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7700 GI/202 3 (1) रजिस्ट्री सं. डी.एल.- 33004/99 REGD. No . D. L. -33004/99
EXTRAORDINARY
PART II —Section 3 —Sub-section ( i)
PUBLISHED BY AUTHORITY
No. 708] NEW DELHI, TUESDAY , DECEMBER 12 , 2023/ AGRAHAYANA 21, 1945
CG-DL-E-14122023-250657
MINISTRY OF AYUSH
NOTIFICATION
New Delhi, the 12th December, 2023
G.S.R. 891(E). —The following draft of certain rules further to amend the Drugs and Cosmetics Rules, 1945,
which the Central Government proposes to make, in exercise of the powers conferred by section 33 -N of the Drugs
and Cosmetics Act, 1940 (23 of 1940) a nd after consultation of Ayurveda, Siddha, Unani Drug Technical Advisory
Board , is hereby published as required by the said section, for the information of all persons likely to be affected
thereby; and notice is hereby given that the objections or sugge stions of the stakeholders on the said draft rules will be
taken into consideration after the expiry of a period of thirty days from the date on which copies of the Official
Gazette in which this notification is published, are made available to the public;
Any objection or suggestion, which may be received from any person with respect to the said draft rules
within the period specified above, will be taken into consideration by the Central Government;
Objections or suggestions, if any, may be addressed to the Secretary, Ministry of Ayush, AYUSH Bhawan,
‘B’ Block, GPO Complex, INA, New Delhi – 110023 or emailed at [email protected] .
DRAFT RULES
1. Short title, extent and commencement.
(1) These Rules may be ca lled the draft Drugs Rules (Amendment), 2023.
(2) They shall come into force from the date of their final publication in the Official Gazette.
2. In the Drugs Rules, 1945 (hereinafter to be referred as the principle rules), in rule 158B, after sub -rule (V) and the
following sub -rule shall be inserted, namely: —
“VI. For issue of license to the Ayurveda, Siddha and Unani drugs with nasal spray as dosage form, the Licensing
Authorities shall follow the guidelines as per Schedule TB.”
3. After Schedule T A, following Schedule TB shall be inserted –
“SCHEDULE TB
(Refer sub -rule VI of Rule 158 B)
Guidelines for development of nasal spray as dosage form for Ayush, Siddha, Unani and Homoeopathy Drugs
I. Introduction
Any medicine administered through the no se (Nasika ) is considered Nasya (Nasal administration) in Ayurveda.
Usually, all the clinical conditions related to head and neck ( Urdhwajatrugatavikara ) are treated by following
Nasya as the main line of treatment. In conditions like Apasmara and Unamada, procedures like Pradhamana nasy a
provide instant relief by reflex or systemic action.
There are several varieties like Snehana Nasya (medicated oil / ghee used as nasal drops), Shamana Nasya
(fresh herbal juices / decoctions used for nasal administration) , Avapeedana Nasya (fresh herbs squeezed and the juice
used as nasal drops), Pradhama Nasya (powdered herbs forcedly sprayed into the nose) and Dhumana Nasya
(medicated fumes inhaled). For example, Anutaila nasya is indicated for daily usage; Dadimapushpa sv arasa / durva
svarasa is used in Nasagata Raktapitta (~epistaxis); Avapeedana Nasya is used in Ardhavabhedaka; Trikatu churna
or Pippali churna is used as Nasya in Apasmara . The Nasya procedures like Snehana, Avapeedana Nasya etc. are used
in the gravitation al direction as the other methods like Dhumananasya and Pradhamananasya are use d against
gravitational force. Acharya Charaka contraindicated herbs like Kushtha (Saussurea lappa D C Clarke) and Tagara
(Valeriana wallachii DC) from using in Shiro -virechana . This shows the safety consciousness of Ayurveda practice.
In Siddha system, Nasiyam (Nasal drops) and Nasika aparanam (Medicated snuff) are the types of external
medication applied through nostrils. Nasiyam (Nasal instillation) is a process of instillati on of drugs in liquid form
through the nostrils while Nasika aparanam (medicated snuff) is inhalation of medicated substances in powder form.
In the Unani system, various nasal dosage forms are used and most are nervine tonics and stimulants,
especially h elpful in neurological diseases. Dosage form of Nasal drop or fine powder used in the Unani system of
Medicine comes under Drug & Cosmetic Act (Reference - IlajulAmraz Page No. 189 -190, 193, 196 -201).
• Saoot (Nasal drop)/Qutoor: A liquid preparation which is used as nasal drop
• Shamoom: Smelling of the drugs which may be in dry or liquid form so that volatile substances reach the nasal
cavity and respiratory tubes
• Nashuq/Naswar (Insufflation): A liquid preparation or powder that is used for insufflation
• Bakhoo r/Dhuni (Fumigation): Smoking an affected organ by burning the drugs
In Homeopathy system, administration of medicine through nasal route is mentioned under authoritative books of
Homoeopathy medicines. .
II. Definition
A nasal spray is a liquid/powder fo rmulation dispensed as a fine spray from a container/device into the
nostril. In this combination of formulation and device, the end user sprays the nasal spray formulation into the nostril
while breathing in through his/her nose. Nasal sprays are used to deliver medications locally in the nasal cavity.
III. Differentiation from nasya
Though the route of administration for Nasya and Nasal Spray is the same (nose), the main differentiating
aspect between traditional Nasya and the new dosage form of Ayush nasal spray is that “ in the traditional method
medicated juices/oils are administered through the nasal route without the support of any specialised instrument/
device. Whereas the nasal spray is administered by using a specific device ”. The present definition o r introduction of
Nasal Spray shall not interfere with the existing Nasal drops used in the form of oils or decoctions etc. The respective
existing nasya methods shall continue. The medication standards for those items remain to be the same as indicated in
the Ayurvedic Pharmacopoeia of India (API), Part -II (example for Anutaila and Shadbindutaila ). The Standard
Operating Procedures (SOPs) for the performance of Nasya shall also be the same as those developed by CCRAS at
National Institute for Panchakarma, Cherthurthy, Kerala. The standards for the new dosage form “Nasal Spray” and
the guidelines for the usage of the new device are defined in this document.
IV. Guidelines for active ingredient selection
Active Ingredients should be selected as per the definitio n of ASU Drugs in Section 3(h) under the Drugs
and Cosmetics (D&C) Act, 1940 and Rules 1945.
V. Guidelines for excipient selection
Selection of excipients should be as per the provisions and terms and conditions provided under Rule 169 of
the D&C Rules, 1945 and amendments therein.
VI. Specifications for the device (As per the details provided by the manufacturer)
The following quality parameters provide guidance for the selection of packaging material. The data for
these parameters can be obtained from the pac kaging material supplier and consistency across the manufacturing lots
can be confirmed, based on the certificate of analysis.
Sr. No. Parameter Description Specifications/Limit
Details for Bottle/ other components
1. Material of construction of
Bottl e Glass, HDPE or Suitable and
compatible material Specify
2. Bottle dimensions ReferAnnexure1for details Specify
Details for Pump and Actuator (with dust cap) / other components
3. Name and Material of
construction of Pump Suitable and compatible mater ial Specify
4. Pump dimensions Refer Annexure 1 for details Specify
Sr. No. Parameter Description Specifications/Limit
5. Material of construction of
Actuator & Dust cap Suitable and compatible material Specify
6. Dimensions of Actuator &
Dust cap Refer Annexure1 for details Specify
7. Priming and Repr iming Specify (Shot weight should be
between90% to 110%)
VII. Specifications for the finished product (mandatory)
Sr. No. Parameter Specifications/Limit
1. Description A qualitative description of the dosage form should be provided (e.g.,
size, shape,an d color)
2. Assay of Active ingredients Basis vendor CoA of Raw material Specification or Extract
Specification or Pharmacpoeial reference or Using Pharmacopeial
method
3. Assay of Preservatives and
Stabilizing excipients Content limits of 90 -110%
4. Pump Delivery (Liquid dosage
form) Weight delivery acceptance criteria should control the weight of the
individual sprays to within "15 percent of the target weight and their
mean weight to within "10 percent of the target weight. However, for
small dosag e pumps(e.g.,20mL) other acceptance criteria maybe
justified
5. Net Content Basis number of dose requirement
6. pH value (Liquid dosage form) The pH or apparent pH, as appropriate, of the formulation should be
tested and an appropriate acceptance criteri on to be established
7. Osmolality (Liquid dosage form) The osmolality of the formulation should be tested and controlled
during release of product with an appropriate procedure and
acceptance Criterion, as applicable based on the ingredients used
8. Microbial / Microbiological
limits Pharmacopeia of concern system, Coliforms – Absent
9. Number of actuations per
container The number of actuations per container should be demonstrated to be
not less than the labelled number of actuations.
10. Heavy Metals Pharmacopiea of concerned system
11. Pesticide Residues Pharmacopiea of concerned system
12. Aflatoxins Pharmacopiea of concerned system
13. Moisture Content (Powder
dosage form) The limit for moisture content should be established based on results
seen in stability studies. If the results are stable throughout the shelf
life of the product, or if any changes in moisture content do not result
in changes to any other parameters, it may be acceptable to omit this
test from the specification; this should be fully explained in the
Justification of Specification(s) section.
VIII. Specifications for the finished product (optional)
Sr. No. Parameter Specifications/Limit
1. Droplet Size Distribution
/ Particle Size
Distribution* If a laser diffraction method is used , droplet size/ particle distribution can be
controlled in terms of ranges for the D10, D50, D90, span[(D90 -D10)/D50],
and percentage of droplets less than 10 mm. For nasal sprays, mean D10,
D50, D90 values for a given bottle or canister can be computed f rom the
mean of up to three consecutive sprays from that unit at each life stage.
However, to assess precision, the data of each spray would also be reported.
Single spray droplet size distribution and span would be reported based on
volume (mass) rather t han count (number of droplets). The data be provided
for nasal sprays at: Fully developed phase only, Two distances from the
actuator orifice. For the increased ability to detect potential differences
between products, it is recommended that the studies be performed within a
range of 2 to 7 cm from the orifice, with the two distances separated by 3 cm
or more. Other Methods that can be used: Microscopy, Cascade impactor, and
Laser Diffraction.
2. Aerodynamic Particle
Size measurement
(Powder dosage form) The Particle or droplet size distribution in the plume discharged from
inhalation aerosols and sprays and the particle size distribution in the cloud
discharged from inhalation powders are the important characteristics used in
judging product performance. A lthough particle size measurement by
microscopy can be used to evaluate the number of large particles,
agglomerates, and foreign particles in the emissions of inhaled aerosols and
sprays, whenever possible, this test should be replaced with a method to
determine the aerodynamic size distribution of the drug aerosol leaving the
product.
3. Spray Pattern The acceptance criteria for the spray pattern should include the shape (e.g.,
ellipsoid of relative uniform density) as well as the size of the pattern (e.g ., no
axis is greater than x millimeters and the ratio of the longest to the shortest
axes should lie in a specified range, for example, 1.00 - 1.30). Data should be
provided to demonstrate that the collection distance selected for the spray
pattern test w ill provide the optimal discriminatory capability. For nasal
sprays, these distances are recommended to be at least3cmapartwithin the
range of 3to7 cm.
4. Plume Geometry Plume geometry describes a side view of the aerosol cloud parallel to the axis
of the plume, and we recommend it be based on high -speed photography, a
laser light sheet and high - speed digital camera, or other suitable methods.
Plume geometry can be evaluated by a variety of procedures (e.g., the time
sequence sound -triggered high speed fl ash
photography method, videotape recording and taking pictures of different
frames).Photographs should be of high quality. The approaches used should
allow monitoring the plume development to define the shape (e.g., two side
views, at 90° to each other a nd relative to the axis of the plume) of the
individual spray plume over time.
Plume geometry would be performed at: Beginning life stage only, One side
view only, A single delay time. We recommend plume geometry
measurements be summarized as mean, geometr ic mean, and %CV.
5. Effect of Dosing
Orientation Determine the comparative performance of the devices in terms of Spray
Content Uniformity and particle/droplet size distribution at various dosing
orientations
6. ProfilingofSprays Near
Container Exhausti on
(Tail off Characteristics) Determine the profiles of Spray Content Uniformity and droplet/ particle
size distribution of each individual spray after the point at which the labeled
number of sprays have been dispensed until no more sprays are possible
(i.e., the container is empty.
7. Effect of Storage on the
ParticleSize Distribution Particle size distribution to be evaluated
8. Effect of Resting Time Determine the effect of increasing resting time on the first spray of unprimed
units, followed immedia tely by the second and the third sprays. Uniformity
of the formulation delivered in the first, second and third spray (no priming)
should be determined.
IX. One-time studies as part of Product Development (to be submitted along with the license applied)
Man datory
For the most part, these should be one -time studies, preferably performed on multiple batches (e.g. three or
more) of the product, representative of the product intended for distribution.
Sr. No. Parameter Description
1. Priming and Repriming inVar ious
Orientations (Liquid dosage
form) Determine number of Sprays recommended to prime or reprime
the unit and approximate interval that can pass before the drug
product should be reprimed.
2. Temperature Cycling Determine effect of variation in temperatu re on finished goods
parameters, as applicable.
3. Preservative Effectiveness test If preservatives are used n the formulation, the minimum content
limit should be demonstrated as microbiologically effective by
performing amicrobial challenge assay.
4. Stability Studies Standard Stability Studies shall be conducted.
Optional: Photostability studies should be performed using
appropriate test conditions, if warranted by the immediate
container, i.e., the formulation in the primary container can receive
light exposure. These studies should be conducted in the absence of
any additional packaging(e.g., foil overwrap)
5. Cleaning Instructions Through in -use studies determine the frequency and instructions
for cleaning
6. Drug Deposition on Mouthpiece
and/or Ac cessories (Powder
dosage form) The purpose of these studies is to determine the amount of drug
deposited within the device constituent part during use, which can
relate to cleaning requirements. Study Design: Measure the mean
amount of drug deposited per a ctuation on the mouthpiece or other
device constituent part components (e.g., spacers or valved holding
chambers).
7. Specific Rotation (Powder dosage
form) As applicable, based on the pure form of active used.
8. Robustness (Powder dosage
form) Vibratio nal stability of powder mixtures should be demonstrated,
in order to simulate vibrations during transport and use. Significant
variations in the delivered dose and/or fine particle mass should be
fully discussed in terms of the safety and efficacy of the p roduct.
Sr. No. Parameter Description
9. Weight Loss Nasal spray products should include acceptance criteria for weight
loss during stability
10. Leachable (Liquid dosage
form) The Ayush product should be evaluated for compounds that leach
from elastomeric or plastic components of t he container closure
system or justified otherwise.
11. Spray content
uniformity(SCU) The spray discharged from then as alactuator should be thoroughly
analysed for the Ayush active content. This should be performed
using individual container, between con tainers and multiple
batches. Suitable in house analytical methods may be deployed and
communicated to the Ayurveda, Siddha and Unani Licensing
Authority.
X. STABILITY GUIDELINES
As per the guidelines provided in concerned Pharmacopeia.
XI. Safety and Efficacy Studies
Broadly safety and efficacy studies need to be conducted as per the guidelines provided in Rule 158(B) of the
Drug and Cosmetics Rules, 1945 and Amendments as well as those provided in General Guidelines for
Safety/Toxicity Evaluation of Ayush form ulations, CCRAS, Ministry of Ayush, Govt. of India.
As per the requirement, safety/toxicity of the intended therapeutic formulation in its final form must be
justified through appropriate means as relevant, such as ingredient literature as per text, indica tion (e.g.
textbook rationale), classical medicine or proprietary medicine, hydro -alcoholic extract or other, mucosal
irritation test on experimental animals and/or clinical studies on safety, efficacy and tolerability as per Good
Clinical Practice guideli nes for clinical trials in Ayurveda, Siddha and Unani medicine (GCP -ASU), 2013 and
ICMR - National Ethical Guidelines For Biomedical and Health Research involving Human Participants - 2017
and other guidelines as appropriate.
Annexure 1
Additional detaile d specifications for device
Sr. No. Parameter Description Specifications/Limit
Details for Bottle (Note: Attach Bottle drawing for reference)
1. Bottle dimensions Base color of Bottle Specify bottle color
Weight of Bottle, gm Specify bottle weighty
Overfill capacity of Bottle, ml Specify
Bottle Height, mm Specify dimension
Bottle Body diameter, mm Specify dimension
Bottle Neck type Screw -on/Crimp -on /Press -fit
Bottle Neck Bore(ID), mm Specify dimension
Bottle Neck Outer Dia(OD), mm Specify dimension
Details for Pump and Actuator (with dust cap)
2. Pump dimensions Neck of Pump Specify Neck size and type
Material of construction of Pump Specify details of each component
Pump closure OD,mm Specify
Diptube length, mm Specify
Pump output, mcl/stroke Specify
3. Pump dimensions Gasket thickness, mm Specify
Pump and bottle fitment As per approved sample
Strokes to prime Specify
4. Dimensions of
Actuator & Dustcap Actuator OD (at base), mm Specify
Actuator shoulder heigh t, mm Specify
Total actuator+ overcap height, mm Specify
Total actuator (without overcap) Specify
Sr. No. Parameter Description Specifications/Limit
height, mm
Weight of actuator, gm Specify
Weight of overcap, gm Specify
Pump and Actuator Fitment As per approved sample
4. In Schedule M -I, after sub -clause 3.7, the following sub -clause 3.8 shall be inserted, namely: —
“3.8. For issue of license to the homoeopathy medicine with nasal spray as dosage form, the Licensing Authorities
shall follow the guidelines as per Schedule TB.”
[F. No. T.11 011/3/2023 -DCC]
B. K. SINGH, J t. Secy
Note: The principal rules were published in the Gazette of India, vide, notification No. F. 28 -10/45 -H(1), dated the
21st December, 1945 and last amended, vide, notification number G.S.R. -, dated the -.
Uploade d by Dte. of Printing at Government of India Press, Ring R oad, Mayapuri, New Delhi -110064
and Published by the Controller of Publications, Delhi -110054.
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