Exam 3- Lecture 4: Shelf-life & Stability

Why is stability important?

• Stability studies & their interpretation provide a mechanism that ensures safety, efficacy, & quality of drug products throughout their lifecycle

• A drug product’s stability provides an immediate impact on expiration date, storage conditions, & patient based outcomes

• Stability studies are required by FDA & many other regulatory bodies

What is chemical stability?

Drug potency (concentration)

What is physical stability?

Appearance, dissolution, phase matter

What is microbiological stability?

• Sterility

• Preservative

• Effectiveness

What is therapeutic stability?

Efficacy

What is toxicological stability?

Toxic metabolites

What are factors impacting drug product stability?

• Environmental

• Formulation

• Packaging

What are environmental factors?

• Temperature

• Humidity

• O2

What are formulation factors?

• pH

• Excipients

• Dosage form

What are packaging factors?

• Containers

• Vials

• Blister packs

• Enclosure

• Closure systems

What does long-term (real-time) stability testing attempt to understand?

Impact of various factors on drug product under conditions it is recommended to be stored at

What does accelerated stability testing use?

Elevated storage conditions to speed degradation, & uses reasonable mathematical models to estimate drug product stabiltiy

What kinetics might be applied follow accelerated stability tests?

Arrhenius kinetics

What do intermediate stability tests provide?

A mechanism attain stability data quicker than long-term testing, but in conditions that are less harsh than accelerated stability testing when those tests provide clear results

What does stress testing utilize?

Extreme conditions to identify degradation pathways

• Hydrolysis

• Oxidation

• Photodegradation

• Thermal degradation

• pH-dependent degradation

• Physical instability issues

What are stability tests conducted utilizing?

Controlled environmental stability cabinet w/ more specialized equipment used to perform stress tests

What is a stability commitment?

A promise the manufacturer makes to perform long-term stability testing on large scale, production batches confirming the product maintains quality though labeled shelf-life

What does stability data obtained using accelerated & stress stability tests support?

Initial approval of drug, while stability data obtained from a batch designated in a stability commitment confirms that a drug product is stable consistent w/ its labelled shelf-life

What is an expiration date?

Last date a product is guaranteed by MANUFACTURER to retain > than 90% label claim, safety, & quality

What is beyond use date?

Date after which a compounded or altered product should NOT be used & assigned by compounding PHARMACIST

What are the aspects to an expiration date? (Know)

• Assigned by manufacturer

• Applies to commercial products

• Basis: extensive stability data

• Packaging: original container

• Microbial risk: controller/validated

• Typical length: longer

What are the aspects of beyond-use date (BUD)? (Know)

• Assigned by pharmacist

• Applies to compounded/reconstituted/altered

• Basis: limited data & guidelines

• Packaging: new/altered container

• Microbial risk: often a key limitation

• Typical length: shorter

What is shelf-life (t90)?

The time it takes for a drug product to degrade such that it retains 90% of labelled potency (active ingredient) & therefore remains stable

What is t90 (shelf life) determined by?

Manufacturer during stability studies & tested even after product hits shelf to ensure labelled expiration date is accurate