3 ROOA (Cross Pollination of Misconceptions related to Stability Studies and Shelf Life)

Misconceptions & its Cross-Pollination

An Instrument to Damage Evolution Process of

Pharmaceutical Development

Roohi B. ObaidCivil Service Officer, Member, ISPE, PDA

26 March 2017

Misconception Myth

Misconception 1 of 3

API

Batch 1

Batch 2

Batch 3

Batch 4

API

Expiry Expiry

FG

Mfg Mfg

API

Expiry Expiry

FG

Mfg Mfg

Relationship ???

API

Expiry Expiry

FG

Mfg Mfg

Relationship ???

If life of a raw

material is more,

the shelf life of

drug product will

be more

?

1

If life of a raw

material is more,

the shelf life of

drug product will

be more

If life of a raw

material is less,

the shelf life of

drug product will

be more

?

?

?

1

2

If life of a raw

material is more,

the shelf life of

drug product will

be more

If life of a raw

material is less,

the shelf life of

drug product will

be more

If life of a raw

material is more,

the shelf life of

drug product will

be less

?

?

?

?

1

2

3

Lets resolve

We know

Both DS & DP

have their own

manufacturing

& own

life/period

Raw Material

Drug Product

StabilityLets resolve

We know

Both DS & DP

have their own

manufacturing

& own

life/period

Expiry/retest date of

Drug Substance Expiry date of

Drug Product

Relationship ?

Expiry/retest date of

Drug Substance Expiry date of

Drug Product

Relationship ?

Yes/ No

Life of raw material will

increase life of product

Life of raw material will

increase life of product

Life of raw material will

decrease life of product

Batch 1

Inj. Gentamicin is

manufactured in Jan

2015 in which expiry of

used API was Feb 2015

Batch 1

Inj. Gentamicin is

manufactured in Jan

2015 in which expiry of

used API was Feb 2015

Batch 2

Inj. Gentamicin is

manufactured in Jan

2015 in which expiry of

used API was Feb 2018

Batch 1

Inj. Gentamicin is

manufactured in Jan

2015 in which expiry of

used API was Feb 2015

Batch 2

Inj. Gentamicin is

manufactured in Jan

2015 in which expiry of

used API was Feb 2018

Different Same BothExpiry may be

Batch 1

Inj. Gentamicin is

manufactured in Jan

2015 in which expiry of

used API was Feb 2015

Batch 2

Inj. Gentamicin is

manufactured in Jan

2015 in which expiry of

used API was Feb 2018

Expiry may be Different Same Both

Batch 1

Inj. Gentamicin is

manufactured in Jan

2015 in which expiry of

used API was Feb 2015

Batch 2

Inj. Gentamicin is

manufactured in Jan

2015 in which expiry of

used API was Feb 2018

Different Same BothExpiry may be

Both are

Independent

Both are

Independent

Both based

on study

Both are

Independent

Both based

on study

There is NO

relationship

Lets make Science visible to catch

Philosophy and Logic behind the

Principle of Stability

Take a look at Scenario “A of B”

Jan to Dec 2015

Jan to Dec 2015

Feb

2015

Jan to Dec 2015

Feb

2015

May

2015

Jan to Dec 2015

Feb

2015

May

2015

Aug

2015

Jan to Dec 2015

Feb

2015

May

2015

Aug

2015

Nov

2015

Saturday Monday

TuesdayFriday

Take a look at Scenario “B of B”

Whose life is greater & what is maximum life

Suppose life is 10 days best to use,

impact will be observed everyday

If converted to pickle, life of product

is more likely to increase many fold

A January 2015

B March 2018

C February 2017

D November 2019

E April 2015

Raw material & their Expiries

What will

be its expiry

now?

Drug

product

Mfg started

in Dec 2014

Misconception 2 of 3

Lets try to resolve

Date of Manufacturing & Date of Expiry

Drug

Substance

Processed

(pellets)

Drug

Product

Can expiry of Pellets (Drug) remain same upon

converting into finished drug product via primary

packaging

Scenario

A of B

Do humidity and temperature have an impact on Pellets (Drug)?

Do humidity & temperature have relation with Primary Packaging?

Does this relation has an impact on shelf life?

1

2

3

Do humidity and temperature have an impact on Pellets (Drug)?

Do humidity & temperature have relation with Primary Packaging?

Does this relation has an impact on shelf life?

1

2

3

Yes

Yes

Yes

Drug Substance

PelletsFinished Product

X year Y Year Z Year

Conclusively based on Study

Nothing More, Nothing Less

Can expiry of Bulk Powder (Ceftriaxone Sodium)

remain same upon filling into Unit Dosage Form

Packaging as Finished Drug Product

Scenario

B of B

Do humidity and temperature have an impact on Bulk Powder (Drug)?

Do humidity & temperature have relation with Primary Packaging?

Does this relation has an impact on shelf life?

1

2

3

Do humidity and temperature have an impact on Bulk Powder (Drug)?

Do humidity & temperature have relation with Primary Packaging?

Does this relation has an impact on shelf life?

1

2

3

Yes

Yes

Yes

Drug Substance

Finished Product

X year Y Year

Conclusively based on Study

Nothing More, Nothing Less