Health Ministry Revises BA/BE Study Rules: Minimum Sample Size Set at 18

New Delhi: In a key regulatory update impacting India’s clinical research framework, the Ministry of Health and Family Welfare (MoHFW) has revised its August draft amendment to the New Drugs and Clinical Trials Rules, 2019, introducing a key change in the sample size requirement for bioavailability and bioequivalence (BA/BE) studies of new or investigational drugs.

The Ministry of Health and Family Welfare (MoHFW) has issued a corrigendum to its earlier draft notification—G.S.R. 587(E) dated August 27, 2025—which proposed amendments to the New Drugs and Clinical Trials (NDCT) Rules, 2019. The corrigendum, published on October 31, 2025 as G.S.R. 810(E), modifies the sample size condition under para 2 of the draft rules.

Earlier, the Medical Dialogues Team had reported that the Ministry of Health and Family Welfare had proposed an amendment to the New Drugs and Clinical Trials Rules, 2019 that would allow certain bioavailability and bioequivalence (BA/BE) studies for export purposes to be conducted on the basis of a simple online notification instead of prior approval from the Central Licensing Authority.

The draft, notified on August 27, 2025, had specified that in case of single-dose, two-period, two-sequence, two-treatment, bioavailability or bioequivalence studies in normal healthy adult human volunteers (for export purpose only), of oral dosage form of a drug (other than drugs of Cytotoxic, Hormone, Narcotic and Psychotropic substances categories and not a drug of Narrow Therapeutic Index or a drug having highly variable pharmacokinetics) already approved in the Country or any one of the countries namely, USA, EU, Japan, Australia, Canada and UK, the studies may be conducted after submission of an online application as notification and its acknowledgement by the Central Licensing Authority, subject to the following conditions:

1. The application for the notification must be accompanied with approval of the ethics committee registered with Central Licensing Authority under rule 8.

2. The Ethics Committee shall maintain separately the record of review and approval of such bioavailability or bioequivalence studies being conducted under this notification process which shall be reviewed by the Central Licensing Authority at the time of renewal of the Registration of the Ethics Committee.

3. The samples size should not be more than 48."

As per the latest corrigendum (G.S.R. 810(E)) issued on October 31, 2025, the earlier clause—“The sample size should not be more than 48”—has been replaced with “The sample size should be more than or equal to 18.”

The notice states,

In the draft notification of the Government of India, Ministry of Health and Family Welfare, published in the Gazette of India, Extraordinary Part II, Section 3, Sub-Section(i) vide G.S.R. 587 (E) dated the 27th August, 2025―

(i) In para 2 under the draft rules, the condition no. 3 of the Proviso for the words “The samples size should not be more than 48” the following shall be substituted as, :- “The samples size should be more than or equal to 18”.

The corrigendum continues to uphold all other provisions of the August draft, which sought to streamline the approval pathway for certain bioavailability and bioequivalence studies involving orally administered drugs already approved in India or in key international markets such as the USA, EU, Japan, Australia, Canada, and the UK. These studies can be initiated after online notification and acknowledgement by the Central Licensing Authority, provided all ethical and procedural safeguards are met.

The Ministry has invited objections and suggestions on the revised clause within 15 days of publication. Inputs may be submitted to the Director (Drugs), MoHFW, at Room No. 407, A Wing, Nirman Bhavan, New Delhi – 110011, or via email at drugsdiv-mohfw@gov.in