Lok Sabha Question No. 1118 (UNSTARRED), answered on 2015-12-04
Subject: Clinical Trials
Ministry: HEALTH AND FAMILY WELFARE
Asked by: V. SATHYABAMA, VIRENDRA  KUMAR, JYOTIRADITYA MADHAVRAO SCINDIA

## GOVERNMENT OF INDIA MINISTRY OF HEALTH AND FAMILY WELFARE DEPARTMENT OF HEALTH AND FAMILY WELFARE

## LOK SABHA UNSTARRED QUESTION NO. 1118 TO BE ANSWERED ON 4 TH DECEMBER, 2015

## CLINICAL TRIALS

## 1118. SHRIMATI V. SATHYA BAMA: DR. VIRENDRA KUMAR: SHRI JYOTIRADITYA M. SCINDIA:

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

- (a) the number of clinical trial applications received for imported and indigenously developed medicines,separately and granted permission by the Central DrugsStandard Control Organization (CDSCO) during each of the last three years and the current year;
- (b)  the  cases  of  irregularities  and  noncompliance of  clinical  trial  governing  rules/ guidelines reported and the action taken/ proposed to be taken by the Gove rnment thereon during the said period, State/UTwise;
- (c)  the  number  of  clinical  trial  related injuries  and  casualties  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 laws to ensure safety and protection  of  the  rights of  the  human  subjects  during  clinical  trial or  medical  and  scientific research?

## ANSWER THE MINISTER OF HEALTH AND FAMILY WELFARE (SHRI JAGAT PRAKASH NADDA)

- (a) :  The number of clinical trial for new drug (s) related applications received and number of permissions granted by Central Drugs Standard Control Organization during last three year current year is as under:
- (b) : During last three years and the current year, action has been taken by the Governm 13  cases  against  persons  /hospitals  /investigators  and sponsors  (pharmaceutical  companies) found involved in irregular trial (Annexure).
- (c): The number of Serious Adverse Events (SAEs) of death and Injury (other than deat reported during the clinical trials during last three years and current year are as under:

| Year                   |   No. of Application Received |   No. of Permission |
|------------------------|-------------------------------|---------------------|
| 2012                   |                           480 |                 253 |
| 2013                   |                           207 |                  73 |
| 2014                   |                           230 |                 198 |
| 2015 (ason 27/11/2015) |                           170 |                 191 |

be

Clinical

| Year                     | Nos. of SAEs where death was reported.   | Nos. where death established be related Clinical Trial.   | to to Nos. where SAEs (other than death), i.e., was reported.   |   injury Nos. where injury established to related to Trial. |
|--------------------------|------------------------------------------|-----------------------------------------------------------|-----------------------------------------------------------------|-------------------------------------------------------------|
| 2012                     | 436                                      | 16                                                        | 2786                                                            |                                                         184 |
| 2013                     | 590*                                     | 46                                                        | 1122                                                            |                                                         159 |
| 2014                     | 443 a                                    | 22                                                        | 1326 b                                                          |                                                          95 |
| 2015 (as on 27/11/ 2015) | 330                                      | Under Examination                                         | 2137 c                                                          |                                                          16 |

- a -out of 443 reports, 345 reports of SAEs of death have been examined and the remaining are under examination.
- b -relatedness has been examined in 1200 out of 1326 cases.
- c -relatedness has been examined in 1050 out of 2137 cases.

Compensation has been paid till November, 2015 i n following related cases of death and injury: -

| Year   | Compensation paid in related cases   | Compensation paid in related cases   |
|--------|--------------------------------------|--------------------------------------|
|        | Death                                | Injury                               |
| 2012   | 16                                   | 112                                  |
| 2013   | 41                                   | 127                                  |
| 2014   | 18                                   | 58                                   |
| 2015   | Nil                                  | 02                                   |

(d): 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 S death  related  to  Clinical  Trial,  one  each  for  2005,  2006  and  2010  has  not  been  paid whereabouts of the legal heir could not be located.

(e)  :  Ad equate  provisions  have  been  made  in  rules  122DA,  122DAA,  122DAB,  122DAC, 122DD  and  122E  of  the  Drugs  and  Cosmetics  Rules,  1945  to  specify  the  requirements  f conducting  clinical  trials  in  India.    Further,  Schedule - Y  of  the  said  Rules  prescribes  the respon sibilities of the Sponsor, Investigator and Ethics Committee to protect the rights and well - being of clinical trial subjects. The measures taken in the recent past to stren regulation of clinical trials include evaluation of the clinical t rial proposals by the Subject Expert Committees/  Investigational  New  Drugs  Committee,  review  of  their  recommendations  by  th Technical  Committee  and,  thereafter,  approval  by  the  Apex  Committee.  Compensation  i required to be paid in case of trial related i njury or death within the prescribed timelines. It ha been made mandatory for the sponsor or his representatives to furnish details of the entered  into  by  the  sponsor  with  the  investigator  with  regard  to  financial  suppor honorarium, payme nts, etc. Further, it has also been decided that with effect from 30.11.2 all clinical trials, in addition to the requirement of obtaining written informed cons -visual informed consent will also be recorded in respect of each trial su .

Annexure

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|   S. N o. |   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 tetanus toxoid conjugate vaccine  Diphtheria - Tetanus - whole cell Pertussis - Hepatitis B vaccine  Rabeparazole  Virosomal hepatitis A virus (HAV) vaccine  MonovalentType 1 Oral Poliomyelitis Vaccine  Bivalent Oral poliovirus vaccine (bOPV)  Haemophilus influenzae b conjugate vaccine  Easyfive TM Vaccine  DTwP Vaccine  Inactivated Polio Vaccine | b Based on press reports and the complaint conduct of illegal clinical trials on at M/s. Chacha Nehru Hospital, Indoreby Dr. Hemant team of officials from CDSCO had carried inspe ction (from 16 th to 20 th April 2012) of trials conducted at this site. It was observed that 26 clinical trials were by Dr. Hemant Jain during the period 2006 to For the clinical trials conducted by the sponsors/CROs under the investigator Dr. Jain, the Office of DCGI issued warning 1. M/s. Glaxo SmithKline Pharmaceuticals Mumbai 2. M/s. Siro Clinpharm Pvt. Ltd. Thane. 3. M/s. LG Life Sciences India Pvt. Delhi 4. M/s. Quintiles Research (India) Private Limited, Bangalore. 5. M/s. Progenitor Clinical Research Pvt. Ahmedabad 6. M/s. PPD Pharmaceutical Development Pvt. Ltd, Mumbai. Moreover The Office of DCG(I) af ter issuing cause notices and obtaining their replies matter further and restricted the conduct of any new clinical trial for a |

(Principal were

acute enrolment.

or the

the

|                                                                                                                                                                                                                                                                                                                                                                       |                                                                                                                                                                                                                                                                                                                                                                       |                                                                                                                                                                                                                                                                                                                                                                       |                                                                                                                                                                                                                                                                                                                                                                       |  Monovalent H1N1 Influenza A  Valsartan  Multivalent Human Papillomavirus [HPV] L1 Virus - Like Particle [VLP] Vaccine  Montelukast                                                                                                                                                                                                                               | months vide orders dated 05.12.2013. 1. Dr. Hemant Jain, M. G. M. Medical M . Y. Hospital, Indore, M.P. Investigator) 2. Ethics Committee, M. G. M. Medical & M. Y. Hospital, Indore, M.P.. 3. M/s Panacea Biotec Ltd, New Delhi 4. M/s MSD Pharmaceuticals Pvt. Ltd.,                                                                                                                                         |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 2                                                                                                                                                                                                                                                                                                                                                                     | 2013                                                                                                                                                                                                                                                                                                                                                                  | Pharmaceutical Companies/Clinical TrialApplicant: 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 months dt. 20.08.2014 Reasons:  Protocol Violation: The antibiotics administered one and half days before injection instead of 3 days as per oved protocol.  The ICF contents were not in conformance 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 of CDSCO. Explanation/clarification from the sponsors, PI's and Ethics Committees has been called for. The responses are reviewed and s uitable action is being initiated as per rule, if the explanation is not satisfactory. | #During the Year 2013 -2014 routine surveillance inspection at clinical trial sites for GCP compliance were conducted by the zonal/sub of CDSCO. Explanation/clarification from the sponsors, PI's and Ethics Committees has been called for. The responses are reviewed and s uitable action is being initiated as per rule, if the explanation is not satisfactory. | #During the Year 2013 -2014 routine surveillance inspection at clinical trial sites for GCP compliance were conducted by the zonal/sub of CDSCO. Explanation/clarification from the sponsors, PI's and Ethics Committees has been called for. The responses are reviewed and s uitable action is being initiated as per rule, if the explanation is not satisfactory. | #During the Year 2013 -2014 routine surveillance inspection at clinical trial sites for GCP compliance were conducted by the zonal/sub of CDSCO. Explanation/clarification from the sponsors, PI's and Ethics Committees has been called for. The responses are reviewed and s uitable action is being initiated as per rule, if the explanation is not satisfactory. | #During the Year 2013 -2014 routine surveillance inspection at clinical trial sites for GCP compliance were conducted by the zonal/sub of CDSCO. Explanation/clarification from the sponsors, PI's and Ethics Committees has been called for. The responses are reviewed and s uitable action is being initiated as per rule, if the explanation is not satisfactory. | #During the Year 2013 -2014 routine surveillance inspection at clinical trial sites for GCP compliance were conducted by the zonal/sub of CDSCO. Explanation/clarification from the sponsors, PI's and Ethics Committees has been called for. The responses are reviewed and s uitable 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. Road No. 14, Banjara Hills, Hyderabad-500034                                                                                                                                                                                          | 298, 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 exacerbation of schizophrenia at However, the informed consent in the legally acceptable representative and impartial witness were not obtained.  There were no doc umentary evidence for travel expenses reimbursement to subjects.(Patient's rights have been affected, Totally 33 patients were participated in |

|   4 |   2013 | Manufacturer/Pharmaceutical Companies/Clinical Trial Applicant: M/s ISSAR Pharmaceutical Pvt. Seren Chambers, 3rd Floor, Banjara Hills, Hyderabad - 500 034   | Ltd., Telangana   | GENOPEP 1 (ISSAR 1)                                                                 | Debarred for 1 year vide order dt. 20.08.2014 Reasons:  The Investigational Medicinal Product manufactured without following th e tenets GMP and certain QC test on the finished form/investigational medicinal product performed.  IP dose calculation for the trial 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 of India and is under sub - judice to Court of Kolkata.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          |
|   6 |   2014 | M/s Apac Biotech, Gurgaon                                                                                                                                     | Haryana           | Autologous preparation containing mature Dendritic (Brand Name: APCEDEN)            | cell  The firm did not take clinical trial for the conduct of the trial as per of Drugs and Cosmetics Rules 1945.  The product falls under the purview of Cosmetics Act and Rules there under firm provided autologous matured Cell product to some patients without permission under Rule 122 B.  An order was issued on 15.07.2014 to collection and sale of Autologous containing mature Dendritic cell (Brand APCEDEN).  An order was issued on 19.08.2015 revocation of order dated 15.07.2015 purpose of conducting clinical trial, permitted & also require the firm to the product for using i n particular only after it is permitted. |
|   7 |   2014 | M/s Denvax Clinic, Institute Cellular Therapies Pvt. Ltd., Noida                                                                                              | of Haryana        | Autologous Dendritic cell vaccine (Brand Name: DENVAX)                              | cancer  The firm did not take clinical trial for the conduct of the trial as per Rule of Drugs and Cosmetics Rules 1945.  The product falls under the purview of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  |

was for

for

|    |      |                                                          |             |                                       | and Cosmetics Act 1940 and Rules made under and the firm was administering patients without new drug permission Rule122 B.  An order was issued on 23.07.2014 collection of blood from any new processing, packaging of product -Dendritic preparation.  The matter is under -sub judice to High Court Delhi.             |
|----|------|----------------------------------------------------------|-------------|---------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
|  8 | 2014 | M/s Nichi - In Centre for Regenerative Medicine, Chennai | Tamilnadu   | Natural Killer and T Cells            | Cell  The product falls under the purview of and Cosmetics Act 1940 and Rules made under and the firm was administering patients without new drug permission Rule 12 2 B.  An order was issued on 25.08.2014 collection of blood from any new processing and administration of Natural Cell and T Cells.                  |
|  9 | 2014 | M/s Wellness Solution, Bangalore                         | Karnataka   | Dendritic cell vaccine                | cancer  The product falls under the purview of and Cosmetics Act 1940 and Rules made under and the firm was administering patients without new drug permission Rule 122 B.  An order was issued on 28.08.2014 collection of blood from any new pati ents processing, packaging and administration Dendritic cell vaccine. |
| 10 | 2014 | M/s Chaitanaya Hospital, Pune                            | Maharashtra | Bone marrow derived Stem Cell Product |  The firm did not take clinical trial for the conduct of the trial as per 122 DA of Drugs and Cosmetics Rules 1945.  An order was issued on 11.12.2014 to treatment with stem cell products to the in the name of clinical trial.                                                                                         |

| 11   | 2015   | Clinical Trial Sponsor: M/s MSD Pharmaceuticals Pvt. Gurgaon- 122 002. Investigator - a) Dr. A. Sharda, Endocrinology Diabetes Centre, Indira Nagar, Bangalore - 560 038 b) Dr. S. S. Srikanta Jnana Sanjeevini Medical Centre, Marenahalli, J.P. Nagar, nd Phase, Bangalore - 560 078 c) Dr. S. R. Aravind ,   | 2 Haryana      | &   | Sitagliptin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        |
|------|--------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------|-----|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
|      |        | Diacon Hospital Rajajinagar, Bangalore - 560010.                                                                                                                                                                                                                                                                | Ltd. Karnataka |     | Sponsor debarred for 4 months and Investigators (a & b) for 6 months Investigator (c) for 3 months from new clinical trial vide order dated Reasons: Sponsor- (i)No oversight over the clinical trial MK - 0431- 082], like SAE reporting, & due analysis etc. (ii) This is subsequent -non compliance(s) by MSD. Investigator [ for (a) & (b)]: No Investigational Medicinal Product titration as pe r protocol in spite of the the subject had low eGFR (violation of care and protocol). Investigator (a) CRF & subject's medical record after receiving query from O/o DCGI. Neither SAE reported nor SAE due reported to O/o DCGI. No in - house labs for testing of CT trial subjects but printed the tests another lab (M/s Clumax Diagnostics) site(s) letter head, no data/record authenticity of test results (data No legal/for mal contract entered between PI/site since 26/09/2014, however patient data & information is shared without any legal contract/agreement. Investigator [for (c)]: No Investigational Medicinal Product titration as per protocol in spite of the subject had low eGFR (violation of care and protocol). |

two months

and r protocol in spite of the fact that

for

t

|   12 |   2015 | Clinical Trial site: Karnataka Cancer Hospital & Research Centre, Department of Clinical Research Karnataka Cancer Hospital & Research Centre, J.B. Karal Nandhini Layout Krishnanandannagar, Bangalore - 560096   | Karnataka   | Not applicable   | O/o DCGI received a complaint vide letter 20/07/2015 from a Social Scientist. Wherein the basis of a local newspaper report alleged that the hospital had no 'histopathology Dept.' but all report issue in Karnataka Cancer Hospital only and they manipulate the Vide letter dated 30/07/2015 order u d to inspect the site and ascertain the Inspection was carried out and further process.                                             |
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|   13 |   2015 | Ethics Committee: Hippocrates Independent Ethics Committee (HIEC), Street No. 7, New T Block, Phase II, Nanhe Park, Uttam Nagar, New Delhi -110 059                                                                | Delhi       | Not applicable   | A number of complaints received in Aug. 2015 by O/o DCGI via email(s) Investigator(s) about the irregular and misconduct of said HIEC in approving clinical trials & BA/BE studies. A team constituted by CDSCO conducted inspection of the said EC on 07/08/2015. Thereafter based on - compliances reported, a Show Cause (SCN) was issued to HIEC on HIEC reply to SCN was received on and the matter is under process for as per rules. |

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