Complex Generic Development

Complex Generic Development

With decades of experience in simple and complex generic product development, PharmSky’s scientists are well versed to assist in the development of your generic, value-added and differentiated generics. With a deep understanding of the ANDA and 505(b)(2) registration pathways, PharmSky can guide you through the processes required to get your product onto the market as efficiently as possible. Whether it is a simple replication of an existing product or a request to transform a product into a long-acting formulation, we accept any challenge.

For value-added and differentiated generic formulations, PharmSky can provide the following services:

Working closely with the client, we will develop a quality target product profile (QTPP) that meets their requirements. By carefully considering all available information, we will identify the most viable and promising formulation, or process options. If required, this will include an assessment of existing patents and their claims, strategies to design around these, and options for new intellectual property (IP) development.

To identify the most likely formulation candidates, different formulation options will be rapidly screened. This may include accelerated solubility, pH, excipient compatibility and/or headspace screening. In the case of complex formulations, this will be more in depth, exploring the feasibility of using the proposed compound in appropriate complex matrices (e.g. nanoparticles, hydrogels) and the likely challenges that will be encountered. At the end of this stage, PharmSky’s team will have identified the most promising candidates which can move to the development phase. This early-stage feasibility work will minimise the risks and costs associated with a complex development program.


Upon completion of successful early stage feasibility studies, we can help you execute a full product development program ready for ANDA or 505b(2) submission. This program will typically include, but is not limited to the following activities:

  • Sourcing, assessment and selection of a suitable API
  • Innovator assessment and de-formulation
  • Formulation development
  • Container/closure selection
  • E&L studies/testing 
  • Sterilisation method selection/justifications (for sterile products)
  • Filter selection and compatibility studies (for sterile products)
  • Manufacturing process development, scale up and validation
  • Surface compatibility studies
  • Analytical method development and validation
  • Exhibit batch manufacture
  • Stability studies as per ICH guideline requirements
  • Compilation of Pharmaceutical Development section (Modules 2.3.P, 3.2.P) of dossier

Generic and value-added drug products can take advantage of the abbreviated approval pathways available for drug product registration, potentially shortening the time to market. An abbreviated new drug application (ANDA) is typically used for a duplicate of a previously approved drug product. It relies on the prior finding that the approved drug is safe and effective and must have the same active ingredient, conditions of use, route of administration, dosage form, strength, and labelling. A 505(b)(2) application is a new drug application where at least some of the information required for approval comes from studies not conducted by the applicant. The application may only rely on the findings of the referenced drug product to the extent that the products share characteristics. Bridging justifications and data must be provided to support the differences between the two products and demonstrate that reliance on the listed drug is scientifically justified. PharmSky’s regulatory specialists are experts in navigating these pathways and can help ensure you have everything in place to get your product approved as quickly as possible.

There are many reasons why companies pursue the development of value-added and differentiated generic products. Primarily, the goal is to improve upon the product by making it more user friendly (healthcare provider and patient), improving its efficacy, reducing its toxicity or overcoming other, more specific problems. Some of the ideas commonly explored include:

Extended release generics are designed to release the active ingredient over an extended period, allowing for less frequent dosing and improved patient compliance compared to immediate release formulations. Controlled release generics deliver the active ingredient at a controlled rate to maintain therapeutic levels in the body over an extended period. These formulations can help reduce fluctuations in drug concentration, minimise side effects, and improve treatment outcomes. Examples include the use of thermosensitive hydrogels to form an intramuscular depot and the use of nanoparticle systems with prolonged circulation/retention in the body.

A value-added topical generic can be designed to offer enhanced drug delivery through the skin which may lead to lower dose requirements and improved drug absorption. In some cases, this can be as simple as modifying the formulation with an improved permeation enhancer.

Modifications to the formulation of a lyophilised drug product can enable production of a stable liquid product, removing the need for a reconstitution step, the difficulties associated with this step and saving time at the point of use. Similar modifications can be made to convert a product with a low temperature storage condition into a stable system at room temperature. Typically, reformulation involves making changes to solvents, the incorporation of stabilising excipients or other modifications targeted towards the reduction or prevention of degradation reactions.

Parenteral products are typically supplied in vials. In recent times there has been a surge in the use of alternate technologies such as pre-filled syringes and auto-injectors. While the registration of these products can be more complicated, the benefits at the site of use include fewer administration errors, reduced likelihood of contamination and, in the case of auto-injectors, easy use by the patient or their carer.

Incorporation of API into a nanoparticle system can lead to reduced side effects and even enable use of the drug at higher levels than previously approved. Nanoparticles such as liposomes can encapsulate the active compound potentially preventing accumulation in or contact with cells/tissues which cause toxic side effects. Similar reformulation activities for topical products can utilise alternate excipients to reduce the irritation/sensitisation of skin upon application.

Efforts directed towards the development of an improved formulation of an existing intravenous product may allow for delivery via intramuscular or subcutaneous injection or in rare cases oral administration. A typical example where this may be possible is for an intravenous drug with significant solubility issues. Reformulation into a product with a higher concentration may allow for intramuscular delivery.

Value added or differentiated generics often have rapid uptake by the medical community given that reformulation activities are directed towards improved ease of use and patient tolerability. Along with the benefits outlined above, complex or value-added generics can create new intellectual property opportunities and market protection. Get in touch with PharmSky to discuss reformulation options and unlock the full potential of your product.

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