Line Extension

Line extensions occur when a company introduces additional items in the same product category under the same brand name such as new flavors, forms, colors, added ingredients, package sizes

Changes to the Active Substance(s)

• Replacement of the active substance(s) by a different salt/ester complex/derivative (with the same therapeutic moiety) where the efficacy/safety characteristics are not significantly different
• Replacement by a different isomer, a different mixture of isomers, of a mixture by an isolated isomer (e.g. racemate by a single enantiomer) where the efficacy/safety characteristic are not significantly different
• Replacement of a biological substance or product of biotechnology with one of a slightly different molecular structure
• A new ligand or coupling mechanism for radiopharmaceutical
• Change to the extraction solvent or the ratio of herbal drug to herbal drug preparation where the efficacy/safety characteristic are not significantly different

Changes to the strength, pharmaceutical form and route of administration

• Change of bio-availability
• Change of pharmaco-kinetics, e.g. change of rate of release
• Change or addition of a new strength/potency
• Change or addition of a new pharmaceutical form
• Change or addition of a new route of administration

In the US, there is no line extension applications. The major amendments or changes that are made to existing NDAs or ANDAs are submitted in form of supplementary NDAs (SNDAs)

A change which includes changes to the drug substance or the drug product (categorized for certain changes as line extensions in the EU) is considered a major change in the USA.

Approval Routes for Line Extensions

There are several routes that an applicant can use to submit a line extension application to Member States. Basically, the understanding is that Extension applications are submitted using procedures which are dependent on the procedure which was used at the time of obtaining the initial marketing authorization(s). Previously approved originator drugs with new dosage forms, strengths and route of administration can have these new forms approved through either the national or mutual recognition route or centralized route as line extensions. Therefore, the option for obtaining marketing authorization for line extensions are as follows;

1. When an originator product was granted marketing authorizations through a community procedure, such as the MRP r the CP, the line extension approval would also be granted through the same route
2. When the originator product was granted the marketing authorization through national procedures, there are 2 options:
   1. Apply for line extension through national procedures, where national regulations apply
   1. Apply for line extension through mutual recognition procedure, which requires the applicant to harmonize the nationally approved SmPCs in order to support the applications in all the concerned Member State with the same application.

The harmonization of SmPCs can be done in 2 different ways:

1. Through a series of coordinated national variation application so that the end results is a harmonized SmPC across all the concerned Member States
2. The applicant makes a referral to Article 30 of Directive 2001/83/EC on a voluntary basis in order to harmonize the originator product SmPC using this procedure.

• If the application does not want to use either of the above two methods for submission of the line extension, he can submit a complete application for the new line extension, provided he has all the information required from the previous submission to apply for an authorization.

The mutual recognition procedure must be used for standalone applications and abridged applications provided the application is legally valid. Once the procedure has been used, all variations to these medicinal products must use the mutual recognition procedure.

The mutual recognition procedure is also applicable for line extensions of existing national marketing authorizations. In order to fulfil the criteria of identically of the dossier prior to a mutual recognition procedure, the application will have to harmonize the already approved national SmPCs. This harmonization can be achieved through coordinated national variation procedures. The applicant can also apply a completely new dossier as a stand-alone application for the line extension. Otherwise, the national procedure remains possible