2. GMP refers to the integrated management control
system inclusive of the “methods used in, and the
facilities and controls used for the manufacturing,
packing, storage, and installation of the finished
devices intended for human use.
To assure that such devices will be safe and effective.
3. Manufacturing processes are clearly defined and controlled. All critical
processes are validated to ensure consistency and compliance with
specifications.
Manufacturing processes are controlled, and any changes to the process are
evaluated. Changes that have an impact on the quality of the drug are validated
as necessary.
Instructions and procedures are written in clear. (Good Documentation
Practices)
Operators are trained to carry out and document procedures.
Records are made, manually or by instruments, during manufacture that
demonstrate that all the steps required by the defined procedures and
instructions were in fact taken and that the quantity and quality of the drug
was as expected. Deviations are investigated and documented.
Records of manufacture (including distribution) that enable the complete
history of a batch to be traced are retained in a comprehensible and accessible
form.
Complaints about marketed drugs are examined, the causes of quality defects
are investigated, and appropriate measures are taken with respect to the
defective drugs and to prevent recurrence.
4. GMPs are enforced in the United States by the US
FDA, under Section 501(B) of the 1938 Food, Drug, and
Cosmetic Act (21 USCS § 351).
The regulations use the phrase "current good
manufacturing practices" (cGMP) to describe these
guidelines. Courts may theoretically hold that a drug
product is adulterated even if there is no specific
regulatory requirement that was violated as long as the
process was not performed according to industry
standards.
As of June 2010, a different set of cGMP requirements
apply to all manufacturers of dietary supplements.
5. The World Health Organization (WHO) version of GMP is
used by pharmaceutical regulators and the pharmaceutical
industry in over one hundred countries worldwide,
primarily in the developing world.
The European Union's GMP (EU-GMP) enforces similar
requirements to WHO GMP, as does the Food and Drug
Administration's version in the US. Similar GMPs are used
in other countries, with Australia, Canada, Japan,
Singapore and others having highly
developed/sophisticated GMP requirements.
In the United Kingdom, the Medicines Act (1968) covers
most aspects of GMP in what is commonly referred to as
"The Orange Guide", which is named so because of the
color of its cover; it is officially known as Rules and
Guidance for Pharmaceutical Manufacturers and
Distributors.
6. Within the European Union, GMP inspections are performed by
National Regulatory Agencies
In the United Kingdom by the Medicines and Healthcare
products Regulatory Agency (MHRA)).
in the Republic of Korea (South Korea) by the Korea Food &
Drug Administration (KFDA).
In Australia by the Therapeutical Goods Administration
(TGA).
In South Africa by the Medicines Control Council (MCC).
In Brazil by the National Health Surveillance Agency Brazil
(ANVISA).
In Iran, in India gmp inspections are carried out by state FDA
and these FDA report to Central Drugs Standard Control
Organization.
Pakistan by the Ministry of Health. Each of the inspectorates
carry out routine GMP inspections to ensure that drug products
are produced safely and correctly; additionally, many countries
perform pre-approval inspections (PAI) for GMP compliance
prior to the approval of a new drug for marketing.
7. The regulations in this part contain the minimum
current good manufacturing practice for preparation
of drug products for administration to humans or
animals
8. Quality control is the part of GMP that is concerned with
sampling, specifications, testing, documentation, and
release procedures.
Quality control ensures that the necessary and relevant
tests are carried out and that raw materials, packaging
materials, and products are released for use or sale, only if
their quality is satisfactory. Quality control is not confined
to laboratory operations but must be incorporated into all
activities and decisions concerning the quality of the
product.
It has a responsibility and authority to approve or reject all
components, drug product containers, closures, in process
materials, packing material, labeling, and drug products.
9. Adequate facilities, trained personnel, and approved procedures are
available for sampling, inspecting and testing of raw materials,
packaging materials, intermediate bulk and finished products, and,
where appropriate monitoring environmental conditions for GMP
purposes;
Samples of raw materials, packaging materials, and intermediate, bulk,
and finished products are taken according to procedures approved by
the quality control department;
Test methods are validated;
Records demonstrate that all the required sampling, inspecting, and
testing procedures were carried out, and any deviations are recorded
and investigated;
Records are made of the results of the inspection and testing of
materials and finished products against specifications;
The procedures for product release include a review and evaluation of
relevant production documentation and an assessment of deviations
from specified procedures
No drug is released for sale or supply prior to approval by the quality
control department;
Sufficient samples of raw material and finished product are retained to
permit future examination if necessary.
10. Quality assurance is a wide-ranging concept that
covers all matters that individually or collectively
influence the quality of a drug. It is the total of the
organized arrangements made with the objective of
ensuring that drugs are of the quality required for their
intended use. Quality assurance therefore incorporates
GMP, along with other factors that are outside the
scope of these guidelines.
A system of quality assurance appropriate for the
fabrication, packaging, labelling, testing, distribution,
importation, and wholesale of drugs should ensure
that:
Contd.
11. Systems, facilities and procedures are adequate and qualified;
Production and control operations are clearly specified;
Analytical methods and critical processes are validated;
Arrangements are made for the supply and use of the correct raw
and packaging materials;
All necessary control on intermediates, and any other in-process
monitoring is carried out;
Outsourced activities are subject to appropriate controls and
meet GMP requirements;
Fabrication, packaging/labelling, testing, distribution,
importation, and wholesaling are performed in accordance with
established procedures;
Drugs are not sold or supplied before the quality control
department has certified that each lot has been produced and
controlled in accordance with the marketing authorization and
of any other regulations relevant to the production, control and
release of drugs;
Satisfactory arrangements exist for ensuring that the drugs are
stored, distributed, and subsequently handled in such a way that
quality is maintained throughout their shelf life;
12. The quality risk management system should ensure
that:
the evaluation of the risk to quality is based on scientific
knowledge, experience with the process and ultimately links
to the protection of the patient
the level of effort, formality and documentation of the quality
risk management process is commensurate with the level of
risk.
The effectiveness, applicability, and continuous
improvement of the quality management system is
ensured through regular management review and self-
inspection;
An annual product quality review of all drugs should
be conducted with the objective of verifying the
consistency of the existing process, the
appropriateness of current specifications for both raw
materials and finished product to highlight any trends
and to identify product and process improvements.
13. Building and Facilities.
Design and construction features
Lighting
Ventilation, air filtration, air heating and cooling
Sewage and refuse
Washing and toilet facilities
Sanitation
Maintenance
Equipment
Equipment design, size, location.
Equipment construction
Equipment cleaning and maintenance
Automatic, mechanical, and electronic equipment.
Filters
contd…
14. There shall be a written procedure describing in sufficient detail the
receipt, identification, storage, handling, sampling, testing, and
approval or rejection of components and drug product containers and
closures .
Upon receipt and before acceptance drug product containers shall be
examined visually for appropriate labeling as to contents, containers
damage or broken seals and contamination.
Testing and approval or rejection of components, drug product
containers.
Use of approved components, drug product containers.
Retesting of approved components, drug product containers.
Rejected components, drug product containers.
Drug product containers shall not be reactive, additive/ absorptive so
as to alter safety, identity, strength, quality or purity of the drug beyond
the official or established requirements.
15. 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 microbial contamination.
Reprocessing.
16. Materials examination and usage criteria
Labeling issuance
Packaging and labeling operations.
Drug product inspection.
Expiration dating
Distribution procedures.
17. Equipment cleaning and use log.
Component, drug containers and labeling records.
Each batch production and control records
Production record review
Laboratory records
Distribution records
Compliant files
Records of returned drug product
Drug product salvaging
Contd…
18. General laboratory controls
Testing of intermediate and APIs
Validation procedures and analysis
Certificate of analysis
Stability Monitoring of APIs
Expiry and retest Dating
Rejection and re use of materials.
Traceability of Distributed APIs and Intermediates.
Repacking relabeling and holding of APIs and
intermediates.
Complaints.
Contract manufactures
19. Quality
Appropriate GMP concepts should be applied in the
production of API for use of clinical trials with in a
suitable mechanism of approval of each batch.
Equipment and facilities.
Control of Raw materials.
Production of APIs
Validation
Changes
Documentation
