Biopharmaceutics Bioequivalence Requirements for BCS Class II & IV Drugs in India

Introduction

Biopharmaceutics India’s pharmaceutical industry stands tall as one of the largest suppliers of generic medicines to the world. With exports crossing USD 25 billion annually, Indian manufacturers have positioned themselves as reliable suppliers of high-quality, affordable medicines to both developed and developing countries. However, with global expansion comes the need to comply with increasingly stringent regulatory frameworks, especially concerning drug safety, efficacy, and quality.

A recent communication from the Office of the Controller, Food and Drugs Administration (FDA), Madhya Pradesh, has brought focus to an important issue — the manufacture and export of oral solid dosage forms falling under the Biopharmaceutical Classification System (BCS) Class II and Class IV.

The matter gains significance because these categories of drugs are often associated with complex absorption profiles, bioavailability challenges, and variable patient response. Consequently, regulators demand stricter proof of bioequivalence (BE) before approving manufacturing licenses.

This blog takes a deep dive into the recent guidance, its implications for pharmaceutical exporters in Madhya Pradesh and beyond, and the broader regulatory context that shapes such decisions.

Understanding BCS Classification

The Biopharmaceutical Classification System (BCS) is a scientific framework that categorizes drugs based on their solubility and permeability:

• Class I: High solubility, high permeability
• Class II: Low solubility, high permeability
• Class III: High solubility, low permeability
• Class IV: Low solubility, low permeability

Why does this matter?

• Class II drugs may dissolve slowly but are absorbed once in solution.
• Class IV drugs present the biggest challenge — they have poor solubility and poor permeability, making consistent absorption a regulatory concern.

For regulators, drugs in Class II & IV represent higher risks, since even small variations in formulation may impact efficacy or safety. That’s why bioequivalence studies are a mandatory part of the licensing process.

Key Highlights from FDA Madhya Pradesh Communication

The letter issued on 23rd September 2025 outlines several important directives and queries addressed to the Drugs Controller General of India (DCGI). Let’s break it down in simple terms:

• Submission of Bioequivalence Study Results:
  FDA Madhya Pradesh has directed all manufacturers to submit BE study results before grant of manufacturing licenses for oral solid dosage forms under BCS Class II & IV.
• Export License Applications:
  Manufacturers in Madhya Pradesh are applying for inclusion of additional drugs in their existing manufacturing licenses, specifically for export purposes.
• Supporting Documents Required:
  Such inclusion applications are generally backed by either:
  • An NOC (No Objection Certificate) from Deputy Drugs Controller, CDSCO Subzone Indore.
  • Proof that the drug has been approved by DCGI for more than four years and falls under BCS Class II/IV.
• Regulatory Query:
  The FDA MP has asked DCGI for guidance — Should such inclusions, solely for export purposes, be permitted or not?

Regulatory Requirement: Bioequivalence Studies

What is a Bioequivalence Study?

A bioequivalence (BE) study compares the pharmacokinetic profile (absorption, distribution, metabolism, and excretion) of a test drug with that of a reference drug. The goal is to prove that both products deliver the same therapeutic effect in patients.

For BCS II & IV drugs, BE studies are crucial because:

• Small formulation changes can impact absorption.
• Variability in solubility and permeability raises patient safety concerns.
• International importers often demand BE data as part of Good Manufacturing Practice (GMP) compliance.

Indian Context

The Central Drugs Standard Control Organisation (CDSCO) mandates BE studies for many formulations, particularly those with complex absorption. State FDA authorities, like FDA MP, play a critical role in ensuring compliance before granting licenses.

Why Export Licensing Needs Special Consideration

Export is the backbone of India’s pharmaceutical growth. However, export-only manufacturing licenses often raise tricky questions:

• Should drugs not permitted for domestic sale be allowed to be manufactured only for export?
• If importing countries accept documentation such as an NOC or long-standing DCGI approval, should India’s FDA authorities relax their stance?
• How can India strike a balance between supporting exporters and upholding regulatory credibility?

The FDA MP communication reflects exactly this dilemma. While manufacturers demand easier pathways for export, regulators remain cautious about potential misuse.

Opportunities for Pharma Exporters

Despite the challenges, there are significant opportunities arising from this directive:

• Clarity in Regulatory Framework:
  Seeking DCGI’s formal guidance ensures a clear, uniform policy across states, reducing confusion for manufacturers.
• Boost in Export Confidence:
  Once DCGI clarifies the rules, exporters can confidently approach global buyers, highlighting India’s strong regulatory oversight.
• Market Expansion:
  Export-only licenses may help Indian companies tap into emerging markets in Africa, Asia, and Latin America, where demand for affordable generics is rising.
• Investment in R&D:
  Stricter BE requirements encourage companies to invest in formulation development and clinical research, strengthening their global competitiveness.

Challenges for Manufacturers

At the same time, several challenges exist:

• Cost of BE Studies: Small and medium-scale manufacturers may struggle to finance bioequivalence studies, which can run into crores of rupees.
• Regulatory Uncertainty: Until DCGI provides clear guidance, companies face delays in license approvals.
• Risk of Export-Only Licenses: Export-only licenses may limit flexibility, since the same products may not be sold in the domestic market.
• Compliance Burden: Smaller manufacturers in Madhya Pradesh, often focused on cost-competitive production, may find it hard to meet international regulatory expectations.

Industry Reactions

Associations like the M.P. Small Scale Drugs Manufacturing Association and the Indian Drugs Manufacturers Association (IDMA) have been looped into the communication. This indicates that regulators are keeping industry stakeholders informed while awaiting DCGI’s final say.

Industry experts note that such dialogues between state regulators and DCGI are healthy, as they reflect India’s commitment to a transparent, consultative regulatory ecosystem.

Broader Implications for Indian Pharma Policy

This issue goes beyond Madhya Pradesh. It reflects a national-level debate on how India should handle export-only manufacturing:

• Countries like the US and EU demand rigorous compliance.
• Some emerging markets, however, accept approvals based on less stringent documentation.
• Should India harmonize its export licensing rules to the highest global standards, or allow flexibility based on importing country requirements?

The answer to this question will shape India’s export competitiveness for years to come.

Expert Insight: Balancing Regulation with Growth

Regulators like FDA MP are walking a tightrope. On one hand, they must protect patient safety and uphold India’s reputation as a supplier of quality generics. On the other hand, they cannot ignore the commercial pressures faced by exporters.

A possible solution lies in a tiered regulatory framework:

• Tier 1: For exports to regulated markets (US, EU, Japan) → BE studies mandatory.
• Tier 2: For exports to semi-regulated markets → Documentation like NOC and long-standing approval may suffice.
• Tier 3: For exports to unregulated markets → Export-only licenses may be granted with limited paperwork.

Such a model could balance safety with practicality, while giving smaller manufacturers room to grow.

Conclusion

The recent communication from FDA Madhya Pradesh brings to light a crucial regulatory question: Should oral solid dosage form drugs under BCS Class II & IV be included in export licenses based solely on NOC or long-standing approval?

While the final decision rests with the DCGI, this episode highlights the importance of bioequivalence studies, uniform policy, and industry consultation in shaping India’s pharma export future.

For manufacturers, the message is clear:

• Stay updated on regulatory requirements.
• Invest in compliance and R&D.
• Engage with associations like IDMA to represent industry concerns.

India’s pharmaceutical exports thrive because of its balance of affordability and quality. With clear regulatory guidance, the industry can further strengthen its global standing while ensuring patient safety across borders.