Introduction to GMP

1
Introduction to GMP
2
Objectives

• Acquire basic knowledge of Good Manufacturing
  Practices (GMP)
• What are GMPs ?
• Why are they important ?

3
History of Food and Drugs Act

• Government Authorities
• Canada Health Canada Health Products and Food
  Branch (HPFB)
• USA Food Drug Administration (FDA)
• Europe EC Directives

4
History

• Food and Drugs Act
• Food and Drug Regulations
• Division 2 Good Manufacturing Practices
• 1900s- Adulterated Food
• First purity laws enacted
• 1930s- Sulfanilimide
• Drugs had to be proven safe
• 1960s- Thalidomide
• Drugs had to be proven safe and effective through
  clinical trials

5
Why are GMPs important?

• Government requirement
• Ensure quality product
• Reduce rejects, recalls
• Satisfied customers
• Maintain manufacturing consistency
• Company image and reputation

6
Drugs

• HPFB Definition Any substance or mixture of
  substances manufactured, sold or represented for
  use in
• a) the diagnosis, treatment, mitigation or
  prevention of a disease, a disorder, an abnormal
  physical state or the symptoms thereof in humans
  or animals
• b) restoring, correcting or modifying organic
  functions in humans or animals
• c) disinfection in premises in which food is
  manufactured, prepared or kept
• DIN
• Label Claim

7
Food and Drugs Act

• Establishment license
• Site Reference File
• HPFB Inspections

8
Production Goals

• Safety
• Product is free of unwanted side effects when
  used appropriately by patient
• Identity
• Product exactly matches the labelling and related
  documents
• Strength
• Product has correct concentration, potency or
  therapeutic activity of active ingredient
• Purity
• Product is free from contamination
• Quality
• Product meets all standards, expectations
  performs as claimed
• Product made consistently

9
GMP Categories

• Sale
• Premises
• Equipment
• Personnel
• Sanitation
• Raw Material Testing
• Manufacturing Control

• Quality Control Department
• Packaging Material Testing
• Finished Product Testing
• Records
• Samples
• Stability
• Sterile Products
• Medical Gases

10
Sale C.02.003

• No distributor and no importer shall sell a
  drug unless it has been fabricated,
  packaged/labeled, tested, and stored in
  accordance with the requirements of this Division

11
Premises C.02.004Equipment C.02.005

• Permits effective cleaning
• Prevents contamination
• Orderly conditions
• Good state of repair

12
Personnel C.02.006

• Appropriate education, training and experience
• Sufficient number of people
• Receive GMP training
• Initial and continuing training as relevant to
  job responsibilities

13
Sanitation C.02.007 - .008

• Sanitation Program to prevent contamination
• Limit the sources and types of contamination
• Cleaning procedures for facilities equipment
• Pest control
• Environmental monitoring
• Documented evidence

14
Sanitation C.02.008

• Hygiene
• Health and eye examinations
• Report adverse health conditions
• Clothing requirements
• No direct skin contact with product
• Wash hands
• No jewelry or excessive makeup
• No smoking, eating, drinking, chewing, or keeping
  of plants in operations areas

15
Raw Material Testing C.02.009 - .010

• each lot or batch of raw material is tested
• three objectives
• confirm the identity of the raw materials
• provide assurance that quality of the drug in
  dosage form will not be altered by raw material
  defects
• assure that raw materials have the
  characteristics that will provide the desired
  quantity or yield in manufacturing process

16
Raw Material, Packaging Material and Finished
Product Testing

• Samples of incoming materials are collected and
  tested before use
• Approved test methods and specifications are used
• Results must conform to specifications for
  release for use or sale
• Transportation and storage records

17
Manufacturing Control C.02.011

• Written procedures are established and followed
• Master formulae, manufacturing order and
  packaging order
• Critical processes are validated
• 2nd person verification of activities
• Quarantine system
• Labelling requirements

18
Manufacturing Control C.02.012

• Recall Programme
• Self-Inspection Programme
• Ensure compliance with vendors/contractors

19
Manufacturing Control (contd)

• Validation the documented act of demonstrating
  that any procedure, process, equipment, material,
  activity, or system will consistently lead to the
  expected results
• TPP 1998 Edition

• Design Qualification (DQ)
• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)

20
Quality Control DepartmentC.02.013 - C.02.015

• Quality Control Responsibilities
• Testing of bulk components prior to use by
  production
• Testing of finished product prior to release for
  sale
• Stability program (in association with QA)

21
Quality Control DepartmentC.02.013 - C.02.015

• Quality Assurance Responsibilities
• Ensure GMP compliance
• Review batch records, labels
• Release product, based on QC test results
• Authorize all master documents and SOPs
• Training, auditing
• Customer complaints
• Recall

22
Key Quality Terms

• CHANGE CONTROL
• written procedure that describes the action to be
  taken if a change is proposed to facilities, etc.
  used in fabrication, packaging, and testing of
  drugs or any change that may affect quality or
  support system operation
• DEVIATION
• Planned or unplanned temporary departure from an
  approved process, specification or procedure with
  the potential to impact product quality

23
Records C.02.020 - C.02.024

• Document all GMP activities
• Use Good Documentation Practices (GDP)
• Records must be readily available
• Needed to prove activities were done

24
Good Documentation Practices

• Documentation must be
• permanent (black or blue ink)
• legible, clear, concise
• accurate
• timely
• consistent
• complete

25
Samples and Stability

• Samples
• Retain samples of each lot of raw material and
  finished product for specified period of time
• Stability
• Establish the length of time in which theproduct
  meets all specifications
• Monitor the drug for this period of time

26
Sterile Products C.02.029

• Sterile Products
• Packaged in separate enclosed area by trained
  personnel using method to ensure sterility

27
Summary

• Pharmaceutical Industry is regulated by GMPs
• Good Manufacturing Practices must be followed
• GMPs ensure drug products are safe, pure and
  effective.