Orally Inhaled & Nasal Drug Products: delivery systems, components and specialist services for a growing industry sector” This edition is one in the series of ONdrugDelivery publications.

1. 1
Orally Inhaled &
Nasal Drug

2. REFERENCE LISTED DRUG (RLD)
1. RX EU US ANZ
OTC
2 Patent & Exclusivity
Expired
3 Analytical Monograph
In-Vitro/ Bio waiver
Available
can be done
4 Formulation Technology Aqueous Suspension based & pH
dependent
5 Stability Shelf life 3 year ,storage condition 25°C
6 Packaging Metered dose spray bottle
7 Clinical Studies Required
 YES  YES
 YES
 YES
1
Nasonex Allergy – Mometasone Furoa

3. REFERENCE LISTED DRUG (RLD)
1. RX EU US ANZ
OTC
2 Patent & Exclusivity Expired
3 Analytical Monograph
In-vitro / Bio waiver
Available
Can be done
4 Formulation Technology Aqueous Suspension based & pH dependent
5 Stability It has a shelf-life of 2 years and should be
stored in temperatures not exceeding 30°C.
6 Packaging Metered dose spray bottle
7 Clinical Studies Required
 YES
 YES  YES
2
Rhinocort Allergy Spray - Budesonide

4. REFERENCE LISTED DRUG (RLD)
1. RX EU US ANZ
OTC
Expired
3 Analytical Monograph
In-vitro /Bio waiver
Available
Can be done
4 Formulation Technology Aqueous Suspension based & pH dependent
5 Stability The shelf-life of Nasacort Allergy or Triamcinolone
Nasal Spray is 24 months. The shelf life after the
bottle is first opened is 1 month.
6 Packaging Nasal Spray is contained in high density
polyethylene (HDPE) bottle fitted with a metered-
dose spray pump unit.
7 Clinical Studies Required
 YES  YES  YES
3
Nasacort Allergy 24hr – Triamcinolone Acetonide

5. REFERENCE LISTED DRUG (RLD)
1. RX EU US ANZ
OTC
2 Patent & Exclusivity Expired
3 Analytical Monograph
In-Vitro Bio waiver
Available
Can be done
4 Formulation Technology Aqueous Suspension based product & pH dependant
5 Stability
Twenty-four months stability data at the long-term
storage condition of 30°C/65% RH and 6 months
data at the accelerated storage condition of
40°C/75% RH
6 Reverse Engineering Metered spray/ amber colour glass bottle
7 Clinical Studies Required
 YES
4
CaliSpray Nasal allergy spray- Fluticasone Propionate

6. REFERENCE LISTED DRUG (RLD)
1. RX EU US ANZ
OTC
2 Patent & Exclusivity Expired
3 Analytical Monograph
In-Vitro/ Bio waiver
Available
Available/class I
4 Formulation Technology Aqueous Suspension based product & pH dependant
5 Stability
Twenty-four months stability data at the long-term
storage condition of 30°C/65% RH and 6 months data
at the accelerated storage condition of 40°C/75% RH
6 Packaging Metered spray/ amber colour glass bottle
7 Clinical Studies Available
 YES  YES  YES
5
Flonase Allergy Relief- Flucticasone Propionate

7. REFERENCE LISTED DRUG (RLD)
1. RX EU US ANZ
OTC
2 Patent & Exclusivity - - -
3 Analytical Monograph
In-Vitro /Bio waiver
Available
Can be done
4 Formulation Technology Aqueous Solution based
5 Stability The data from these studies support a shelf-
life of 2 years (unopened) and 6 months ( after
first opening)
6 Packaging
high density polyethylene bottle and with a
multi component pump unit and protective
plypropylene overcap
7 Clinical Studies Required
 YES  YES  YES
6
Dobendan Direkt- Flurbiprofen Spray

8. Characterization Techniques
 Appearance
 Color, and Clarity
 Identification
 Drug content (Assay)
 Impurities and Degradation Products (RS)
 Preservative(s) and Stabilizing Excipient(s) Assay
 Pump Delivery
 Spray content uniformity
 Spray Content Uniformity (SCU) through
 Container Life
 Spray Pattern and Plume Geometry
 PH
 Osmolality
 Droplet Size Distribution
 Particle size distribution
 Foreign Particulates
 Net Content and Weight Loss
 (Stability)
 Leachable (Stability)
 Microbial limit
 Preservative Effectiveness
7

9. In-vitro Studies
Single Actuation Content (SAC) based on Delivery of Drug discharged using
stability indicating chemical assay
Droplet Size Distribution by Laser Diffraction
Priming and Re-priming- Based on SAC
Plume Geometry by High Speed Photography
Spray Pattern by TLC
Drug Particle Size Distribution by Microscopy
Drug in Small Particles/Droplets, or Particle/Droplet Size Distribution by Cascade
Impactor
1
2
3
4
5
6
7
8

10. Approved Only By In-vitro
 A greater number of nasal and orally inhaled product ANDAs were approved by
the US FDA in 2016 than in 2015 and 2014 combined.
 However, advances in analytical technology has meant that the U.S. Food & Drug
Administration (FDA) Centre for Drug Evaluation and Research (CDER) were
able to grant approval to Apotex’s abbreviated new drug application (ANDA) for
Mometasone Furoate nasal spray without PD data.
9

11. Reverse Engineering Program
Dobendan
Direkt
ClariSpray/Flonase
Allergy Spray
Nasacort
Allergy Relief
Nasonex
Nasal Spray
Rhinocort
Allergy Spray
 Identification by
IR & UV
Spectroscopy
 Melting point
 Loss on Drying
 Residue on
Ignition
 RS by HPLC
 Residues solvent
 Assay by titration
 Identification by IR
 Specific Rotation
 RS by HPLC
 Bromofluromethane
 content by HPLC
 Acetone content
 Residual solvent
 Assay by HPLC
 Content of Disodium
 Edetate analysis by
HPLC
 Content of
Benzalkonium chloride
 Delivered dosage
 Uniformity(between
 containers & within
 containers)
 Impurities analysis
 Identification by
IR
 Loss on Drying
 Residue on
Ignition
 RS by TLC
 Residual Solvents
 Assay by HPLC
 Assay by HPLC
 Impurities
identification
 Impurities
Analysis
10

12. Timeline For Development
US EU ROW
1. Method Development & Reverse Engineering 1- 2 months
1- 2 months 1- 2 months
2. Regulatory communication 1 months 1 month -
3. Approval for Q1 and Q2 sameness 3 to 4 months 3 to 4 months -
4. Pilot In-vitro study 2 months 2 months Limited in-vitro study
5. Stability 7 months 7 months
-
6. Exhibit Batch/ validation 1 to 2 months 1 to 2 months -
7. Pivotal In-vitro study 3 to 6 months 3 to 6 months -
8. Filing 1 month 1 month
11

13. Regulatory Pathway For OTC Spray
 It establishes a way for OTC drug products to come into market
without individual FDA evaluation and approval.
 No pre-market approval – FDA sets forth specific conditions for
GRASE, or in the case of a developing monograph, sets forth
conditions that allow for continued marketing pending a final
monograph. Oversight occurs on a post- marketing basis.
 No user fees
 No marketing exclusivity
 No review of trade name prior to marketing. Once marketed, FDA
can review the trade name at any time.
12

14. 13
Stability
Center
2010
2012
2013
2014
2015
2016
2017
2018
2019
Health
Canada
Approval
WHO(Geneva),
ISO –
17025,Product
Certification
Center
Bio Waiver
Division
Formulation
Development
Center
Platform
Technology
Center
Metabolism
& Infection
(AMR)
Commerciali
zation of
Technology
Clinical
Supply
History
Started Operation
p
Preservative
free product
Technology
2020

15. Than
Business Development Team
+91 80 41250324
bd@stabicon.com
www.Stabicon.com
Thank You
Business Development Team
www.stabicon.com
+91 80 41250324
bd@stabicon.com