Transcript Good Manufacturing Practices for Pharmaceuticals

GOOD MANUFACTURING
PRACTICES FOR
PHARMACEUTICALS
Dr. Basavaraj K. Nanjwade
M. Pharm., Ph. D
Department of Pharmaceutics
Faculty of Pharmacy
Omer Al-Mukhtar University
Tobruk, Libya.
E-mail: [email protected]
2014/02/18
Faculty of Pharmacy, Omar Al-Mukhtar University,
Tobruk, Libya.
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CONTENTS
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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
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Tobruk, Libya.
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Introduction
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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.
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Good Manufacturing Practices
• 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.
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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.
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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.
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GMP
QA
GMP
QC
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QA: Quality Assurance
GMP: Good Manufacturing Practices
QC: Quality Control
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Tobruk, Libya.
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
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GMP
GMP
Is that part of Quality Assurance
aimed at ensuring that products
are consistently manufactured to
a quality appropriate to their
intended use
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QA, GMP & QC inter-relationship
QC
Is that part of GMP concerned with
sampling, specification & testing,
documentation & release procedures
which ensure that the necessary &
relevant tests are performed & the
product is released for use only after
ascertaining it’s quality
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QC and QA
• QC is that part of GMP which • QA is the sum total of
is concerned with sampling,
organized arrangements
specifications, testing and
made with the object of
with in the organization,
ensuring that product
documentation and release
will be of the Quality
procedures which ensure that
required
by
their
the necessary and relevant
tests are carried out
intended use.
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QC and QA
• Operational laboratory • All those planned or
techniques and activities
systematic
actions
used to fulfill the
necessary to provide
requirement of Quality
adequate
confidence
that a product will
satisfy the requirements
for quality
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QC and QA
• QC is lab based
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• QA is company based
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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!
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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.
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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.
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GMP guidelines
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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
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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
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GMP
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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
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Ten 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
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List of important
documents in GMP
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Policies
SOP (Standard Operating Procedure)
Specifications
MFR (Master Formula Record)
BMR (Batch Manufacturing Record)
Manuals
Master plans/ files
Validation protocols
Forms and Formats
Records
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10 attributes of a good document
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Accurate
Clear
Complete
Consistent
Indelible
Legible
Timely
Direct
Authentic
Authorized
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API Manufacturing Process
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Secondary Manufacturing
Dosage Forms
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Secondary Manufacturing
Process - Tablets
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Secondary Manufacturing
Process – Sterile parenteral for
injection
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Biotechnology
Manufacturing Process
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Current GMP in manufacturing
processes (cGMP)
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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
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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.
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Packaging
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Packaging
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Packaging
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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.
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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.
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General provisions
• The processing of dry materials and products
creates problems of dust control and crosscontamination. 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.
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Organization and personnel
1. Responsibilities of quality control unit.
2. Personnel qualifications.
3. Personnel responsibilities.
4. Consultants.
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Building and facilities
1. Design and construction features.
2. Lighting.
3. Ventilation, air filtration, air heating and
cooling.
4. Plumbing.
5. Sewage and refuse.
6. Washing and toilet facilities.
7. Sanitation.
8. Maintenance.
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Equipment
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Equipment design, size, and location.
Equipment construction.
Equipment cleaning and maintenance.
Automatic, mechanical, and electronic
equipment.
5. Filters.
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Control of components
1. General requirements.
2. Receipt & storage of untested components, drug
product containers and closures.
3. Testing and approval or rejection of components,
drug product containers and closures.
4. Use of approved components, drug product
containers, and closures.
5. Retesting of approved components, drug product
containers, and closures.
6. Rejected components, drug product containers, and
closures.
7. Drug product containers and closures.
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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.
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Production and process
control
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Written procedures; deviations.
Charge-in of components.
Calculation of yield.
Equipment identification.
Sampling and testing of in-process materials
and drug products.
6. Time limitations on production.
7. Control of microbiological contamination.
8. Reprocessing.
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Packaging and labeling
control
1.
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4.
Materials examination and usage criteria.
Labeling issuance.
Packaging and labeling operations.
Tamper-evident packaging requirements for
over-the-counter (OTC) human drug
products.
5. Drug product inspection.
6. Expiration dating.
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Packaging and labeling
control
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Holding and distribution
1. Warehousing procedures.
2. Distribution procedures.
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Holding and distribution
• 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.
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Holding and distribution
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Records and reports
1. General requirements.
2. Equipment cleaning and use log.
3. Component, drug product container, closure, and
labeling records.
4. Master production and control records.
5. Batch production and control records.
6. Production record review.
7. Laboratory records.
8. Distribution records.
9. Complaint files.
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Returned savaged drug
products
1. Returned drug products.
2. Drug product salvaging.
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Returned savaged drug
products
• 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.
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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.
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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.
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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
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E-mail: [email protected]
2014/02/18
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Tobruk, Libya.
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