INTERNATIONAL DRUG STANDARDS

REGULATIONS
Federal control for the protection of consumers who used
drugs did not exist until the beginning of the twentieth century.
After a number of catastrophic incidents in which death
resulted from the use of adulterated drugs, the first federal
statutee controlling the manufacture of drugs was passed – the
Food and Drug Act of 1906. It required that all drugs marketed
in the United States meet minimal standards of strength, purity
and quality.

The act also established the U.S. Pharmacopoeia (USP)

and the National Formulatory (NF) as the official legal
standards for drugs in the United States. Federal Food, Dru
and Cosmetic Act of 1938 added the requirement that a drug be
shown to be safe before it could be distributed in interstate
commerce.

An amendment to this act known as the

Durham-Humphrey Amendment, was enacted in 1952. It
required that certain drugs be classified as legend drugs and
that they be labelled with the legend “Caution- Federal law
prohibits dispensing without prescription.” It also specified that
all other drugs approved for use be considered
nonprescription drugs. These could be sold directly to the
consumer without the need for a prescription.

In 1962, this act was again amended by the Kefauver -

Harris Amendment. It added the requirement that both
prescription and nonprescription drugs be shown to be
effective as well as safe.

This was followed in 1970 by the Comprehensive Drug

Abuse Prevention and Control Act also known as Controlled
substance Act of 1970 which further classified drugs according
to their potential for physical or psychological dependence
and abuse. It also regulated the manufacture and distribution
of drugs considered capable of causing dependence.

As a result of these federal statutes, all drugs may be

classified into Four Categories:
1. Prescription or legend drugs
○ Before such drugs can be marketed in the United
States, the manufacturer must file a New Drug
Application (NDA) with the FDA.
○ This action must include a detailed description of the
drug, it’s toxicity and the results of all experimental
clinical trials of the drug in clients.
○ May be prescribed by health care providers, dentists,
veterinarians, or other legally authorized health
practitioners as part of their specific practice.
2. Nonprescription or over the counter (OTC) drugs
○ Drugs that may be legally acquired by the client
without a prescription are known as nonprescription
or OTC drugs.
○ Such agents are considered to be relatively safe for
the lay person to use when taken according to
directions provided by the manufacturer and when
given to treat conditions for which they are intended.
○ Even though a prescription is not required for their
purchase, OTC medications are capable of producing
considerable toxicity if they are not used in
accordance with their labelled direction.
○ Vitamins and herbal agents currently do not require
FDA approval for safety and efficacy.
3. Investigational drugs
○ To fulfill the requirements of the FDA, a manufacturer
that seeks to market a new drug must perform a wide
 array of animal studies and carry out clinical testing
of the drug in human subjects.
○ To accomplish this, the manufacturer must file a
“Noticce of Claimed Investigational Exemption for a
New Drug (IND) with the FDA.
○ Clinical studies performed on human subjects prior
to the marketing of a drug are usually divided into
four phases.
4. Illicit or street drugs
○ They are used and distributed illegally.
○ They may be
i. Drugs that are not legal for sale under any
circumstances in the Unite States Eg. Heroine
ii. Drugs that may be sold legally under certain
circumstance (e.g. With a prescription) but that
have been manufactured illegally or diverted or
stolen from normal channels of distribution.
5. Orphan Drugs
○ The Drug Enforcement Administration and the
Orphan Drug Acts (1983)
○ They are drugs that have been discovered but are not
financially viable and therefore have not been
“adopted” by any drug company.

STAGES OF DRUG DEVELOPMENT

1. Pre-Clinical Trials
○ Chemicals that may have therapeutic value are tested
on laboratory animals for two main purposes:
i. To determine whether they have the presumed
effects in living tissue
ii. To evaluate any adverse effects
○ Animal testing is important because unique
biological differences can cause very different
reactions to the chemical.
 ○ At the end of the preclinical trials, some chemicals
are discarded for the ff reasons:
i. Chemicals lacks therapeutic activity when used
with living animals
ii. Chemicals is too toxic
iii. Chemicals are highly teratogenic
2. Phase I Studies
○ Uses human volunteers to test the drugs.
○ These studies are more tightly controlled than
preclinical trials and are performed by specially
trained clinical investigators.
○ The volunteers are fully informed of possible risks
and may be paid for their participation.
○ Usually the volunteers are healthy, young men.
○ Investigators in Phase I studies scrutinize the drugs
being tested for effects in human.
○ Many chemicals are dropped for the ff reasons.
i. They lack therapeutic effect in humans.
ii. They cause unacceptable adverse effects.
iii. They are highly teratogenic.
iv. They are too toxic.
○ Some chemicals move to the next stage of testing
despite undesirable effects.
○ Like the hypertensive drug: Minoxidil (Loniten) was
found to effectively treat malignant hypertension but
it caused unusual hair growth on the palms and other
body areas.
3. Phase II Studies
○ Allows clinical investigators to try out the drug in
patients who have the disease that the drug is
designed to treat.
○ Patients are told about the possible benefits of the
drug and are invited to participate in the study.
○ Various sites across the country.
 ○ May be removed from further investigation for the
following reasons:
i. It is less effective than anticipated
ii. It is too toxic when used with patients
iii. It produces unacceptable adverse effects
iv. Has low benefit to risk ration - therapeutic
benefit it provide does not outweigh the risk of
potential
4. Phase III Studies
○ Involves use of the drug in a vast clinical market
○ Prescribers are informed of all the known reactions to
the drug and precautions required for its safe use.
○ Patients will be observered very closely and
monitored.
○ Asked to make journals and record any symptoms
they experience
○ Drugs that finish Phase III studies are evaluated by
the FDA, which relies on committees of experts
familiar with the specialty area in which drugs will be
used
○ Only those drugs that receive FDA committee
approval may be marketed.
5. Phase IV studies
○ After a drug is approved for marketing, it enters a
phase of continual evaluation.
○ Prescribers are obligated to report to the FDA any
untoward are unexpected adverse effects associated
with drugs.
SAFETY DURING PREGNANCY

FDA PREGNANCY CATEGORIES

Category Description
Adequate studies in pregnant women have not
demonstrated a risk to the fetus in the first
Category A
trimester of pregnancy, there is no evidence of
risk in later trimesters.
Animal studies have not demonstrated a risk
Category B to the fetus but there are no adequate studies
in pregnant woman or animal studies.
Animal studies have shown an adverse effect
on the fetus but there are no adequate
Category C studies in humans; the benefits from the use
of the drug in pregnant women may be
acceptable despite its potential risk.
There is evidence of human fetal risk, but the
potential benefits from the use of the drug in
Category D
pregnant women may be acceptable despite
its potential risk
Studies in animals or humans demonstrate
Category X fetal abnormalities or adverse reaction;
reports indicate evidence of fetal risk
CONTROLLED SUBSTANCES SCHEDULES
The Controlled Substances Act of 1970 regulates the
manufacturing, distribution, and dispensing of drugs that are
known to have abuse potential.
❖ Schedule I (C-I)
➢ Drugs in Schedule I have a high potential for abuse
and no accepted medical use in the United States.
➢ Eg. Heroin, LSD, Ecstasy
❖ Schedule II (C-II)
➢ Drugs in Schedule II also have a high potential for
abuse, but do have a currently accepted medical use
in the United States. It has been determined that
abuse of a drug included in this schedule may lead to
a severe psychological or physical dependence.
➢ Eg. Meperidine, morphine, cocaine, oxycodone
❖ Schedule III (C-III)
➢ Schedule III drugs have accepted medical uses in the
United States, but they have a lower potential for
abuse than drugs in Schedules I and II
➢ Eg. Acetaminophen with codeine, hydrocodone
❖ Schedule IV (C-IV)
➢ Schedule IV drugs have a low potential for abuse
relative to Schedule III drugs. Abuse of Schedule IV
drugs may lead to limited physical or psychological
dependence as compared with Schedule III drugs.
➢ Eg. Librium, Valium
❖ Schedule V (C-V)
➢ Schedule V drugs have the lowest abuse potential of
the controlled substances. They consist of
preparations containing limited quantities of certain
narcotic drugs generally used for antitussive and
antidiarrheal properties.
➢ Eg. Lomotil Robitussin