chapt 1 CGMP

ways to obtain modern pharmaceuticals

• molecular optimization

• computer modeling

• genetic engineering

molecular optimization

changing the chemical structure of existing molecules

computer modeling

using computers to design new drugs

genetic engineering

the ultimate treatment - gene therapy

odds of molecule screened making it to market as new drug

one in every 5000-10000

new drug development process

• screen thousands of compounds, identify lead compounds useful to biological activity

the new drug development process

1. drug discovery

2. selection of potential drug candidate

drug discovery 4

• natural product screening

• hypothesis testing

• computer modeling to modify an existing drug/design

• high-throughput screening

selection of potential drug candidate

• initial product characterization

  • pre-formulation studies

pre-formulation studies 5

• physico-chemical properties

• dosage form design

• patenting

• pre-clinical testing

• clinical trials

physico-chemical properties

1. solubility

2. stability

3. crystal structure

dosage form design

oral-tablets/capsules,

injections,

topical

patenting

• patent application lasts 20 years

• non-obviousness but sufficiency of disclosure

• more details the better chances of securing a patent

pre-clinical testing

check for:

• quality

• safety

• efficacy

clinical trials

• show the regulatory authorities that the claims being made for the medicine have a scientific basis

clinical trial phases

• phase 1: healthy volunteers

• phase 2 and 3: patient volunteers

phase 1

• 20 to 100 healthy human volunteers

• determine safety and dosage

• physiological measurements taken

• duration: 3-6months

phase 2

• several hundred patients

• 6 months-2years

• evaluate effectiveness, look for side effects

• blind trails (placebo vs drug)

blind trial

• drug vs placebo

• single blind trial: patients do not know if they are receiving the drug or placebo

• double blind trial: both patient and clinical investigators do not know which agent the patient is receiving

phase 3

• several hundred to several thousands patients

• 1 to 5 years

• confirm effectiveness

• monitor long term effects

phase 4

• post market surveillance

post market surveillance

• drug company can apply to regulatory authorities to register and market the drug

• only 1 in 3 drugs succeeds

• company must still monitor performance of drug while still in the market

• withdrawal of a drug from the market is not uncommon (thalidomide)

why do pharmaceutical industry need to increase R&D productivity

• average cost per new prescription drug 2.6B

• about 12 out of 100 drugs that begin human clinical testing will eventually get approved

• increased regulatory hurdles will impact drug approvals

drug manufacturing process

• one of the most highly regulated and rigorously controlled manufacturing processes known

producer has to?

• prove to the regulatory authority that:

• the product itself is safe and effective

• all aspects of the proposed manufacturing process comply with highest safety and quality standards

overview of production process

1. primary process

   • production of bulk drug (API)

2. secondary process

   • bulk drug to packed dosage form

possible product line of a company

• tablets

• capsules

• liquids

possible product line of a company for tablets

• coated

• multi-layer

• repeat dosage

possible product line of a company capsules

• sustained release

possible product line of a company for liquids

• external

• oral