Questions, Answers, Comments & Clarifications Obaid Ali Civil Service Officer, Member, ISPE, PDA 26 March 2017
Questions, Answers,
Comments & Clarifications
Obaid AliCivil Service Officer, Member, ISPE, PDA
26 March 2017
Not the view of DRAP
Current judgment
No obligation on DRAP
Regulatory experience
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References US-FDA WHO ICH NRAs
Intermediate Studies
Intermediate Studies Required …. Yes/ No
If Yes ….
When (What is appropriate time to introduce) & Why?
All together with
Accelerated and long term
To encounter in case of
failure of accelerated
Significant change at Accelerated
Condition
What should be done?
If one among the three batches in accelerated conditions
show a significant change
Intermediate data of all three
batches need to be submitted
Furthermore, a failure
analysis focusing discussion
outcome on the observed
discrepancies
Data provision
in weeks instead of months
Can the recommendation for 6 month accelerated
stability data be met by providing 24 weeks of data (as 12 weeks is usually accepted equivalent to 3 months)
No, it cannot be
ICH stability guidance
refer to timeframes in
terms of months not
weeks
One Bulk Solution for
Three Batches
Can the split bulk solution filled into different fill
volumes be considered separate batches?
NO
3 Batches of different
bulk solution, not from a
single bulk solution
Size of lab scale batch
What is meant by Lab (3rd small) scale?
Oral dosage forms
NLT 25% of the
pilot scale batch
Powders/solutions/
suspensions
NLT 25% of the
pilot scale batch Transdermal patches
NLT 60% of the
pilot scale batch
Parenteral
NLT 25% of the pilot scale batch
(50 Lit if unit is > 2ml)
(30 Lit if unit is up to 2ml)
Cream/ Ointment/Gel
Not less than 40% of Pilot
(At least 100 kg or 10% of
proposed commercial batch,
whichever is larger)
Manufacturing outside
GMP zone
Is it acceptable to manufacture small scale batches in a
outside GMP (University etc.)?
NO
All generic submission
batches should
manufactured following
cGMP
Sterile product
in a non-sterile facility
Is it wrong to manufacture small scale batches for sterile
products in a non-sterile facility?
Yes
It is wrong
Sterility, particulate
matter etc. are critical
attributes of sterile
products
Small scale in
commercial equipment
Can a small scale batch be produced at the commercial
drug manufacturing facility?
Yes
It is always good
In this way,
understanding &
knowledge will give
more efficient strategy
of control
Position of Products
in a Stability Program
Is the placement position of drug
in a Stability Chamber, a matter of concern?
For liquids, solutions,
semi-solids and
suspensions, the products
should be placed in an
inverted or horizontal
position and an upright or
vertical position.
In case of routine stability
studies, one should pick
the worst case orientation
Preservative Effectiveness &
Number of Batches
What do you think, how many batches?
1 or 2 or 3 or more
Content in 3 lots Effectiveness in one lot
Extractable Leaching Testing &
Number of Batches
What do you think, how many batches?
1 or 2 or 3 or more
One time
Rationale to go for more
if any change in
container/closure, then
rationale exist
…. Anything you may
contribute ….
Active Pharmaceutical Ingredient &
Generics
How many lots of API
1 or 2 or 3 …. or 5 … or 10 …
Minimum 2 lots for
3 primary batches
But
3 lots for nasal
aerosols or sprays
(formulations)