Transcript INDIAN PHARMACOPOEIA - Indian Pharmaceutical Association

INDIAN PHARMACOPOEIA
MONOGRAPH DEVELOPMENT
INDIAN PHARMACOPOEIA
MONOGRAPH DEVELOPMENT
Indian Pharmacopoeia Commission (IPC)
Vision The IPC is committed to the promotion of the
highest standards for drugs for use in the prevention and
treatment of diseases in human beings and animals keeping
in view the special features of the pharmaceutical industry
in India.
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MONOGRAPH DEVELOPMENT
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Objectives The overall objective has been the creation of a
compilation of standards that reflect the state of the
industry in the country and the production and testing
capabilities of units varying in size from the small to the
very big.
Special efforts have been made to safeguard the interests of
the weaker sectors of the industry without compromising
the safety and efficacy of the medicines included in the
Indian Pharmacopoeia (IP).
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MONOGRAPH DEVELOPMENT
 Priority given to monographs of drugs included
in the National Essential Drugs List and their dosage
forms.
 Regular upgradation of monographs but consistent with
the level and degree of sophistication acceptable to the
majority of manufacturers.
 Harmonization of IP standards with international
acceptance criteria for drug quality
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Quality Standards
 Neither high nor low
 A compromise between the desirable and the achievable
 Avoidance of sophisticated instrumentation or
methodology
 Recognition of the difficulties of the small- and mediumsized units of the industry
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 Retention of simple tests where complicated methods offer
no advantage
 No compromise on limitation of toxic impurities
 Gradual tightening of standards over the years
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Overall philosophy
 The Indian Pharmacopoeia is the official book of standards
and medicines produced in India must comply with the
specified standards
 Pharmacopoeial standards and acceptance criteria are set
with the intention that they be used only as compliance
requirements and not as requirements to guarantee total
quality assurance
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 Pharmacopoeial standards are the minimum ones with
which a manufacturer must comply before release of a
product for sale or distribution
 It is recognized that changes in quality may occur during
storage and distribution and the pharmacopoeial
requirements are set to define acceptable levels of change
and to reject materials or products showing unacceptable
levels
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 It is the responsibility of the manufacturer to ensure that
the product is manufactured in accordance with current
Good Manufacturing Practices and that sufficiently
stringent limits of acceptance are applied at the time of
release of a batch of material or product so that the
compendial standards are met until the expiry date under
the storage conditions specified
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 Pharmacopoeial requirements for drug substances have
been drawn up to provide appropriate limits for potential
impurities rather than to provide against all possible
impurities and adulterants.
 Material found to contain an impurity that cannot be
detected by means of the prescribed tests is to be
considered as not of pharmacopoeial quality if the nature
or amount of the impurity found is not compatible with
good manufacturing practices.
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General considerations
 Specifications designed for licensing, for compliance by
manufacturers and for the guidance of suppliers, users and
for those representing consumers
 Specifications valid for the entire period of use claimed by
the manufacturer for the product
 As a corollary, the test methods of the pharmacopoeia are
applicable for ascertaining compliance at any time during
the shelf life of the article.
 Test methods need to be robust because they are intended
to be used in a wide range of laboratories.
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Monograph Development Process
 Individual monographs are designed to be followed along
with the requirements of the General Notices of the
Pharmacopoeia, to the general test methods (described in a
separate volume of the compendium) and to other
information given in the General Chapters.
 A final assessment of the quality of an article is to be done
on a total evaluation of compliance with all these
requirements and not in relation to only the contents of
individual monographs.
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 In the process of developing a monograph the requirements
and recommendations of the drug licensing authorities are
also taken into account.
 Continuous dialogue with manufacturers and users is an
integral part of the process.
 Firming up of a monograph takes place only after
comments on test methods and limits of acceptance are
agreed to by users subject to, in some cases, approval by
licensing authorities
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Bulk Drug Substances
 Standards generally based on the methods of manufacture
used by the industry in the country
 However, the interests of the protection of the public are
kept in mind in deciding the appropriate level of control
 Types of tests for determining compliance are also related
to the quality requirement and sophistication of testing
equipment
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Normal Format
 Description. Physical form of the material, whether
hygroscopic, odour, if apparent and indication of
polymorphism, if applicable
 Identification
Tests
usually
including
infrared
spectrometry, if appropriate
 Non-specific purity tests, such as light absorption, optical
rotation, sulphated ash etc
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 Impurities , both related substances and impurities that
may be present as a result of the method of manufacture or
from degradation on storage
 Impurities other than related substances that may require
control such as heavy metals, inorganic impurities,
residues of solvents and reagents used during synthesis and
purification
 Other tests such as loss on drying or water
 Assay and limits for purity calculated on the anhydrous,
dried or solvent-free basis, as appropriate
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 To the extent possible, for assay, a robust and precise,
though not specific method is given rather than a specific
stability-indicating and complex one. With increasing
emphasis on stability, the latter is often unavoidable
 In the case of non-specific assay methods, control of
impurities is provided separately by means of specific
impurity tests.
 Each monograph is designed to be considered as a whole
and should provide a reliable basis for judging the quality
of the drug substance.
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Dosage Forms
 Monographs are designed to be read in conjunction with
the general monograph for the dosage form. The latter
provides for the general requirements and any exceptions
to, or modifications of, these requirements.
 The applicability of the tests of a monograph must be
ensured by the manufacturer by the proper choice of
excipients and other pharmaceutical aids.
 Limits for known impurities are given in many
monographs but manufacturers are expected to also limit
unknown impurities arising out of manufacture and
storage.
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Normal Format
 Description of the preparation in terms of the active
ingredient(s) and , where applicable, the manner in which
it is presented
 Additional specific information on the product is given in
some cases e.g. for tablets, whether or not they are coated.
 A statement of the limits of acceptance of the content in
terms of percentage of the labelled content of the active
ingredient. In many cases, the content is expressed in terms
of the therapeutically active part of the molecule.
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 Identification tests based on those for the parent drug
substance, where applicable, with suitable details for
isolation of the active ingredient from the excipients.
 Impurities as in the case of drug substances but
additionally including those arising on manufacture or
storage of the dosage form.
 Carry-over of impurities from the drug substance used in
the dosage form to be determined, wherever possible, with
any necessary modification, to demonstrate that drug
substance of pharmacopoeial quality had been used in the
formulated product.
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 Assay methods, to the extent possible, are stability-
indicating subject to the easy availability of the reference
substance of the active ingredient(s)
 Other tests such as pH, appearance of solution, dissolution
test and for single-dose preparations, a test for uniformity
of content may be specified.
 In general, standards for a dosage form are expected to be
indicative of the strength, stability and where applicable,
the safety of the product
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Test methods
 Generally provided by manufacturers and users and
expected to be suitable, validated, robust and reproducible.
 The method is applicable throughout the shelf-life of the
dosage form or throughout the period of use recommended
by the manufacturer for a dug substance.
 It is not expected that excipients used in a formulation
interfere in the test and cause errors in testing or in the
estimation of the active ingredient(s)
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 The results obtained by testing taken as a whole should
enable an independent and correct judgement as to the
quality of an article and to an assurance of compliance
with the published standards.
 Pharmacopoeial methods usually prescribe the use of
testing equipment available to most manufacturers and
public testing laboratories.
 Test methods are described in a clear language and in
sufficient detail that they can be followed in any laboratory
by a trained analyst.
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 New methods and revisions to existing ones are evaluated
by expert groups of the Scientific Body of the IPC and in
many cases, verification is done by the laboratory of the
IPC in consultation with the proposers of the methods.
 Comments on the proposed or revised methods are invited
before finalisation and inclusion in a monograph.
 Notwithstanding the assurance that a method given in a
monograph is valid, the user is expected to confirm that it
is applicable to the particular material or product being
examined.