- December 11, 2018, 4:02 pm
Of the 110 anti-TB (tuberculosis) Fixed Dose Combinations (FDCs) available in India, only 32 (less than 30%) have been approved by the Central Drugs Standard Control Organisation (CDSCO), the country’s drug regulator. In the case of malaria FDCs, only eight out of 20 (40%), have been approved.
These statistics, that give rise to safety and efficacy concerns, have been brought out in a study published online in the journal Tropical Medicine and International Health by researchers from the Manipal College of Pharmaceutical Sciences.
HIGHLIGHTS OF THE STUDY
- An opaque regulatory framework and ambiguity over licensing powers have contributed to the problem.
- As of April, the CDSCO had approved 1,288 FDCs. This is disproportionately high compared with the availability in a tightly regulated market like USFDA, which has only a few hundred approved FDCs.
- Pointing out that even the World Health Organisation’s (WHO) list of essential medicines mentions only 24 FDCs, it is unfortunate that a majority of approved FDCs in the Indian market are irrational and lack scientific justification.
- The study quoted the Parliamentary Standing Committee on Health and Family Welfare, which in its 59th report in 2012, pointed out multiple deficiencies in the CDSCO’s approval process for FDCs.
- It highlighted institutional problems such as understaffing, lack of skills, and inadequate infrastructure.
- However, the most significant observation concerned the issuance of manufacturing licenses by the State Licensing Authority without the prior clearance of the Drug Controller General of India DCG(I), the head of CDSCO which is the main problem.
- The problem of unapproved FDCs mainly affects those who get treated in the private sector.
- In the absence of a strong pharma co-vigilance mechanism in India, there is no data on adverse events of these unapproved FDCs.
FIXED DOSE COMBINATION
An FDC or combination product is a formulation with more than one active pharmaceutical ingredient (API) in a fixed ratio of doses formulated into a single dosage form.
SIGNIFICANCE OF FDC
FDCs offer simple dosage schedule which improves patient compliance and therefore improves treatment outcomes. This is especially important in elderly patients or patients suffering from multiple disorders. FDCs are more economic than single ingredient drugs. The use of FDCs may improve the clinical benefit of two drugs at lower doses. FDCs’ popularity in India is due to advantages such as increased efficacy, better compliance, reduced cost and simpler logistics of distribution. FDCs have shown to be particularly useful in the treatment of infectious diseases like HIV, malaria and tuberculosis, where giving multiple antimicrobial agents is the norm.
APPROVAL OF FDCS IN INDIA
FDC in India is treated as new drug as per the Rule 122 E of Drugs and Cosmetics Rules. This is because of the fact that by combining two or more drugs, the safety, efficacy, and bioavailability of the individual Active Pharmaceutical Ingredient (API) may change. DCGI is the licensing authority notified under section 21(b) of Drugs and Cosmetics Act.The safety and efficacy of the FDC is later ascertained by conducting clinical trial and bioequivalence studies. Once the data from clinical studies has been found satisfactory by the DCGI, permission to manufacture and market the FDC is granted. It is pertinent to note that recently DCG(I) office has made guidelines for submission of proposals for FDCs for the purpose of market authorization in the country.
ILL-EFFECTS OF FDC
- FDCs could be unsafe for consumption with potential health risks since the side-effects of the combined product in FDC are different from those of its individual ingredients.
- Sometimes, the combination can come with risks that are not originally existed in the individual ingredients.
- When an adverse reaction happens in a patient, it is very difficult to identify which ingredient caused that reaction.
- Many studies have pointed out that many of these combinations don’t have any advantage over individual drugs.
- Rampant use of FDCs in India enabled anti-biotic resistance to grow at a significant rate. A good example is an emergence of “ciprofloxacin resistant?—?salmonella typhi strains”, that have made typhoid treatment very difficult and expensive in India.
- FDCs are famous, not because of its therapeutic effect, but because of the profits that are earned by the Pharmaceutical companies due to low production cost and high demand.