|
Current
Good Manufacturing Practices in Manufacturing, Processing, Packaging or
General Holding of Drugs
|
|
21 CFR
211
|
Current
Good Manufacturing Practices for Finished Pharmaceuticals
|
|
·
Part C
|
Building
and Facilities
|
|
·
Part D
|
Equipment
|
|
21 CFR
600
|
General
Biological Products
|
|
21 CFR
820
|
Quality
Systems Regulations
|
Future Implications
GMP guideline is constantly evolving
with technology to accommodate rising demand for quality and value products. The
future of global pharmaceutical industry is going to be “dynamic and highly
responsive to marketing and regulatory forces”1. There will be
higher expectations from manufacturing facilities to keep up with economic and
regulatory requirements in order to maintain flexibility, safety, value and
speed to market. Good design practices will apply to all manufacturers as they
try to achieve business objectives and at the same time conform to globally
harmonised guidelines which address an increasingly safety and quality
conscious community.
Reference/Further Reading:
[1] Good Design Practices for GMP
Pharmaceutical Facilities: Drugs and the pharmaceutical industry, Andrew A.
Signore, Terry Jacobs Vol. 146 [2005]
[2] Good Manufacturing Practices for
Pharmaceuticals: A plan for Total Quality Control, Sidney H. Willig, Murray M.
Tuckerman and William S. Hatchings IV, [2nd / 3rd
Edition]
[3] Modern Pharmaceutics, edited by
Gilbert S. Banker and Christopher T.
Rhodes
[4] Pharmaceutical Process
Validation, edited by Bernard T. Loftus
and Robert A. Nash
[5] Handbook of Pharmaceutical
Granulation Technology, edited by Dilip M. Parikh
[6] Automation and Validation of
Information in Pharmaceutical Processing, edited by Joseph F. deSpautz
[7] Pharmaceutical Process
Engineering, Anthony J. Hickey and David Ganderton*
