Lok Sabha Question No. 2065 (UNSTARRED), answered on 2015-07-31
Subject: Clinical Trials
Ministry: HEALTH AND FAMILY WELFARE
Asked by: SRINIVAS KESINENI, KUNWAR PUSHPENDRA SINGH CHANDEL, OM PRAKASH YADAV, JYOTIRADITYA MADHAVRAO SCINDIA, KAVITHA KALVAKUNTLA, GOPALAKRISHNAN CHINNARAJ, SUSHMITA DEV, B. SREERAMULU

**GOVERNMENT OF INDIA**

**MINISTRY OF HEALTH AND FAMILY WELFARE**

**DEPARTMENT OF HEALTH AND FAMILY WELFARE**

**LOK SABHA**

**UNSTARRED QUESTION NO.2065**

**TO BE ANSWERED ON 31** **ST** **JULY, 2015**

**Clinical Trials**

**2065. 	SHRI KESINENI NANI:**

**SHRI KUNWAR PUSHPENDRA SINGH CHANDEL:**

**SHRI OM PRAKASH YADAV:**

**SHRI JYOTIRADITYA M. SCINDIA:**

**SHRIMATI KAVITHA KALVAKUNTLA:**

**DR. C. GOPALAKRISHNAN:**

**KUMARI SUSHMITA DEV:**

**SHRI B. SRIRAMULU:**

Will the Minister of **HEALTH AND FAMILY WELFARE** be pleased to state:

(a) the number of clinical trial related applications received and permissions granted by the Central Drugs Standard Control Organization (CDSCO) during each of the last three years and the current year;

(b) the details of the cases of irregularities and non-compliance of rules/ guidelines relating to conduct of clinical trial of drugs reported and the action taken/ proposed to be taken by the Government thereon during the said period, State/UTwise;

(c) the number of clinical trial related injuries and deaths reported along with the compensation paid in each of these cases during the said period, State/UT-wise;

(d) the number of complaints for nonpayment of compensation received and the action taken/proposed to be taken by the Government thereon during the said period; and

(e) the corrective steps being taken by the Government to strengthen and harmonize the clinical trial related laws and regulatory/monitoring mechanism with international guidelines and enhance e-governance to enable a company to file, track and receive online approval for clinical trials?

**ANSWER**

**THE MINISTER OF HEALTH AND FAMILY WELFARE**

**(SHRI JAGAT PRAKASH NADDA)**

(a): The number of clinical trial applications received and permissions granted by the Central Drugs Standard Control Organization (CDSCO) during last three years and the current year are as follows:

| **Year**                   | **No. of application received**   | **No. of permission granted***   |
|----------------------------|-----------------------------------|----------------------------------|
| **2012**                   | **480**                           | **253**                          |
| **2013**                   | **207**                           | **73**                           |
| **2014**                   | **230**                           | **198**                          |
| **2015 (till 30/06/2015)** | **87**                            | **137**                          |

* Includes permissions granted for applications received during previous years.

(b):	A statement containing details of irregularities reported during 2012, 2013 and 2014 and action taken thereon by the CDSCO is at Annexure.  No violation has been reported upto        June 30, 2015 during the current year.

(c) & (d):	The number of Serious Adverse Events (SAEs) of death and injury (other than death) reported during last three years and the current year are as follows:

| **Year**                 | **Nos. of SAEs where death was reported.**   | **Nos. where death established to be related to CT.**   | **Nos.  where SAEs (other than death), i.e., injury was reported.**   | **Nos. where injury established to be related to CT.**   | **Nos. of cases in which compensation has been paid**     |
|--------------------------|----------------------------------------------|---------------------------------------------------------|-----------------------------------------------------------------------|----------------------------------------------------------|-----------------------------------------------------------|
| 2012                     | 436                                          | 16                                                      | 2786                                                                  | 184                                                      | Compensation in all 16 death related cases has been paid. |
| 2013                     | 590                                          | 46 @                                                    | 1122                                                                  | 159                                                      | Compensation has been paid in 33 death related cases.     |
| 2014                     | 443 #                                        | 12                                                      | 1326 *                                                                |                                                          | -                                                         |
| 2015$ (as on 27/07/2015) | 208                                          |                                                         | 1338                                                                  |                                                          | -                                                         |

* Details of the relatedness of SAE with injury will be available only after causes have been established after examination.

@ The relatedness has been examined in 519 out of 590 cases.

# Out of 443 reports, 300 reports of SAEs of death have been examined and remaining are under examination.

$ Details of the relatedness of SAE with death/injury will be available only after causes have been established after examination.

No complaint of non-payment of compensation has been received by Drugs Controller General (India). However, as per information available, compensation in three cases of SAEs of death related to Clinical Trial, one each for 2005, 2006 and 2010 has not been paid as the whereabouts of the legal heir could not be located.

(e):	Rules 122DA, 122DAA, 122DAB, 122DAC, 122DD and 122E of the Drugs and Cosmetics Rules, 1945 specify the requirements for conducting clinical trials in India.  Further, Schedule-Y of the said Rules prescribes the responsibilities of the Sponsor, Investigator and Ethics Committee to protect the rights, safety and well-being of clinical trial subjects. The measures taken in the recent past to strengthen the regulation of clinical trials include evaluation of the clinical trial proposals by the Subject Expert Committees/ Investigational New Drugs Committee, review of their recommendations by the Technical Committee and, thereafter, approval by the Apex Committee. Compensation is required to be paid in case of trial related injury or death within the prescribed timelines. It has been made mandatory for the sponsor or his representatives to furnish the details of the contract entered by the sponsor with the investigator with regard to financial support, fees, honorarium, payments, etc. Further, it has also been decided that with effect from 30.11.2013, in all clinical trials, in addition to the requirement of obtaining written informed consent, audio-visual informed consent will also be recorded in respect of each trial subject.

The task relating to organization wise e-Governance software and clinical trials software has been entrusted to Center for Development of Advanced Computing and National Informatics Center, respectively.

**Annexure**

**Statement indicating the irregularities reported during 2012, 2013 and 2014**

| **S.N.**                                                                                                                                                                                                                                                                                                                                                                              | **Year**   | **Name of the Firm/Sponsor/CRO/Principal Investigator**                                                                                                                                                                                                                                         | **State /U-T**   | **Investigational Medicinal Product (IMP)**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 | **Action Taken**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| **1**                                                                                                                                                                                                                                                                                                                                                                                 | **2012**   | Dr. Hemant Jain, Chacha Nehru Hospital, Indore                                                                                                                                                                                                                                                  | Madhya Pradesh   | - G-Meningococcal conjugate vaccine - Diphtheria-Tetanus-whole cell Pertussis-Hepatitis B and LBVH0101 Haemophilus influenzae type b tetanus toxoid conjugate vaccine - Diphtheria-Tetanus-whole cell Pertussis-Hepatitis B vaccine - Rabeparazole - Virosomal hepatitis A virus (HAV) vaccine - Monovalent Type 1 Oral Poliomyelitis Vaccine - Bivalent Oral poliovirus vaccine (bOPV) - Haemophilus influenzae b conjugate vaccine - Easyfive TM Vaccine - DTwP Vaccine - Inactivated Polio Vaccine - Monovalent H1N1 Influenza A - Valsartan - Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine - Montelukast | Based on press reports and the complaint  regarding conduct of illegal clinical trials on children, at M/s. Chacha Nehru Hospital, Indoreby Dr. Hemant Jain, a team of officials from CDSCO had carried out inspection (from 16  th  to 20  th  April 2012) of clinical trials conducted at this site.  It was observed that 26 clinical trials were conducted by Dr. Hemant Jain during the period 2006 to 2010.  For the clinical trials conducted by the following sponsors/CROs under the investigator Dr. Hemant Jain, the Office of DCGI issued warning letters to:  1. M/s. Glaxo SmithKline Pharmaceuticals Ltd, Mumbai 2. M/s. Siro Clinpharm Pvt. Ltd. Thane. 3. M/s. LG Life Sciences India Pvt. Ltd.,New Delhi 4. M/s. Quintiles Research (India) Private Limited, Bangalore. 5. M/s. Progenitor Clinical Research Pvt. Ltd., Ahmedabad 6. M/s. PPD Pharmaceutical Development India Pvt. Ltd, Mumbai.  Moreover The Office of DCG(I) after issuing show cause notices and obtaining their replies reviewed the matter further and  restricted the following from conduct of any new clinical trial for a period of 3 months vide orders dated 05.12.2013.  1. Dr. Hemant Jain, M. G. M. Medical College & M. Y. Hospital, Indore, M.P. (Principal Investigator) 2. Ethics Committee, M. G. M. Medical College & M. Y. Hospital, Indore, M.P.. 3. M/s Panacea Biotec Ltd, New Delhi 4. M/s MSD Pharmaceuticals Pvt. Ltd., Gurgaon. |
| **2**                                                                                                                                                                                                                                                                                                                                                                                 | **2013**   | **Pharmaceutical Companies/Clinical Trial Applicant:**  M/s SIRO Clinpharm Pvt. Ltd.,Thane (W) - 400 610, Maharashtra  **PI-**  Dr. Kim Ramasamy, Arvind Eye Hospital & PG Institute of Ophthalmology, Madurai  **EC**  - Arvind Eye Hospital & PG Institute of Ophthalmology, Madurai. | **Tamilnadu**    | Vitreosolve for ophthalmic interavitreal injection                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          | Debarred from initiating any new clinical trial for 3 months dt. 20.08.2014  Reasons:  - Protocol Violation: The antibiotics were administered one and half days before intravitreal injection instead of 3 days as per approved protocol. - The ICF contents were not in conformance with the requirements of GCP.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    |
| **#During the Year 2013-2014 routine surveillance inspection at clinical trial sites for GCP compliance were conducted by the zonal/sub zonal offices of CDSCO. Explanation/clarification from the sponsors, PI’s and Ethics Committees has been called for. The responses are reviewed and suitable action is being initiated as per rule, if the explanation is not satisfactory.** |            |                                                                                                                                                                                                                                                                                                 |                  |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        |
| **3**                                                                                                                                                                                                                                                                                                                                                                                 | **2013**   | **Clinical Trial Applicant:**  M/s. CliniRx, Research Pvt. Ltd., New Delhi.  **PI-**  Dr. Gundugurti Prasad Rao  M/s Asha Hospital, Plot No. 298, Road No. 14, Banjara Hills, Hyderabad- 500034                                                                                                 | **Telangana**    | CYP-1020 compared to Risperidone in patients with schizophrenia.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            | Debarred for 1 year vide order dt. 06.02.2014  Reasons:  - The patients were experiencing an acute exacerbation of schizophrenia at enrolment. However, the informed consent in the presence of legally acceptable representative and or the impartial witness were not obtained. - There were no documentary evidence for the travel expenses reimbursement to the subjects.(Patient’s rights have been affected, Totally 33 patients were participated in the trial.)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                |
| **4**                                                                                                                                                                                                                                                                                                                                                                                 | **2013**   | **Manufacturer/Pharmaceutical Companies/Clinical Trial Applicant:**  M/s ISSAR Pharmaceutical Pvt. Ltd., Seren Chambers, 3rd Floor, Banjara Hills, Hyderabad-500 034                                                                                                                            | **Telangana**    | GENOPEP 1 (ISSAR 1)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | Debarred for 1 year vide order dt. 20.08.2014  Reasons:  - The Investigational Medicinal Product was manufactured without following the tenets of GMP and certain QC test on the finished dosage form/investigational medicinal product were not performed. - IP dose calculation for the trial subjects was ambiguous.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                |
| **5**                                                                                                                                                                                                                                                                                                                                                                                 | **2013**   | Calcutta School of Tropical Medicine, Govt. of West Bengal                                                                                                                                                                                                                                      | **West Bengal**  | Amniotic membrane, amniotic fluid and placental dressing in advanced burn patients.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | The matter has referred to Medical Council of India and is under sub-judice to high Court of Kolkata.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  |
| **6**                                                                                                                                                                                                                                                                                                                                                                                 | **2014**   | M/s Apac Biotech, Gurgaon                                                                                                                                                                                                                                                                       | **Haryana**      | Autologous preparation containing mature Dendritic cell (Brand Name: APCEDEN)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | - The firm did not take clinical trial permission for the conduct of the trial as per Rule 122 DA of Drugs and Cosmetics Rules 1945. - The product falls under the purview of Drugs & Cosmetics Act and Rules there under and the firm provided autologous matured Dendritic Cell product to some patients without new drug permission under Rule 122 B. - An order was issued on 15.07.2014  to stop the collection and sale of Autologous preparation containing mature Dendritic cell (Brand Name: APCEDEN)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     |
| **7**                                                                                                                                                                                                                                                                                                                                                                                 | **2014**   | M/s Denvax Clinic, Institute of Cellular Therapies Pvt. Ltd., Noida                                                                                                                                                                                                                             | **Haryana**      | Autologous Dendritic cell cancer vaccine (Brand Name: DENVAX)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | - The firm did not take clinical trial permission for the conduct of the trial as per Rule 122 DA of Drugs and Cosmetics Rules 1945. - The product falls under the purview of Drugs and Cosmetics Act 1940 and Rules made there under and the firm was administering to the patients without new drug permission under Rule 122 B. - An order was issued on 23.07.2014  to stop collection of blood from any new patients for processing, packaging of product- Dendritic cell preparation.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            |
| **8**                                                                                                                                                                                                                                                                                                                                                                                 | **2014**   | M/s Nichi-In Centre for Regenerative Medicine, Chennai                                                                                                                                                                                                                                          | **Tamilnadu**    | Natural Killer Cell and T Cells                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             | - The product falls under the purview of Drugs and Cosmetics Act 1940 and Rules made there under and the firm was administering to the patients without new drug permission under Rule 122 B. - An order was issued on 25.08.2014  to stop collection of blood from any new patients for processing and administration of Natural Killer Cell and T Cells.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |
| **9**                                                                                                                                                                                                                                                                                                                                                                                 | **2014**   | M/s Wellness Solution, Bangalore                                                                                                                                                                                                                                                                | **Karnataka**    | Dendritic cell cancer vaccine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | - The product falls under the purview of Drugs and Cosmetics Act 1940 and Rules made there under and the firm was administering to the patients without new drug permission under Rule 122 B. - An order was issued on 28.08.2014  to stop collection of blood from any new patients for processing, packaging and administration of Dendritic cell vaccine.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |
| **10**                                                                                                                                                                                                                                                                                                                                                                                | **2014**   | M/s Chaitanaya Hospital, Pune                                                                                                                                                                                                                                                                   | **Maharashtra**  | Bone marrow derived Stem Cell Product                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       | - The firm did not take clinical trial permission for the conduct of the trial as per Rule 122 DA of Drugs and Cosmetics Rules 1945. - An order was issued on 11.12.2014 to stop the treatment with stem cell products to the patients in the name of clinical trial.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  |