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Generic Drug Development Process


GENERIC DRUG

A generic drug is a pharmaceutical drug product that is pharmaceutically equivalent to a RLD/RS in dosage, strength, route of administration, quality, performance, and intended use, but does not carry the same brand name. 


For Development of Generic Drug Product Following Points to be Consider

  • Patent expiration, exclusivity and legal issues: the expiration date of the patents for formulation composition and process must be considered.
  • Facilities & Technology: Availability of fcilities and technology and cost of acquiring technology for development and manufacturing of generic drug product also to be considered.
  • API availability: DMF availability, Impurity profile and stability, Potential Polymorphic forms, Physical specifications e.g. Bulk density and Particle size distribution, Cost of API and Impurities to be considered.
  • RLD/RS selection: RLD or RS to be selected as per target regulatory market requirement (e.g., For USA market RLD or RS must be FDA approved or FDA orange book listed).
  • Sales and potential market share/volume
  • Formulation experts


A TYPICAL PROCESS FLOW OF GENERIC DRUG DEVELOPMENT

  • Obtain project proposal from project management department
  • Perform literature review and request to the TSD/SCM for RLD/ Reference/ Market sample
  • Raise requisition for new API, excipients, packaging materials and analytical requirements to TSD/SCM 
  • Perform RLD/ Reference/ Market sample characterization
  • Identify QTPP and CQA
  • Perform Preformulation Study and compile information
  • Collect, Review and study the DMF (if available)
  • Select Tooling
  • Design a prototype formulation
  • Perform Drug excipient compatibility study (if required)
  • Identify the lead formulation 
  • Perform stress study (if required)
  • Initiate preliminary method development activities
  • Manufacture three laboratory batches on the lead formulation
  • Select packaging components and submit sample to the packaging department and PMD for evaluation
  • Initiate stability study
  • Order RMs for PO batch(es) (if required)
  • Prepare the recipe for submission/regulatory approval
  • Raise CCR and conduct the risk assessment to manufacture PO batch(es) 
  • Initiate discussion for cleaning validation
  • Prepare and obtain approval of process optimization protocol and BMR (if required)
  • Manufacture the process optimization batch(es) (if required)
  • Submit sample for packaging trial
  • Initiate Method Validation activities
  • Review stability data and declare shelf life of the product
  • Prepare and submit the annexure
  • Request PMD/RA to obtain approval for inclusion materials and price from regulatory authority
  • Request MMIC to raise the requisition for RMs and PMs for PV batch(es)
  • Raise CCR and conduct the risk assessment (if required)
  • Prepare and obtain approval of protocol for process and packaging validation batch
  • Provide approved BMR and BPR to Production
  • Conduct pre-validation meeting and establish roles & responsibility
  • Manufacture the process validation batch(es)
  • Prepare product development report (PDR) of the drug product


AUTHORIZED GENERIC DRUG

An authorized generic is considered to be therapeutically equivalent to its brand-name drug because it is the same drug. This is true even if the brand-name drug is “single source,” meaning there are no ANDAs approved for that product, or coded as non-equivalent (e.g., BN) by FDA in the Orange Book.


Authorized generics examples

  • Prasco Laboratories' colchicine (authorized generic of Colcrys)
  • Watson/Actavis' methylphenidate ER (authorized generic of Concerta)
  • Greenstone's celecoxib (authorized generic of Celebrex)
  • Prasco Laboratories' Hydroxychloroquine (authorized generic of Plaquenil)


FDA New Drug Development Process Include Following Stages

  1. Discovery and Development
  2. Preclinical Research 
  3. Clinical Research
  4. FDA Review
  5. FDA Post-Marketing Safety Monitoring


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