A generic drug product is a medication that contains the same active pharmaceutical ingredient (API) as a brand-name drug and is designed to be interchangeable with the brand-name drug in terms of safety, efficacy, and quality.
Once a brand-name drug’s patent protection expires, other manufacturers are allowed to produce and sell generic versions of the drug, as long as they can demonstrate that their product meets the same standards for safety, efficacy, and quality as the brand-name drug.
Nowadays, the pharmaceutical industries focus on the development of generic product as this does not need to conduct expensive clinical trials or invest in extensive marketing campaigns. Hence it does not require that much time and cost compared to the innovator company.
Generic drug products are usually sold at a lower cost than brand-name drugs because the manufacturer.
The key steps in generic product development include the following:
1. Research and Development:
In this stage, the generic drug manufacturer conducts a thorough review of the reference drug (the brand-name drug that the generic drug is copying), including its chemical composition, manufacturing process, dosage form, and intended use. The manufacturer will also conduct pre-clinical studies to evaluate the safety and efficacy of the drug.
2. Formulation Development:
After completing the research and development stage, the manufacturer formulates the generic drug product. This involves selecting the appropriate active pharmaceutical ingredient (API) and excipients (inactive ingredients), and determining the optimal dosage form (e.g. tablets, capsules, injectable).
Formulation and development of the generic drug products includes, Pre-Formulation Study, Excipient Selection and Designing of Formulation Method, Selection of Manufacturing Method, Experimental Formulation Development, Scale-Up, Technology Transfer or Pivotal Bio Batches, Drug Stability Study.
3. Analytical Testing:
The manufacturer conducts analytical methods development and methods validation to ensure that the generic drug product meets the same quality, safety, and efficacy standards as the reference drug. This includes testing the drug for purity, potency, and stability.
4. Bioavailability and Bio-Equivalence:
Bioavailability and bioequivalence studies are important aspects of generic drug development. Bioavailability refers to the extent and rate at which the active pharmaceutical ingredient (API) in a drug product is absorbed into the bloodstream and becomes available at the site of action. Bioequivalence refers to the similarity in bioavailability between a generic drug product and its corresponding brand-name reference drug.
Bioavailability studies are conducted to evaluate how much of the API in a drug product is absorbed into the bloodstream, and how quickly this occurs. These studies typically involve administering a single dose of the drug product to a group of healthy volunteers, and then measuring the concentration of the API in their blood over time.
Bioequivalence studies are conducted to demonstrate that a generic drug product is therapeutically equivalent to its corresponding brand-name reference drug. These studies compare the bioavailability of the API in the generic drug product to that of the reference drug, using the same dosage form and route of administration. If the bioavailability of the generic drug product is within a specified range of that of the reference drug, it is considered to be bioequivalent.
Bioavailability and bioequivalence studies are essential for demonstrating the safety and efficacy of generic drug products, and for obtaining regulatory approval to market these products. They help ensure that generic drug products are as safe and effective as their brand-name counterparts, and can be used interchangeably in clinical practice.
5. Regulatory Approval:
Once the manufacturer has completed all of the necessary testing and bio studies, they submit an Abbreviated New Drug Application (ANDA) application for regulatory approval to the relevant authorities (e.g. FDA in the United States). This ANDA application should include data from your Bioavailability and bioequivalence studies, as well as information on your drug product’s manufacturing process and labeling. The FDA will review your ANDA to determine if your drug product is safe and effective, and if it is bioequivalent to the brand-name reference drug. This review process typically takes several months. If your drug product is approved, you will receive a letter from the FDA granting you permission to market your product. You will then be able to manufacture and sell your generic drug product in the United States.
6. Manufacturing and Commercialization:
Once the generic drug product has been approved, the manufacturer can begin manufacturing and commercializing the drug. This involves setting up a manufacturing facility, validating the manufacturing process, obtaining the necessary permits and licenses, and marketing the drug to healthcare professionals and patients.
7.Technology Transfer, Scale-Up, Post-approval Changes, and Post-Marketing Surveillance
Technology transfer: If the manufacturer wants to transfer the manufacturing process to a new site, it will need to conduct a technology transfer. This involves transferring the knowledge and expertise required to manufacture the product from the original site to the new site. The transfer may involve training new personnel, transferring equipment and technology, and conducting a risk assessment to identify any potential issues.
If the new site is located in a different country or region, the manufacturer may need to submit a new regulatory application or a supplement to the original ANDA to gain approval for the new site. This may involve submitting data from the process validation and verification studies, as well as data on the stability and shelf-life of the product.
Scale-up: Once the manufacturing process has been validated and technology transfer has been completed, the manufacturer can begin the scale-up process. This involves increasing the production volume of the drug product to meet the demands of the market. The manufacturer will need to carefully monitor the process to ensure that the product maintains its quality and consistency.
Post-approval Changes: After an Abbreviated New Drug Application (ANDA) for a generic drug product has been approved by the regulatory authority, there may be a need to make changes to the product or its labeling. For examples changes to its manufacturing process, material or equipment, labeling changes, Change in ownership or manufacturing site, Changes to packaging or container closure systems. it may need to submit a supplement to its ANDA application to document the changes and demonstrate that they do not affect the safety, efficacy, or quality of the product.
Post-marketing surveillance: After your product is approved and marketed, the regulatory authority may continue to monitor its safety and efficacy through post-marketing surveillance activities, such as adverse event reporting and periodic safety updates.
8. Legal and Legislative Hurdles to Generic Drug Development, Approval and Marketing
Generic drug development, approval, and marketing can face various legal and legislative hurdles. Some of the common ones are:
Patent protection: Brand-name drugs are typically protected by patents, which give the patent holder exclusive rights to manufacture and sell the drug for a specified period of time. This can limit the ability of generic drug manufacturers to enter the market until the patent has expired or been invalidated.
Regulatory requirements: The regulatory requirements for generic drug approval can be complex and time-consuming, which can delay the introduction of generic products to the market. The regulatory authorities may require extensive pre-clinical and clinical studies to demonstrate the safety, efficacy, and bioequivalence of the generic drug product.
Data exclusivity: Some countries have data exclusivity laws, which give the original drug manufacturer exclusive rights to the clinical trial data used to support the approval of the drug for a certain period of time. This can prevent generic manufacturers from relying on the same data to support their own applications for approval.
Market exclusivity: In some cases, the original drug manufacturer may be granted market exclusivity, which gives them a temporary monopoly on the market for the drug. This can limit the ability of generic drug manufacturers to enter the market until the exclusivity period has expired.
Litigation: Brand-name drug manufacturers may use litigation to delay the entry of generic products into the market, such as by filing patent infringement lawsuits or seeking injunctions against the approval or marketing of generic products.
Pricing and reimbursement: Even after a generic drug product is approved and marketed, it may face hurdles related to pricing and reimbursement. Health insurance plans and government programs may negotiate lower prices for generic drugs, which can limit the profit margins for generic manufacturers.
These legal and legislative hurdles can make it challenging for generic drug manufacturers to compete with brand-name drug manufacturers. However, the development and availability of generic drugs can have significant benefits for patients and healthcare systems, including increased access to affordable medications and reduced healthcare costs.