This document summarizes a seminar on compendial testing. Compendial testing involves analytical methods to prove the identity, efficacy, and safety of drug products. A variety of techniques are used depending on the drug's characteristics and dosage form. Four core tests are described: description, identification, assay, and impurities. Identification confirms the drug's identity using techniques like spectroscopy. Assay determines purity or amount of active ingredient using methods like HPLC or titration. Impurities testing identifies organic, inorganic, and residual solvent impurities. Validation of tests and harmonization of methods across regions were also discussed.

1. A SEMINAR ON
COMPENDIAL TESTING
Prepared by:
Yachita Rajwadwala
M.Pharm(Q.A)

2. content
• Introduction
• Compendial testing for formulated products and
active ingredients
• Which compendium to use and when to use it
• Validation
• Harmonization of testing methods for
multicountry submission
• Conclusion
• Reference
Yachita Rajwadwala 2

3. compendial testing-introduction
 Compendial testing comprises all of the analytical
testing required to prove the IDENTITY, EFFICACY,
and SAFETY of drug products before they are
packaged or distributed.
 A variety of analytical techniques are used, ranging
from very simple physical testing to complex
chromatographic separations.
 The degree of testing that a product requires
depends on the characteristics of the compound, the
number of components in the product, and the
dosage form.
3Yachita Rajwadwala

4. COMPENDIAL TESTING FOR FORMULATED
PRODUCTS AND ACTIVE INGREDIENTS
 When new drug applications (NDAs) are submitted,
sometimes,the regulatory agencies will not agree on
the degree of testing, and additional testing could be
required for products to be distributed in certain
countries.
• There are four analytical tests that are considered
universal by the FDA for formulated products:
A. Description
B. Identification
C. Assay
D. Impurities 4Yachita Rajwadwala

5.  These tests represent the minimum testing
requirements for a batch of drug product to be
released by the QA laboratory.
 Quality standards (QS) exist for each product and
strength.
 The QS contain the testing methods and
specifications for releasing a batch of that product.
 Additionally, the QS may also contain sample of HPLC
chromatograms, UV/VISIBLE spectra, and IR spectra
to aid the analyst in carrying out each test.
5Yachita Rajwadwala

6. A. Descriptions of Active Ingredients and solid oral dosage forms
 A description test is a qualitative physical
description of the drug product any visual
characteristics: size, shape, color, and any other
identifying markings.
 The description test is critical and if it is incorrect,
that particular batch of product is immediately
considered defective.
 Description testing is not included in the USP
because the physical description of products is
unique to the manufacturer.
6Yachita Rajwadwala

7.  Generic products containing the same drug
substance have their own identifying markings
different from those of the branded product.
Yachita Rajwadwala 7

8. B. Identification of Active Pharmaceutical Ingredients
 Identification testing is designed to confirm the
identity or presence of the active ingredient by
employing a variety of analytical techniques and
methods.
 For drug formulations, the drug substance may need
to be extracted from the dosage form.
 New techniques such as near-IR spectroscopy may
eliminate the need to isolate the active ingredient.
Once the pure compound is obtained, a spectroscopic
technique such as UV, IR, or melting point will be used
to compare the sample identity to that of a standard
that has been similarly prepared.
Yachita Rajwadwala 8

9.  The characteristics of the compound will help
define which type of spectroscopy will be most
useful.
 One of the most important goals of identification
testing is that it must be specific enough to
distinguish between compounds with similar
structures including starting materials and
degradation products.
Yachita Rajwadwala 9

10. 1. Active Ingredients and Solid Oral Dosage Forms
Metoprolol tratrate Carbamazepin
 FOR EPILEPS
• The carbamazepine active
ingredient has an identification test
unique for testing raw materials, X-
ray diffraction.
•Each crystalline form of a
compound yields its own unique X-
ray diffraction pattern, which is
considered a form of identification.
 FOR HYPERTENSION
• The drug substance is a 2:1 salt
that contains a racemic mixture of
optical isomers of metaprolol and
naturally occurring dextro tartaric
acid.
10Yachita Rajwadwala

11. IR SPECTROSCOPY
 Dissolve 136mg of finely
ground tablets in 25ml of water
with 4ml of ammonium
hydroxide (1:3)
 After extraction with
chloroform, the organic layer is
dried over anhydrous sodium
sulfate, evaporated, and placed
in a freezer
 The crystals formed are
triturated with potassium
bromide and used in pellet form
to obtain an IR spectrum
 That is then compared to that of
a standard similarly prepared.
 To carry out the test,360mg of
powdered tablets is boiled in
15ml of acetone
 Filter and evaporate to around
5ml using a stream of nitrogen.
 Cooling in an ice bath gives rise
to crystals, which after filtration
and drying are used in a nujol
mull to obtain an IR spectrum.
11Yachita Rajwadwala

12. 2. Identification Tests Specific to Active Ingredients
Imiprimine is a hydrochloride salt available in tablet and injectable
dosage forms.
sample powder is dissolved in alcohol
2 N nitric acid is added along with 3 drops of a silver nitrate test
solution.
white precipitate of silver chloride is form
which dissolves upon addition of ammonium hydroxide
the presence of the chloride ion is confirmed
TEST

13. c. Assay
 Used to determine the purity of an active
substance or the amount of an active ingredient
present in a dosage form.
 Common methods are UV spectroscopy, titration,
and HPLC.
 Interesting assay tests are those where more than
one drug substance is present in the dosage form.
 One of the most fascinating products containing
multiple components is a combination of the
natural product reserpine, hydralazine
hydrochloride and hydrochlorothiazide
13Yachita Rajwadwala

14.  This drug product - available in tablet form and
contains 0.1mg of reserpine USP,
25mg of hydralazine hydrochloride,
15mg of hydralazine.
 Reserpine is an indole alkaloid derived from the
dried root of Rauwolfia serpentina and is well
known for its complex molecular architecture, the
challenges faced during its total synthesis, and its
profound effect on the central nervous system as
an antihypertensive.
 Hydralazine is also an antihypertensive and
hydrochlorothiazide has diuretic Properties.
14Yachita Rajwadwala

15.  The combination of these three very different molecular
structures brings diversity to the analytical testing
required.
 The typical assay procedure compares an external
standard solution of known concentration to that of the
sample of the same concentration using a form of
spectroscopy or titrimetric technique.
 Due to the unique nature of the three-component
product and the different properties of each, three
different assay procedures are required.
 UV spectroscopy is the most common spectroscopic
technique of choice for quantitative analysis.
 The compound must be able to absorb UV light at a
specific wavelength, which will then be used to
determine the absorbance of both the standard and
sample solutions. 15Yachita Rajwadwala

16. d. Impurities
• Impurity testing is required to determine the
purity of the drug product.
• There are three categories of impurities:
1. Organic Impurities
2. Inorganic Impurities
3. Residual Solvents.
16Yachita Rajwadwala

17. 1. Organic Impurities
 Organic impurities can result either from the
synthesis of the drug substance or from
degradation of the drug substance under storage of
the drug product.
 There are two class: identified or unidentified.
-Identified impurities are those whose structure
has been determined.
-Unidentified impurities are those whose structure
and toxicology are unknown.
 Organic impurities can include starting materials,
by-products, intermediates, degradation
products, reagents, ligands, or catalysts.
17Yachita Rajwadwala

18. Hydrochlorothiazide has a known degradation
pathway through which it degrades to the starting
material in its synthesis, a disulfonamide which is
known organic impurity usually found in acceptable
quantities in the final dosage form.
- An external standard solution of known
concentration of disulphonamide is prepared and the
peak responses recorded are used to calculate the
amount of disulphonamide present in the sample.
Yachita Rajwadwala 18

19. 2. Inorganic Impurities
 Inorganic impurities commonly arise from the
manufacturing process and are usually known and
identified.
 Normally, inorganic impurities are determined
when the drug substance is tested, not in the final
dosage form.
 They include reagents, ligands, catalysts, heavy
metals, and inorganic salts.
19Yachita Rajwadwala

20. 3. Residual Solvents
 Residual solvents are solvents that are used during
the manufacturing process and may be detected
after the product is in its final form.
 Some of the common solvents are benzene,
chloroform, 1,4-dioxane, methylene chloride,
and trichloroethylene.
 The most common technique for measuring
residual solvents is gas chromatography(GC)
because of the small size and volatile nature of
solvent molecules.
20Yachita Rajwadwala

21. Additional Tests
In addition to for basic test:
• Dissolution test
• Disintegration
• Friability
• Hardness
21Yachita Rajwadwala

22. WHICH COMPENDIUM TO USE AND WHEN TO
USE IT
 If the product contains a new drug substance, the
testing methods will come from the development
phase of the drug discovery process.
 If testing methods are submitted to the USP, they will
then become the compendial methods.
 Typically, the USP and other pharmacopeias will
approach the manufacturer and request the testing
methods that will be used so that they can be
incorporated into the pharmacopeia.
 If provided, the testing methods become the official
compendial methods. Otherwise, the USP will
develop its own methods. 22Yachita Rajwadwala

23. VALIDATION
23Yachita Rajwadwala
 Validation of an analytical procedure is a process
required to demonstrate that the procedure is
suitable for its intended use.
 Almost all analytical tests require some type of
validation. The amount and type of validation will
depend on the test procedure.
 Validation is necessary before an analytical test
can become a test procedure in the QC laboratory.
 The FDA has identified seven validation
characteristics: accuracy, precision, specificity,
detection limit, quantitation limit, linearity,
and range.

24. HARMONIZATION OF TESTING METHODS FOR
MULTICOUNTRY SUBMISSION
 The main goal is to harmonize the testing,
validation, and validation requirements associated
with pharmaceutical materials.
 Consequently, the International Conference on
Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use
(ICH) was established.
 The ICH is a unique project that brings together the
aforementioned regulatory agencies as well as
experts from the pharmaceutical industry to discuss
scientific and technical aspects of product
registration.
24Yachita Rajwadwala

25.  Reduction of duplicate testing carried out during
the research, development, and testing of new
medicines are necessary.
 Increased harmonization provides a more
economical use of human, animal, and material
resources and eliminates unnecessary delays in the
global development and availability of new
medicines while maintaining quality, safety, efficacy,
and regulatory obligations to protect public health.
 Each region has two seats on the ICH steering
committee that oversees the harmonization
activities.
25Yachita Rajwadwala

26. CONCLUSIONS
 The quality assurance function is critical to assure that
only effective and safe products are released to the
market place.
 The QC analytical laboratory is the final stage in a long
line of processes through which many individuals from
diverse departments take part to ensure the safety,
efficacy, and quality of drug products.
 Producing quality products requires not only a good
testing laboratory, but an organization that is empowered
to identify problems and develop innovative solutions.
 Analytical testing is one of the more interesting ways for
scientists to take part in the quality process by providing
actual data on the identity, content, and purity of drug
products.
26Yachita Rajwadwala

27. REFRENCES
• Handbook Of Modern Pharmaceutical Analysis By
Satinder Ahuja, Stephen Scypinski, Volume-3
,Chapter :- 9,Page No:325-44
• Website :- www.usp.org
27Yachita Rajwadwala

28. Thank you
Yachita Rajwadwala 28