Introduction
505(b)(2) process is relatively new and evolving with interesting way of approval pathway. In
recent years 505(b)(2) filing process in increasing from 20% in year 2006 to
more than 50% NDA filing in year 2008. The percentage of 505(b)(2) filing is as
high as 90% and this is the reason it is
lucrative pathway of filing.
505(b)(2) is a application which gives guidance for Industry
for NDA filling. The main purpose of this filling is to provide new drug
application.
Section 505 of the Act describes three types of new drug
applications (NDA):
(1) an application that contains full reports of investigations of safety and effectiveness (section 505(b)(1));
(2) an application that contains full reports of investigations of safety and effectiveness but where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference (section 505(b)(2)); and
(3) an application that contains information to show that the proposed product is identical in active ingredient, dosage form, strength, route of administration, labeling, quality, performance characteristics, and intended use, among other things, to a previously approved product (section 505(j)). This filling is also considered as ANDA (Abbreviated New drug application or Generic Filing)
Clinical trial process
is a long and expensive process to establish safety and efficacy of the product
so, the Second option of 505 (b)(2) is the easiest route for small firms to
take a chance to generate a good revenue from their product. This was added to Federal
Food, Drug, and Cosmetic Act Act by the Drug price competition and Patent Term
Restoration Act of 1984 (Hatch-Waxman Amendments) where the applicant are encouraged to make small
modifications for those products which has already been approved by FDA. Such
product often shows advancing the medication for the patients’ benefit.
The applicant can submit 505(b)(2) application through the
following changes made
Dosage form: An application for a change of
dosage form, such as a change from a solid oral dosage form to a transdermal
patch, that relies to some extent upon the Agency's finding of safety and/or
effectiveness for an approved drug
Strength: An application for a change to a lower
or higher strength.
Route of administration: An application for a
change in the route of administration, such as a change from an intravenous to
intrathecal route. This route has been extensively exploited in recent days. We
have tried to enlist the examples in table 1.
Substitution of an active ingredient in a
combination product: An application for a change in one of the active
ingredients of an approved combination product for another active ingredient
that has or has not been previously approved
Rx/OTC switch: An application where a drug is
switched from a prescription category to OTC (over the counter) indication.
Table 1. Examples of 505 (b) (2) approved
products
Name of Product 505 (b) (1)
|
Previous Dosage form/Route
|
Name of Product
|
NDA applicant
|
Naproxen Sodium and
Diphenhydramine Hydrochloride
|
Tablets/Oral
|
Naproxen Sodium and
Diphenhydramine Hydrochloride
|
Bayer Healthcare
|
Diclofenac Sodium
|
Tablets/Oral
|
Diclofenac Sodium Topical Solution
2%
|
Mallinckrodt Inc.
|
Indomethacin
|
Tablets/Oral
|
Indomethacin Injection
|
Iroko Pharmaceuticals LLC
|
Topiramate
|
Tablets/oral
|
Topiramate Capsule, Extended
Release
|
Upsher Smith
|
Ketorolac Tromethamine;
Phenylephrine Hydrochloride
|
Oral
|
Ketorolac Tromethamine;
Phenylephrine Hydrochloride/Injection
|
Omeros
|
Methotrexate
|
Oral
|
Methotrexate Injection
|
Medac Pharma
|
Advantages of 505(b)(2)
505(b)(2) is particularly valuable for pharmaceutical and
generics companies looking to alleviate competitive forces in their
environments while still wanting to benefit from a development process that
eliminates most nonclinical studies as well as extensive safety and efficacy
tests.
-
Relatively low risk because of previous drug
approval- Safety profile is already established
-
Lower cost, accelerated development due to fewer
studies
-
May qualify for three, five or seven years of
market exclusivity
Idea feature of Molecule for 505(b)(2)
-
Drugs with new indications
-
Drugs with changes in dosage form, strength,
formulation, dosing regimen or route of administration
-
New combination products
-
Prodrugs of an existing drug
-
In some cases, drugs with new active ingredients
The following are few strategic issues for a 505(b)(2) product:
1. Extent of innovation/modification made to the
innovator product: these modifications decide whether the product is applicable
for a 505(b)(2) review or not, and facilitate verify the quantity of years of
market exclusivity granted.
2. Development
strategy: careful analysis of data should lead to a list of the additional
studies that may be required for a given 505(b)(2) product; bridging studies
are required to show that changes to the innovator product lead to the desired
impact on safety, efficacy and tolerance of the proposed drug product.
3. As
505(b) (2) products are generally more expensive than generic versions of the
innovator drug, the manufacturer ought to have a strong selling arrangement.
Table 2. Comparision
of NDA 505 (b) (1) /(2) and 505(J)
Conclusion
505 (b) (2) application is meant to promote innovation by
eliminating repetition of clinical trials. Exploitation of this pathway drug
will simply enter into market with less value on investment and generate more
revenue.
Reference:
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Regulatory
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