GOOD
MANUFACTURING PRACTICE
CONTENTS
Current GMP in manufacturing processes
Packaging and holding of drugs
Finished pharmaceuticals
General provisions
Organization and personnel
Building and facilities
Equipment
Control of components
Containers and closures
Production and process control
Packaging and labeling control
Holding and distribution
Records and reports
Returned savaged drug products
The inspection for compliance with GMP regulations
Controlled substances safeguards
References
What is GMP?
(Good Manufacturing Practices)
• GMP
is that part of Quality assurance which ensures
that the products are consistently manufactured and controlled to the Quality standards
appropriate to their intended use
• 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.
• A
basic tenet of GMP is that quality cannot be tested into a batch of product but
must be built into each batch of product during all stages of the manufacturing
process.
• It
is designed to minimize the risks involved in any pharmaceutical production
that cannot be eliminated through testing the final product.
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.
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.
GMP
QA, GMP & QC inter-relationship
QA
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
GMP
GMP is that part of Quality Assurance aimed at ensuring that
products are consistently manufactured to a quality appropriate to their
intended use
QC and QA
QC is that part of GMP which is concerned with sampling, specifications,
testing and within the organization, documentation and release procedures which
ensure that the necessary and relevant tests are carried out
• QA
is the sum total of organized arrangements made with the object of ensuring
that product will be of the Quality required by their intended use.
• Operational
laboratory techniques and activities used to fulfill the requirement of Quality
• All
those planned or systematic actions necessary to provide adequate confidence that
a product will satisfy the
requirements for quality
• QC
is lab based
• QA
is company based
GMP
• The
Quality of a formulation or a bulk drug
depends on the Quality of those producing it
• GMP
is the magic key that opens the door of
the Quality
• In
matter of GMP, swim with the current and in matter
of Quality stand like a rock!
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.
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.
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
• 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
GMP
• GMP
in solid dosage forms
• GMP
in semisolid dosage forms
• GMP
in Liquid orals
• GMP
in Parenterals Production
• GMP
in Ayurvedic medicines
• GMP
in Bio technological products
• GMP
in Nutraceuticals and cosmeceuticals
Ten Principles of GMP
- Design
and construct the facilities and equipments properly - Follow
written procedures and Instructions - Document
work - Validate
work - Monitor
facilities and equipment - Write step by step operating procedures and
work on instructions - Design
,develop and demonstrate job competence - Protect
against contamination - Control
components and product related processes - Conduct
planned and periodic audits
List of important documents in GMP
• Policies
• SOP
(Standard Operating Procedure)
• Specifications
• MFR
(Master Formula Record)
• BMR
(Batch Manufacturing Record)
• Manuals
• Master
plans/ files
• Validation
protocols
• Forms
and Formats
• Records
10 attributes of a good document
- Accurate
- Clear
- Complete
- Consistent
- Indelible
- Legible
- Timely
- Direct
- Authentic
- Authorized
API Manufacturing Process
Secondary Manufacturing Dosage Forms
Secondary Manufacturing Process – Tablets
Secondary Manufacturing Process – Sterile parenteral for
injection
Biotechnology Manufacturing Process
What are cGMPs?
• cGMP
refers to the Current Good Manufacturing
Practice regulations enforced by the US Food and Drug Administration (FDA).
• cGMP
provide for systems that assure proper design,
monitoring and control of manufacturing processes and facilities.
• Adherence
to the cGMP regulations assures the
identity, strength, quality and purity of drug products by requiring that manufacturers of
medications adequately control
manufacturing operations
Why are cGMP so important?
• A
consumer usually cannot detect (through smell, touch, or sight) that a drug
product is safe or if it will work.
• While
cGMPs require testing, testing alone is not adequate to ensure quality.
• In
most instances testing is done on a small sample of a batch (for example, a
drug manufacturer may test 1000 tablets from a batch that contains 2 million
tablets), so that most of the batch can be used for patients rather than
destroyed by testing.
Packaging
Primary packaging is the packaging used to form a container for product and which is in
direct contact with the product.
Eg. Sterile vials,
medicine bottle, tablet blisters pack.
Secondary Packaging
is any subsequent packaging which helps to inform about, display and product. It
include all required labeling and information leaflets.
Tertiary Packaging
is any final packaging grouping the products for storage and transportation.
Packaging and holding of drugs
• Care
shall be taken when using automatic tablet and capsule counting, strip and blister
packaging equipment to ensure that all ‘rogue’ tablets, capsules or foils from packaging
operation are removed before a new packaging operation is commenced.
• There
shall be an independent recorded check of the equipment before a new batch of tablets
or capsules is handled.
Finished pharmaceuticals
Appropriate specifications for finished products shall
include: –
• The
designated name of the product and the code reference.
• The
formula or a reference to the formula and the pharmacopoeial reference.
• Directions
for sampling and testing or a reference to procedures.
General provisions
• The
processing of dry materials and products creates problems of dust control and
cross- contamination. Special attention is therefore, needed in the design,
maintenance and use of premises and equipment in order to overcome these problems.
Wherever required, enclosed dust control manufacturing systems shall be
employed.
Organization and personnel
- Responsibilities
of quality control unit. - Personnel
qualifications. - Personnel
responsibilities. - Consultants.
Building and facilities
- Design
and construction features. - Lighting.
- Ventilation,
air filtration, air heating and cooling. - Plumbing.
- Sewage
and refuse. - Washing
and toilet facilities. - Sanitation.
- Maintenance.
Equipment
- Equipment
design, size, and location. - Equipment
construction. - Equipment
cleaning and maintenance. - Automatic,
mechanical, and electronic equipment. - Filters.
Control of components
- General
requirements. - Receipt
& storage of untested components, drug product containers and
closures. - Testing
and approval or rejection of components, drug product containers and
closures. - Use
of approved components, drug product containers, and closures. - Retesting
of approved components, drug product containers, and closures. - Rejected
components, drug product containers, and closures. - Drug
product containers and closures.
Containers and closures
• All
containers and closures intended for use shall comply with the pharmacopoeial
requirements. Suitable validated test
methods, sample sizes, specifications, cleaning procedure and sterilization procedure,
wherever indicated, shall be strictly followed to ensure that these are not
reactive, additive, absorptive, or leach to an extent that significantly
affects the quality or purity of the drug. No second hand or used containers and
closures shall be used.
Production and process control
- Written
procedures; deviations. - Charge-in
of components. - Calculation
of yield. - Equipment
identification. - Sampling
and testing of in-process materials and drug products. - Time
limitations on production. - Control
of microbiological contamination. - Reprocessing.
Packaging and labeling control
- Materials
examination and usage criteria. - Labeling
issuance. - Packaging
and labeling operations. - Tamper-evident
packaging requirements for over-the-counter (OTC) human drug products. - Drug
product inspection. - Expiration
dating.
Holding and distribution
- Warehousing
procedures. - Distribution
procedures. - Prior
to distribution or dispatch of given batch of a drug, it shall be ensure that the batch has been
duly tested, approved and released
by the quality control personnel. Pre-dispatch inspection shall be
performed on each consignment on a random basis to ensure that only the
correct goods are dispatched. Detailed instructions for warehousing and stocking
of Large Volume Parenterals, if stocked, shall be in existence and shall
be complied with after the batch is released for distribution. Periodic
audits of warehousing practices followed at distribution centers shall be
carried out and records thereof shall be maintained. Standard Operating
Procedures shall be developed for warehousing of products.
Records and reports
- General
requirements. - Equipment
cleaning and use log. - Component,
drug product container, closure, and labeling records. - Master
production and control records. - Batch
production and control records. - Production
record review. - Laboratory
records. - Distribution
records. - Complaint
files.
Returned savaged drug products
- Returned
drug products. - Drug
product salvaging. - Adequate
areas shall be designed to allow sufficient and orderly warehousing of returned
or recalled products. - Segregation
shall be provided for the storage of rejected, recalled or returned
materials or products.
The inspection for compliance with GMP regulations
• Short
description of the self-inspection system indicating whether an outside, independent
and experienced external export was involved in evaluating the manufacturer’s compliance
with Good manufacturing Practices in all aspects of production.
• Periodic
inspection of the garments shall be done by responsible staff.
Controlled substances safeguards
• Hazardous,
toxic substances and flammable materials shall be stored in suitably designed
and segregated, enclosed areas in conformity with Central and State
Legislations.
• Highly
hazardous, poisonous and explosive materials such as narcotics, psychotropic
drugs and substances presenting potential risks of abuse, fire or explosion
shall be stored in safe and secure areas. Adequate fire protection measures
shall be provided in conformity with the rules of the concerned civic
authority.
References
• 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