Good Manufacturing Practices

Self-inspection Manager
Mohamed Hassanin Mohamed
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 Learning objectives:

Global Regulatory
Brief history of GMP
Framework

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 What
would
you
expect
from
your
medicine
?
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1)
Brief history (Tragedies created systems)

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Medicines are considered as old as mankind.

❖ The ancient humans used the juice of

plant leaves to treat wounds.

❖ Medicines were restricted to priests in

temples using herbs and religious
incantations.

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09-Nov-24 6
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In 1900s,
Medicines were sold as bottles of ointment or “miracle elixir ”.

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In addition,
syrup medicines for babies and adults often
contained alcohol, opium, or morphine, which
addicted many people who used them.

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 THE JUNGLE, 1906

A novel by the American journalist and novelist

Upton Sinclair
, portrays the harsh conditions and exploited
lives of immigrants in the United States in
Chicago and similar industrialized cities; It had
a major impact on American public opinion.

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 Pure Food and Drug Act, 1906
✓ For the first time it became illegal to sell
contaminated (adulterated) food or meat.
✓ Also, for the first time, labelling had to be
truthful.
“no one could promise the moon and the stars on a label anymore”

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The act created one of the first government regulatory agencies,
now known as the FDA
, and it also allowed for the seizure of illegal foods and drugs.

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 AMERICAN CHAMBER OF HORRORS,
1933

In 1933 FDA exhibit of dangerous food,

medicines, medical devices, and cosmetics
illustrated the shortcomings of the 1906 law.
➢ The First Lady Eleanor Roosevelt was
interested in the exhibit and invited the
Congressional wives to visit the exhibit,
which brought an unusually influential
audience.
➢ This exhibit was called “American
Chamber of Horrors”.

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 SULFANILAMIDE TRAGEDY, 1935

Sulfa drugs were introduced in 1935.

• Many manufacturers began making the
new anti-infectives.
• One company used “Diethylene glycol” as
an antifreeze, in an oral “Elixir of
Sulfanilamide”.
Before the problem was discovered, 107
people died, many of them children.

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Federal Food, Drug and Cosmetic (FD&C) Act,
1938
✓ For the first time, companies were required
to prove that their products were safe
before marketing them.
✓ FDA expanded oversight on cosmetics and
medical devices, inspecting licensed
factories, and added standards for food
and drug manufacturing.

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 SULFATHIAZOLE TRAGEDY, 1941

In 1941 nearly 300 people were killed by a

company’s Sulfathiazole tablets,
the sulfa drug was tainted with the sedative,
Phenobarbital.

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This incident caused FDA to revise manufacturing and quality control
requirements drastically, leading to what would later be called GMP.

✓ FDA required companies to submit samples

from certain drugs from each lot for testing,
and the agency would give permission for
their release.
✓ That practice, begun in 1941 for Insulin and
1945 for Penicillin, was later expanded to
include all antibiotics.

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 THALIDOMIDE TRAGEDY, 1957

Thalidomide tablets were marketed in

Europe as a sleeping pills.
▪ One of its side effects was prevention of
morning sickness for pregnancy women.
▪ It caused serious deformities in
developing fetuses.
▪ An estimated 10,000 cases of infant
deformities in Europe were linked to
Thalidomide use.

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Frances Oldham Kelsey was a pharmacologist
and physician who worked as a reviewer for the
U.S. Food and Drug Administration (FDA).
▪ She refused to authorize Thalidomide for
market because she had concerns about the
lack of evidence regarding the drug's safety.
▪ In 1962, President Kennedy awarded her the
President’s (Distinguished Federal Civilian
Service Award), the highest honor a
government employee may earn as a
civilian.

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In 1962, two legislators pushed more stringent legislation
through Congress that:
▪ Drug manufacturers are required to test their
products to ensure safety and efficacy.
▪ Regulating clinical trials, the amendments required
drugs to be tested in animals before people.
▪ Drug manufacturers must inform the volunteers about
testing investigational medicinal products and obtain
their consent.
▪ Drug manufacturers must report any unexpected
harm (adverse events) to FDA (Pharmacovigilance).

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The 1970s were a watershed for product
regulation.
✓ 1978 - GMPs for drugs (21 CFR, Parts 210
and 211) and medical devices (21 CFR 820).
✓ 1979 - GLPs Final Rule (21 CFR, Part 58).

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 TYLENOL® CAPSULES, 1982

Tylenol® capsules was one of the largest-

selling over-the-counter (OTC) medicines in
the U.S.
▪ About seven people died from
poisoning with Tylenol® capsules
laced with cyanide.
▪ Johnson & Johnson announced a
nationwide recall of 31 million bottles
of Tylenol® and destroyed them.

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Federal Anti-Tampering Act, 1983
▪ The Congress passed an act that considered
it a crime to tamper with packaged
consumer products.
▪ FDA issued tamper-resistant packaging
regulations for all OTC human drug products
and incorporated them into the GMPs.
21 CFR 211, Subpart G § 211.132 Tamper-evident packaging
requirements for over-the-counter (OTC) human drug
products.

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2)
Global Regulatory
Framework.

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PIC/S (Pharmaceutical Inspection Cooperation
Scheme) was founded in 1995 as an extension to PIC
(Pharmaceutical Inspection Convention) which was
founded in 1970 by EFTA (European Free Trade
Association).
The initial Members of PIC are:
1) Austria, 6) Norway,
2) Denmark, 7) Portugal,
3) Finland, 8) Sweden,
4) Iceland, 9) Switzerland,
5) Liechtenstein, 10) United Kingdom.

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The original goals of PIC were:
✓ Mutual recognition of inspections.
✓ Harmonization of GMP requirements.
✓ Uniform inspection systems.
✓ Training of inspectors.
✓ Exchange of information.
✓ Mutual confidence.

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PIC/S main benefits:
1) Training opportunities and high
standards.
2) Reduced duplication of inspections.
3) Cost savings (more effective use of
resources).
4) Export facilitation (including to non-
PIC/S countries).
5) Enhanced market access.

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While PIC/S Aide Memoires have been
written for GMP inspectors, they can be
very useful for a company’s internal audits.
❖ Inspection of Pharmaceutical Quality
Control Laboratories – (PI 023–2).
❖ Inspection of Utilities – (PI 009-4).
❖ Explanatory notes for
Pharmaceutical Manufacturers on
The Preparation of a Site Master File
– (PE 008-4).
[Link]
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EUDRALEX - EU LEGISLATION

Volume 4 - Good Manufacturing Practice

(GMP) guidelines –
Part I - Basic Requirements for Medicinal
Products
• Chapter 1 - Pharmaceutical Quality
System
• Chapter 2 - Personnel
• Chapter 3 - Premise and Equipment
• Chapter 4 - Documentation
• Chapter 5 - Production
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EUDRALEX - EU LEGISLATION

Volume 4 - Good Manufacturing Practice

(GMP) guidelines –
Part I - Basic Requirements for Medicinal
Products
• Chapter 6 - Quality Control
• Chapter 7 - Outsourced activities
• Chapter 8 - Complaints and Product
Recall
• Chapter 9 - Self Inspection
[Link]
products/eudralex/eudralex-volume-4_en
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THE WORLD NEEDS TO HARMONIZE

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The birth of ICH took place at a meeting in April
1990,
hosted by the European Federation of
Pharmaceutical Industries and Associations
(EFPIA) in Brussels,
between the representatives of the regulatory
agencies and industry associations of Europe,
Japan, and the United States.
[Link]

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Good manufacturing practice

is that part of quality management which ensures

that products are consistently produced and controlled
according to the quality standards appropriate to their
intended use and as required by the marketing
authorization, clinical trial authorization or product
specification (WHO TRS 986, 2014, Annex 2, 2.1).

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References:
1. A brief history of the GMPs for pharmaceuticals, Barbara K. Immel.
2. [Link]
211?toc=1
3. [Link]
volume-4_en#part-i---basic-requirements-for-medicinal-productss
4. [Link]
5. WHO TRS No. 986, 2014, Annex 2, Good manufacturing practices
for pharmaceutical products: main principles.

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Thank you
Mohamed Hassanin Mohamed
Self-inspection Manager
MHassanin@[Link]
01027995122

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