Introduction to GMP

1. GMP
Good Manufacturing Practice
What is it ?
Why Bother ?
Mr.Rajendra Sadare
Senior Software Engineer-Testing And
Validation
Arisglogal Software Pvt.Ltd

2. Today’s Agenda
Medicines - why should they be
any different to other products ?
Regulations & Guidelines
- History & Current
GMP
QA
- What do they
QC mean ?

3. Quality Choices
Engine size
Make and model Age /
registration
Colour Documents /
Condition previous history
You can tell by looking

4. Quality Choices
Engine size
Make and model Right strength
Age / registration
Right product
Right expiry date
Colour
right
appearance Documents /
previous history
Condition Batch Record
No contamination
You can’t tell just by looking

5. THE TRUST CHAIN
PATIENT
TRUSTS DOCTOR/
PHARMACIST
TRUSTS
MANUFACTURER

6. GMP - THE HISTORY
1960 THALIDOMIDE marketed in West Germany then
Canada & Britain as sleeping tablet, treatment for colds,
flu etc. Pregnant women used for nausea.
1961 Alarm at the sudden increase in the birth of deformed
infants ESTIMATED 10,000 INFANTS DEFORMED
1961 Withdrawal of Thalidomide
DEMONSTRATED THAT SAFETY REQUIREMENTS OF
NEW DRUGS HAD TO BE TIGHTENED

7. GMP - THE HISTORY
1962 World Health Assembly set out resolutions on drug
safety and monitoring
1968 The Medicines Act
introduced systems for
• Product Licencing covering old (pre1968)
and new medicines
• Licencing of manufacturing sites
• Licencing of Clinical Trials

8. GMP - Rules & Guidance
• The Rules Governing Medicinal Products in
the European Union
• “Rules & Guidance for Pharmaceutical
Manufacturers and Distributors 1997
(Orange Guide)
• Annex 13 : Manufacture of Investigational
Medicinal Products
Guide only
- no legal standing for
clinical trials

9. EU Clinical Trials Directive
• Directive 2001/20/EC
• Implemented by 01May 2004
• Makes GMP & GCP a legal requirement
• Requirement for QP to certify IMPs
• Requires that IMP has been manufactured,
packaged and distributed according to standards of
GMP at least equivalent to 91/356/EEC
• Audit of facility by MCA

10. Why GMP ?
 Consistency
 Control
Quality Product

11. To achieve a quality product we must
BUILD QUALITY
into our systems and processes
Q
U A
L IT Y
We can’t TEST QUALITY into a
product at the end

12. Building Blocks of GMP
GMP
Controlling Controlling
Quality + Processes
Quality Control Well trained staff Quality Assurance
(QC) is about + (QA) is about
testing materials testing processes
Documentation
+
Good
Premises/Equipment
High Quality Product

13. Quality Standards
GMP
QA
QC
practice
theory Q
Quality
Product

14. GMP - Why bother ?
Mid 1980s
• Several patients being treated for shock
probably
• Given Hydrocortisone Injection
• Patients stops breathing and die
• Warning issued on national news
• Immediate MCA Investigation

15. Potential for Disaster
Norcuron Hydrocortisone
(Vecuronium Bromide) • Steroid
• Musle relaxant used in • Anti inflammatory
• Can help breathing
surgery
• relaxes respiratory
muscles
• patient can’t breathe
unaided
Both products filled into identical ampoules

16. GMP - Why ?
• Both products were manufactured at same site
( Holland)
• Batch of product dosed to baby was labelled
at a different site in the UK
Long, difficult investigation
 manufacturing problem ?
 labelling mix up ?

17. GMP - Why ?
• Ampoules segregated on different tables but
inspected in the same room
• Samples of Norcuron, removed for in-process
sample, were returned ( to save product /
cost) to the batch
• Samples returned to the wrong table
• Appeared identical so not visually identified
• Norcuron labelled as Hydrocortisone
• Life saving drug mixed up with potentially
life threatening drug

18. GMP - Why ?
• Design of area for inspection (Not one
product in area at one time)
• Insufficient reconciliation ?
• Documented evidence of sampling ?
• Ampoules not differentiated ?
• No investment in facilities ?
• Management attitude to GMP

19. Quality Standards
GMP
is everyone’s
responsibility

20. Mistakes - The Cost !
In House After Supply
Waste materials  Product Recall
Labour costs  Lawsuits
Back orders  Reputation

21. Q How do we build a quality product ?
A By completing the jigsaw
Pro
c ess
es
Product
s&
ise t
P rem men
Eq uip
Documentation
nnel
Perso

22. GMP - The Jigsaw