GOOD MANUFACTURING PRACTICE (GMP)

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

       www.ich.org

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

  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

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

  1. Accurate

  2. Clear

  3. Complete

  4. Consistent

  5. Indelible

  6. Legible

  7. Timely

  8. Direct

  9. Authentic

  10. 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

  1. Responsibilities
    of quality control unit.

  2. Personnel
    qualifications.

  3. Personnel
    responsibilities.

  4. Consultants.

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.

Equipment

  1. Equipment
    design, size, and location.

  2. Equipment
    construction.

  3. Equipment
    cleaning and maintenance.

  4. Automatic,
    mechanical, and electronic equipment.

  5. Filters.

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.

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

  1. Written
    procedures; deviations.

  2. Charge-in
    of components.

  3. Calculation
    of yield.

  4. Equipment
    identification.

  5. Sampling
    and testing of in-process materials and drug products.

  6. Time
    limitations on production.

  7. Control
    of microbiological contamination.

  8. Reprocessing.

Packaging and labeling control

  1. Materials
    examination and usage criteria.

  2. Labeling
    issuance.

  3. Packaging
    and labeling operations.

  4. Tamper-evident
    packaging requirements for over-the-counter (OTC) human drug products.

  5. Drug
    product inspection.

  6. Expiration
    dating.

Holding and distribution

  1. Warehousing
    procedures.

  2. Distribution
    procedures.

  3. 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

  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.

Returned savaged drug products

  1. Returned
    drug products.

  2. Drug
    product salvaging.

  3. Adequate
    areas shall be designed to allow sufficient and orderly warehousing of returned
    or recalled products.

  4. 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

 

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