FDC Ban – a well-intended but overdone development
Director, Sathguru Management Consultants
Senior Consultant, Sathguru Management Consultants
On July 26, the sub-committee of Drugs Technical Advisory Board (DTAB), the highest drug advisory body on technical matters in the country formed by the Health Ministry, has recommended prohibition of 343 fixed drug combinations (FDCs) after reviewing 349 and called for regulation and restriction of remaining six. The 12 member DTAB, which was reconstituted in May 2018 with Director General of Health Services (DGHS) Dr Promila Gupta as an ex-officio chairman and Drugs Controller General of India Dr S Eswara Reddy as an ex-officio Member Secretary with 8 members (including Pankaj Patel, Chairman and Managing Director, Zydus Cadila Group) and 2 special invitees. The expert sub-committee in its reports suggested banning 343 FDCs, three should be restricted for specific indications or diseases and other three FDCs should be restricted to specific quantities of ingredients and for specific indications. It stated that for most FDCs, their use will lead to unnecessary overuse and patients will be exposed to risk of multiple ingredients when one will suffice.
Although the report of the Drug Testing Advisory Board (DTAB) sub-committee constituted to review 343 (plus 6) Fixed Dose Combinations (FDCs) is not yet in public domain, it is akin to an execution sentence for several companies and brands they have toiled to create. While the coffin is still not nailed, it has been an arduous and long drawn journey so far for the 343 FDCs - On 10th March, 2016, based on the Kokate Committee report, the health ministry banned 344 FDC drugs. Given the sweeping business implications of this decision, pharma companies moved the Delhi High Court with 454 petitions challenging the decision and claiming it was not done through a statutory body consultation process. While this led to a withdrawal of the ban, the government took this matter to the Supreme Court which mandated the DTAB to make final recommendations. The proposed ban and the impending judgment is bound to have far reaching implications for both, the Pharma industry and the Indian patients:
FDCs are not always harmful and are clinically preferred in several cases
There is no denying that overuse or abuse of combinations could result in unintended harm to patients. Specifically, FDCs with pharmacodynamic mismatch between the two components, chemical non-compatibility and bizarre combinations of many ingredients with or without rationality for their presence and in the quantity combined are not acceptable. However, unlike the popular inference from developments over the last couple of years, FDCs are not always harmful. In fact, FDCs are required for the treatment of infectious diseases like HIV, hepatitis-C, malaria and tuberculosis, where usage of multiple antimicrobial agents is necessary to combat the disease. The clinical importance of FDCs is evident from the fact that even WHO’s list of Essential medicines includes about more than 30 FDCs as these drugs are useful for chronic conditions, especially when multiple disorders co-exist. Not just in infectious diseases, there is also significant clinical justification for use of FDCs in various chronic conditions. Globally, they have gained popularity as a means of ensuring ease of use and administration as well. Given that no two FDCs are comparable on clinical rationale or harm to patients, it is surprising that a blanket decision has been made with a single lens for the 343 FDCs currently under consideration.
Regulatory gaps that led to the problem continue to remain unplugged
Although Appendix VI of Schedule Y (Drugs & Cosmetics Rules 1945, India) provides details about the requirements for manufacture/import approval and marketing of various types of FDCs which in general, seeks justification and therapeutic rationale for combination of active substances, level of requirement to generate new data is unclear. There is also no specific pathway for approval of OTC drugs. In the absence of regulatory clarity, some of the drugs currently banned were approved by State Licensing Authority with no approval from the CDSCO and the others have approval from no regulator in India. The problem was trigged by a combination of regulatory ambiguity as well as the tendency of some companies to take advantage of regulatory gaps to launch unapproved combinations.
The regulatory gaps are emphatically evident when compared to a more evolved global context such as the US where there are separate regulatory pathways for various drug categories including New Drug Applications for NCES, reformulated or repurposed drugs through the 505(b)(2) pathway and the OTC pathway with Product Monograph for OTCs. While the 505(b)(2) pathway allows referencing of data from the previously approved drugs, the OTC pathway allows drugs to be launched without any additional approval from USFDA if active ingredients (and dosage) being used are as stated in the OTC monograph. The missing OTC regulatory pathway particularly represents a glaring gap in the current landscape.
Emphatic example of stretching too far – globally sold OTC products are now banned in India
While the ban against 343 drugs and is justifiable in part of the list, merit of enforcing the axe in several cases is questionable. Most poignant examples of this regulatory action being more extreme than needed are the long suite of OTC drugs that are banned. Several OTC combinations have been globally driven by clinician or consumer preference, ease of use and clinical/ non-clinical benefit. Even the WHO and FDA indicate ‘Ease of use’ for patients and prescribers as a potential advantage of FDCs. It is alarming to note that many of the OTC combinations drugs banned are popular off the shelf products across several highly regulated markets such as UK, US et al. In these regulated markets, similar OTC formulations are sold and are found to be in compliance with formulations permissible per the OTC monographs. As illustrated below, Vicks Action 500 now banned in India has the same combination as Theraflu sold in USA, UK. The only addition ingredient in Vicks Action 500 is caffeine with levels comparable to a can of coke or one third cup of coffee.
A final mixed outcome – patient benefit in some cases but erosion of consumer choice and markets in others
The ban is estimated to shave off close to Rs 7000 crore of erstwhile peak revenues from the Pharma Industry. It is a significant blow to the industry that has found itself in the midst of a perfect storm – two quarters impacted by demonization and GST in India, the FDC axe, API supply constraints and pervasive pricing pressure across global markets.
From a consumer perspective, it is encouraging to see proactive regulatory action in the interest of patient safety and benefit. However, with blanket decisions underlined by redundancy in action, patients could be denied access to convenient choices that citizens in several other countries continue to have. If OTC drugs available in several other countries are banned in India and no clear regulatory pathway is created for OTC drugs in India, both industry and consumers stand to lose. Most importantly, a regulatory environment that is not industry friendly could threaten domestic selfsufficiency in the longer term, and the Indian patients should be most insecure about this implication. To ensure such casualties don’t repeat in the future, it is also important that we urgently bridge regulatory gaps and points of ambiguity – especially with creation of a globally comparable OTC pathway. The patient should continue to be at the heart of every regulatory decision – but with greater understanding of implications for today, tomorrow and the longer term.
(Note: The opinions discussed here are based on the assumption that the DTAB sub-committee report has
recommended ban of all 343 drugs reviewed.)
Shree Divyya, Senior Consultant, Sathguru Management Consultants
Pushpa Vijayraghavan, Director, Sathguru Management Consultants