Drug and Therapeutics Committee

1
Drug and Therapeutics Committee

• Session 5.
• Pharmaceutical Quality Assurance

2
Acknowledgment

• Material for this session is adapted from Chapter
  18, Quality Assurance for Drug Procurement, of
  Managing Drug Supply 2nd ed. Management Sciences
  for Health and World Health Organization, 1997.

3
Objectives

• Define medicine quality
• Understand how medicine quality is assessed
• Understand how medicine quality is ensured
• Describe the role of the DTC in pharmaceutical
  quality assurance

4
Outline

• Key definitions
• Introduction
• Determinants of medicine quality
• How is quality assessed?
• How is quality assured?
• Important pharmaceutical quality issues
• for the DTC
• Implications for the DTC

5
Key Definitions (1)

• Pharmaceutical quality assurance (QA)Sum of all
  activities and responsibilities required to
  ensure that the medicine that reaches the patient
  is safe, effective, and acceptable to the patient
• Pharmaceutical quality controlProcess concerned
  with medicine sampling, specifications, and
  testing, and with the organizations release
  procedures that ensure that the necessary tests
  are carried out and that the materials are not
  released for use, nor products released for sale
  or supply, until their quality has been judged
  satisfactory

6
Key Definitions (2)

• Good Manufacturing Practices (GMP)Performance
  standards that WHO and many national governments
  established for pharmaceutical manufacturers
  covering, for example, personnel, facilities,
  packaging, and quality control.
• GMPs are part of the quality assurance activities
  that ensure that products are consistently
  produced and controlled to the quality standards
  appropriate to their intended use and required by
  the drug regulatory authorities.

7
Introduction Goals of Medicine QA Programs

• To make certain that each medicine reaching a
  patient is safe, effective, and of standard
  quality
• Obtaining quality products that are safe and
  effective through structured selection and
  procurement methods
• Maintaining quality products through the
  appropriate storage, distribution, monitoring,
  and use by prescribers, dispensers, and
  consumers

8
Characteristics of a Comprehensive QA Program (1)

• Medicines are selected on the basis of safety and
  efficacy, in an appropriate dosage form with the
  longest shelf life
• Suppliers with acceptable quality standards are
  selected
• Medicines received from suppliers and donors are
  monitored to meet quality standards
• Medicine packaging meets contract specifications

9
Characteristics of a Comprehensive QA Program (2)

• Repackaging activities and dispensing practices
  maintain quality
• Adequate storage conditions in all pharmaceutical
  areas are maintained
• Transportation conditions are adequate
• Product quality concerns are reported and
  monitored

10
Impacts of Low-Quality Medicines

• ?
• MEDICINE
• QUALITY

11
Determinants of Medicine Quality

• Identity Active ingredient
• Purity Not contaminated with potentially harmful
  substances
• Potency Usually 90110 of the labeled amount
• Uniformity Consistency of color, shape, size
• Bioavailability Interchangeable products?
• Stability Ensuring medicine activity for stated
  period

Identity, purity, potency, uniformity are defined
in pharmacopoeias and stated in certificate of
analysis (COA)
12
Potential Bioavailability Problems

• Aminophylline
• Ampicillin
• Carbamazepine
• Chloroquine
• Digoxin
• Dihydroergotamine
• Ergotamine
• Erythromycin
• Estrogens
• Furosemide
• Glibenclamide
• Glyceryl trinitrate
• Iron sulfate
• Isosorbide dinitrate

• Levodopa
• Levothyroxine
• Methyldopa
• Nitrofurantoin
• Phenytoin
• Prednisolone
• Prednisone
• Quinidine
• Rifampicin
• Spironolactone
• Theophylline
• Warfarin

• Medicines with narrow therapeutic range
• Slow-release formulations
• New formulations (e.g., rectal paracetamol)

13
Standard Method for Bioavailability Studies

• Subject adult, healthy, nonsmoker, nondrinker
• Design cross-over, 1214 subjects
• Medicine administration overnight fast, single
  dose
• Serial blood sampling minimum 3? T1/2
• Medicine assay in plasma
• Parameters
• Cmax
• Tmax
• AUC0-?
• Judgment for bioequivalency lt20 difference

14
Rifampicin 450 mg Capsules gt 100
Variation among Brand Names
Source Suryawati (1992)
15
Captopril 25 mg Variation among Brand Names
N number of studies
16
Nifedipine 20 mg Generic vs. Brand Name
Plasma concentration (ng/ml)
180
Generic
160
Brandname
140
120
100
80
60
40
20
0
0
3
6
9
1.5
4.5
7.5
12
15
18
21
24
10.5
13.5
16.5
19.5
22.5
Time (hours)
Source Suryawati and Santoso (1995).
17
Slow-Release Diclofenac Tablet
Plasma concentration (ng/mL)
Imported product
MEC 20 ng/mL
Time (hours)
Source Suryawati (1989).
18
Medicines with a Stability Problem

• Tablets
• Acetylsalicylic acid
• Amoxicillin
• Ampicillin
• Penicillin V
• Retinol

• Oral liquids
• Paracetamol

• Injectable
• Ergometrine
• Methylergometrine

• Select the most stable formulation with adequate
  packaging

19
How Is Quality Assessed?

• INSPECTION of products on arrival
• Visual inspection
• Product specification review (including
  expiration dates)
• LABORATORY TESTING for compliance with
  pharmacopoeial standards
• International Pharmacopoeia
• European Pharmacopoeia
• U. S. Pharmacopeia
• British Pharmacopoeia
• National Pharmacopoeia
• BIOAVAILABILITY DATA

20
How Is Medicine Quality Assured? (1)

• Product selection
• Long shelf-life
• Acceptable stability
• Acceptable bioavailability
• Selection of appropriate suppliers
• Supplier pre-qualification
• Request samples from new suppliers
• Request specific reports and data for certain
  medicines (e.g., bioavailability and stability
  studies)
• Collect and maintain information on supplier
  performance
• Product certification
• GMP certificate of manufacturer
• Product/batch certification (COA)
• Random local testing

21
How Is Medicine Quality Assured? (2)

• Contract and procurement specifications
• Pharmacopeia reference standard
• Local language for product label
• Standards for packaging to meet specific storage
  and transport conditions

22
How Is Medicine Quality Assured? (3)

• Appropriate storage, transport, dispensing, and
  use procedures
• Pharmaceutical distribution and inventory control
  procedures
• Provision for appropriate storage and transport
  including adequate temperature control, security,
  and cleanliness
• Explicit enforcement of cold chain procedures
• Appropriate dispensing containers, labeling,
  counseling
• Avoidance of repacking unless quality control in
  place

23
How Is Medicine Quality Assured? (4)

• Product monitoring system
• Problem reporting who, how, where, and to whom
  what additional measures what follow-up
  information
• Product recalls hospital or country level

24
Who Ensures Medicine Quality?

• Drug regulatory authority

25
Implications of Pharmaceutical QA for the DTC

• Providing technical advice on procurement of
  pharmaceuticals
• Defining product specifications
• Generic medicines
• Bioavailability issues
• Stability issues
• Defining minimum laboratory testing
• Providing technical advice to hospital
  departments
• Medicine transportation and storage
• Dispensing
• Analyzing product problem reports
• Quality complaints
• Medicine recall system

26
Activity (30 minutes)

• Pharmaceutical quality assurance issues and
  concerns on
• Obtaining quality products
• Maintaining quality products
• Examples of poor quality
• Discussion
• Are you satisfied with the quality of medicines
  you receive?
• Is quality maintained throughout your
  distribution network?
• Are there complaints of poor quality by patients
  or health workers?
• Is there a formal mechanism for reporting and
  investigating complaints?
• What role do you see for the DTC in improving and
  maintaining quality in your health care system?

at hospital level
27
Summary (1)

• Ensuring quality of a product from selection to
  use
• Obtaining quality products that are safe and
  effective through structured selection and
  procurement methods
• Maintaining quality products through appropriate
  storage, distribution, monitoring, and use
  methods

28
Summary (2)

• Assessing quality includes
• Inspection of medicines
• Laboratory testing when necessary

29
Summary (3)

• Assuring quality includes
• Selection of medicines, dosage forms, and
  packaging
• Use of prequalified suppliers
• Product certification
• Preparation and enforcement of quality-related
  contract specification
• Appropriate storage, transport, dispensing, and
  use
• Product monitoring systems