C1: Where do Drugs and Medicines come from ? Flashcards
(46 cards)
What is the components of QA + what do they control
- GLP - Good Laboratory Practice (Labs and
Animal tests) - GCP - Good Clinical Practice (Human Clinical
trials) - GMP- Good Manufacturing Practice
(Production)
— Quality control - GPvP- Good Pharmcovigilance Practice (After
launch)
What is quality by design
A systematic approach to development that
begins with predefined objectives and
emphasizes product and process
understanding and process control, based on
sound science and quality risk management
Good clinical practise
international ethical and scientific
quality standard for designing, conducting,
recording & reporting trials that involve
participation of human subjects
Good laboratory practise
Good laboratory practice embodies a set of
principles that provide a framework within which
laboratory studies are planned, performed ,
monitored, recorded, reported and archived
Assures that data submitted to regulatory authorities
is a true reflection of results obtained during a study
& can be relied upon when making risk/safety
assessments
Good manufacturing practise
The part of quality assurance which is aimed at ensuring
that products are consistently manufactured to a quality
appropriate to their intended use
Quality is fitness for purpose
- Right product
- Right strength
- Free from contamination
- Correct container
- Correct label
Why Do We Need GMP
- Pharmaceuticals are the only product specifically
designed to be given to people who are already ill! - Pharmaceuticals are potent substances which can
improve or maintain life - Impossible to judge the quality of pharmaceuticals
visually
What aspects does GMP control
- Personnel
- Premises and Equipment
- Documentation
- Quality Control
- Complaints and Product Recall
Personnel
Key personnel
- Head of Production
- Head of Quality Control
- Qualified Person
Head of Production and Head of Quality Control must be
independent of each other
Qualified person (EU only)-legal and personal liability to ensure that the principles and guidelines of GMP have been followed - Training required for all personnel - Personal hygiene standards must be maintained
Premises
- Minimise the risk of cross contamination
- Maintenance procedures must be in place
- The environment in the facility should be controlled to ensure that it does not affect product quality
- Adequate pest control procedures should be in place
- Access to the production environment should be controlled
- The design of production areas should facilitate cleaning
Equipment
- Manufacturing equipment should be designed, located and maintained to suit its intended purpose
- Equipment should be designed so that it is easily cleaned
- Effectiveness of cleaning procedures must be demonstrated
General Documentation Principles
- Documentation provides enhanced process control and enables batch history to be traced
- Records should be made at the time the action is taken
- Records should be maintained for a year after the end of the product shelf-life
Documentation Used in GMP
- Standard operating procedures (SOPs )- how to carry out procedures
- Batch records -Provide a detailed history of a product
batch - Labelling (materials, products, equipment, rooms)
- Log books for equipment and rooms
- Test methods: there should be written procedures for
testing materials and products - Specifications- physical, chemical or microbiological
criteria that the material/product must meet - Problem investigations-Initiated following an unusual or
unwanted occurrence.
Complaints + product recall
- Written procedures should be available detailing the action to be taken in the event of complaint
- Complaint records should be reviewed regularly to identify trends and recurring problems
- Complaints relating to serious quality problems should be notified to the relevant regulatory authorities
- It should be possible to initiate recall procedures swiftly
- Relevant regulatory authorities (MHRA in the UK) must be informed of any product recall.
Complaints + product recall
- Written procedures should be available detailing the action to be taken in the event of complaint
- Complaint records should be reviewed regularly to identify trends and recurring problems
- Complaints relating to serious quality problems should be notified to the relevant regulatory authorities
- It should be possible to initiate recall procedures swiftly
- Relevant regulatory authorities (MHRA in the UK) must be informed of any product recall.
What are the origins of the pharmaceutical industry?
Pharmacy, Chemistry + Microbiology
When was the ‘golden age’ of drug discovery?
1940s-1960s is regarded as the “Golden Age”
- wide range of diseases came under control
“miracle cures” – with spectacular benefits to patients
Why may we be entering a new ‘golden age’ of drug discovery?
In this century our new ability to develop ‘biologics’
promises another Golden age
What are Biologics
Analogues, extracts, or modified versions of active biological compounds - Antibodies - Proteins - Nucleic acids
How come the golden age success did not work
The same formula for success was used in the 1970s-80s but huge commitment to R&D intensive marketing and promotion
What problems are faced by the pharmaceutical industry?
1) Tighter Government regulatory controls on development and marketing
2) Governments want to reduce costs of healthcare = - Cheaper ‘ Generics’ now favoured: reduced profits for industry
3) Success of companies depends on their innovation (But other companies may develop similar drugs, which dilutes
any new market)
4) R&D commitment is out of balance with cash flow (It costs $ 100s of millions to bring a new drug
to market; Companies must therefore develop ‘blockbuster’ drugs)
5) Prolonged development time for a new product means a reduced time (for sales and profits) when drug is under patent
—- Patent life is only 20 years, and you may spend 10 years testing, developing and getting approval for the product.
6) Earlier “Random synthesis” approach to finding drugs is now too hit and miss. (To find a new drug you have to be far more sophisticated; Companies must adopt a rational drug design)
Major sources of new drugs
(A) Chemical synthesis.
(B) Old compounds with a new use.
(C) ‘Natural Products’ Natural molecules with drug activity
from microorganisms, plants, animals and human sources.
(D) New drugs (chemicals or biological molecules)
synthesized using a knowledge of the proposed site of
action. This is called rational or targeted drug design
and is a more effective strategy than random synthesis.
Computer-based molecular models of
drugs/receptors/proteins used.
Natural product source
Drugs from plants, marine organisms,
bacteria, fungi, animals, human origin.
- 60% current drugs originate plant/microbial sources
- Only a fraction of Earth’s living species have been tested for activity
- Current effort : secondary metabolites
as sources of new drugs.
Targeted drug-design & synthesis source
Based on current knowledge of cellular/biochemical
mechanisms & receptor sites :
- Most targets are proteins especially G-protein coupled
receptors (GPCRs) & protein kinases.
- Computer/theoretical models are used to predict activity of new molecules
—-QSAR - Quantitative Structure-Activity Relationships
—-CADD - Computer-Aided Drug-Design
- Chemical modifications are used to improve potency,
bioavailability, duration of action and reduce side-effects
How is a lead compound identified ?
- Chemical Libraries & computer design
- New biological targets / medical conditions
- Advances in biological knowledge
- Human Genome Project ( completed 2003)
- Biological agents as drugs (‘Biologics’)
- Automated Screening Methods
