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)