Adulterated & Misbranded drugs

• Adulterated – means that the product has a problem with its

composition, such as containing impure, unsafe, or unapproved
ingredients
• Misbranded- means that the product has a problem with its labeling,
such as being false, misleading, or violating statutory requirements
• Adulterated and mislabeled products can harm your health
Cross contamination
• Cross contamination in the pharmaceutical industry can be described
as an accidental inclusion of product of another batch or unknown
foreign material into a finished batch, which was not intended or not
mentioned on the label.
• Put this into different way, cross contamination may occur by the transfer
of substances, microorganisms or other unwanted material from one
product to another, leading to contamination of the final product.
• Cross contamination is dangerous in pharmaceutical industry as it can
severely compromise patient safety if the content is not pure and the
product package differs from what is written on the label.
5 Common Errors In Pharmaceutical
Labeling 
• 1. Compliance Risks 

• As mentioned before, pharmaceutical brands are under constant

scrutiny. It's important they adhere to safety regulations for all their
products. Local regulations are often complex and brands need to be
fluent in the requirements. 

• Depending on the category of medicines, pharmaceutical brands have

to follow other mandatory regulations. As the number of regulations
increase, so does the difficulty to stay in compliance
• Incorrect Information
• An incorrect pharmaceutical label can
put patient safety at risk.
• For example, Endo Pharmaceuticals in
Ireland had to recall two batches of
Robaxin® 750mg Tablets 100, owing
to an error in the amount of dosage.
In UAE, JulpharGulf Pharmaceutical
Industries had to recall Laxocodyl
because of a certain medicine for
adults that was instead labeled as
being for children.
• Such recalls are not only expensive
but damaging to the manufacturer’s
reputation.
• 3. Quality Issues
• Quality issues may persist throughout the entire artwork development and proofing process. Furthermore,
they can lead to inconsistencies in product packaging. These problems are not extreme enough to result in a
recall but affect branding.

Misplaced or distorted graphics, inconsistency in colors and fonts, are common issues. This can make a
product look unauthentic, and in certain pharmaceutical products, give out the wrong information due to the
use of incorrect color codes.

• 4. Translation Errors
• Pharmaceutical industries have limited time to get a product out in the market and in the hands of those
who need it. Often medicines are imported from other countries. In such cases, translation comes into play.

Proofing translated labels are a major task undertaken by professional translators. Any errors in the language
can make the content unclear, delaying the product’s launch.
• 5. Improper Inspection

• Manual proofing of pharmaceutical labeling is a time-consuming job. Sometimes, developing labelling

artwork involves many teams from different locations. Often, the volume of the artwork is also quite large.
Orchestrating all the activities and integrating different processes creates more difficulties.
SINGLE DOSE VS. MULTIPLE DOSE
• Single-Dose Container
• A single-dose container is a container of a parenteral preparation that is not
required to meet the antimicrobial effectiveness testing requirements. A single-
dose container is designed for use with a single patient as a single injection/
infusion. Examples of single-dose containers are vials, ampules, and prefilled
syringes.
• Multiple-Dose Container
• A multiple-dose container is a container of a parenteral preparation that has met
antimicrobial effectiveness testing requirements, or is excluded from such testing
requirements by FDA regulation. It is intended to contain more than one dose of
the drug product. Multiple-dose containers are generally expected to contain 30
mL or less of product. The beyond-use date for an opened or entered (e.g.,
needle-punctured) multiple-dose container is 28 days, unless otherwise specified
by the manufacturer on the label. An example of a multiple-dose container is a
vial.
TYPES OF GLASSES
• Type I borosilicate glass has a high melting point, so it can withstand high temperatures, has high hydrolytic
resistance, is resistant to chemical substances, provides reduced leaching action, and can withstand sterilization.
- Type I borosilicate glass is used for laboratory glass apparatus; water for injection and for parenteral and non-
parenteral use.
- Contains 10%of boric acid, 80% of silica, and small quantities of both Al2O3 and Na2O
- The boric acid makes it highly hydrolytically resistant and chemically inert.
- The coefficient of expansion is very low; the thermal shock property is quite high

• Type II treated soda-lime

- Modified type 3 container
- Generally, type 3 containers that have been treated with sulfur. – helps in preventing weathering from
containers
- Glass is fairly resistant to attack by water for a period of time. Sulfur treatment neutralizes the alkaline oxides
on the surface, thereby rendering the glass more chemically resistant. It has a high hydrolytic resistance. Type II
treated soda-lime glass is used for alkali-sensitive products, infusion fluids, blood and plasma, and large-volume
containers.
• Type III regular soda-lime glass
- containers high concentrations of alkaline oxides and impart alkalinity to aqueous substances,
flakes easily, and may crack due to sudden change of temperature. It has a moderate hydrolytic
resistance. Type III regular soda-lime glass is used for all solid dosage forms (tablets, powders, and
so on) and oily injections.
- 10% CaO, 15% NaO, and 75% silica

• Type IV (NP) general-purpose soda-lime glass is non-parenteral glass. Type NP general-purpose

soda-lime glass is only used for oral and topical purposes.
- Have low hydrolytic resistance
- Usually used for
• The glass is tested using various types of tests such as Glass Grains Test and Surface Glass Test for
hydrolytic resistance to determine the glass type.
Polyethylene Terephthalate (PET)
• Plastic bottles
• Widely used for packaging foods and beverages
Polyvinyl Chloride (PVC)
• Used in blister packs( capsules and tablets)
• Low cost
Elixir of Sulfanilamide
• Antibiotic for streptococcal infections
• In 1937, one company in Tennessee, USA began selling bottles of Elixir Sulfanilamide,
a liquid version of a popular antibiotic of the day. But more than 100 people died
after taking the drug, and investigators from the US Food and Drug Administration
(FDA) identified the drug’s solvent, diethylene glycol, as the killer 3.
• 
• In response, US Congress passed the Federal Food, Drug and Cosmetic (FD&C) Act of
1938. For the first time, companies were required to prove that their products were
safe before marketing them. It extended FDA oversight to cosmetics and therapeutic
devices, explicitly authorized factory inspections, required standards for foods, and
added injunctions to previous penalties of seizures and criminal prosecutions 2.
• The 1941 – Sulfathiazole Disaster
• In 1941, Nearly 300 people were killed or injured by Winthrop’s sulfathiazole tablets, a sulfa drug tainted
with the sedative, phenobarbital. Each sulfathiazole tablet was contaminated with about 350 mg of
phenobarbital. Investigation by US Food and Drug Administration and the findings resulted into actions. The
incident was influential in the introduction of Good Manufacturing Practices for drugs 4. Winthrop became
the first company since the 1938 law was passed to have its new drug application suspended15.
• 
• That incident caused FDA to revise manufacturing and quality control requirements drastically, leading to
what would later be called GMPs. The Public Health Services Act, passed in 1944, covered a broad spectrum
of concerns, including regulation of biological products and control of communicable diseases2.
• 
• Batch certification by FDA became a requirement for certain drugs. It required companies to submit samples
from each lot to FDA 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. By 1983, the
requirement for batch certification of drug was dropped2.
• The 1962 - The thalidomide disaster
• The thalidomide disaster is one of the darkest episodes in pharmaceutical research history. The drug was
marketed as a mild sleeping pill safe even for pregnant women. When regulatory agencies gave permission to
sell the drug for that indication; they had no knowledge of its serious side effects. It turned out to be teratogenic
and it caused serious deformities in developing fetuses. Children whose mothers took thalidomide in the first
trimester were born with severely deformed arms and legs. An estimated 10,000 case of infant deformities with
malformed limbs in Europe were linked to thalidomide use3.
• 
• Picture 1: Babies with deformities due to Thalidomide tragedy
• 
• The product was not allowed on the market in the United States by Frances Kelsey. In 1962 President Kennedy
awarded her the President’s Distinguished Federal Civilian Service Award, the highest honour 3.
• 
• Two legislators, Kefauver and Harris, pushed more-stringent legislation through congress that required
companies to test not only to ensure that products were safe, but that they were efficacious for their intended
uses. Regulating clinical trials, amendments required drugs to be tested in animals before people. They made
investigators responsible for supervising drugs under study. Manufacturers were expected to inform participants
if a drug was being used for investigational purposes and to obtain their consent before testing it on them.
Drugs had to be shown to work before going in the market. Manufacturers were required to report unexpected
harm (adverse events) and USFDA was given authority to regulate advertising of prescription drugs 2.
• The 1982 - Tylenol capsules Disaster
• In 1982, twelve-year-old child died after taking Extra-Strength of Tylenol capsules (acetaminophen
 capsules). Later on, six another people died and Investigators soon discovered the Tylenol link.
Urgent warnings were broadcasted, and police drove through Chicago neighbourhoods issuing
warnings over loudspeakers.
• 
• Johnson & Johnson distributed warnings to hospitals and distributors and halted Tylenol production
and advertising. On October 5, 1982, it issued a nationwide recall of Tylenol products; an estimated
31 million bottles were in circulation. The company also advertised in the national media for
individuals not to consume any products that contained acetaminophen.
• 
• The acetaminophen tragedy had a major impact on the industry and the 1982 incident inspired the
pharmaceutical, food, and consumer product industries to develop tamper-resistant packaging,
such as induction seals and improved quality control methods 8.
• 
• FDA issued tamper-resistant packaging regulations for all OTC human drug products and
incorporated them into the GMPs; US Congress passed the Federal anti-Tampering Act in 1983,
making it a crime to tamper with packaged consumer products 9.