FINAL L 6 - Quality and the FDA

Question 1

ICH Q10 Objectives

Answer 1

-Achieve product realization
-Establish and maintain a state of control
-Facilitate continuous improvement

Question 2

IND

Answer 2

-Typical Drug substance specifications
-Typical Drug product specifications

Question 3

Common Technical Document

Answer 3

(Slide 32): Module 2, Module 3, Module 4, and Module 5

Question 4

Module 2:

Answer 4

-Quality/overall summary
-Nonclinical overview
-Nonclinical summaries
-Clinical overview
-Clinical summary

Question 5

Module 3:

Answer 5

Quality 3.0

Question 6

Module 4:

Answer 6

-Nonclinical study
-Reports 4.0

Question 7

Module 5:

Answer 7

-Clinical study
Reports 5.0

Question 8

FDA Mission:

Answer 8

Protect the health and safety of consumers by ensuing that drug, biological and medical device products are SAFE and EFFECTIVE and by ensuring that products such as FOOD and COSMETICS are safe and are made under sanitary conditions. Also, to ensure that all product packaging and labeling is truthful, informative and not deceptive

Question 9

Components of an NDA pt.1:

Answer 9

1. Tablet of contents
2. Summary
3. Evaluation of safety and effectiveness
4. Copies of the label and all other labeling to be used for the drug
5. A statement as to whether the drug is (or is not) limited in its labeling and by this application to use under the professional supervision of a practitioner licensed by law to administer it

Question 10

Components of an NDA pt. 2

Answer 10

6. A full list of the articles used as components of the drug
7. A full statement of the composition of the drug
8. A full description of the methods used in, and the facilities and controls used for the manufacture, processing and packing of the drug
9. Samples of the drug and articles used as components
10. List of investigators

Question 11

Components of an NDA -3

Answer 11

11. Full reports of preclinical investigations that have been made to show whether or not the drug is safe for use and effective in use
12. Full reports of clinical investigations that have been made to show whether or not the drug is safe for use and effective in use
13. If this is a supplemental application, full information on each proposed change concerning any statement made in the approved application

Question 12

ANDAs

Answer 12

-Provide for review and approval of generic product (pharm. equivalence; sameness)
-Generic drug product comparable to innovator in:
-Quality
-Performance characteristics
-Intended Use
-Called abbreviated because:
-Do not include preclinical and clinical data
-Instead generic applicants must scientifically demonstrate bioequivalence
-24-36 healthy human volunteers

Question 13

Six Systems:

Answer 13

-Production
-Facilities and Equipment
-Laboratory Controls
-Materials
-Packaging and Labeling
-QUALITY SYSTEM

Question 14

Impurity definitions:

Answer 14

Any component of a drug substance that is NOT the chemical entity defined as the drug substance
-Unwanted coexisting components in bulk pharmaceutical chemicals that arise during manufacture and/or subsequent storage

Question 15

impurity profile:

Answer 15

Description of the identified and unidentified impurities present in a new drug substance
-Monitored on an ongoing basis through stability studies

Question 16

Impurity Profiles:

Answer 16

Determined at the time of:
-IND filing
-NDA filing
-Post NDA approval
-ANDA filing
Reconfirmed after changes in:
-Synthesis of the bulk drug substance
-Drug product process or formulation

Question 17

ICH Q3A Impurities in New Drug Substances (R2) October 2006

Answer 17

Organic:
-Process related and drug substance related
-Last step intermediates
-Reagents (carried over as trace impurities)
-Side reactions (incomplete reaction, over reaction, isomerization, rearrangement)
-Impurities in starting materials (positional isomers) or their reaction products
-Degradation products
Inorganic:
-Reagents, ligands, and catalysts
-Heavy metals or other residual metals
-Inorganic salts
-Other materials (eg, filter aids, charcoal)
-Residual solvents

Question 18

ICH Q3A meaning

Answer 18

International committee of harmonization guidance (there are about 14 and they provide everyone with an outline of drug quality)

Question 19

USP Chapters Regarding Impurities

Answer 19

<197> Spectrophotometric Identification Tests
<232> Elemental Impurities-List
<233> Elemental Impurities-Procedures
<466> Ordinary Impurities (phasing out)
<476> General Chapter
<467>Organic Volatile impurities
<1086> Impurities in Drug Substances and Drug Products

Question 20

Impurities Schematic

Answer 20

-Starting Materials
-Intermediates
-Drug Substance
Introduced during manufacture
Degradation
Reaction byproducts

Question 21

Thresholds for impurities

Answer 21

-1,Max Dose
-2,3Reporting 3,Threshold
-3,Identification Threshold
-3,Qualification Threshold
1 - The amount of drug substance administered per day
2-Higher reporting thresholds should be scientifically justified
3 - Lower thresholds can be appropriate if the impurity is unusually toxic