QC

HERBAL

Dr. Manisha Assistant

professor
Department of
Pharmacognosy
K.K.Wagh
KrupanidhiCollege
Collegeof
ofPharmacy,
Pharmacy Nashik 1
 Introduction

• Quality can be defined as the status of a drug that is determined by identity,

purity, content, and other chemical, physical, or biological properties, or by the
manufacturing processes. Quality control is a term that refers to processes
involved in maintaining the quality and validity of a manufactured product.

• In general, all medicines, whether they are of synthetic or of plant origin, should
fulfill the basic requirements of being efficacious and safe.

• The term “herbal drugs” denotes plants or plant parts that have been converted
into phytopharmaceuticals by means of simple processes involving harvesting,
drying, and storage. A practical addition to the definition is also to include other
crude products derived from plants, which no longer show any organic structure,
such as essential oils, fatty oils, resins, and gums.

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 Evaluation or Q. C. methods for medicinal plant material
as per W. H. O.
• Determination of foreign matter
• Macroscopic and microscopic examination
• Thin-layer chromatography
• Determination of ash
• Determination of extractable matter
• Determination of water and volatile matter
• Determination of volatile oils
• Determination of bitterness value
• Determination of haemolytic activity
• Determination of tannins
• Determination of swelling index
• Determination of foaming index
• Determination of pesticide residues
• Determination of arsenic and heavy metals
• Determination of microorganisms
• Radioactive contamination
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 Foreign Organic Matter

Definition: Foreign organic matter is the material consisting of any or all of the following.
1)Parts of the organ or organs from which the drug is derived other than the parts named in
the definition and description or for which the limit is prescribed in the individual
monograph.
2) Any organs other than those named in the definition and description.
3) Matter not coming from the source plant and
4) Moulds, insects or other animal contamination.
Method
• Weigh 100 to 500 g, or the quantity specified in the individual monograph, of the original
sample and spread it out in a thin layer. Inspect the sample with the unaided eye or with
the use of a 6x lens and separate the foreign organic matter manually as completely as
possible. Weigh and determine the percentage of foreign organic matter from the weight
of the drug taken. Use the maximum quantity of sample for coarse or bulky drugs.
• With the help of a suitable sieve, according to the requirements for the specific plant
material. Sift the remainder of the sample through a no. 250 seive, dust is regarded as
mineral admixture, weigh the portions of this sorted foreign matter to within 0.05g.

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 Organoleptic / Morphological evaluation

• Organoleptic evaluation of drugs refers to the evaluation of a drug by

colour, odour, size, shape, taste and special features including touch, texture
etc. Since the majority of information on the identity, purity and quality of
the material can be drawn from these observations, they are of primary
importance before any further testing can be carried out.
• For this purpose authentic specimen of the material under study and
samples of pharmacopoeial quality should be available to serve as a
reference.
• This evaluation procedure provides the simplest and quickest means to
establish the identity and purity and thereby ensure quality of a particular
sample.

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 Microscopic evaluation

• This allows more detailed examination of a drug and it can be used to identify the
organised drugs by their known histological character.
• This mostly used for qualitative evaluation of organised
crude drugs in entire and powdered forms and can be used to distinguish
cellular structure.
• For the effective results, various reagents can be used to distinguish cellular structure.
e.g. A drop of phloroglucinol and conc. HCl gives red stain with lignin. Mucilage is
stained with rhuthenium red to give pink color.
Following are the parameter evaluated by histological examination:
• Stomatal index : is the percentage which give the number of stomata to total number
of epidermal cells.
S. I. = S / E + S X 100
where, S = no. of stomata per unit area, E = no. of epidernal cells in unit area.
• Stomatal no.: is the average no. of stomata present per sq mm of epidermal cell.
• Palisade ratio : is the average no. of palisade cells beneath each epidermal cell.
• Vein islet & veinlet termination number : is the no. of vein islets & veinlet termination
per sq mm of the leaf surface midway between midrib and margin.

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 Ash value

The ash remaining following ignition of medicinal plant materials is determined by

three different methods which measure total ash, acid-insoluble ash and water-
soluble ash.
The total ash method is designed to measure the total amount of material
remaining after ignition. This includes both "physiological ash", which is derived
from the plant tissue itself, and "non-physiological" ash, which is the residue of
the extraneous matter (e.g. sand and soil) adhering to the plant surface.
Acid-insoluble ash is the residue obtained after boiling the total ash with
dilute hydrochloric acid, and igniting the remaining insoluble matter. This
measures the amount of silica present, especially as sand and siliceous earth.
Water-soluble ash is the difference in weight between the total ash and the
residue after treatment of the total ash with water.

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Total ash
Place about 2-4g of the ground air-dried material, accurately weighed, in a
previously ignited and tared crucible (usually of platinum or silica). Spread the
material in an even layer and ignite it by gradually increasing the heat to 500-
600°C until it is white, indicating the absence of carbon. Cool in a desiccator and
weigh. If carbon-free ash cannot be obtained in this manner, cool the crucible
and moisten the residue with about 2 ml of water or a saturated solution of
ammonium nitrate R. Dry on a water-bath, then on a hot-plate and ignite to
constant weight. Allow the residue to cool in a suitable desiccator for 30
minutes, then weigh without delay. Calculate the content of total ash in mg per g
of air-dried material.
Acid-insoluble ash
To the crucible containing the total ash, add 25 ml of hydrochloric acid (-70g/l)
TS, cover with a watch-glass and boil gently for 5 minutes Rinse the watch-glass
with 5 ml of hot water and add this liquid to the crucible. Collect the insoluble
matter on an ashless filter-paper and wash with hot water until the filtrate is
neutral. Transfer the filter-paper containing the insoluble matter to the original
crucible, dry on a hot-plate and ignite to constant weight. Allow the residue to
cool in a suitable desiccator for 30 minutes, then weigh without delay. Calculate
the content of acid-insoluble ash in mg per g of air-dried material.
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Water-soluble ash
To the crucible containing the total ash, add 25 ml of water and boil for 5
minutes. Collect the insoluble matter in a sintered-glass crucible or on an
ashless filter-paper. Wash with hot water and ignite in a crucible for 15
minutes at a temperature not exceeding 450°C Subtract the weight of this
residue in mg from the weight of total ash. Calculate the content of water-
soluble ash in mg per g of air-dried material.

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 Extractive value

This method determines the amount of active constituents extracted with

solvents from a given amount of medicinal plant material. It is employed for
materials for which as yet no suitable chemical or biological assay exists.
Method 1. HOT extraction
Place about 4.0g of coarsely powdered air-dried material, accurately weighed, in a
glass-stoppered conical flask. Add 100 ml of water and weigh to obtain the
total weight including the. flask. Shake well and allow to stand for 1 hour. Attach
a reflux condenser to the flask and boil gently for 1 hour; cool and weigh.
Readjust to the original total weight with the solvent specified in the test
procedure for the plant material concerned. Shake well and filter rapidly
through a dry filter. Transfer 25 ml of the filtrate to a tared flat-bottomed dish
and evaporate to dryness on a water-bath. Dry at 105 °C for 6 hours, cool in a
desiccator for 30 minutes, then weigh without delay. Calculate the content of
extractable matter in mg per g of air-dried material.

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Method 2. Cold maceration
Place about 4.0g of coarsely powdered air-dried material, accurately
weighed, in a glass-stoppered conical flask. Macerate with 100 ml of the
solvent specified for the plant material concerned for 6 hours, shaking
frequently, then allow to stand for 18 hours. Filter rapidly taking care not
to lose any solvent, transfer 25 ml of the filtrate to a tared flat-bottomed
dish and evaporate to dryness on a water-bath. Dry at 105 °C for 6 hours,
cool in a desiccator for 30 minutes and weigh without delay. Calculate the
content of extractable matter in mg per g of air-dried material.
For ethanol-soluble extractable matter, use the concentration of solvent
specified in the test procedure for the plant material concerned; for water-
soluble extractable matter, use water as the solvent (As per IP Use
chloroform water). Use other solvents as specified in the test procedure.

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 Determination of water and volatile matter

• The apparatus (Figure) consists of a glass flask (A) connected

by a tube (D) to a cylindrical tube (B) fitted with a graduated
receiving tube (E) and a reflux condenser (C). The receiving
tube (E) is graduated in 0.1-m1 divisions so that the error of
readings does not exceed 0.05 ml. The preferred source of
heat is an electric heater with a rheostat control, or an oil-
bath. The upper portion of the flask and the connecting
tube may be insulated.
• Thoroughly clean the receiving tube and the condenser of the
apparatus, rinse with water and dry. Introduce 200ml of
toluene R and about 2 ml of water into a dry flask. Heat the
flask to distil the liquid over a period of 2 hours, allow to cool
for about 30 minutes and read off the volume of water to an
accuracy of 0.05 ml (first distillation).
Figure: Deane stark apparatus

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•Weigh accurately a quantity of the material expected to give about 2-3ml of
water and transfer to the flask. (For weighing material with a paste-like character,
use a boat of metal foil.) Add a few pieces of porous porcelain and heat the flask
gently for 15 minutes. When boiling begins, distil at a rate of 2 drops per second
until most of the water has distilled over, then increase the rate of distillation to
about 4 drops per second. As soon as the water has been completely distilled,
rinse the inside of the condenser tube with toluene R. Continue the distillation for
5 more minutes, remove the heat, allow the receiving tube to cool to room
temperature and dislodge any droplets of water adhering to the walls of the
receiving tube by tapping the tube. Allow the water and toluene layers to
separate and read off the volume of water
𝒏𝟏
% of water =
where −�𝒏
�
w = the weight in g of the material being examined
n = the number of ml of water obtained in the first distillation
n1 = the total number of ml of water obtained in both distillations
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2. Loss on drying (gravimetric determination)
Place about 2-5 g of the prepared air-dried material, or the quantity
specified in the test procedure for the plant material concerned, accurately
weighed, in a previously dried and tared flat weighing bottle. Dry the
sample by one of the following techniques:
— in an oven at 100-105°C;
— in a desiccator over phosphorus pentoxide R under atmospheric pressure
or reduced pressure and at room temperature.

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 IR balance

Karl Fischer Titration Ingredients of KF reagents

Iodine, sulphur dioxide, pyridine and methanol
Principle
 I2 + + H2O  2HI+SO3
 SO3 + C5H5N C5H5N. SO3
 HI + C5H5N C5H5N. HI
 C5H5N. SO3 + CH3OH  C5H5N. HSO4 CH3

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 Determination of volatile oils

Apparatus
A suitable apparatus is made from resistant glass with a low expansion coefficient,
and has the following parts:
 a round-bottomed, short-necked flask, capacity 500 or 1000 ml, the internal
diameter of the ground-glass neck being 29 mm at the widest end;
 the following sections fused into one piece
— a vertical tube (AC), 210-260 mm long, with an external diameter of 13-15
mm;
— a bent tube (CDE), CD and DE each being 145-155 mm long, and having
an
external diameter of 10 mm;
— a bulb-condenser (FG), 145-155 mm long;
— a tube (GH) 30-40mm long, with a side-arm tube (HK), at an angle of 30-40°;
— a vented ground-glass stopper (K') and a tube (K) with an internal diameter of 10
mm, thewideendbeing of ground glass;
— a pear-shaped bulb (J) with a volume of 3 ml;
— a tube with a volume of 1 ml (JL), graduated over 100-110mm in divisions of 0.01
ml;
— a bulb-like swelling (L), with a volume of about 2 ml;
— a three-way tap (M);
— a connecting tube (BM), with an external diameter of 7-8mm, which is fitted in the
middle with a security tube (N); the junction (B) should be 20-25mm higher than the
uppermost graduation;
• a burner allowing fine control and fitted with a flue, or an electric heating device;
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• a vertical Pharmacywith a horizontal ring covered with insulating material.
 Bitterness value

The bitter properties of plant material are determined by comparing the threshold
bitter concentration of an extract of the materials with that of a dilute solution of
quinine hydrochloride R. The bitterness value is expressed in units equivalent to the
bitterness of a solution containing I. g of quinine hydrochloride R in 2000ml.

Stock and diluted Quinine hydrochloride solutions

Dissolve 0.100 g of of Quinine hydrochloride R in sufficient safe drinking water to
produce 100ml. Further dilute 5ml of this solution to 500ml with safe drinking
water. This stock solution of Quinine hydrochloride (Sq) contain 0.01mg/ml. use
nine test tubes for serial dilution for initial test as given in table 1.
Table 1:
Tube number
1 2 3 4 5 6 7 8 9
Sq (ml) 4.2 4.4 4.6 4.8 5.0 5.2 5.4 5.6 5.8
Safe drinking water(ml) 5.8 5.6 5.4 5.2 5.0 4.8 4.6 4.4 4.2
Quinine HCl in 10ml of solution 0.04 0.04 0.04 0.04 0.05 0.05 0.05 0.05 0.05
(mg) 2 4 6 8 0 2 4 6 8
Sq= stock solution of Quinine HCl
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Stock and diluted solutions of plant material
Prepare the solution as specified in the test procedure for given plant material
(ST). use ten test tubes for serial dilution for test as given in table 2.
Table 2

Tube number
1 2 3 4 5 6 7 8 9 10
ST (ml) 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 10.0
Safe drinking water(ml) 9.00 8.00 7.00 6.00 5.00 4.00 3.00 2.00 1.00 --
ST= stock solution of plant material being examined

Bitterness 200 X c
value= aXb

where a = the concentration of the stock solution (ST) (mg/ml),

b = the volume of ST (in ml) in the tube with the threshold bitter con-centration,
c = the quantity of quinine hydrochloride R (in mg) in the tube with the threshold
bitter concentration.

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 Determination of haemolytic activity

The haemolytic activity of plant material is determined by comparison with reference material,
saponin R, which has haemolytic activity of 1000 units per gm. A suspension of erythrocyte is
mixed with equal volume of serial dilution of plant material extract. The lowest concentration
cause complete haemolysis is determined after allowing mixtures to stand for a given period of
time. A similar test is carried out simultaneously with saponin R.
Preliminary test: Prepare serial dilution of plant material extract with phosphate buffer 7.4 and
blood suspension (2%) using four Test tube as follow:
Tube number
1 2 3 4
Plant material (ml) 0.10 0.20 0.50 1.00
Phosphate buffer pH 7.4(ml) 0.90 0.80 0.50 -
Blood suspension (2%) (ml) 1.00 1.00 1.00 1.00
Mix, avoiding formation of foam, allow to stand for 6 hr at room temperature. Examine tube &
record dilution for total haemolysis & proceed as follows :
• If total haemolysis is observed only in tube no. 4, use original extract.
• If observed in 3, 4, prepare 2 fold dilution of original extract.
• If observed in 2, 3, 4, prepare 5 fold dilution of original extract.
• If all tubes contain, clear, red solution, prepare 10 fold dilution of original extract.

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Main test: Prepare serial dilution of plant material extract diluted / undiluted with
phosphate buffer 7.4 and blood suspension (2%) using 13 Test tube as follow:
Tube number
Serial i1o o2r 3m n4t t 5 6 7 8 9 10 11 12 13
dilut nf the ai es
Plant material (Diluted if 0.4 0.45 0.5 0.5 0.6 0.6 0.7 0.7 0.8 0.8 0.9 0.9 1.0
necessary) (ml) 0 5 0 5 0 5 0 5 0 5 0
Phosphate buffer pH 7.4(ml) 0.6 0.55 0.5 0.4 0.4 0.3 0.3 0.2 0.2 0.1 0.1 0.0 -
0 5 0 5 0 5 0 5 0 5
Blood suspension (2%) (ml) 1.0 1.00 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
0 0 0 0 0 0 0 0 0 0 0 0
Mix, observe
ST= stock result
solution after
of plant 24 being
material hr. Calculate
amount material in gm that produce complete
examined
haemolysis . Prepare similar dilutions of saponin R & calculate quantity of saponin R in g that
produce complete haemolysis .
Haemolytic activity of material using following formula:

Haemolytic Activity = 1000 X a

Where b
a = Quantity of saponin R that produce total haemolysis
b = Quantity of material that produce total haemolysis

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 Determination of Tannins

• Tannins are substances capable of turning animal hides into leather by binding proteins to
form water-insoluble substances that are resistant to proteolytic enzymes. This process,
when applied to living tissue, is known as an "astringent" action and is the reason for the
therapeutic application of tannins. Chemically, tannins are complex substances; they
usually occur as mixtures of polyphenols that are difficult to separate and crystallize. They
are easily oxidized, polymerized in solution, form colloidal solution with water & non
crystalline compound.

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• Procedure : Weighed accurately a quantity of powder into a conical flask. Add 150 ml of
water and heat over a boiling water-bath for 30 minutes. Cool, transfer the mixture to a
250-ml volumetric flask and dilute to volume with water. Allow the solid material to settle
and filter the liquid through a filter-paper, discarding the first 50 ml of the filtrate. To
determine the total amount of material that is extractable into water, evaporate 50.0 ml of
the plant material extract to dryness, dry the residue in an oven at 105°C for 4 hours and
weigh (W 1 ).
• To determine the amount of plant material not bound to hide powder that is extractable
into water, take 80.0ml of the plant material extract, add 6.0g of hide powder R and shake
well for 60 minutes. Filter and evaporate 50.0ml of the clear filtrate to dryness. Dry the
residue in an oven at 105°C and weigh (W 2 ).
• To determine the solubility of hide powder, take 6.0 g of hide powder R, add 80.0ml of
water and shake well for 60 minutes. Filter and evaporate 50.0ml of the clear filtrate to
dryness. Dry the residue in an oven at 105°C and weigh (W 3 ).
• Calculate the quantity of tannins as a percentage using the following formula:
% tannins= W 1 - ( W 2 - W 3 ) / w X 500
where w = the weight of the plant material in grams.

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 Determination of Swelling index

• The swelling index is the volume in ml taken up by the swelling of 1 g of plant

material under specified conditions.
• Many medicinal plant materials are of specific therapeutic or pharmaceutical
utility because of their swelling properties, especially gums and those containing
an appreciable amount of mucilage, pectin or hemicellulose.
• Its determination is based on the addition of water or a swelling agent as specified
in the test procedure for each individual plant material (either whole, cut or
pulverized).
• Using a glass- stoppered measuring cylinder, the material is shaken repeatedly for
1 hour and then allowed to stand for a required period of time. The volume of the
mixture (in ml) is then read.
• The mixture of whole plant material with the swelling agent is easy to achieve, but
cut or pulverized material requires vigorous shaking at specified intervals to
ensure even distribution of the material in the swelling agent

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Carry out simultaneously no fewer than three determinations for any given
material. Introduce the specified quantity of the plant material concerned,
previously reduced to the required fineness and accurately weighed, into a 25-ml
glass-stoppered measuring cylinder. The internal diameter of the cylinder should
be about 16mm, the length of the graduated portion about 125 mm, marked in
0.2m1 divisions from 0 to 25 ml in an upwards direction. Unless otherwise
indicated in the test procedure, add 25 ml of water and shake the mixture
thoroughly every 10 minutes for 1 hour. Allow to stand for 3 hours at room
temperature, or as specified. Measure the volume in ml occupied by the plant
material, including any sticky mucilage. Calculate the mean value of the
individual determinations, related to 1g of plant material.

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 Determination of foaming index
Many medicinal plant materials contain saponins that can cause a persistent foam
when an aqueous decoction is shaken. The foaming ability of an aqueous decoction of plant
materials and their extracts is measured in terms of a foaming index.
• Procedure
Weigh accurately 1 g coarse powder, transferred to 5ooml conical flask containing 100ml boiling
water. Boil for 30 min. Cool, filter to 100 ml volumetric flask & make up volume to 100ml.
• Take 10 Test tubes, Mark with 1 to 10, add 1ml, 2ml, 3ml etc. upto solution 10ml to test tubes.
Make up volume with water to 10 ml in each test tube. Shake them in a lengthwise motion for
15 seconds, two shakes per second. Allow to stand for 15 minutes and measure the height of
the foam.
Result
If height of foam is less than 1cm = foaming index is less than 100.
If height of foam in is more than 1cm in each test tube, foaming index is more than 1000. in
this case repeat the determination using new series of dilutions of the decoctions in order to
obtain result.
If a height of foam is 1 cm in any tube, then according to volume of plant material decoction in
this tube (a) is used determine index. Foaming index is calculated by formula :
Foaming index = 1000 / a
Where, a = volume of filtrate added to test tube where height of foam is 1 cm

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 Determination of Pesticides
• Pesticides are chemicals derived from synthetic and natural sources which are
effective in small concentrations against pest. Even though there are no serious reports of toxicity
due to the presence of pesticides and fumigants, it is important that herbs and herbal products
are free of these chemicals or at least are controlled for the absence of unsafe levels. Herbal drugs
are liable to contain pesticide residues, which accumulate from agricultural practices, such as
spraying, treatment of soils during cultivation, and administering of fumigants during storage.
• Classification of pesticides (according to pest they control):
A) Fungicides:
a. disinfectants for seed: parathion, carboxins .
b. disinfectants for soil:
c. Leaf fungicides: colloidal sulphur , barium sulphide , dithiocarbamates .
B) Herbicides:
a. Total herbicides
b. Selective herbicides (widely used)
c. Water weed killers
d. Harvesting aids e.g. carbamates, urea derivatives, triazines, 4o ammonium salts.
C) Insecticides:
a. Inorganic insecticides: arsenic comp. (lead arsenate), flourine comp. (sodium floride).
b. Orgenic insecticides: nicotine, pyrethrum
D) Others like nematocides , rodenticides , bactericides.

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Methods for the determination of pesticide residues
Chromatography (mostly column and gas) is recommended as the principal method for the
determinati on of pesti cide residues. Samples are extracted by a of that particular pesticide
residue should be employed.
Standard procedure, impurities are removed by partition and/or adsorption, and the presence of
a moderately broad spectrum of pesti cides is measured in a single determinati on. However,
these techniques are not universally applicable. Some pesticides are satisfactorily carried through
the extraction and clean-up procedures, others are recovered with a poor yield, and some are
lost entirely. In chromatography, the separations may not always be complete, pesticides may
decompose or metabolize, and many of the metabolic products are still unknown. Consequently,
as a result of limitations in the analytical technique and incomplete knowledge of pesticide
interaction with the environment, it is not yet possible to apply an integrated set of methods that
will be satisfactory in all situations.

It is therefore desirable to test plant materials of unknown history for broad groups of compounds
rather than for individual pesticides. A variety of methods meet these requirements. Chlorinated
hydrocarbons and other pesticides containing chlorine in the molecule, for
example, can be by the measurement of total
detected containing organic chlorine; insecticides be measured by
pesticides containing arsenic and
phosphate lead can be total
analysisfor detectedorganic
by measurement
phosphorus,of total arsenic or total
while
lead, respectively.
can Similarly, the measurement of total bound carbon disulfi de in a sample will
provide information on whether residues of the dithiocarbamate family of fungicides are
present.
If the pesticide to which the plant material has been exposed is known or can be identified by
suitable means, an established method for the determinati on

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 Maximum limit of pesticide residues for medicinal plant materials
The toxicological evaluation of pesticide residues in medicinal plant materials should be based
on the likely intake of the material by patients. In general, the intake of residues from
medicinal plant materials should account for no more than 1% of total intake from all sources,
including food and drinking-water. Certain plant materials may contain extremely high levels of
pesticide residues, but the levels remaining after extraction are usually much lower, because of
the low solubility in water or ethanol.
It is therefore important to determine the actual quantity of residues consumed in the final
dosage form.
Where the nature of the pesticide to which the plant material has been exposed is
unknown, it is sufficient to determine the content of total chlorine and to base the calculation
on the acceptable residue level (ARL) of the most toxic chlorine- containing pesticide (e.g.
aldrin or dieldrin).

ADI = maximum acceptable daily intake of pesticide (mg/kg of body weight);

E = extraction factor, which determines the transition rate of the pesticide from the
plant material into the dosage form;
MDI = mean daily intake of medicinal plant product.

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 Determination of arsenic and heavy metals

• Determination of arsenic
• Preparation of the sample (by acid digestion): Place35-70 g of coarsely ground
material, accurately weighed, in a Kjeldahl flask, capacity 800-1000 ml. +(10-25 ml)
water + (25-50 ml) nitric acid + carefully add (20 ml) sulphuric acid. Heat Gradually add
nitric acid (~1000 g/l), drop by drop, until all the organic matter is destroyed. a clear
solution with copious vapours of sulfur trioxide is obtained. Cool add (75 ml) water +
(25 ml) ammonium oxalate. Heat again until sulfur trioxide vapours develop. Cool,
transfer to a 250-ml volumetric flask and dilute to volume with water.
• Preparation of standard stain: Add (10 ml) hydrochloric acid + 1 ml dilute arsenic As to
50 ml water. The resulting solution, when treated as described in the general test yields a
stain on mercuric bromide paper. standard stain (10 μg As)
• Method:
• Into the lower tube insert 50 to 60 mg of lead acetate cotton, loosely packed, or a small
plug of cotton and a rolled piece of lead acetate paper weighing 50 to 60 mg. Between
the flat surfaces of the tubes place a disc or a small square of mercuric chloride paper
large enough to cover the orifice of the tube (15 mm × 15 mm).
• Take an aliquot (25-50 ml) of the test solution +1 g of potassium iodide + l0 g of
granulated zinc in the wide mouthed bottle place the prepared glass tube assembly
quickly in position. reaction 40 minutes,40oc temp. Compare any yellow stain that is
produced on the mercuric bromide paper with a standard stain produced in a similar
manner with a known quantity of dilute arsenic.

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 Determination of Cadmium and lead
Apparatus
The equipment consists of a digestion vessel, consisting of a vitreous silica crucible (DIN 12904), "tall form", height
62mm, diameter 50mm, capacity 75ml, with a vitreous silica cover.
Materials used are:
- digestion mixture: 2 parts by weight of nitric acid (~1000g/l) TS and 1 part by weight of perchloric acid (~1170g/l) TS.
- reference materials: olive leaves (Olea europaea)1 and hay powder.
Clean scrupulously with nitric acid (~1000g/l) TS the digestion vessel and all other equipment to be used for the
determination, rinse thoroughly several times with water and dry at 120°C.
Preparation of the sample
For the wet digestion method in an open system, place 200-250mg of air-dried plant material, accurately weighed, finely
cut and homogeneously mixed, into a cleaned silica crucible. Add 1.0ml of the digestion mixture, cover the crucible
without exerting pressure and place it in an oven with a controlled temperature and time regulator (computer-
controlled, if available).
Heat slowly to 100°C and maintain at this temperature for up to 3 hours; then heat to 120°C and maintain at
this temperature for 2 hours. Raise the temperature very slowly to 240°C, avoiding losses due to possible violent
reactions especially in the temperature range of 160-200°C, and maintain at this temperature for 4 hours. Dissolve the
remaining dry inorganic residue in 2.5 ml of nitric acid (~1000g/l) TS and use for the determination of heavy metals.
Every sample should be tested in parallel with a blank.
Method
The contents of lead and cadmium may be determined by inverse voltametry or by atomic absorption
spectrophotometry. The following maximum amounts in dried plant materials, which are based on the ADI values, are
proposed:
- lead, 10 mg/kg;
- -cadmium, 0.3 mg/kg

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 Determination of microorganisms

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 Microbial contamination limits in medicinal plant materials

Different limits are set according to the use of the material and the material itself.
For contamination of "crude" plant material intended for further processing (including additional
decontamination by a physical or chemical process) the limits, adapted from the provisional
guidelines established by an international consultative group , are given for untreated plant
material harvested under acceptable hygienic conditions:
 Escherichia coli, maximum 104 per gram;
 Mould propagules, maximum 105 per gram.
For plant materials that have been pretreated (e.g. with boiling water as used for herbal teas
and infusions) or that are used as topical dosage forms:
 Aerobic bacteria, maximum 107 per gram;
 Yeasts and moulds, maximum 104 per gram;
 Escherichia coli, maximum 102 per gram;
 Other enterobacteria, maximum 104 per gram; - salmonellae, none.
For other plant materials for internal use:
 Aerobic bacteria, maximum 105 per gram;
 Yeasts and moulds, maximum 103 per gram;
 Escherichia coli, maximum 10 per gram;
 Other enterobacteria, maximum 103, per gram;
 Salmonellae, none.
- Alflatoxin –none (Free )

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 Radioactive contamination

• A certain amount of exposure to ionizing radiation cannot be avoided since there are many sources, including
radionuclides occurring naturally in the ground and the atmosphere. These sources are described extensively in the
booklet Facts about low-level radiation.
• Dangerous contamination may be the consequence of a nuclear accident. The World Health Organization, in close
collaboration with several other international organizations, has developed guidelines for use in the event of
widespread contamination by radionuclides resulting from a major nuclear accident. This publication emphasizes that
the health risks from food accidentally contaminated by radionuclides depend not only on the specific radionuclide
and the level of contamination but also on the quantity of food consumed.
• The range of radionuclides that may be released into the environment as the result of a nuclear accident might include
long-lived and short-lived fission products, actinides, and activation products. The nature and the intensity of
radionuclides released may differ markedly and depend on the source (reactor, reprocessing plant, fuel fabrication
plant, isotope production unit, etc.).
• The amount of exposure to radiation depends on the intake of radionuclides and other variables such as age,
metabolic kinetics, and weight of the individual (also known as the dose conversion factor).
• Even at maximum observed levels of radioactive contamination with the more dangerous radionuclides, significant
risk is associated only with consumption of quantities of over 20 kg of plant material per year so that a risk to health
is most unlikely to be encountered given the amount of medicinal plant materials that would need to be ingested.
Additionally, the level of contamination might be reduced during the manufacturing process. Therefore, no limits for
radioactive contamination are proposed.
Method of measurement
• Since radionuclides from accidental discharges vary with the type of facility involved, a generalized method of
measurement is so far not available. However, should such contamination be of concern, suspect samples can be
analysed by a competent laboratory. Details of laboratory techniques are available from the International Atomic
Energy Agency (IAEA)

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 Guidelines for the Assessment of Herbal Drugs

• Exceptionally, in some countries herbal medicines may also contain, by tradition,

natural organic or inorganic active ingredients which are not of plant origin.
• The past decade has seen a significant increase in the use of herbal medicines. As
a result of WHO’s promotion of traditional medicines, countries have been
seeking the assisstance of WHO in identifying safe and effective herbal
medicines for use in national health care system.
• In both developed and developing countries, consumers and health care providers
need to be supplied with up-to-date and authoritative information on the
beneficial properties and possible harm full effects ,of all herbal medicines.

K.K.Wagh College
Krupanidhi CollegeofofPharmacy,
Pharmacy Nashik 34
Assessment of Quality, Safety and Efficacy and Intended use

• Stability:
– The physical and chemical stability of the product in the final marketing
container should be tested under defined storage conditions and the shelf-life
should be established.
• Safety assessment:
– This part should cover all the relavent aspects of the safety assessment of a
medicinal product has been traditionally used with out demonstrated harm no
specific restrictive regulatory action should be undertaken unless new evidence
demands a revised risk-benefit assessment.
• Toxicological studies:
– If any toxicological studies are available, they should be part of the assessment.
If a toxicological risk is known, toxicity data have to be submited. Risk
assessment, whether it is independent of dose (eg, special danger allergies) ,or
whether it is a function of dose should be documented.

K.K.Wagh College
Krupanidhi CollegeofofPharmacy,
Pharmacy Nashik 3 5
 Stability testing of Herbal drugs

 Stability is the capacity of specific formulation in a particular container/closer

system to remain within its prescribed limits like physical, chemical,
microbiological, toxicological, therapeutic specification.
 Stability is defined as, “the capacity of a drug to remain within established
specifications limits to maintain its identity, strength, quality and purity
throughout the retest or expiration dating periods”.
 Shelf life is defined as, “ the time duration upto which it is expected to retain
90% of its active ingredients when stored in recommended condition”.
 The guidelines on stability testing of drug substances and related finished
products was established for chemically- defined substances, and therefore,
does not take account of the particular case of HMPs. Herbal drug substances
should be tested at 25ºC/ 60% RH.

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 Different ICH guidelines on stability testing

> ICH Q5C Stability testing of biotechnological/biological products - Scientific

guideline

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• The need for Stability Studies:
– Well- being of the patient and manufacturer by ensuring product quality.
– For selection of adequate formulation, determination of shelf- life and storage
conditions.
– Preparation and substantiation of the claimed shelf- life
for the registration dossier.
– To provide evidence on how quality of drug/
product varies with time under influence of environment.
• Advantages of stability testing:
– Helps in determination of shelf life and storage conditions.
– Helps in selection of suitable formulations, excipients and
container closure systems for a product.
– Well being of the patient and manufacturer by ensuring the good product quality
and enhance patient confidence in herbal drugs and improve compliance.

Krupanidhi College of Pharmacy 33

8 8
 Types of Stability testing methods
• Accelerated Testing:
– Product subjected to high temperature, humidity, light, etc. 40ºC/ 75%
RH. At 3rd and 6th month.
• Real Time( long-term) Testing:
– Longer duration. 25-30ºC & 35- 75% RH(depending on climatic zone),
for 3rd, 6th, 9th, 12th, 18th, 24th, and 36th month.
• Intermediate Testing:
– Conducted when accelerated studies fail. At 25ºC for longer duration
of time.
• Stress Testing:
– Includes effects of temperature, i.e., above 40ºC and ≥75% RH.
• Forced Degradation Testing:
– Performed to provide intrinsic stability assessment of drug.

Krupanidhi College of Pharmacy 33

9 8
 Protocols for Stability Testing

1. Selection of Batches and Samples

2. Test Attributes
3. Analytical procedures
4. Acceptance Criteria
5. Storage Conditions & Storage period
6. Testing Frequency
7. Sampling Plan
8. Container closure system
9.Evaluation 10.Statements labeling

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0
 Climatic zones and long- term stability conditions as per ICH &
WHO

Climatic Climate Countries MAT/ Long term

Zone MAPWP Testing
condition
I Temperate UK, Northern <15ºC/ , 21ºC/ 45%RH
Europe, US <11hPa
II Subtropical & Japan, Southern >15-22ºC/ 25ºC/ 60%RH
Mediterranean Europe >11-18hPa
III Hot & Dry Iraq, India >22ºC/ 30ºC/ 35%RH
<15hPa
IV a Hot & Humid Iran, Egypt >22ºC/ 30ºC/ 65%RH
>15-27hPa
IV b Hot & Very Brazil, >22ºC/ 30ºC/ 75%RH
Humid Singapore >27hPa

MAT: Mean annual temperature measured in open air,

MAPWP: Mean annual partial water vapor pressure
hPa: Hectopasacal

Krupanidhi College of Pharmacy 44

1 1
Stability Testing Storage Conditions for drugs as per ICH & the
WHO

Krupanidhi College of Pharmacy 44

2 1
 Test Schedule for Stability of new Products

Method and climatic zone Environment Time points for sampling

Long term for climatic zone I and 25oC/60% RH 3, 6, 9, 12, 18, 24, 36
IV months
Long term for climatic zone III 30oC/35% RH 3, 6, 9, 12, 18, 24, 36
months
Long term for climatic zone Iva / 30oC/65% RH 3, 6, 9, 12, 18, 24, 36
intermediate for zone I and II months
Long term for climatic zone 30oC/75% RH 3, 6, 9, 12, 18, 24, 36
IVb / intermediate for zone I months
and II
Accelerated condition for all zone 40oC/75% RH 3, 6 months

Krupanidhi College of Pharmacy 44

3 1
 Evaluation parameters during stability

• ORGANOLEPTIC ANALYSIS:
– Colour
– Odour
– Taste
• PHYSICO CHEMICAL ANALYSIS:
– Determination of pH
– Extractive value
– Ash value: Acid insoluble & total ash.
– Moisture Content
• QUANTITATIVE ANALYSIS:
– Specific biomarker
– Group of compounds
– Reference to comparable herbal formulation.
– Fingerprinting Profile
• MICROBIOLOGICAL ANALYSIS:
– Total microbial count

Krupanidhi College of Pharmacy 44

4 1
 Issues related to stability of herbal drugs

• Physical instability
• Processing environment
• Chemical stability
• Drug interaction

Krupanidhi College of Pharmacy 44

5 1
 Patenting & Regulatory requirements of natural
products

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 Content
• IPR
• Patent
• Farmers right
• Breeder’s right
• Bioprospecting and Biopiracy
• Patenting aspects of Traditional knowledge and Natural
products
• Case study of Curcuma and Neem

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 Intellectual Property Right

• An investor, having spent huge money and efforts, requires a sort of

protection for his intellectual property. Such protection allows him
to gain the deserved incentive for his innovation/invention. IPR
provides such protection.
• Defined as the Legitimate rights of the inventor for protection of
his intellectual property thus excluding others from making,
copying, using or selling his proprietary subject matter.
• ‘Intellectual Property’, means the property which is created with
intellect, and the legal rights conferred on such property are called
as “Intellectual Property Right”

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 Types of IPR

Types of IPR Law Protection given Application Duration in years

Patents Indian Patent Act, Discoveries & Drugs, medicines, 20 years after filing,
1970 inventions scientific discoveries can’t be renewed

Trademarks Trademarks Act, Phrases, symbols Business, branding 10 years, can be

/Trade Secrets 1999 & designs renewed for 10 years
again.
Copyright Copyright Act, Musical, literary Books, drama, Lifetime of
1957 & artistic work literature author/artist & 60
years after death
Industrial Design Act, 2000 Design of Manufacture of 10 years, can be
design machined, equipment, extended 5 more years
equipments, etc industries
Plants The Plant Variety Plant variety, Farmer 15 years from the date
Protection Act, farmers right, of registration
1970 trees
Geographical The Geographical Certain goods Basmati rice, 10 Years can be
goods Indication of Banarasi silk, extended for another
Goods Act, 1999 Madhubani Painting 10 years.

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 PATENT

It is a grant by a state to an inventor or

to his assignee, giving exclusive rights to make, use,
exercise and vend the inventions for limited period ,in exchange
for Disclosure in a patent specification.
Objective -
Giving a legal monopoly to patentee to reap the economic benefit

• Facilitating the improvements or providing alternative

the approaches to develop the new ideas or and
products.
• Invention of new drugs

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• Advantages of Patent:

– Avoids duplication of research.

– Keeps abreast with latest development in different fields of technology.

– Helps industry to improve existing technology to

produce cheaper and better products.
– Serve as an indicator of achievements in R and D institutions and ability
of individual researcher.
– Helps to frame business strategy according to trend of technology

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 PROCEDURE FOR PATENTING

• Steps:
– Filling an application with provisional or Complete Specification
– Examination of the application by the patents office
– Opposition , if any to the claims of patent
– Granting and sealing of the patent
– Revocation of the granted patent

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– Filling an application
 Name, address and nationality of the applicant
 Title, Name, address and nationality of the inventor, if he is not the applicant or
co-applicant
 Specifications (provisional and complete) giving the details of the invention
 Claims, definition and scope of the invention
• Examination of the application:
 Prior approved patents or applications filed
 Novelty
 Usefulness
 Nature of claims
• Opposition:
 A three month time period is given for any opposition.
 Contrary claims can be filed and contested

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• Granting & sealing of patent :
In case of no opposition or clearing satisfactorily all the objections by the
applicant, patent is granted and sealed by the patent office by publishing in the
official gazette.
• Revocation :
The validity of the patent can be challenged in High court under specified
grounds. The patent will be revoked if the court upholds the challenge
• Term of a patent
20 Years period from the date of of filing application

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 Farmers right

– The protection of Plant Varieties and Farmer’s Right Act, 2001 is an act brought
into force for the protection of plant varieties, the rights of the farmers and plant
breeders and to encourage the development of new varieties of plants.

• Main objective of this act:

– To protect rights of farmer by conserving plants genetic resources.
– To protect breeders right and stimulate research development.
– To facilitate growth of seed industry.
– To comply the regulation as per article 27.3b of TRIPs.

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 Farmers right

• Protection of plant varieties and farmers right act 2001 (PPVFR)

– This law for protection of plants and related IPR issues was necessary due
increased bio-prospecting and use of plant by human is increased.
– International union for Protection of New Plant Varieties of Palnt (UPOV) is an
intergovernmental organization established according to International
Convection for the Protection of New Varieties of Plants.
– This convection was adopted in 1961 and later revised in the year 1972, 1978,
1991.
– As India become signatory to WTO/TRIPs, it becomes mandatory to give
protection to plants. According to article 27.3b of TRIPs introduction of some
intellectual property protection for plant varieties was needed.

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• In chapter VI of this PPVFR act, Farmer’s Rights are also given from clause
number 39 to 46.
• According to section 39, Farmer’s Rights have made following provisions to the
farmers:
– A farmer who has bred or developed a new variety shall be entitled for
registration and other protection in like manner as a breeder of a variety under
this Act.
– The farmer’s variety shall be entitled for registration if the application contains
declaration as specified in clause (h) of sub-section (1) of section 18.
– A farmer who is engaged in the conservation of genetic resources of land races
and wild relatives of economic plants and their improvement through selection
and preservation shall be entitled in the prescribed manner for recognition and
reward for gene fund.
– Provided that, material so selected and preserved has been used as a donors of
genes in varieties registrable under this act.

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• A Farmer have right to save, , use, sow, re-sow, exchange, share or sell his
farm product including seeds of variety under this act in the same manner as
he was entitled before coming into force of this act. But the farmer cannot sell
branded seed of a variety protected under this act. This clearly means, branded
seeds are the seeds packed in container and labeled.
– Any one person or group of persons, government or
Non governmental organization can make claim.
– There is provision for protection of innocent
infringement of law in case farmer is a number of provisions in
this act.
– The central government shall constituted fund to be called the national gene
fund for the sharing of benefits to farmers.
– After 3 years from registration of variety, if needed, government can issue
compulsory license for production, distribution, and sale of SEED or other
propagating material of that variety.

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 Breeder’s right

• The Plant breeders' Rights programme was first established in 1987 under the
Plant Variety Rights Act (PVR), which was succeeded by the current Plant
breeders' Rights Act 1994.
• Plant breeders' Rights are also known as Plant Variety Rights (PVR), are
intellectual property rights granted to the breeder of a new variety of plant.
• Plant breeders' Rights are granted to novel plant varieties that are distinctive,
uniform, and stable (e.g., cultivar breed true-to-type for desired traits.
• Exclusive commercial rights for a registered variety of plant.
• Intellectual property (IP) such as patents, trademarks and designs.
• Protects plant breeders and gives them a commercial monopoly for a period of
time (EU 25-30 years/PT 15-20 years)
• Allow the breeders' to have a return of the investment.
• Protect the breeders' work.
• Stimulate development of new varieties.
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 • Protected Rights:
– Rights for commercial seed production.
– Rights for marketing.
– Rights to export and import.
– Rights of authorization.
– Rights to prevent infringement.

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 • Advantages of Plant breeders' Rights:
– Protecting the breeders' work.
– breeders' get benefit of their variety.
– PBR help in faster development of seed industry.
– PBR lead to improvement in quality because of competition.
– PBR help in enrichment of genetic resources

• Disadvantages of Plant breeders' Rights:

– It will promote monopoly.
– It may lead to increase in prices.
– There will be reduction in genetic variability.
– There will be compulsion to purchase fresh seed every year.

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 Bio-prospecting and Biopiracy
• Bio-prospecting:
 The process of finding new chemicals or drugs from various resources is called as bio-prospecting.
 Bio-prospecting is the process of discovery and development of new molecules from different biological
resources.
 Bio-prospecting is branch of science which is required for new drug discovery and development.
• Biopiracy:
 It mainly focuses on the use of biological resources and knowledge of indigenous tribes or
communities
without giving those benefits.
 Biopiracy is an injustice relating to patent or intellectual property related to biological materials and
traditional knowledge without sufficient authorization and or compensation.
 Various International organizations like secretariat of United Nations convention on biological diversity
(CBD), the World Intellectual Property organization (WIPO) and the World Trade Organization (WTO) are
associated with this issue.
 Incidents related to biopiracy are not necessarily related with the money but also pride of country and
people.
 Above organizations deal with these issues related to bio-prospecting and biopiracy by avoiding conflict
with the help of international laws administered by the CBD and the WTO.
 The term biopiracy was coined in 1993 by Pat Mooney.
 It means the use of intellectual property to legitimize the Exclusive ownership and control of biological
resources and knowledge, without giving any benefit or compensation to indigenous contributors.

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 • Some important points related to bio prospecting and biopiracy:
 Bioprospecting have attracted attention of vast number of multinational
companies. This has resulted in growing concern about the collection and
conservation of plants, animals, biological materials and ecosystem.
 Also at the same time, issues related to intellectual property or ownership
over the biological resources need to be addressed.
 Because of biotechnological advances or manipulation of biological
resources through Recombinant DNA technology, Or genetic engineering
issues related to ownership have become more complicated necessitating
new regulations

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  Regulations related to both have found difficult to control as there is
absence of one single International Treaty or agreement that fully
captures all the issues involved. Rather most laws are country-specific.
 Some cases of biopiracy involved the grant of patent over some product
of derivative from biological resources and or traditional knowledge.
 At the same time there are some cases where patent protection is not
present, is a typical cases are called as non-patent biopiracy incidence.
 Biopiracy can have direct as well as indirect implications, like loss of
income, traditional knowledge.

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Patents Aspects of Traditional Knowledge And Natural Products

 The traditional knowledge can be said as the knowledge of practice and the
skills which have been developed or sustained and that which passed from
generation to generation within a community which forms a part of its cultural
or spiritual identity often.
 Traditional Knowledge per se that is the knowledge that has ancient roots and
is often informal and oral, is not protected by conventional intellectual
property protection systems.
 This scenario has prompted many developing countries to develop their own
specific and special systems for protecting traditional knowledge.
 India has played a very significant role in the documentation of traditional
knowledge thereby bringing the protection of traditional knowledge at the
centre stage of the International Intellectual Property System.

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• Provision of Traditional Knowledge Digital Library (TKDL) Access (Non-
Disclosure) Agreements with several international patent office's including USPTO,
EPO, JPO etc. by Indian Government has led to many patent applications concerning
India's traditional knowledge have either been cancelled or withdrawn or claims have
been amended in several international patent offices.
• TKDL provides contents of the ancient texts on Indian Systems of Medicines i.e.
Ayurveda, Siddha, Unani and Yoga, into five international languages, namely,
English, Japanese, French, German and Spanish, with the help of information
technology tools and an innovative classification system – Traditional Knowledge
Resource Classification (TKRC) Bio-piracy and Misappropriation of TK.
• The clues/ leads provided by TK can be utilized to develop best practices/processes/
system for mankind without the investment of huge amount of money for research
and results validation through clinical trials in labs, above all such knowledge saves
time.
• In the recent past, several cases of bio-piracy of TK from India have been reported.
The following are the most prominent cases with regards to misappropriation of TK
from India.
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 Turmeric Patent –Case Study

• Turmeric is a tropical herb grown in east India. Turmeric powder is widely used
in India as a medicine, a food ingredient and a dye to name a few of its uses.
• For instance, it is used as a blood purifier, in treating the common cold, and as an
antiparasitic for many skin infections. It is also used as an essential ingredient in
cooking many Indian dishes.
• Patent:
• In 1995, the United States (USPTO) granted patent on turmeric to University
of Mississippi medical center for wound healing property.
• The claimed subject matter was the use of "turmeric powder and its
administration", both oral as well as topical, for wound healing. An
Exclusive right has been granted to sell and distribute.

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 • The Indian Council for Scientific and Industrial Research (CSIR)
had opposed to the patent granted and provided documented evidences
of the prior art to USPTO.
• Though it was a well known fact that the use of turmeric was known in
every household since ages in India, it was a herculean task to find
published information on the use of turmeric powder through oral as
well as topical route for wound healing.
• Due to extensive researches, 32 references were located in different
languages namely Sanskrit, Urdu and Hindi.
• Therefore, the USPTO revoked the patent, stating that the claims
made in the patent were obvious and anticipated, and agreeing that the
use of turmeric was an old art of healing wounds.
• Therefore, the TK that belonged to India was safeguarded in Turmeric
case.

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 Neem Patent-case study

• The patent for Neem was first filed by W.R. Grace and the
Department of Agriculture, USA in European Patent Office.
• The said patent is A method of controlling fungi on
plants comprising of contacting the fungi with a Neem oil formulation.
• A legal opposition has been filed by India against the grant of the patent.
• The legal opposition to this patent was lodged by the New Delhi-based Research
Foundation for Science, Technology and Ecology (RFSTE), in co-operation with
the International Federation of Organic Agriculture Movements (IFOAM) and
Magda Aelvoet, former green Member of the European Parliament (MEP).
• A tree legendary to India, from its roots to its spreading crown, the Neem tree
contains a number of potent compounds, notably a chemical found in its seeds
named azadirachtin.

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• The barks, leaves, flowers, seeds of neem tree are used to treat a variety of diseases
ranging from leprosy to diabetes, skin disorders and ulcers.
• Neem twigs are used as antiseptic tooth brushes since time immemorial.
• The opponents submitted evidence of ancient Indian ayurvedic texts that have
described the hydrophobic extracts of neem seeds were known and used for centuries
in India, both in curing dermatological diseases in humans and in protecting
agricultural plants form fungal infections.
• The EPO identified the lack of novelty, inventive step and possibly form a relevant
prior art and revoked the patent.
• Apart from this, several US patents were recently revoked Neem-based emulsions
and solutions.

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 Regulatory Issue

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 Need for regulation

• Regulationsprovide protection to natural products

users and nature also.
• It improves use of natural products and encourages research.
• It establishes system for control of all
activities like manufacturing, sales and use of medicines.
• It gives penalty or punishment for persons who
do not follow certain standards and rules.
• It prepares and amends laws, and enforces them to control natural
products, thus provides safe and effective medicine.

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 Regulations in India

• Herbal drugs are regulated under the Drug and Cosmetic Act (D&C)
1940 and Rules 1945 in India, where regulatory provisions for
Ayurveda, Unani, Sidha medicine are clearly laid down.
• Department of AYUSH is the regulatory authority and mandate that any
manufacture or marketing of herbal drugs have to be done after
obtaining manufacturing license, as applicable.
• The D & C Act extends the control over licensing, formulation
composition, manufacture, labeling, packing, quality and export.

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 ASU DTAB

• Ayurvedic, Siddha and Unani Drug Technical Advisory Board (ASU

DTAB)
– The Central Government constitutes a “Ayurvedic, Siddha and
Unani Drugs Technical Advisory Board” under sec. 33-C of the
Act.
– The board advises the Central and State Government on technical
matters arising out of chapter to such drugs and performs such
other functions as assigned to it, by Central Government related to
such drugs.

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 Constitution of ASU DTAB

ASU-DTAB Board consists of the following members:

I. Ex-officio members
a. The Director General of Health Services.
b. The Drugs Controller, India.
c. The Principal Officer, of the Indian System of Medicines in the
Ministry of Health .
d. The Director of the Central Drugs Laboratory, Calcutta.

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II) Nominated by the Central Government:
a. One Government Analyst for Ayurvedic, Siddha and Unani Drugs.
b. One Pharmacognosist.
c. One phytochemist.
d. Four persons of which-
• Two from Ayurvedic Pharmacopeia Committee.
• One from Unani Pharmacopeia Committee.
• One from Siddha Pharmacopeia Committee.
e. One teacher in Dravyaguna and Bhaishajya Kalpana.
f. One teacher in ILM-UL-ADVIA and TALIT-WA-DWASAZI.
g. One teacher in Gunapadam.
h. Three practitioners, one each from Ayurvedic, Siddha and Unani Tibb.
Systems of medicines.
i. Three practitioners, one each to represents the Ayurvedic, Siddha and
Unani Drug industry.

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 Central Government appoints a member of Board as its Chairman
and appoints a secretary of the Board and also provides with clerical
and other staff as considers necessary.
 The nominated members of the Board shall hold office for three
years but shall be eligible for renomination.
 The Board may, subject to the previous approval of the Central
Government, make bye-laws fixing a quorum and regulating its own
procedure and conduct of all business to be transacted by it.

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 ASU DCC

• The Ayurvedic, Siddha and Unani Drugs Consultative Committee

(ASU-DCC). Central government constitutes above mentioned
committee to advise, to Central and State Government and to Board on
any matter arising in the administration of the Act, to secure uniformity
throughout India.
• The central government may constitute an advisory committee as
mentioned in thesection33-D of the Drugs and Cosmetics
• The committee consists of
• Two representatives of Nominated by Central Government and
• One representative of each state Government Nominated by respective
Governments.

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 Manufacture of ASU

• Ayurvedic, Siddha and Unani drugs are required to manufacture according to

the formula prescribed under second schedule.
• Licence is required for manufacture of these drugs.
Separate licence is required to carry out manufacturing at different premises.
• Application for the grant of licence shall be made in form 24-D and on
satisfying by licensing authority, licence is issued in form 25-D, loan licence
for manufacturing of such drugs granted in form 25-E, for the grant of
which application shall be made in form 24-E.
• Application shall be accompanied with prescribed fees.
Granted licence valid for a period up to 31st December following the year in
which licence is granted or renewed.

Krupanidhi College of Pharmacy

 Conditions for grant or renewal of licence

• Manufacturing of Ayurvedic Siddha and Unani drugs shall be carried out in search of
premises and under such hygienic conditions as specified in schedule T
• Manufacturing carried out under the direction and supervision of qualified technical
staff, who possesses:
a) A degree in ayurveda, ayurvedic pharmacy, Siddha or Unani system of
medicine as the case may be.
b)A diploma in Ayurveda,siddha or Unani system of medicine, recognised by central
government.
c) Graduate in pharmacy or pharmaceutical chemistry or chemistry or botany
with atleast two years post graduate experience in manufacturing of Ayurvedic
Siddha or Unani drugs.
d)Vaidya aur Hakim registered in a state register of practitioner of indigenous system
of medicine with at least four years experience in manufacturing of Siddha or Unani
drugs.
e) Pharmacist in Ayurvedic, Siddha or Unani system of medicine with not less
than 8 years of experience in manufacture of Ayurvedic or Siddha Or Unani drugs.
• The competent technical staff to direct and supervise manufacturing of Ayurvedic or
Sidharth or Unani drugs shall have qualifications in the respective System of medicines.
Krupanidhi College of Pharmacy
 Conditions of Licence

• The licensee maintain proper records of details of manufacture and test if any
carried out by him, of the raw materials and finished products.
• The licensee shall allow any Inspector to enter and inspect premises, to take samples
of raw materials and finished products and to inspect records maintained under the
rules.
• The licensee shall maintain inspection book in form 35
Cancellation and suspension of Licence

• The granted or renewed licence may be suspended aur cancel at the discretion of
licensing authority.
• A licensee whose licence has been suspended or cancelled may appeal to the state
government within 3 months from the date of receipt of such order. The decision of
the government is final.

Krupanidhi College of Pharmacy

Prohibition of manufacture certain Ayurvedic Siddha and Unani
drugs

• No person shall manufacture for sale:

1) Any misbranded adulterated or spurious Ayurvedic Siddha Unani drugs.
2) Any patent or proprietary medicine the true list of ingredients is not displayed
on the label or container in a prescribed manner.
3) Any Ayurvedic Siddha or Unani drug in contravention of any of the provisions
of the act and rule thereunder related to search drug.
• Sale, stock or distribute any drug manufactured in contravention of any of the
provisions of the act and rules there under.
• Any drug not manufactured in accordance with the conditions of the licence.

Krupanidhi College of Pharmacy

 Penalty for manufacture of Ayurvedic Siddha and Unani
drugs in contravention related to manufacture of such drugs

• Manufacture of drug Deemed to be adulterated or,

• Manufacture of a drug without a valid licence, shall be punishable with
imprisonment upto 1 year & not less than 2000 rupees.
• Manufacture of any Ayurvedic Siddha or Unani drug deemed to be spurious,
punishable with imprisonment not less than one year which may extend upto 3
years and with fine not less than 5000.
• Contravention of any other provisions related to Ayurvedic Siddha or Unani drugs
punishable with imprisonment upto 3 months and with fine not less than 500
rupees.
• For any subsequent offence under:
a)will be punishable with imprisonment upto 2 years and fine not less than 2000 rupees and
under.
b)with imprisonment not less than 2 years which may extend upto 6 years and with fine not less
than 5000 rupees and under.
c) with imprisonment upto 6 months and with fine not less than 1000 rupees.

Krupanidhi College of Pharmacy

 Schedule Z (Proposed)

The draft of Schedule Z as prepared by the sub-committee of Ayurveda, Siddha,

Unani Drug Technical Advisory proposed to make clinical trials mandatory for all
the patent or proprietary) medicines so as to examine the shelf life of ASU
medicines. The revised version of the Schedule Z of the Good clinical practices for
clinical trials on ASU medicines as issued by the Department of AYUSH was faced
vehement opposition from the AYUSH drug industry. The AYUSH drug industry
considered the revised Schedule Z as highly unreasonable at the part of the ministry
of AYUSH. The AYUSH drug industry suggested that implementation of the
provisions of Schedule Z shall have a detrimental effect on the AYUSH formulation
market.
Requirements and guidelines for permission to manufacture of ASU drugs for sale or
to undertake clinical trials.
In brief these guidelines consists of information on the-
• Protocol, • Data management,
• Ethical issues, • Quality assurance,
• Safety considerations, • Record keeping &
• Informed consent process, • Statistics
Krupanidhi College of Pharmacy
 Thank
you

Krupanidhi College of Pharmacy