Good Manufacturing Practices in Pharmaceuticals

1. KEY ELEMENTS AND
BASIC PRINCIPLES OF
GMP
Rai Waqas Ali
Entrepreneur, R.Ph Pakistan
Email:raiwaqas98@gamil.com
+92305-7973726

2. CONTENTS
• Definition of GMP and cGMP.
• Characteristics of GMP-compliant product
• Key elements of GMP
• Good practices in Production
• Good practices in Quality control
• Why GMP is important
• Objectives of GMP
• Relationship of QA, GMP, QC
• Basic principles of GMP
• GMP Guidelines
• Benefits of GMP
• Importance of training
• References

3. SOME OF THE MAIN RISKS
ARE
• Unexpected contamination of products,
causing damage to health or even death.
• Incorrect labels on containers, which could
mean that patients receive the wrong
medicine.
• Insufficient or too much active ingredient,
resulting in ineffective treatment or adverse
effects.

4. According to FDA a drug is defined as
Adulterated if method used in its
manufacturing or processing, testing, packaging,
storing did not conform to the GMPs.
• As a result of this, GMPs were first established in June
1963. The concept was born in U.S.A

5. WHAT IS GMP ?
Good Manufacturing Practices
“A set of principles and procedures which, when
followed by manufacturers for therapeutic
goods, helps ensure that the products
manufacture will have the required quality”.
As per WHO
GMP is that part of quality assurance, which ensures
that products are consistently produced and
controlled to the quality standards appropriate to
their intended use and as required by the marketing
authorization.

6. WHAT IS cGMP?
• There is the current practice which is going on
regularly in the plant should maintain precautions
and should follow all the rules and regulation made
by the GMP.
• cGMP provide for systems that assure proper
design, monitoring and control of manufacturing
processes and facilities.

7. GMP covers all aspects of production from the
starting materials, premises, and equipment to the
training and personal hygiene of staff. Detailed
written procedures are essential for each process that
could affect the quality of the finished product. There
must be systems to provide documented proof that
correct procedures are consistently followed at each
step in the manufacturing process - every time a
product is made.

8. WHO GMP ensures the following:
• Avoidance of Cross- Contamination
• Prevention of Mix-ups
• Provide Traceability
• Accountability of actions
• Responsibility
• Product Performance Guarantee

9. WHY GMP IS IMPORTANT
A poor quality medicine
may contain toxic
substances that have been
unintentionally added.
A medicine that contains
little or none of the
claimed ingredient will not
have the intended
therapeutic effect.

10. RELATIONSHIP OF QA, GMP,
QC
QC
GMP
QA

11. QUALITY ASSURANCE
It is the sum total of the organized arrangements with the
objective of ensuring that
• products will be of the quality required for their intended
use
The totality of the arrangements
• Ensure pharmaceutical products quality
• Incorporates cGMP, QC, design and developments and
GLP.
• Company based.
• Process based.
• Facts finding.

12. QUALITY CONTROL
• The part of GMP concerned with sampling,
specifications, testing, documentation, and
release procedures
• Quality judgement involved in all decisions
concerning the quality of the products
• Lab. Based
• Product based
Faults finding

13. BASIC PRINCIPLES OF GMP
1. Design and construct the facilities and equipments
properly
2. Follow written procedures and Instructions
3. Document work
4. Validate work
5. Monitor facilities and equipment
6. Write step by step operating procedures and work
on instructions
7. Design ,develop and demonstrate job competence
8. Protect against contamination
9. Control components and product related processes
10. Conduct planned and periodic audits

14. Drugs being a very important component of health
care system need special attention in regard to their
• Quality
• Safety
• Efficacy

15. CHARACTERISTICS OF
GMP-COMPLIANT PRODUCT
GMP
Safety
Strength
QualityPurity
Identity

16. Safety:
The product is free from unknown side effects when used as directed.
Identity:
The product is what the label describe it to be.
Strength (or potency):
The product delivers what its label claims throughout the product’s shelf
life.
Purity:
The product is free from microbial, chemical and physical contamination.
Quality:-
The product can be made consistently, time after time, meeting the same
specifications.

17. KEY ELEMENTS OF GMP
GMP
Elements
Personnel
Premises
Equipments
Materials
Sanitation
/
Hygiene
Validation
Recalls/
Returns
Self
Inspection
/
Audits
Documenta
tion
Storage

18. PERSONNEL
• Sufficient qualified personnel to carry out
tasks
• Aware of the principles of GMP
• Trained appropriate to their duties
• Job descriptions of key personnel
• Prohibition of unauthorized persons to
production, storage, quality control
• Health examination prior to and/or during
employment
• Good practices in personnel hygiene

19. PREMISES
Premises must be located, designed,
constructed and maintained for the
operations:
• Minimize risks of errors and cross-
contamination
• Permit effective cleaning
• Permit effective maintenance
• Minimize build-up of dirt and dust
• Eliminate any adverse effects on quality
• Process flow, material flow, people flow
• Suitably lit and ventilated
• Controlled temp. & humidity

20. EQUIPMENTS
Equipment layout and design must aim:
 to minimize risks of error
 to permit effective cleaning and maintenance
To avoid:
 cross-contamination, dust and dirt build-up
 any adverse effect on the quality of products
Measuring equipments to be calibrated
Defective equipments to be removed or labeled to
prevent use

21. MATERIALS
• Objective of the pharmaceutical manufacturer:
• produce finished products from a combination of
materials
• Materials combined:
• active pharmaceutical ingredients (APIs)
• auxiliary materials (excipients)
• packaging materials

22. MATERIALS
To review specific requirements for each type of material:
• Starting materials
• Packaging materials
• Intermediate and bulk products
• Finished products
• Rejected and recovered materials
• Recalled products
• Returned goods
• Reagents and culture media
• Reference standards
• Waste materials
• Miscellaneous materials (insecticides, sanitizing
materials)

23. SANITATION AND HYGIENE
• Written sanitation program
• Review measures to ensure good sanitation in:
Premises and personnel
Equipment and apparatus
Processes, materials and containers
•Cleaning intervals
•Pest control measures
•Prevent contamination of drug when rodenticides,
insecticides, & fumigation agents are used
•Microbial & environmental monitoring

24. SANITATION AND HYGIENE
Check change rooms/changing facilities
 Hand washing, signs, drying of hands
 Used clothing stored in separate closed containers while
awaiting cleaning
 Laundering of clean area clothing according to an SOP and
in an appropriate facility
 Procedure for disinfecting and sterilizing when required

25. SANITATION AND HYGIENE
• Health examinations:
Before and during employment
Periodic eye examinations for those who do visual
inspections
• Illness or open lesions:
May affect the quality of products
Should not handle starting materials, intermediates or
finished products, etc.
Instruction and encouragement to report to supervisors
• Direct contact between product and operator:
Should be avoided for Starting materials, primary
packaging materials, intermediate and bulk product

26. SANITATION AND HYGIENE
• Protection of product from contamination:
Clean clothes appropriate to personnel
activities
Including hair covering (e.g. caps)
• Smoking, eating and drinking not allowed in
production areas, laboratories and storage areas
• No chewing (e.g. gum), or keeping food or
personal medicine or plant or drinks allowed
• Toilets should not open directly into production or
storage areas

27. VALIDATION
WHO validation definition
• The documented act of proving
that any procedure, process,
equipment, material, activity,
or system actually leads to the
expected results.

28. PRODUCT RECALLS
• Recall definition
Removal from the market of specified batches of a
product
May refer to one batch or all batches of product
Requirements
• Designated responsible person to execute & coordinate recall
• Written Procedure
• Availability of distribution record
• Monitor and record the progress during the recall
• Final report should include reconciliation between delivered
and recovered products
• Secure storage of recall drugs until any decision

29. SELF INSPECTION
• Purpose of self-inspection is to evaluate whether a
company’s operations remain compliant with GMP
• Assists in ensuring quality improvement
• The programme should
cover all aspects of production and quality control
be designed to detect shortcomings in the
implementation of GMP
recommend corrective actions
set a timetable for corrective action to be completed
• Performed routinely
• Covering all aspects of GMP

30. DOCUMENTATION
• Documents should be designed, prepared, reviewed
& distributed with care
• Comply with marketing authorization
Types of Documents
• Labels
• Specifications and testing procedures
• Master formulae and instructions
• Batch processing and batch packaging records
• Standard Operating Procedures (SOPs)
• Records

31. STORAGE
• Sufficient Capacity
• Design assure good storage conditions, i.e., clean, dry, lit, within
controlled temp. & humidity
• Receiving & dispatching bays
• Quarantine
• Sampling
• Special materials
• Rejected materials
• Packing materials
• Weighing areas
• Stock rotation by FIFO/FEFO & control

32. GOOD PRACTICES IN
PRODUCTION
• Handling of materials & products should be done in
accordance with SOPs.
• Deviations should be avoided.
• Yield check at all stages.
• Operations on different products should not be carried
out in the same room.
• At all time during processing, all materials,
equipments,areas, packaging lines should be labeled.
• Access of production premises restricted.
• In-process controls performed within production area.
• Area clearance check.
• Fixed pipe work should be labeled with Content and
Direction of Flow.

33. Good Practices in Quality
Control
 QC should be independent from other depts.
 Should have adequate facilities, trained personnel &
approved procedures.
 Equipment qualifications & method validation must be
performed.
 Records for sampling & testing should be present.
 Sufficient samples of starting materials/products must
be retained.
 Environmental monitoring must be performed.
 Stability studies program of FPPs.
 OOS investigation must be performed.
 Microbiological section should be separate and with
separate HVAC unit

34. GMP GUIDELINES
• GMP as per Schedule “M”
• GMP as per WHO
• GMP as per MCA now known as MHRA
• GMP as per TGA
• GMP as per US FDA
• GMP as per ICH guidelines
• WHO: World Health Organization
• MHRA: Ministry of Health and Regulatory Affairs
• TGA: Therapeutic Goods Affairs
• FDA: Food And Drug Administration
• ICH: International Conference on Harmonization

35. GMP guidelines
• GMP as per Schedule “M”
www.cdsco.nic.in
• GMP as per WHO
www.who.int
• GMP as per MCA now known as MHRA
www.mca.gov.uk
• GMP as per TGA
www.tga.gov.au
• GMP as per US FDA
www.fda.gov
• GMP as per ICH guidelines
www.ich.org

36. OBJECTIVES OF GMP
• To produce products conforming to the
predetermined specifications
• To produce products of consistent
quality
• To minimize contamination
• To eliminate errors

37. • They outline a Quality System that reduces or
prevents errors
• Ensures products are safe for use in humans
• Prevent/control contamination and cross-
contamination
• Minimizes variations in potency of the drug
• Ensures reproducible physiological activity
• Prevent side effects and toxicity due to variations in
drug content and potency
• Prevents mislabeling and adulteration

38. GMP helps boost Pharmaceutical Export
Opportunities
• Most countries will only accept import and sale of
medicines that have been manufactured to
internationally recognized GMP.
• Governments seeking to promote their countries export
of pharmaceuticals can do so by making GMP
mandatory for all pharmaceutical production and by
training their inspectors in GMP requirements.

39. SOME BENEFITS OF GMP
Quality & Safety
High Efficacy
High Purity
High Work Speed
 (Efficient & Effective)
Cost Control
High Profit
Reduced Wastages
Less Deviations
 (Internal Customers)
Less Complaints
 (External Customers)
Less Recalls
Less Returns
Helpful for moving
International Commerce
Challenge of WTO
WHO Certification Scheme
Continual Improvement

40. • To provide instruction
• So people know what to do
• To promote understanding
• Understanding leads to involvements and commitment
• To promote consistency
• The task is performed in the right way each time
• To modify behavior
• To correct bad habits
• To remind
• So people continue to do the right thing

41. • Regulators demand it :
“Training in current good manufacturing practices shall
be on a continuing basis and with sufficient frequency to
assure that employees remain familiar with cGMP
requirements applicable to them"." All personnel shall
be aware of the principles of GMP that affect them &
receive initial & continuing training,………..”
(Training is Compulsory not Optional)

42. QUALITY IS EVERYBODY’S BUSINESS
No Wonder we failed to get the contract for the
Channel Tunnel !!

43. • EU Good Manufacturing Practice (GMP) Guidelines, Volume 4
of “The rules governing medicinal products in the European
Union”
• US FDA current Good Manufacturing Practice (cGMP) for
finished pharmaceuticals, 21 CFR, 210 and 211
• WHO Good Manufacturing Practices for pharmaceutical
products, Annex 4 to WHO Technical Report Series, No. 908,
2003. Good Pharmaceutical Manufacturing Practice Rationale
and Compliance