Salient points of boyd lectures

Question 1

NDA Components

Answer 1

Drug substance consists of:

General information: Nomenclature, structure, general properties
Characterization: Elucidation of structure and other characteristics, likely impurities to be present (i.e. hydrolysis product)
Control of drug substance: Specification, Analytical procedures, Validation of analytical procedures, Batch analysis and justification of the specification.
Stability: Stability summary and conclusions, Stability data

Drug product consists of:

Product description and composition:
Manufacture:
Control of excipients: Specification, Analytical procedures, Validation of analytical procedures, Batch analysis and justification of the specification.
Control of drug product: Specification, Analytical procedures, Validation of analytical procedures, Batch analysis and justification of the specification.
Container closure:
Stability: Leachables and extractables

Question 2

NDA purpose

Answer 2

The document hence exists to ensure verify the quality of the product to regulatory authorities and also provides a reference for the company to ensure that the batches it produces meet these standards of quality.
The batch record shows that the quality standard is maintained, with the results of the tests specified in the product specification thereby assuring the quality of that specific batch.

Question 3

Pharmacopeia, monograaphs

Answer 3

• Provide standardized tests for medicinal products and goods. This ensures that people follow the same standards in ensuring quality of a product. Provides standard tests, analytical methods and acceptance criteria

Information is collected into monographs. Which seek to ask:

• What is it and how do we prove it ?
• What is its quality and how do we test it ?
• How much is there and how do we quantify it ?

Medicinal substance monographs i.e. paracetamol

Identification: What is it

• i.e. use IR or MP analysis

Tests: What is its quality

• appearance on solution
• loss on drying
• heavy metals

Assay: How much ?

i.e. Titration, HPLC

• General monographs: general tests for a dosage form i.e uniformity of content
• Specific monographs: for a specific medicinal substance in a dosage form i.e. paracetamol tablets

Question 4

Modified release, relating studies

Answer 4

• Modified release formulations are advantageous as they allow for the modification in dose frequency which can improve product in nature and also patient compliance
• A sipping study is a proof of concept study which simulates the rate of modified release input whereas a regional drug absorption study uses a electromechanical capsule device to match drug release to absorption in different areas of the GI tract

Question 5

Extractales and leachables (definition)

Answer 5

Extractables are chemical compounds which are known to migrate into solution under controlled conditions. Extractables are used to identify and qualify potential leachables.

Leachables are components of a container closure system which will migrate into a drug product over the course of its shelf life. Leachables are usually present in drug product matrices at trace levels

Question 6

Design of an extractable leachables study:

Answer 6

• Potential leachables within the primary container closure system are stressed in at least two different solvents with varying solvating power i.e. water and methanol. Solvating power should not be too strong otherwise all material will extract. Products are then incubated under stressful conditions for varied amounts of time. I.e 100 C for 2 hours, 50 C for 10 hours 37 C for 24 hours
• The solvent then undergoes analysis, major means are LCMS and GC