www.cdsco.nic.in/writereaddata/Final%20IND_Minutes_06-08-15.pdf
"Item No. 6. Import and marketing proposal of Diperoxochloric acid concentrate
solution of M/s Centaur Pharmaceuticals for topical use.
M/s. Centaur Pharmaceuticals Pvt. Ltd. has applied for import and marketing of
Diperoxochloric acid (DPOCL) topical solution to be reconstituted with sterile Sodium
Chloride solution BP 0.9% w/v (Cutaneous solution) and indicated for wound healing
in diabetic neuropathic ulcers of skin and subcutaneous tissues.
DPOCL is a new chemical entity with a mitogenic activity on fibroblasts, supporting
proliferation and also has an antibacterial property especially against gram-negative
germs, lasting longer than 24 hours. Repacking will be done at Centaur
Pharmaceuticals as bottle A in 10 ml bottle alongwith Sodium Chloride in 30ml bottle.
The drug is not approved anywhere in the world including exporting country,
Germany.
The firm has conducted phase-III clinical study, wherein the efficacy and safety of
DPOCL was investigated in over 300 patients suffering from diabetic foot ulcer in
comparison with active-control solution i.e. isotonic normal saline (0.9%). It is
reported that more than 90% of the patients treated with DPOCL had positive
response as compared to 66% of active-control (treatment response defined by at
least 50% wound reduction in 4 weeks).
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Phase-III clinical study report was deliberated in IND Committee held on 30.05.2014.
The Committee noted that less number of patients required the use of antibiotics and
reported faster healing in the test drug arm when compared to the comparator arm.
After deliberation the Committee recommended for the grant of permission for the
import and marketing of Diperoxochloric acid (DPOCL) along with sterile sodium
chloride solution BP 0.9% w/v (Cutaneous solution) in the country to be indicated for
wound healing in diabetic neuropathic ulcers of skin and subcutaneous tissues
subject to the condition that following is required to be submitted to the DCGI before
the grant of approval.
1. Long term stability data of drug substance and formulation as per Appendix
IX of Schedule Y.
2. Stability testing of formulation after constitution or dilution as per Appendix IX
of Schedule Y.
The firm has submitted response to query related to stability data and animal toxicity
study. Further the firm mentioned that they have submitted wrong label earlier with
storage condition at 30ºC, whereas the corrected label is that the product to be
stored at 25ºC. The product is not yet approved in the exporting country.
Recommendations: The firm presented the stability report of DPOCL and that of the
reconstituted solution in normal saline. The stability study data presented was
examined and it was observed that the firm has submitted 14 days stability data of
reconstituted solution. The Committee asked the firm the reason for not conducting
the study for more than 14 days e.g 1 month or till it is stable to determine the
stability of the reconstituted solution to be used for diabetic foot ulcers which is
expected to be used for much longer time.
The Committee was of the opinion that the indication of the product should be wound
healing in diabetic foot ulcer instead of diabetic neuropathic foot ulcer. However as
the Phase III clinical trial conducted was for diabetic neuropathic foot ulcers,
therefore the Committee decided that the indication may not be revised at this stage.
Accordingly the Committee recommended that the firm is required to submit stability
study report of reconstituted solution for more than 14 days or till such time it is
actually stable (i.e,16 days, 17 days, 1 months etc.). The firm shall also revise their
Prescribing Information with following corrections:
1. Contraindication: It is contraindicated in patients hypersensitive to the
products.(rather than ingredient)
2. Drug Interactions: “Conducted over 400 patients” to be deleted and written as
the Phase-II and III clinical trials did not reveal any data towards drug-drug
interaction.
3. “Overdosage”: “Absorption is insignificant” shall be replaced indicating
“whether there is absorption or no absorption”.
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4. The maximum days allowed for storage after reconstitution at specific
temperature condition shall be specified.
5. Storage condition on the label shall match with the stability studies (i.e., below
25°C)
The Committee recommended for grant of permission to the Investigational
New Drug DPOCL for import of bulk and filling of formulation in India on
submission of revised package insert and details of stability studies as
proposed.
The meeting ended with vote of thanks to all the experts."