Generic drug product development Pharmaceutical Regulatory Science Notes
Current development and approval of generic drug products were associated with issues concerning. Safety, efficacy and therapeutic equivalence of such products early compared to the innovator or brand-name drug product for obtaining marketing approval.
However, the generic pharmaceutical industry is still challenged by legislative, regulatory and scientific issues that must be addressed to allow for the manufacture, approval and marketing of generic drug products. Generic drug product manufacturers must formulate a drug product that will have the same therapeutic efficacy and clinical performance as their brand-name counterparts.
SELECTION OF GENERIC DRUGS FOR MANUFACTURE
The main driving force for the selection of generic drug products for manufacture is the estimated sales volume for the branded product.
The firm’s potential market share expects to have once the generic drug product is manufactured and approved for marketing. In addition to the expiration date of the patent for the active ingredient, the generic firm must consider any other patent claims and exclusivities that the innovator firm has filed
The generic drug manufacturer needs to consider:
The lead time that is needed to make the product and submission an Abbreviated New Drug Application (ANDA) to the U.S.FDA for approval.
Moreover, there is a financial incentive to being the first generic drug product filed and approved by FDA.
180-days exclusivity is given under certain conditions, for the generic manufacturer who is to file first.
Formulation considerations for generic drugs include:
The availability of raw materials, chemical purity, and polymorphic form.
Particle size of the active pharmaceutical ingredient.
Any patents that the innovator company has filed, including patents for the synthesis of the active pharmaceutical ingredient and composition of the dosage form
GENERIC DRUG APPROVAL PROCESS:
The FDA’s Office of Generic Drugs is responsible for reviewing the ANDA and approving the drugs products marketing.
The FDA’s Office of Generic drugs has a website http//www.fda.gov.org that provides additional information for manufacturers of generic drug products including a flow chart presentation of the ANDA review process.
It also describes how FDA determines the quality, safety, and efficacy of generic drug products prior to the approval for marketing.
Generic drug application reviewers focus on bioequivalence data, chemistry and manufacture quality, microbiology data where relevant, requests for plant inspection, and drug labelling information
The ANDA for generic drug product approval is based on bioequivalence to the brand name product, appropriate chemistry and manufacturing information, and appropriate labelling.
Generic drug sponsors do not have to perform the nonclinical animal toxicity studies or expensive clinical efficacy and safety studies that are included in the new drug application.
NDA which is submitted to the FDA for market approval of the brand name drug product.
The ANDA contains data which is then submitted to FDA’s Center for drug evaluation and research for the generic drugs.
FDA approved generic drugs must meet the same rigid standards as the innovator drug.
To obtain FDA approval, a generic drug product must- contain the same active ingredient as an approved drug product the inactive ingredients may vary.
Be identical strength, dosage form, route of administration, same indications, bioequivalent, and meet the batch requirements.
The FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations and lists of the all approved products, both innovator and generic are included in the orange book
STEPS IN GENERIC DRUG PRODUCT DEVELOPMENT PROCESS
CONCEPT DEVELOPMENT
The needs of the target market are identified, alternative product concepts are generated and evaluated, and a single concept is selected for further development
SYSTEM LEVEL DESIGN
It includes the definition of the product into subsystems and components. The final assembly scheme for the production system is usually defined during this phase
DETAIL DESIGN
Includes the complete specifications of the geometry, materials and tolerances of all the unique parts in the product and the identification of all the standards parts to be purchased from suppliers.
A process plan is established and tooling is designed for the each part to be fabricated within the production system.
It involves the construction and evaluation of multiple pre-production versions of the product. Early prototypes are usually built with production-intent parts(parts with the same geometry and material properties as intended for the production version of the product).
Early prototypes are tested to determine whether the product will work as designed and whether it satisfies the customer’s needs. The goal of prototypes is usually used to answer questions about performance and reliability in order to identify changes for the final product
PRODUCTION RAMP UP
The purpose is to train the work force and to work out any remaining problems in the production process.
The artifacts produced during production ramp up are sometimes supplied to the preferred customer and are carefully evaluated to identify any remaining flaws.
Suggested readings:
Recommended readings:
- New Drug Application NDA
- Blue waffle disease
- Innovator and generics
- Pharmaceutical Biotechnology Theory
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Reference:
Powerpoint presentation by Sachin.J.Gaddimath and Mr. Prabhu Halakatti Dept. of Pharmaceutics HSKCOP, BAGALKOT.
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