ICH Seeks to Harmonize Generic Drug Standards

Regulatory NewsRegulatory News | 06 February 2019 |  By 

With an aim to harmonize the technical and scientific standards for generic drugs across borders, the International Council on Harmonization (ICH) on Wednesday released a reflection paper outlining an approach to begin supporting such efforts.

The reflection paper offers recommendations to develop a series of ICH guidelines on standards for demonstrating bioequivalence for non-complex and more complex dosage forms and products. It also describes the remit of the Informal Generic drug Discussion Group (IGDG), to be established by ICH in 2019 and to serve as a technical discussion group recommending areas for harmonization and assessing feasibility within existing regional regulatory frameworks.

“At present, a lack of harmonized standards reduces the number of potential markets in which data and information submitted in support of a generic drug marketing application can be used by a developer to support marketing authorization in another jurisdiction,” the paper says. “This can lead to monopolies or limited sources of drugs in those markets in which approval is not sought due to the additional development burdens.”

The push for harmonization comes as FDA recently noted a disconnect between countries in terms of which generics are available.

By contrast, harmonization may allow generic developers to use their data and meet multiple jurisdictions’ regulatory requirements for marketing authorization. Harmonization could also increase the size of generic drug markets and attract more competition, which would mean lower costs and expanded patient access in jurisdictions in which developers otherwise may have decided not to pursue, the paper adds.

In addition, harmonization may streamline generic drug development and make it more cost-effective, including by potentially reducing the number of duplicative studies and by increasing the quality of generic medicines by establishing a globally consistent quality culture.


For non-complex drugs, the reflection paper proposes developing guidelines on bioequivalence studies for immediate-release oral dosage forms, including study design (e.g., crossover vs. parallel, subject, sample size, fasting vs. fed, replicate design) and data analysis (e.g., statistical methods for BE assessment, handling outlier data, average bioequivalence vs. scaled bioequivalence, parent vs. metabolite).

For more complex dosage forms or products, ICH says, “One such guideline may address bioequivalence studies for modified-release oral dosage forms, which could address scientific considerations such as ‘waivers’ for additional strengths for modified-release products and when partial Area Under the Curve (pAUC) measurements may be important.”

Other guidelines could address pharmaceutical equivalence and bioequivalence standards for products with complex active pharmaceutical ingredients (e.g., peptides, oligonucleotides), products with complex formulations (e.g., liposomal products), locally acting products (e.g., topical dermatological and orally inhaled products) and drug-device combination products.

“As experience is gained, ICH may refocus its harmonization efforts to more complex topic areas where harmonization may not seem feasible at present. To assist in this effort, it is recommended that as a next step, ICH establish a discussion group to assess the feasibility of harmonization of various topic areas specific to standards for generic drugs and to assist in prioritizing work areas to ensure appropriate use of resources,” the paper adds.

ICH Reflection Paper: Further Opportunities for Harmonization of Standards for Generic Drugs

Remit of the Informal Generic Drug Discussion Group


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