Case Studies

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

Case

Study 1

Lets have a look at

Real CasesFrom the personal

experience

A very famous product

Everybody knows about it

Millions of capsules/week manufactured since

years and years

Stability failed

100’s of batches recalled

Factory shut down for years

Several people lost their jobs

Corporate could not sustain

Source of gelatin was changed

Assessment was weak

Change impact was not appropriately studied

Stability program was weak

Inspector asked to perform disintegration

test of capsule manufactured a year before

A month old batch found not qualified for

disintegration test

Failed

Failed

Failed Failed Failed

Characterization of Gelatin is very difficult

Because it is from natural source

Storage, Transportation and its Handling require narrow

control range for humidity & temperature

A lot of variation potential

Lets Understand Gelatin

Case

Study 2

Fluocinonide Cream 0.05% (36 month shelf life)1

24 Lots

21 Lots Complied

3 lots failed

SD RSD

T

M

B

6%

Fluocinonide Cream 0.05% (36 month shelf life)1

6% Uniformity

?

Fluocinonide Cream 0.05% (36 month shelf life)1

Fluocinonide Cream 0.05% (36 month shelf life)1

3 6

9 12

15 18

21 24 27 30 33 36

Tube

Uniformity

failed

T

M

B

Important

characteristic

failed

Fluocinonide Cream 0.05% (36 month shelf life)1

Shelf life

determination is

not correct

Is it not correct to suggest that

Stability Program is Deficient

Lets keep catching and walking

together with clarity

Commitment on 3 month data

Can a generic product filed with 3 month data and

committed to provide 6 month data in future be accepted?

No, 6 month stability data is

required

Decommissioning of Commissioning

How long do pilot scale batches need to be stored before

they can be destroyed?

At least one year after approval

Manual Operations

Can small scale batches be packed by hand?

No, always avoid doing

anything which is critical in

process by hand

Math with other Science

Can mix and match approach be applied, for e.g. one

batch at 6 month and 2 batches at 3 month

No, not at all

Use math with clear understanding