Tyno SF case Facts v.s Assumptions

Presented by: Seemal Khalid

Reko Pharmacal

Pvt. Ltd

• Reko was established in 1962.

• Today Reko (ISO-9001-2008 certified) is fully operational with over 150 registered products.

• Fully operational QC department and QA

• HVAC system in all production and store areas to ensure cGMP standards.

• Inventory management based on SQL software.

Company Profile

Manufacturing Sections

Sections

• Tablet section

• Injectable

• Capsule

• Liquid syrup

• Dry suspension

• Semi-solid

Liquid Syrup Section Covered area of 2,200 sq. feet

Capacity per shift: 40,000 bottles

8 nozzle automatic syrup filling machine

Automatic labeler

Tyno History

Existing formulation Approved formulation

Each 5ml contains: Dextromethorphan HBr: 15mg

Each 5ml contains: Dextromethorphan HBr:15mg

Phenyl propanolamine HCl: 10mg

Chlorpheniramine Maleate:4mg

Registration of Tyno Syrup 30th September 1976

Change of formulation 4th August 2001

Registration of Tyno-SF 21th April 2011

Dextromethorphan HBr:10mg Chlorpheniramine Maleate:2mg

Tyno SF cough syrup

Safe anti-tussive/cough suppressant.

Safe dosage is 5 ml (10 mg) every 5 to 6 hours, (the dose in Tyno- SF) and the maximum dosage should not exceed 20 ml in three divided doses within 24 hours as per instructions on the label.(Reference- Daily Med)

64 registered Dextromethorphan containing products in Pakistan.

Tyno Competitors

Sr # Product Name Composition Per 5ml Company Price

1 Texcol DM DXM 10mg + Psuedoephedrine HCl 30mg + CPM

4mg Razee 34.62

2 Histamol D DXM 10mg + CPM 5mg + Ephedrine 5mg +

Ammonium Cl 76.66mg + pot. Guaiacol

sulphonate 125mg + Terpin Hydrate 6.66mg

Epla 72.89

3 Corex D DXM 10mg + CPM 4mg + Ephedrine 5mg + Sod.

Citrate 150mg. Pfizer 43.29

4 Combinol D DXM 10mg + Ephedrine 7.5mg + CPM 4mg +

Terpin Hydrate 3.5mg + Ammonium Cl 90mg Atco 43.00

5 Broxol DM Diphenhydramine HCL 5mg + DXM 6.25mg Stanely 31.00

6 Hydrylin DM Diphenhydramine HCL 5mg + DXM 6.25mg+

Ephedrine HCL + Guaiphenesin. Searle 62.00

7 Cosome DXM 10mg + Psuedoephedrine HCl 30mg + CPM

2mg Merck 39.00

8 Adicos M DXM 6.3mg + Diphenhydramine HCL14mg +

Psuedoephedrine HCl 22.5mg + menthol 175mg Zafa 29.00

Sequence of Events

On 24th November 2012 media reported that 11 people died in Shahdara apparently due to over dosage of a cough syrup. Drug inspectors team and police raided Reko’s distribution office SMS and arrested the distributor

On 25th November, at 4.30am police along with the DCO raided the factory premises and shortly afterwards, Provincial drug inspectors team came to seal the production area of Reko.

A case of 302/34 was registered against the Managing Director, Khalid Saleem Mian. MD’s house was raided and his driver was taken into custody.

Sequence of Events

The factory was de-sealed on Tuesday, 27th November 2012 when a group of Provincial, CM team and Federal drug inspectors visited the factory premises and checked all documentation of Tyno raw material and found them to be in order.

The same day, a dozens of media personnel forcibly entered the production areas with the assistance of local Drug Inspectors and started recording ignoring warnings from the factory personnel.

Sequence of Events

Press conference on 27th November 2012 in PPMA Regional office: Mohammad Zaka presented the actual situation of Tyno tragedy and requested the Press to wait for the DTL reports before broadcasting any further negative news against the manufacturers.

LCCI Press Conference on 28th November 2012, President Mr. Farooq Iftikhar said that the incident happened only in Shahdara which is a hub of addicts and law enforcement agencies were fully aware of it

Sequence of Events PPMA Press conference was held in the Press Club on 12th December 2012 in which PPMA members were invited. Vice Chairman PPMA pointed certain pertinent facts to the media: 1. According to Forensic reports , Tyno was not the cause of deaths in the

individuals. 2. The deaths revealed the Punjab government’s inability to address the

root cause of the problem. 3. Media was advised not to pass on incorrect information to the public

as this is a technical field and correct scientific facts should be presented.

4. Finally he announced a closure of all pharmaceutical units in the Punjab due to the unfair treatment of the government (which unfortunately does not happen).

Sequence of Events On 24th January 2013, Inspector Shahdara took the following staff members

in their custody for 3 days without any warrant or written instructions.

•M.A Ghori, Senior QC Manager •Adnan Mateen, Assistant Import Manager •Syed Naqi Abbas, Assistant Store Manager

On 6th February 2013, the liquid section was suspended for one year which further crippled the company sales as production of 13 products was also suspended.

MD Khalid Sleem Mian was put on ECL in March upon his return from China after Liver transplant operation.

CDL Report-12th December 2012

CDL Report of 12th December declares 4 batches of Tyno to be of “standard” quality

Furthermore active raw materials Dextromethorphan and Chlorphenaramine maleate are also declared to be of standard quality.

CDL Report (DXM)

CDL Report

Experiment by University of Veterinary & Animal Sciences on Tyno (30th November 2012)

Tyno Batch no 5601 was administered to 50 mice divided in 10 groups.

The syrup was administered @ dose below, equal and above than the recommended dose.

The 10th group was given 64 times the original dose.

The mice were observed critically for 89 hours.

“During this tenure no death of mice was observed.”

Reports by Punjab Forensic Science Agency

According to Forensic Toxicology Preliminary Report released on 14-12-2012, the following findings were revealed:

1. Out of 12 people whose blood toxicology was determined, 7 of them did not have Chrompeniramine Maleate in their blood which showed that they did not consume TYNO-SF (Dextromethorphan+Chlorpheniramine)

2. 5 victims had Dextromethorphan, Chlorphenaramine Maleate with Opiates, Ethanol,Triazolam and Cannabinoids which showed that they had combined other narcotics with cough syrup. “Mixing DXM with other depressants can result in overdose and result in respiratory failure” (Ref: www.health

homa.com)

Forensic Report Dead body only contains: Dextrometharphan HBr

Name Father’s Name Contents Quantity

Shehzad (Autopsy#MAK-05-762-12)

M.Ashraf 1. Dextrometharphan HBr

2. Ethanol

3. Cannabinoids

4. Opiates

7.3mg/L 0.02 g/dl Identified Identified

M.Javaid (MLC#5067/12) Jalal Din 1. Dextrometharphan HBr

2. Ethanol

3. Methanol

4. Triazolam

5. Cannabinoids

6. Opiates

15mg/L 0.022 g/dl 0.024g/dl Identified Identified Identified

Shehzad (MLC#5066/12)

Palla 1. Dextrometharphan HBr

2. Opiates

33.4mg/L Identified

Wali Muhammad (MLC#5079/12)

M.Anwaar 1. Dextrometharphan HBr

2. Ethanol

3. Midazolam

4. Opiates

41.7mg/L 1.1 g/dl Identified Identified

Waheed (MLC#5094/12)

Abdul Majeed 1. Dextrometharphan HBr

2. Acetone

3. Cannabinoids

4. Opiates

7mg/L 0.003g/dl Identified Identified

Yusaf (MLC#5064/12)

Mubarak 1. Dextrometharphan HBr

2. Cannabinoids

3. Opiates

7.5mg/L Identified Identified

Ramzan (MLC#5086/12)

Sharaf Din 1. Dextrometharphan HBr

2. Opiates

3. Cannabinoids

6.4mg/L Identified Identified

Forensic Report Name

Father’s Name

Contents Quantity

M. Parvaiz (Autopsy#TBH-19/760/12)

Inayat Ali 1. Dextrometharphan HBr

2. Ethanol

3. Opiates

4. Chlorpheniramine

5. Triazolam

23.3mg/L 0.026 g/dl Identified Identified Identified

M.Tariq (Autopsy#MAK -07-767-12)

M .Ibrahem 1. Dextrometharphan HBr

2. Ethanol

3. Opiates

4. Cannabinoids

5. Chlorpheniramine

12.2mg/L 0.02 g/dl Identified Identified Identified

M.Qasim (Autopsy#MAK-06-763-12)

Abdul Ghafoor 1. Dextrometharphan HBr

2. Ethanol

3. Opiates

4. Cannabinoids

5. Chlorpheniramine

25.3mg/L 0.012 g/dl Identified Identified Identified

Shafiq (MLC#5097/12)

M.Hussain 1. Dextrometharphan HBr

2. Chlorpheniramine

3. Opiates

7.0mg/L Identified Identified

Qasim (MLC#5078/12)

Abdul Ghafoor 1. Dextrometharphan HBr

2. Opiates

3. Chlorpheniramine

4. Cannaibinoids

13.1mg/L Identified Identified Identified

Dead body contains:

1-Dextrometharphan

HBr

2-Chlorpheniramine

Maleate

Tyno SF Reports? No protocol for detecting Levomethorphan in BP and USP

DTL issued its report on finished good TYNO-SF batch # 5601 on 11th Jan 2013, which stated that the said batch is declared as Sub-standard on the basis of Optical rotation. (Reference U.S.P) Whereas there is no such test recommended for optical rotation in U.S.P. for cough syrups. There is no protocol for detecting Levomethorphan in BP and USP.

Moreover above 200 samples from 30 batches of Tyno SF syrup were taken and declared to be of “standard” quality by the DTL.

DTL Reports

Long-term repercussions for Reko Reko’s 50 year reputation of being an ethical and quality-conscious has been tarnished by the media and regulatory authorities without following any proper protocols and investigation procedures.

Due to Tyno being one of our highest selling and revenue generating product, we are facing an accumulated loss of Rs 50 million. Currently fighting 4 litigation cases against the local and federal government further adding to our financial crisis.

Oral liquids contributed 55% of our sales, the sealing of this section has affected the sale of 13 other products. Moreover the company had to lay off 30% of its employees.