La Renon's plea to exempt Sodium Valproate from NPPA price cap rejected

In February 2023, the NPPA implemented a price ceiling on Valgress CR-200, a modified release (MR) tablet containing a combination of Sodium Valproate (135mg) and Valproic Acid (58mg). La Renon Healthcare contested this decision, arguing that the unique controlled-release formulation of Valgress CR-200 should not fall under the same pricing restrictions as conventional sodium valproate tablets. The company asserted that its product offers distinct advantages due to its modified release design, which impacts how the drug is delivered and absorbed.

To elaborate, La Renon contended that the NPPA made an error in setting the ceiling price for the drug Valgress CR-200, arguing that it should be revised based on several key grounds. La Renon Healthcare, a privately held company, markets the Valgress CR-200 tablet, which contains a controlled release formulation of Sodium Valproate (135mg) and Valproic Acid (58mg). They argued that this specific formulation does not appear in Schedule-I of the Drugs (Prices Control) Order (DPCO) 2013, as amended on November 11, 2022. Despite this, the NPPA, through Notification No. S.O. 879(E) dated February 24, 2023, included Valgress CR-200’s price in its regulation of 80 scheduled formulations, which La Renon asserts is a non-scheduled formulation and should not be subject to the same ceiling price.

The drug maker further pointed out that Schedule-I of the DPCO 2013 only lists conventional release sodium valproate tablets in specific strengths, including 200mg, 300mg, and 500mg, as well as 300mg and 500mg modified release tablets. They argued that their unique formulation, with Sodium Valproate 135mg and Valproic Acid 58mg in a modified release form, is not specifically listed in Schedule-I and should therefore be treated as a non-scheduled drug. According to La Renon, the NPPA’s decision to group their formulation with conventional 200mg sodium valproate tablets in calculating the ceiling price was incorrect.

In support of their position, La Renon referenced Explanation Note 6 to Schedule-I of the DPCO, which was amended in November 2022. This note states that incremental innovations and novel drug delivery systems, such as modified release formulations, should only be considered within the list if explicitly specified, and that these unique formulations should be evaluated separately for pricing and procurement purposes. La Renon argued that even if Valgress CR-200 were included in Schedule-I, its innovative delivery system would require a distinct ceiling price under this guideline.

The pharma firm contended that the ceiling price for the conventional 200mg sodium valproate tablets should be based solely on conventional forms, without including modified release versions. Including their controlled release formulation in the pricing calculation, they argue, violates Explanation Note 6 of Schedule-I. La Renon maintains that Valgress CR-200, with its unique controlled release combination, should not have been factored into the ceiling price calculation for conventional tablets.

La also referenced the 2022 amendment report to the National List of Essential Medicines (NLEM), which clarifies the unique nature of modified release dosage forms. This report highlights that modified release tablets are designed to provide distinct therapeutic advantages, including improved patient compliance, optimized efficacy, reduced adverse effects, and enhanced bioavailability, all achieved through specific formulation and manufacturing methods. It acknowledges the advantages of modified release forms, such as stable plasma concentration levels and fewer adverse reactions. Consequently, the Applicant argues that the term “Modified Release” used in the NLEM 2022 encompasses controlled release and other incremental innovations in drug delivery, distinguishing these from conventional tablets and capsules.

The Standing National Committee on Medicines (SNCM) has further clarified the difference between conventional and modified release tablets, recognizing the incremental innovations in modified release formulations. La Renon argued that the NLEM 2022 and Schedule-I of DPCO 2013’s inclusion of conventional sodium valproate tablets does not imply the inclusion of modified release formulations. Given these distinctions, La asserted that the NPPA should not have grouped Valgress CR-200 with conventional sodium valproate in its price cap calculations.

La Renon’s appeal rested on three main arguments. First, the company argued that Valgress CR-200 should be classified as a non-scheduled drug, as it is not explicitly listed under Schedule-I of the DPCO, where essential medicines under price regulation are designated. Secondly, La Renon maintained that the controlled-release nature of Valgress CR-200 offers significant therapeutic benefits, such as improved patient compliance and reduced side effects, setting it apart from conventional tablets. Finally, the company highlighted that under DPCO guidelines, innovations in drug delivery systems, like MR formulations, should be assessed independently and should not automatically fall under the same pricing ceiling as standard release drugs unless specifically noted.

Also Read: NPPA Fixes Retail Prices Of 4 Formulations, Details

NPPA argued against the validity of the review appeal, asserting that its pricing methodology was appropriately applied to the modified release (MR) and conventional variants of the drug in question. The NPPA outlined that, according to established guidelines, when an MR variant of a drug is specified in a formulation, only MR data is considered for ceiling price determination. However, if an MR variant is not specifically mentioned, data from both MR and conventional versions are used in calculating the ceiling price. This approach is consistent with the methodology applied under the National List of Essential Medicines (NLEM) 2015. For other specialized formulations, such as dispersible tablets (DT), effervescent, or soluble tablets, a similar principle is followed. When these variants are not separately specified, their data is included with that of the conventional form for price setting.

The NPPA emphasized that MR variants are integral to essential and life-saving medications and that excluding them from price control would go against the Standing National Committee on Medicines’ (SNCM) objectives. The revised Schedule-I of the DPCO and the NLEM explicitly states, "All modified release formulations of the same strength, such as sustained release, controlled release, extended release, and prolonged release, are included." This consistency in methodology from the NLEM 2015 to 2022 ensures essential medicines remain accessible. For instance, in cases where Schedule-I does not specify a conventional or MR form of a drug (e.g., Metformin 500mg), all forms are included in the ceiling price. However, when both conventional and MR forms are listed (e.g., Metformin 1000mg and 1000mg MR), separate prices are set for each. If La's position were accepted, MR formulations would be deregulated when only conventional forms are listed, which conflicts with regulatory intent.

Additionally, the NPPA clarified that Sodium Valproate falls under two sections in Schedule-I of the DPCO, 2013: Section 5.1.10 (Neurological Disorders) and Section 23.2.2.2 (Psychiatric Disorders). In NLEM 2022, modified release formulations of Sodium Valproate 200mg are not specifically differentiated, and thus, all variants are included in the ceiling price determination.

Regarding Sodium Valproate formulations, the NPPA noted that combinations of Sodium Valproate and Valproic Acid can correspond to the stated strength. Specifically, 1mg of Valproic Acid is equivalent to 1.15mg of Sodium Valproate, allowing for formulations like Sodium Valproate 200mg or Sodium Valproate 133.3mg with Valproic Acid 58mg. Market data from July 2022 indicates that modified release Sodium Valproate tablets represent 64.7% of the 200mg formulation's market share. Excluding MR versions from price control, as suggested by La Renon, would effectively deregulate a substantial portion of the market, which runs contrary to the objectives of NLEM 2022.

After examining the issue, the DoP ruled in favor of the NPPA’s decision to uphold the price ceiling for Valgress CR-200, citing the NLEM’s guiding principle of ensuring the affordability and accessibility of essential medicines. The DoP concluded that maintaining regulated pricing for MR formulations like Valgress CR-200 supports the public health objective of the NLEM by discouraging price hikes that could restrict public access to critical medicines. It observed;

"The National List of Essential Medicines (NLEM) prepared by Standing National Committee on Medicines (SNCM) under Ministry of Health and Family Welfare (MoH&FW) forms the basis of Schedule-I of the DPCO 2013, which is amended, whenever the NLEM is revised. The latest NLEM (2022) was notified on 13.09.2022 and accordingly, Schedule-I to DPCO, 2013 was revised on 11.11.2022 vide Gazette Notification SO No. 5249 (E)."

"The NLEM is prepared with the objective of satisfying the priority health care needs of the population. The list is made based on disease prevalence, efficacy, safety and comparative cost-effectiveness of the medicines. The aim behind formulating NLEM is to ensure that these medicines are available in adequate quantity, in appropriate dosage forms and strengths with assured quality. NLEM does recognize such innovations in drugs where substantial improvements, effectiveness and efficacy have been introduced either in terms of quality or in the delivery system or both. Accordingly, NLEM mentions such innovative drugs separately under different categories commonly named as Modified Release (MR) versions in the same list where such criteria are fulfilled. When the same is not mentioned separately, then all such varieties of such drugs for the specified dosages are considered to be part of variants appearing in the list. The objective of NLEM, inter alia, is to ensure availability of the essential drugs as well. This objective may be adversely affected by the exclusion of different variants from the NLEM based on criteria such as MR etc., as such exclusion may encourage essential drugs simply moving out of NLEM. This may not be in line with the spirit and purpose of including these drugs in the list of essential medicines in the first instance."

As a result, La Renon’s request for a review was rejected, leaving the NPPA’s ceiling price for Valgress CR-200 intact. It was noted;

"The action of NPPA fixing the ceiling price of subject formulation vide S.O. No. 879(E) dated 24.02.2023 is upheld and the Review Application under consideration is accordingly rejected."