Context

• A group of academics from India, Qatar and the United Kingdom recently published a worrying new study in a Journal of Pharmaceutical Policy and Practice.
• The journal highlights the volume of unapproved and even banned fixed dose combination (FDC) of antibiotics that are being sold in India.

Key Findings of the Journal

• Using sales data of the pharmaceutical industry, the study documents that in the year 2020, 60.5% FDCs of antibiotics (comprising 239 formulations) were unapproved.
• Another 9.9% (comprising 39 formulations) were being sold despite being banned in the country.
• That so many of these unapproved or banned FDCs contain antibiotics is alarming because of the increasing prevalence of antibacterial microbial resistance (AMR) in India.

Phenomenon of Fixed Dose Combination (FDC)

• FDCs are combinations of one or more known drugs and can be useful in the treatment of some diseases since the combination can improve patient compliance.
  • For instance, if a patient must take three different medications for a particular treatment, she may forget to take one.
  • But if all three medications are combined into one tablet or one syrup, the chance of her forgetting to take one or two of the drugs is reduced.
• For diseases such as AIDS, it is well documented that FDCs have proven to be very useful in improving patient compliance, which at the end of day improves treatment outcomes.

Advantages and Disadvantages of FDCs

• Therapeutic Efficacy
  • The interaction between different drugs can indeed influence their therapeutic efficacy. They may enhance or inhibit each other's effects, leading to unpredictable outcomes.
• Problem of Toxicity
  • There is always a risk of creating metabolites or by-products that could be more toxic than the individual components.
  • This is a serious concern and needs to be thoroughly evaluated during the formulation process.
• Excipient Interaction
  • Excipients, though considered inactive, can play a crucial role.
  • They may interact with the active ingredients or among themselves, affecting the overall performance and safety of the formulation.
• Regulatory Framework Challenges
  • The longstanding issue of unregulated FDCs has been recognized since 1978.
  • Despite regulatory amendments giving the central government the power to prohibit the manufacture of drugs lacking therapeutic value or justification, enforcement has been lacking.
  • The failure of State drug controllers to adhere to the law and issue manufacturing licenses for unapproved FDCs adds to the regulatory challenges.
  • The lack of prosecution for such violations raises questions about regulatory oversight.

Reason Behind Fascination of Pharma Industry with FDCs

• Regulatory Evasion and Pricing Strategies
  • DPCO and Price Control
    • The pharmaceutical industry's use of FDCs to escape the purview of the Drugs (Prices Control) Order (DPCO) is a serious concern.
    • By combining drugs, companies can avoid price regulations set by the government for individual drugs, potentially leading to higher prices and reduced market competition.
  • Lack of Standards
    • The diverse array of FDCs and the absence of clear standards for testing contribute to challenges in ensuring the quality of these combinations.
    • The lack of recognised standards allows manufacturers to set their own protocols for testing, which raises questions about the reliability of the results.
• Dubious FDC Combinations
  • Medical Rationale
    • The introduction of FDCs lacking medical rationale, such as combining anti-inflammatory drugs with vitamins or penicillin with sulphonamides, raises concerns about the safety and efficacy of these combinations.
    • Such combinations without scientific justification can pose risks to patient health.
• Competition and Pseudo-Innovation
  • Market Dynamics
    • The strategy of creating FDCs to avoid intense market competition for individual drugs is a significant issue.
    • Pseudo-innovation, driven by combining existing drugs, allows companies to claim uniqueness and charge higher prices until competitors introduce similar products.

 Way Forward

• Focus on Strict Approval Process Backed by Scientific Evaluation
  • Scientific Evaluation
    • The approval process for FDCs should involve rigorous scientific evaluation.
    • This includes preclinical studies and clinical trials specifically designed to assess the safety, efficacy, and potential interactions of the combined drugs.
• Strict Regulatory Standards Should be Put in Place
  • Regulatory agencies worldwide set strict standards for the approval of FDCs.
  • This involves not only assessing the individual drugs but also studying the interactions and potential synergies or antagonisms.
  • This should be replicated in India as well.
• Post-Market Surveillance
  • Even after approval, post-market surveillance is essential.
  • Monitoring the use of FDCs in the real-world setting helps identify any unexpected side effects or interactions that might not have been apparent during the preapproval stages.
• Prioritise Patient Safety: Patient safety should be at the core of approval process.

 Conclusion

• While FDCs can offer valuable therapeutic advantages, their formulation requires meticulous attention to detail and a comprehensive understanding of how the combined substances will behave in the body.
• The scientific approval process, stringent regulatory standards, and ongoing surveillance are all critical components to ensure the safety and efficacy of fixed-dose combination drugs.