1. Cleaning validation in pharmaceutical manufacturing is important from a regulatory perspective to control contamination and cross-contamination. 2. Contamination can occur during manufacturing processes and proper cleaning between batches of different products or therapeutic classes is necessary to preserve purity and control impurities. 3. Inadequate cleaning procedures, validation studies, and contamination investigations have led to regulatory actions against companies by authorities like the FDA.

1. Cleaning Validation in Pharmaceutical Manufacturing
A Regulatory Perspective
Roohi B. Obaid
06 April 2019
Part 1/3

3. It reflects the views and
understanding of presenter &
may not be construed to
represent the views or policies
of organization or association to
which speaker has ties
Disclaimer
Documents of US-
FDA & Review
Scientific Articles are
used to construct
presentation
Reference

4. Contamination &
Cross-contamination
What is

5. Contamination may be termed as impurity
Can impurity be termed as contamination

6. Contamination may be termed as impurity
Can impurity be termed as contamination
Not always

7. If API is contaminated & the
same contamination is
identified in Finished Good
It may not be appropriate to
say contamination, but
impurity

8. Group Cleaning of utensils used in different products
may increase risk of contamination

9. Group Cleaning of utensils used in different products
may increase risk of contamination
Remember final rinsing is done individually
one by one

10. Contamination &
Cross-contamination
occurs in pharmaceutical
manufacturing process
How

11. Contamination &
Cross-contamination
relationship
GMP &

12. Contamination &
Cross-contamination
Strategies
Control

13. Why do we need to clean between two batches
We are manufacturing xxxxxxxxxxxxxxxx Product
?
Same

14. 1 Preservence of purity & Reduction of Uncertainty

15. 1
2
Preservence of purity & Reduction of Uncertainty
Control of Process & Control of Impurities

16. 1
2
3
Preservence of purity & Reduction of Uncertainty
Control of Process & Control of Impurities
Isolation & Traceability of manufacturing process

17. Why do we need to clean between two batches
We are manufacturing xxxxxxxxxxxxxxxx Product
?
different

18. If it is of same
therapeutic class
For e.g. Ofloxacin
& Ciprofloxacin

19. If it is of different
therapeutic class
For e.g.
Mefenamic acid 500 mg
& Metformin 500 mg

20. If it is of different
therapeutic class
For e.g.
Mefenamic acid 500 mg
& Glimipride 1 mg

21. 1
2
3
Preservance of purity & Reduction of Uncertainty
Control of Process & Control of Impurities
Isolation & Traceability of manufacturing process

22. Adequate
assessment ?
Cross-
contamination
risk
Manufacturing of
several
hazardous
compounds
High powder
generation
operation
Documented
justification
lacking
Well designed
contamination
prevention
strategy lacking
Absence of
sound design &
control approach
w/o proper
separation ….
Lacks assurance
That drug does
not contaminate
another drug
Teva Pharmaceuticals

23. Inadequate
cleaning
procedure
Incomplete
dis-assembly
Preventive maintenance not
robust to detect potential
contamination
Study of placebo
batches instead of
product for
cleaning
Inadequate study
Cleaning procedure should be
robust to ensure that no or
reasonable residue from
previous batch remains
Apotex, Canada

24. Tab Tramadol
contaminated with
Metoprolol HCl (19
Feb 2008)
Tablet Metoprolol
contaminated with
Metformin (25 Feb
2008)
The investigation
was limited to
Tramadol tab after 2
months
Investigation was
not extended to
closely related …
confirm incident
Other potential
impact was not given
priority
Source of
contamination was
neither isolated nor
confirmed
Continued releasing
of drug product at
the same time
……..
Story ended up with
regulatory actions
Caraco Pharmaceuticals, USA

25. Material contaminated with
tank (a waste tank of API,
Intermediates & Solvents)
Aware in Jan
2012
Complete risk
assessment in
April 2013
In b/w assessment
you distributed
the batches
Some batches
were rejected
Assessment
approaches used
were different
Ended up with
warning
letters
GSK, Cork, Ireland

26. Thanks