L3 Quality & preclinical development

Question 1

What is the quality of a product thought to be?

Answer 1

The degree to which a final product batch matches predetermined specifications for that product

Question 2

What are 6 characteristics considered in quality?

Answer 2

Identity
Purity
Potency
Uniformity
Bioavailability
Stability

Question 3

What is the difference between quality control & assurance?

Answer 3

Control is product focused (reactive)
Assurance is process focused (preventative)

Question 4

What does QA do?

Answer 4

Builds in quality to the production process & burden of QC is reduced

Question 5

What are 3 areas of QA/

Answer 5

Product selection
Selection of appropriate supplier
Product certification

Question 6

What is the International Organization for Standardization?

Answer 6

International standard setting body that promotes internationally recognised proprietary, industrial & commercial standards

Question 7

Is ISO governmental?

Answer 7

No - reps from various national standards organisations

Question 8

What is Ireland’s ISO?

Answer 8

NSAI

Question 9

Are ISO standards sufficient for pharmaceuticals & food?

Answer 9

No - lack detail & enforceability

Question 10

What is pharma QA?

Answer 10

sum of all activities & responsibillties required to ensure medicine that reaches pt is safe, effective & acceptable

Question 11

What is pharma QC?

Answer 11

Concerned with medicinal product sampling, product specs & testing to ensure compliance

Question 12

What are GxP standards?

Answer 12

Collective term for good practice quality standards used in many industries but particularly medicines, medicinal products & foods

Question 13

What 2 things does GxP standards allow?

Answer 13

Traceability
Accountability

Question 14

What do GxP & ISO focus on?

Answer 14

QA

Question 15

What is the difference between ISO & GxP?

Answer 15

ISO = generic, compliance is flexible
GxP = detailed & mandatory standards

Question 16

What is GMP?

Answer 16

Industry-specific standard prescribing what process & elements must be present to ensure product safety

Question 17

What can the NCA do with GMP?

Answer 17

Audit & inspect companies for GMP compliance

Question 18

What are GMPs designed to do?

Answer 18

Minimize risks to the quality of any pharma product that cannot be eliminated through testing the final product

Question 19

What are 4 things do GMP guidelines ensure?

Answer 19

Creation of SOPs
Document & record all work
Validate work
Perform quality surveillance of product componenets

Question 20

What 8 regulatory criteria does CMC reg affairs ensure?

Answer 20

Operations of manufacturing team
QC
QA
Supply chain integrity
Labelling and packaging
Interactions with regulators
Authoring & maintenance of Regulatory Dossiers
Communications regarding quality of product

Question 21

What are 3 controls to ensure product quality?

Answer 21

In-process controls
Specifications for testing drug substance & drug product
Stability of the product

Question 22

What are 4 things involved in chemistry?

Answer 22

Synthesis of DS
Structure
Composition of DP
Raw materials

Question 23

What are 3 things involved in manufacturing?

Answer 23

Description of process
Description of equipment used
facility info

Question 24

What is the aim of preclinical development?

Answer 24

To satisfy all regulatory requirements that have to be met before the new compound is deemed ready to be tested for first-in-human trials

Question 25

What are 3 main areas of activity in Preclinical Dev?

Answer 25

Formulation studies Synthesis scale-up Safety/toxicty studies

Question 26

What % of drug candidates survive preclinical testing?

Answer 26

10

Question 27

What does GLP define?

Answer 27

Good practices for non-clinical lab studies that support research or marketing approvals for medicines

Question 28

What 7 things does GLP cover?

Answer 28

Personnel Facilities Equipment Methods Storage Reagents & solutions QA system Study design & implementation Reporting & authoring

Question 29

What does loss of GLP result in?

Answer 29

Loss of GLP-status Invalidation of past work

Question 30

What 6 things does preclinical safety & toxicology studies cover?

Answer 30

Proof of principal (doesnt have to be under GLP) Characterise PK of IMP Identification of toxicological hazards To define parameters for safe transition to human clinical studies Assess business risks Overall strategy as per ICH M3

Question 31

What are 3 in vitro and in vivo pharmacology testing?

Answer 31

Pharmacodynamics PK Safety

Question 32

What does toxicology testing do?

Answer 32

Investigation of adverse effects of IMP (and any proposed excipients)

Question 33

What is primary PD?

Answer 33

Effects of IMP on body mediated by interaction with intended target

Question 34

What does safety pharma assess?

Answer 34

Assess impact of IMP on function of essential body systems as consequence of direct pharmacological activity

Question 35

What are the 3 core battery?

Answer 35

CNS CVS Respiratory

Question 36

What 4 things can safety pharmacology also include?

Answer 36

Renal ANS GI Drug interaction studies

Question 37

When does a drug interaction occur?

Answer 37

When admin of 1 drug alters response to another drug

Question 38

What 3 ways can drugs interact via?

Answer 38

Same site of action Different sites of action with same physiological endpoint Metabolic induction or inhibition

Question 39

What does specific types of toxicity tests performed depend on?

Answer 39

Type of substance, regulations in intended market and nature of use of test agent

Question 40

What are 4 toxicology tests?

Answer 40

Animal toxicology tests (in vivo) Alternative 'in vitro' toxicology testing Toxicology testing on isolated organs/tissues (ex vivo) In silico modeling

Question 41

What does toxicity testing invlove?

Answer 41

Examination of nature of adverse effects & assessment of probability of their occurrence in humans

Question 42

What are 7 toxicity areas in preclinical development?

Answer 42

1. acute - single high dose to rodents 2. chronic - physiological/pathological changes to target organs after repeat dosage 3. reproductive & teratogenicity - ongoing admin at 3 levels to rodents. Males for 60 days & females dosed 14 days before being mated. 4. mutagenicity - in vitro & in vivo 5. carcinogenicity - identify tumorigenic potential in animals & assess relevant risks 6. others -ocular/skin/hypersensitivity/phototoxicty/behavior 7. local - mechanical effects of drug admin/chemical effects & true toxicologgy effects

Question 43

What did the Animal Welfare Directive 2010/63/EU?

Answer 43

Application of 3R

Question 44

What are the 3 Rs?

Answer 44

Replacement - use of animals to greatest extent possible with alternative testing methods Refinement - of scientific procedures to improve animal welfare Reduction - in numbers of animals used

Question 45

What is the ERA?

Answer 45

Evaluation of potential environmental risks posed by a medicinal product

Question 46

What 3 things is ERA required for?

Answer 46

1. All new MAAS for a medicinal product through a centralised, mutual recognition, decentralised or national procedure 2. Type II variation resulting in an increase in environmental exposure 3. Extension application resulting in an increase in environmental exposure

Question 47

What are 6 exemptions to the ERA?

Answer 47

Vitamins Electrolytes AAs, peptides, proteins Carbohydrates & lipids Herbals Vaccines