1. RECOMMENDATIONS OF THE NDAC (Pulmonary) HELD ON 03.12.2011:- The NDAC (Pulmonary) deliberated the proposals on 03.12.2011 and recommended the following:- AGENDA NO. NAME OF DRUG RECOMMENDATIONS Global Clinical Trials BIBF 1120- 1 Approved 150mg/100mg Cap 2 BIBF1120 Approved In principle approved, subject to condition that the firm should submit satisfactory data to the office of DCG (I) in respect of following point before approval is considered. How many sites were approached for selecting the 3 Fluticasone Propionate sites proposed? Sites should have paediatrics department to manage safety in case of emergency. At least co- investigator should be experienced with treating chest disease in paediatrics. Details of ethics committee. 4 QAW039 Approved 5 PH-797804 Approved Rejected as the study is not ethical due to followings: Placebo use in moderate asthma is medically unethical and dangerous which can lead to MLC. Use of placebo in patient 6 Fluticasone Propionate with moderate asthma is not ethical as corticosteroid therapy is required to be given for such patients. Dose findings study cannot be mixed with adult and adolescent. New Drugs (FDC) The expert raised concern over the rationality of combining fluticasone furoate with olopatadine HCl as Fluticasone alone can Olopatadine address the most of the Hydrochloride 665mcg symptom in SAR. Further 1. + Fluticasone Furoate there is no data in support of 13.75mg nasal spray selecting the dose in the proposed FDC. This FDC is not approved in any country. Therefore the experts did not recommend for the proposed Clinical Trial. Paracetamol 325mg The firm telephonically +Phenylephrine confirmed that they are going 2. Hydrochloride to withdraw the proposal, 5mg+Chlorpheniramine hence rejected. 2mg Tablets The firm has proposed this FDC for allergic rhinitis (AR). Use of Ambroxol is not Ambroxol 75mg + justified for AR. Further, there Levocetirizine 5mg + is no supporting data on use 3. Montelukast 10mg of three drugs in combination. tablets This FDC is not approved in any country. Hence, the proposal was not recommended. 2. RECOMMENDATIONS OF THE NDAC (Pulmonary) HELD ON 28.01.2012:- The NDAC (Pulmonary) deliberated the proposals on 28.01.2012 and recommended the following:- AGENDA NAME OF RECOMMENDATIONS NO. DRUG New Drugs Committee opined that the drug seems to be safe and effective in COPD and it might be an addition to available drugs for the indication. However Phase III, 3-arm open comparative clinical trial of Roflumilast + Salmeterol vs Roflumilast + Tiotropium vs Roflumilast in at least 300 patients (100 in each arm) with 24 weeks duration of treatment in at least 4 centres geographically distributed in the country should be conducted. The efficacy assessment should include the assessment of FEV1 and reduction in exacerbation of COPD. Committee also advised that 50% of the clinical trial sites should be in 1 Roflumilast multispeciality hospitals. Ethics Committee should be from the same area where the site is located. Accordingly revised clinical trial protocol, names of sites etc should be submitted for approval of DCG(I). Committee also recommended that all the applicants for this drug should be asked to conduct the clinical trial as above. Single dose bioequivalence study should also be conducted comparing with innovator‟s product as per the protocol submitted by M/s Sun Pharma. Results of local clinical trial and bioequivalence study when completed as above should be placed before the committee for taking decision on approval of the drug in the country. The product seems to be safe and effective. However Committee recommended that phase III clinical trial with the drug should be conducted. Bovine Lung Accordingly protocol etc. should be submitted for 2 Surfactant consideration of the committee. The protocol etc would be deliberated in the next meeting. Two neonatologists should also be invited to participate in the deliberation in the next meeting. Committee opined that the drug seems to be safe Bamifylline and effective as an additional bronchodilator. The 3 Hydrochloride committee recommended for granting permission to conduct the proposed clinical trial as per the protocol submitted subject to the following conditions:- i) Spirometry assessment should be included in the protocol at the time of enrolment of subjects as well as during the study. ii) Study should be completed in 200 patients, 100 each in asthma and COPD patients. It was also advised that i) sites should be geographically distributed in the country. ii) 50% of the clinical trial sites should be in multispeciality hospitals. iii) Ethics Committee should be from the same area where the site is located. Bioequivalence study as proposed may also be approved. Results of local clinical trial and bioequivalence study when completed as above should be placed before the committee for taking decision on approval of the drug in the country. Committee noted that the firm has proposed the drug for different indications viz. diseases of upper and lower respiratory tract: -nasopharyngitis and laryngitis; tracheobronchitis; bronchitis (with chronic respiratory failure or not); bronchial asthma (combined therapy); respiratory effects (cough hoarseness, sore throat) for measles, whooping cough, flu; respiratory infections, accompanied by a cough, when shown a standard antibiotic therapy; otitis media and sinusitis different etiologies. Committee recommended that trial should be 4 Fenspiride conducted on at least 100 patients in each of indications viz. rhinosinusitis and as add on therapy in asthma. Accordingly protocol etc should be submitted for approval of DCGI. It was also advised that i) sites should be geographically distributed in the country. ii) 50% of the clinical trial sites should be in multispeciality hospitals. iii) Ethics Committee should be from the same area where the site is located. 5 Paracetamol Committee noted that the proposed FDC of the 325mg + four drugs is not available in any country. There is Tripolidine no data in support of the proposed FDC. Also for 2.5mg + common cold, all the four drugs may not be Phenylephrine required. Therefore committee opined that the 10mg + proposed FDC is irrational, hence not Caffeine 30mg recommended for approval. sachets Global Clinical Trials a) Recommended for approval with following advice:- i) Patients aged ≥ 40 yrs and ≤ 80 yrs should be enrolled in the study. Tiotropium + ii) Sites should be geographically distributed in 6 Olodaterol the country. iii) 50% of the clinical trial sites should be in multispeciality hospitals. iv) Ethics Committee should be from the same area where the site is located. b) Recommended for approval with following advice:- c) i) Patients aged ≥ 40 yrs and ≤ 80 yrs should be enrolled in the study. ii) Sites should be geographically distributed in Tiotropium + 7 the country. Olodaterol iii) 50% of the clinical trial sites should be in multispeciality hospitals. iv) Ethics Committee should be from the same area where the site is located. During presentation, the firm presented before the committee that the proposed study is already approved in several countries including USA. The committee recommended for approval subject to submission of Regulatory approvals from other participating countries. The study may be Fluticasone approved with the following advice. 8 Furoate i) Sites should be geographically distributed in the country. ii) 50% of the clinical trial sites should be in multispeciality hospitals. iii) Ethics Committee should be from the same area where the site is located. 9 Bosentan Recommended for approval with the following advice. i) Sites should be geographically distributed in the country. ii) 50% of the clinical trial sites should be in multispeciality hospitals. iii) Ethics Committee should be from the same area where the site is located. The firm confirmed through email that the Sponsor 10 Reslizumab is going to withdraw the proposal, hence proposal may be treated as withdrawn. 3. RECOMMENDATIONS OF THE NDAC (PULMONARY) DELIBERATED THE PROPOSALS ON 07-06-2012:- The NDAC (Pulmonary) deliberated the proposals on 07-06-2012 and recommended the following: Agenda Drug Name Recommendations No. Fixed Dose Combination The proposed FDC is not approved in any country. The combined disease i.e asthma and allergic rhinitis is not prevalent in all cases together. Acebrophylline is given for a long term 1. Acebrophylline whereas for rhinitis there is no need for 100mg+Olopatadine5mg long term treatment with Olopatadine. Tablet As there is no rationale for the proposed FDC, committee did not recommend for giving marketing permission of the FDC. The applicant did not appear for technical presentation. The proposed FDC is not approved for children 2. Montelukast anywhere in the world. Due to lack of 5mg/4mg+Fexofenadine safety and efficacy data of proposed 60mg/30mg tablets FDC in children, committee did not recommend for giving marketing permission of the FDC. Committee did not consider the proposed higher strength of the FDC as rationale as it may increase the toxicity and also 3. MDI-Formoterol Fumarate has a chance of misuse. 12mcg+Fluticasone Hence committee did not recommend for Propionate 500mcg MDI giving marketing permission to the proposed higher strength of the FDC. Committee did not consider the proposed higher strength of the FDC as rationale DPI-Formoterol Fumarate as it may increase the toxicity and also 12mcg+Fluticasone has a chance of misuse. 4. Propionate 500mcg DPI Hence committee did not recommend for giving marketing permission to the proposed higher strength of the FDC Such FDC may be required for small percentage of patients, that too for very short period. However, this FDC shall 5. Ebastine have chance of being misused. This 10mg+Phenylephrine 10mg FDC is not approved anywhere in the Tablet world. Thus the FDC is not essential. Hence committee did not recommend for approval of the proposal. The experts opined that the combination is rationale. However, clinical study is required to assess the safety and 6. Ebastine 10mg+Montelukast efficacy of the product.