Injectable, Ophthalmic, Controlled-Release Solid Orals Considering Regulatory Filing

1. Injectable/Ophthalmic/Controlled
-Release Solid Orals Considering
Regulatory Filing
Dr. Basavaraj K. Nanjwade M. Pharm., PhD.
Global Business Development Manager
Legis Consultoria
Mob#: 0091 9742999277
E-mail: nanjwadebk@gmail.com
08/6/2023 DKSH India's Pharmaceuticals, Technical Seminar, Bengaluru 1

2. CONTENTS
• Injectable Development
• Ophthalmic Development
• Controlled-Release Solid Orals Development
• Regulatory Filing
• Intellectual Properties Rights
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3. Injectable Development
• Formulation of a new drug product with
excipients, that have been previously added to
an approved injectable product.
• The Physicians' Desk Reference (PDR) and
Handbook on Injectable Drugs were reviewed,
extracting all information on excipients.
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4. Injectable Types
1. General Injectables
2. Cytotoxic Injectables
3. Freeze Drying Injectables
4. Liquid Injections
5. Powder Injections
6. Beta Lactum Drugs (Injectables)
7. Non-Beta Lactam Drugs (Injectables)
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5. Injectable Development
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6. Long-Acting Injectable
Development
• Durations of release: 1 week to 1 year
• Easily syringable with 18- to 23-gauge needle
• Reconstitutes immediately with sterile water
• Good stability characteristics
• Filled asceptically and terminally sterilized if feasible
• Proven content uniformity
• Proven free of foreign particulate matter
• Microsphere-based, biodegradable polymers such as PLA, PLGA, and
other polymers with demonstrated low toxicity, and sourced from multiple
suppliers
• Finished dosage form typically consist of a lyophilized vial containing
microspheres, a suspending agent and other excipients
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Long-Acting Injectable
Development

8. Ophthalmic Development
• Ophthalmic or ocular formulations are specialized
drug compositions specifically designed and
constructed for delivery of drugs to the surface of the
eye as an eye drop (a topical instillation),
• As an ointment or cream, or for injection into the eye
as an intravitreal (IVT) injection.
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9. Ophthalmic Development
• Short-sightedness (myopia)
• Long sightedness (hypermetropia)
• Astigmatism
• Cataracts
• Pink eye (conjunctivitis)
• Dry eye disease
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10. Ophthalmic Development
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11. Ophthalmic Development
• Cyclodextrin-Surfactants & Solubility Enhancing Agents
• Poloxamer 188-Surfactants & Solubility Enhancing Agents
• Tween® 20 (Polysorbate)-Surfactants & Solubility Enhancing Agents
• Tween® 80 (Polysorbate)-Surfactants & Solubility Enhancing Agents
• Ethanol 96%-Solvents
• Glycerol 85%-Solvents
• Polyethylene glycol (200-600)-Viscosity Enhancers
• Benzalkonium chloride-Antioxidants & Preservatives
• Boric acid powder-Antioxidants & Preservatives
• Boric acid cryst-Antioxidants & Preservatives
• Magnesium chloride hexahydrate cryst-Tonicity Agents
• Boric acid cryst - Buffers & pH Modifiers
• Boric acid powder-Buffers & pH Modifiers
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12. Controlled- Release Solid Orals
• Oral dosage forms are preferred because of their
convenience and cost-effectiveness.
• Releasing drugs according to a predictable and
rational programed rate to achieve the optimal serum-
drug concentration.
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13. Controlled- Release Solid Orals
• Dissolution Controlled Release System.
• Diffusion Controlled Release System
• Osmotically Controlled Release System.
• Dissolution and Diffusion Controlled Release System.
• Ionexchange
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14. Controlled- Release Solid Orals
• This dosage form enhances the safety, efficacy, reliability,
and convenience of drug therapy.
• Sustained release technology is characterized by the slow
releasing of a specific substance at a programmed rate to
deliver the drug for a prolonged period of time.
• This type of technology is used for drugs that are
metabolized too quickly and are eliminated from the body
shortly after administration.
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15. Controlled- Release Solid Orals
• Sustained release is a slow release of medication over
a period of time, whereas control release releases
medication over time in correlation with
concentration.
• Sustained release medication is offered solely by way
of oral dosage, while controlled release can be via
oral, transdermal administration, or other means.
• Sustained release technology is first-order kinetic and
controlled release technology is zero-order kinetic.
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16. Controlled- Release Solid Orals
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17. Controlled- Release Solid Orals
• Microcrystalline Cellulose
• Colloidal Silicon Dioxide,
• Sodium Starch Glycolate,
• Sodium Stearyl Fumarate
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18. Regulatory Filing
• FDA- United States of America
• EMA- European Union
• SwissMedic- Switzerland
• ANVISA- Brazil
• PMDA-Japan
• TGA-Australia
• Health Canada- Canada
• CDSCO- India
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19. Regulatory Filing
Details IND NDA BLA ANDA OTC
Covered under FDC Act FDC Act PHS Act FDC Act, Hatch-
Waxman Act,
BPCIA
FDC Act
Reviewed by CDER/CBER CDER CBER CBER, OGD CDER(ODE IV)
and FTC
Listed in Orange book Purple book Orange book OTC Monograph
and federal
register
Type of application Research Marketing Marketing Marketing Marketing
Data
available/required
Preclinical, CMC,
proposed CT
protocol
Clinical, CMC,
proposed labelling
Clinical, CMC,
proposed labelling
BA/BE Additionally safety
studies, labelling
info
Types Investigator
initiated
emergency
treatment
5O5(b)(1)
5O5(b)(2)
351(a) Generic-5O5 (j)
Biosimilar-351 (k)
--
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20. Regulatory Filing
• New Chemical Entity/New Molecule Entity
(NCE/NME)
• Generic- Prescription
• Generics-OTC
• Biologics
• Vaccines
• Orphan
• Traditional Medicine
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21. Regulatory Filing
Regulatory process 5O5(b)(1) 5O5(b)(2) 5O5(j)
Review classification/Time line 9 Months 9 Months 6-12 Months
New molecular(chemical) entity Yes Yes No
New active moiety Yes Yes No
New indication Yes Yes No
New Route of Administration Yes Yes No
New Formulation Yes Yes No
New Ester, Salt or Other Non-covalent
Derivative
Yes Yes No
New Dosage Form or Strength Yes Yes No
Combination Product Yes Yes May be
Rx/OTC Switch Yes Yes No
Labelling Yes Yes No
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22. Regulatory Filing
• Type I DMF: Manufacturing Site, Facilities, Operating
Procedures, and Personnel (no longer applicable).
• Type II DMF: Drug Substance, Drug Substance
Intermediate, and Material Used in their Preparation, or
Drug Product.
• Type III DMF: Packaging Material.
Type IV DMF: Excipient, Colorant, Flavor, Essence, or
Material Used in their Preparation.
• Type V DMF: FDAAccepted Reference Information.
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23. Regulatory Filing
• See 21 C.F.R. 314.50 Content and format of an NDA
• See 21 C.F.R. 314.52 Notice of certification of invalidity, unenforceability, or
noninfringement of a patent
• See 21 C.F.R. 314.53 Submission of patent information
• See 21 C.F.R. 314.54 Procedure for submission of a 505(b)(2) application requiring
investigations for approval of a new indication for, or other change from, a listed drug
• See 21 C.F.R. 314.60 Amendments to an unapproved NDA, supplement, or resubmission
• See 21 C.F.R. 314.70 Supplements and other changes to an approved NDA
• See 21 C.F.R. 314.94 Content and format of an ANDA
• See 21 C.F.R. 314.95 Notice of certification of invalidity, unenforceability, or
noninfringement of a patent
• See 21 C.F.R. 314.96 Amendments to an unapproved ANDA
• See 21 C.F.R. 314.97 Supplements and other changes to an ANDA
• See 21 C.F.R. 314.101 Filing an NDA and receiving an ANDA
• See 21 C.F.R. 314.107 Date of approval of a 505(b)(2) application or ANDA
• See 21 C.F.R. 314.108 New drug product exclusivity
• See 21 C.F.R. 316.31 Scope of orphan-drug exclusive approval
• See 21 C.F.R. 316.34 FDA recognition of exclusive approval
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24. Intellectual Properties Rights
• The generic company files an Abbreviated New Drug
Application (ANDA) and certifies against patents
listed in the Orange Book.
• If the generic company files an ANDA with a
Paragraph IV certification, then the branded company
is notified.
• After the notice, the branded company has 45 days to
file a patent infringement action against the generic
company.
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25. Intellectual Properties Rights
• Paragraph I certification states that there are no
patents listed,
• Paragraph II certification states that the listed patents
have expired.
• Paragraph III FDA should approve of its generic
version after the date the last patent expires.
• Paragraph IV that its generic product does not
infringe on the listed patents or that those patents are
not enforceable.
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26. Intellectual Properties Rights
• Intellectual property rights, including patents,
trademarks, copyrights, and trade secrets.
• The five primary requirements for patentability are:
(1) Patentable subject matter,
(2) Utility,
(3) Novelty,
(4) Nonobviousness, and
(5) Enablement.
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27. Intellectual Properties Rights
1. Recombinant DNA
2. Recombinant DNA E-Coli
3. Why do we need recombinant DNA Technology
4. Insulin recombinant protein
5. DNA recombinant molecule
6. Recombinant DNA Technology
7. Insert recombinant DNA
8. RDT Genetic Engineering
9. Proteins
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28. References
1. PDA J Pharm Sci Technol. 1997 Jul-Aug;51(4):166-
71.
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29. THANK YOU!
Mob# 0091 9742999277
E-mail: nanjwadebk@gmail.com
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