Poor Quality Medicines: What You Need to Know

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Poor Quality Medicines What You Need to Know
MiniUniversity George Washington
University October 27, 2006
Abdelkrim Smine, Ph.D. Manager Drug Quality
and Training U.S. Pharmacopeia Drug Quality and
Information Program
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Presentation Outlines

• Definitions
• Drug Development
• Quality assurance of medicines
• Drug management cycle
• Poor quality drugs
• Sources, causes, consequences, and extent of
  the problem
• What is being done to deal with poor quality
  drugs
• USP DQI / USAID programs
• Conclusion

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Quality Assurance of Medicines

• The Drug
• The active pharmaceutical ingredient (API)
• The excipients
• The package
• The label
• The storage conditions
• The shelf life
• The indications for its use

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Definitions

• Packaging The container that holds the article
  does not interact physically or chemically with
  the article so as to alter the strength, quality,
  or purity. Primary package is the one in contact
  with the drug.
• Labeling All labels must present information as
  required by the governmental regulatory body in
  addition to pharmacopeial requirements per
  article.

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Definitions

• Fake/counterfeit Deliberately mislabeled for
  identity and/or source. Can be branded or
  generic. May include products with Correct API,
  wrong API(s), without API or with sub-dosed API
  or with fake packaging.
• Substandard Legal branded or generic product,
  but does not meet official standards for
  identity, quality, purity, strength, packaging,
  and labeling.

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Definitions
Critical Attributes for Testing Medicines
Identity, purity, quality, strength,
packaging, and labeling

• Identity
• Assay / dosage (amount of active ingredient on
  the label)
• Disintegration (prerequisite for bioavailability)
  
• Dissolution (higher level of assurance of
  bioavailability)
• Impurities (generally related to active
  pharmaceutical ingredient, similar
  toxicities)
• Uniformity (uniformity of content/dosage, GMP)
• Sterility (injectable solutions)
• Other

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Definitions

• Quality Assurance of drugs are all measures taken
  to assure the quality of the drug from its
  development to its use by the patient.
• In other words QA make sure that the
  pharmaceutical products are FIT FOR THEIR
  INTENDED USE
• Efficacy, quality, strength, purity, packaging,
  labeling, storage, and appropriate use.

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Quality Assurance of Medicines

• Quality Assurance of drugs, are all measures
  taken to
• assure the quality of the drug from its
  development to
• its use by the patient.

When Who How ?
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When Does QA of Medicines Start? End?
GMP-GCP-GLP
GMP-GCP-GLP
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When Does QA of Medicines Start? End?
Development/Procurement

• Drug Development
• Local Production Imports Donations
• GMP compliance Procurement Quality issues
• Storage Legal provisions
• Drug Regulatory Authority
• - National Drug Policy / Drug regulations
• - Registration
• - Inspections
• - Post marketing surveillance
• - Drug informations control and reporting
• Distribution
• - Distribution chains
• - Storage conditions
• - Stock management
• Drug Quality at the Periphery

Use
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Poor Quality Drugs?

• Fake/counterfeit Deliberately mislabeled for
  identity and/or source. (No active ingredient or
  a different active ingredient than on the label)
• Substandard Legal branded or generic product,
  but does not meet official standards for
  identity, quality, purity, strength, packaging,
  and labeling.

Why Where How big is the problem What is
being done to deal with poor quality drugs Who
And How ?!
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What are Quality Standards ?
Drugs should conform to the Standards/specificatio
ns Identity, Purity, quality, strength,
packaging, and labeling

• Internationally recognized pharmacopoeias -
  IP, USP, BP, JP, and EP
• Official national pharmacopoeias
• Standards and analytical methods developed by the
  manufacturer (when monographs are not available)

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An Early USP Monograph
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Isoniazid Monograph
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Why Do We Need Quality Assurance?
Because counterfeit and substandard drugs are
widely available and are

• A constant threat to public health worldwide
• Most affecting people living in countries with
  limited regulatory capacity and resources
• Estimated by the FDA to account for 10 of the
  worldwide drug supply in some countries more
  than 30 of the drug supply is made up of
  counterfeit drugs
• Costing over 22 billion USD per year,
  representing about 7- 10 of world-wide
  pharmaceutical sales. This market is supposed to
  reach 75 billion USD by 2010.
• (www.who.int/mediacentre/factsheets/fs27
  5/)

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Causes of Proliferation of Poor Quality Drugs

• Poor health systems in developing countries
• Lack of legislation
• Weak or absent drug regulatory/control (1/3 of
  African countries)
• Weak law enforcement and penal sanctions
• High drug demands with short supplies
• Imports via Free Trade Zones
• Corruption and conflict of interests
• High cost of drugs-lucrative business

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Consequences of Using Fake and Substandard Drugs

• Diminished trust in health care systems
• Waste of financial resources
• Health at risk
• Prolonged illness, treatment failure, and
  increased drug resistance
• Death

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Extent of the Problem - Facts

• In Panama, a Diethylene glycol (DEG) poisoning
  killed 30 people. In this case, a material
  labeled as glycerin purportedly contained a
  mixture of 1 glycerol, 25 DEG and 75 unknown
  material.
• Same DEG contaminated syrup killed 30 children in
  India in 1998
• Same problem occurred in Haiti, 1995 because of
  DEG contaminated acetaminophen, 109 children had
  renal failure 89 of them died.
• In Niger in 1995, 50,000 were inoculated with
  fake vaccine
• 2500 died.
• In 2006, fake Tamiflu (oseltamivir) was found in
  the USA (FDA alert, 2006). In the Netherlands,
  Tamiflu capsules were found to contain lactose
  and vitamin C. In the UK, officials seized 5000
  packets of counterfeit Tamiflu in early 2006,
  estimated to be worth 500,000

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Extent of the Problem - Facts
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Extent of the Problem - Facts
Percentage of Failure S/P FDC Tablet
Dissolution
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Extent of the Problem - Facts
Ghana (2005)
Cambodia (2003-2005)
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USP Drug Quality and Information Program

• USP DQI is a cooperative agreement between USP
  and USAID since in 1992
• Objectives
• To improve the quality and appropriate use of
  pharmaceutical products
• To increase availability and use of unbiased
  health information

Drug gt Good quality, correct formulation and
amount, adequate storage, and packaging
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Countries Where USP DQI Is Active
Programs Supported by USAID

• Asia
• Cambodia, China, Laos, Thailand, Vietnam, India,
  and the Philippines
• Africa
• Senegal, Ethiopia, Madagascar, Ghana, Uganda,
  Kenya, and Tanzania
• Europe/Eurasia
• Russia, Romania, Moldova, and Central Asian
  Republics
• Latin America
• Brazil, Bolivia, Colombia, Ecuador, Guyana,
  Paraguay, Peru, Suriname, Venezuela

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Focal Activities of USP DQI

• QA/QC assessment
• Post marketing surveillance for quality
• Training, strengthening, and qualification QC
  Labs
• Drug quality testing at peripheral level using
  basic tests
• Collaborative testing of medicines
• Drug registration
• Assistance with GMP to manufacturers
• Centers of Excellence on drug quality assurance
• Database of reported drug quality problems
• Distance learning drug information
• Drug information centers
• USP DQI website, publications

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Health Areas of USP DQI Activities

• Major Diseases
• Tuberculosis
• Malaria
• HIV/AIDS
• Antimicrobial Resistance
• Antibiotics
• Child Survival
• Antidiarrheal
• Maternal Health
• Post-hemorrhage

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USP DQI Collaborations

• The World Health Organization
• Pan American Health Organization
• UNICEF
• USAID
• CDC, US FDA
• Academia
• NGOs
• Ministries of Health

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Testing USP DQI Approach
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CONCLUSION

• Substandard and counterfeit drugs are an
  increasing problem posing a serious impact to
  public health
• All those involved in public health should
  control the quality of medicines used in their
  programs
• Counterfeit and substandard drugs are a growing
  market worldwide
• USAID has been supporting drug quality and drug
  management programs in many countries through
  regional and bilateral initiatives. (USP DQI
  RPM Plus)

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CONCLUSION

• Quality assurance of medicines is a very complex
  issue
• Counterfeit and substandard drugs are widespread
  in many areas around the world
• Counterfeit and substandard drugs are a threat to
  developed as well as developing countries
• Collaboration by governments, regulators, NGOs,
  donors, manufacturers, and all those involved
  from the selection to the use by the patient is
  the key to assuring the efficacy and safety of
  medicines

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COUNTERFEIT DRUGS
Manufacturing
Wholesale
Pharmacy
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Abdelkrim Smine, Ph.D. Manager, Drug Quality
Control and Training Tel [phone] Email
ays_at_usp.org