Central Drugs Standard Control Organization (CDSCO) under the aegis of Ministry of Health and Family Welfare, Government of India has been taking many steps to control the menace of unapproved and irrational Fixed Dose Combinations (FDCs). In this process, government has banned many FDCs due to lack of safety and efficacy data. The complete list of banned FDCs can be referred here. Also, time to time they have been publishing pathways for regularization of FDCs declared as rational.

CDSCO had also published a list of 66 FDCs (49 +17) which were under the consideration of the committee and for which data/information was sought from concerned stakeholders regarding safety and efficacy of the FDCs. The data submitted by the stakeholders has been evaluated by the expert committee (Drug Technical Advisory Board – DTAB) and following decisions has been taken and are communicated vide letters dated 27.08.2021:

A. FDCs requiring data generation by way of conducting Phase IV Trial/ Active PMS study: DTAB has recommended 19 FDCs for which the firms are required to generate data by way of conducting Phase IV Trial/ Active PMS study. The pathway for clearance of such applications are as follows:

  1. Form CT 21 (Duly filled, signed and stamped)
  2. Requisite fees through Bharatkosh
  3. Name and composition of the FDC
  4. Copy of product permission issued by State Licensing Authority (SLA) to any firm prior to 28.11.2007 as available or the documents in supporting strength and dosage form of FDC
  5. Copy of manufacturing License of the applied product issued by SLA
  6. No. of FDC as per the list of 19 FDCs
  7. Stability data
  8. Test specifications of FDCs alongwith Method of Analysis
  9. Phase IV trial protocol/ commitment for conducting Active PMS study as per the recommendations of the committee.

The firms who are not holding manufacturing license for the applied product, need to take form 29 (test license) and generate the technical data required for making the above application.

The firms which are already holding the manufacturing license issued by SLA for such FDCs and do not hold NOC issued by DCG(I)/CDSCO, shall submit their applications to CDSCO within 06 months.

B.FDCs which have been considered rational: DTAB has recommended 31 FDCs as rational. The firms which are already holding the manufacturing license issued by SLA for such FDCs and do not hold NOC issued by DCG(I)/CDSCO, shall submit their applications to CDSCO within 06 months. The firms have to submit the applications as per defined pathway for clearance of the cases.

List of 19 FDCs for which the firms are required to generate data by way of conducting Phase IV Trial/ Active PMS study:

Sr. no. Name of the FDC Recommendations
1. Aceclofenac + Paracetamol+
Chlorzoxazone		 Phase IV clinical trial is required to be conducted.
2. Aceclofenac + Paracetamol + Serratiopeptidase Phase IV clinical trial is required to be conducted.   A randomized comparative superiority trial comparing FDC containing Serratiopeptidase with the FDC    without Serratiopeptidase (other ingredients being the same) and efficacy should be the primary objective and should be conducted in a statistically significant number of patients.
3. Aceclofenac + Paracetamol+ Tizanidine Phase IV clinical trial is required to be conducted.
4. Aceclofenac + Paracetamol+
Tramadol		 Phase IV clinical   trial is required   to be conducted   to demonstrate the superiority of this FDC over two drugs approved FDC.
5. Alprazolam + Melatonin Active PMS study on the FDC is required to be conducted.
6. Alprazolam + Propranolol Phase IV clinical trial is required to be conducted.
7. Calcium dobesilate + Decusate sodium Phase IV clinical trial is required to be conducted to demonstrate the safety and efficacy.
8. Calcium dobesilate+ Lignocaine Phase IV clinical trial is required to be conducted to demonstrate the safety and efficacy.
9. Calcium Dobesilate+ Troxerutin Phase IV clinical trial is required to be conducted to demonstrate the safety and efficacy.
10. Chlorzoxazone +    Paracetamol + Diclofenac Phase IV clinical trial is required to be conducted.
11. Chlorzoxazone + Paracetamol + lbuprofen Phase IV clinical trial is required to be conducted.
12. Chlorzoxazone + Paracetamol +
Nimesulide		 Phase IV clinical trial is required to be conducted.
13. Diclofenac + Paracetamol + Serratiopeptidase Phase IV clinical trial is required to be conducted.   A randomized comparative superiority trial comparing FDC containing Serratiopeptidase with    the    FDC without Serratiopeptidase (other ingredients being the same) with efficacy as the primary objective should be conducted in a statistical significant number of patients.
14. Diclofenac + Paracetamol +
Tizanidine		 Phase IV clinical trial is required to be conducted.
15. Dicyclomine + Diclofenac Sodium +
Paracetamol		 Phase IV clinical trial is required to be conducted.
16. Ibuprofen + Paracetamol+
Serratiopeptidase		 Phase IV clinical trial is required to be conducted.   A randomized comparative superiority trial comparing FDC containing Serratiopeptidase with    the    FDC without Serratiopeptidase (other ingredients being the same) with efficacy as the primary objective should be conducted in a statistical significant number of patients.
17. Nimesulide + Paracetamol +
Serratiopeptidase		 Phase IV clinical trial is required to be conducted provided that paracetamol dose is 325mg.  A    randomized comparative   superiority   trial comparing   FDC containing Serratiopeptidase with the FDC without Serratiopeptidase (other ingredients being the same) with efficacy as the primary   objective   should be conducted   in a statistical significant number of patients.
18. Propranolol + Diazepam Phase IV clinical trial is required to be conducted.
19. Tizanidine + Nimesulide +
Paracetamol		 Phase IV clinical trial is required to be conducted provided that paracetamol dose is 325mg

 

 

List of FDCs which have been considered rational:

S. No. Name of the FDC Recommendations
1. Amoxicillin + Cloxacillin + Lactic acid bacillus Rational
2. Amoxycillin + Clavulanic acid + Lactic
acid bacillus		 Rational
3. Amoxycillin + Lactic acid bacillus Rational
4. Amoxycillin + Lactobacillus acidophilus + Flucloxacillin Sodium Rational
5. Ampicillin + Cloxacillin + Lactic acid
bacillus		 Rational
6. Ampicillin + Lactic acid bacillus Rational
7. Calcium dobesiIate + Lignocaine +
Hydrocortisone		 Rational for short term use
8. Cefadroxyl + Lactic acid bacillus Rational
9. Cefdinir + Lactic acid bacillus Rational
10 Cefixime + Lactic acid bacillus Rational
11 Cefixime + Lactobacillus+ Dicloxacillin Rational if Dicloxacillin is in sustained release form in twice daily doses schedule and Indication of the FDC should be restricted to skin & soft tissue infections
12 Cefpodoxime proxetil + Lactic acid
bacillus		 Rational
13 Cefpodoxime + Cloxacillin + Lactobacillus Rational if Cloxacillin is in sustained release form in
twice daily doses schedule and Indication of the FDC should be restricted to skin & soft tissue infections.
14 Cefprozil + Lactobacillus Rational
15 Cefpodoxime + Cloxacillin + Lactic acid bacillus Rational if Cloxacillin is in sustained release form in
twice daily doses schedule and Indication of the FDC should be restricted to skin & soft tissue infections.
16 Dicyclomine + Ranitidine Rational
17 Domperidone + Paracetamol Rational. FDC is indicated for management of acute migraine.
18 Domperidone + Paracetamol + Tramadol Rational provided that dose of paracetamol is 325mg.
FDC is indicated for management of acute migraine.
19 Doxycycline + Lactobacillus Rational
20 Drotaverine + Nimesulide Rational. FDC is indicated for dysmenorrhoea.
21 Drotaverine + Paracetamol Rational. FDC is indicated for dysmenorrhoea.
22 Lincomycin + Lactobacillus Rational
23 Ofloxacin + Lactic acid bacillus Rational
24 Ondansetron + Ranitidine Rational
25 Torsemide + Spironolactone Rational
26 Allantoin + Dimethicone +
Methylparaben + Propylparaben		 Rational
27 Aloe vera + Vit-E acetate Rational if FDC is in cream and lotion dosage form
only.
28 Aloe + Tocopherol Rational if FDC is in cream and lotion dosage form
only.
29 Aloevera + Glycerine + PEG 100
stearate + Vit E		 Rational if FDC is in cream and lotion dosage form
only.
30 Ampicillin + Flucloxacillin Sodium Salt Rational
31 Ampicillin + Flucloxacillin Sodium   Salt + Lactobacillus Acidophilus Rational

 

Note: Please feel free to contact us on vaayath@gmail.com for any clarification or support in filing of applications. 

 

 Reference:

  1. CDSCO order no. 04-146/2007-DC (Part-I) dated 27.08.2021 regarding 19 FDCs for which the firms are required to generate data by way of conducting Phase IV Trial/ Active PMS study
  2. CDSCO order no. 04-146/2007-DC (Part-I) dated 27.08.2021 regarding 31 rational FDC