Minutes of 259th meeting of central licensing board held on 29th & 30

Decision: RegistrationBoardreferredthemattertoLicensingDivisionforevaluationinlight ofdecisionofDRAP’sauthority in thesubjectmatter.”

The firm has requested to remove provisional approval sentence and removal of Enflor from bracket as they have asked from the Division of Pharmaceutical Evaluation& Research that the active ingredient of registered Product sachet Enflor is Sacharomyces Boulardil which is probiotic.

Proceedings and Decision of Central Licensing Board in 259^thmeeting

The Board considering the facts on the record and after thread bare deliberation decided to substitute the words and phrases “Sachet (Enlor)” with the words and phrases Sachet (Probiotcs)”. However, The Drug Registration Board may decide the matter in the light of the decision of the DRAP Policy Board. The Board also decided to delete the following phrase approved earlier in 238^th meeting held on 19^th December, 2014.

“*The Board has granted provisional approval of amendments/expansion in already existing Sachet (Enflor) section. The active ingredient of Sachet Enflor is Sacharomyces Boulardii is probiotic which is not a drug after the promulgation of the DRAP Act, 2012. Since the firm has registration of Enflor sachet product, therefore the Board directed to refer the case to Division of Pharmaceutical Evaluation & Research, DRAP, Islamabad to take review of registration of probiotic (Sachet Enflor) product of the firm and to inform CLB for necessary action accordingly.”

Item-VI CORRECTION IN THE MINUTES OF 257^thMEETING
The Central Licensing Board (CLB) formally confirmed the minutes of its 258^th meeting held on 08^th March, 2018.

Case No. 1 CHANGE OF TITLE OF M/S PAKHEIM INT’L (PVT) LTD, 28-KM, FEROZEPUR ROAD, LAHORE
M/s Pakheim Int’l (Pvt) Ltd, 28-Km, Ferozepur Road, Lahore under DML No. 000492 by way of formulation has submitted request for change of title of the firm as per Form-29 with prescribed Fee Challan of Rs.50,000/- as under;

Title and legal status of the firm at previous renewal of DML as per Form-1A	Title and legal status of the firm at Current renewal of DML as per Form-1A & Form-29
M/s Pakheim Pharma, 28-Km, Ferozepur Road, Lahore. (Partnership firm)	M/s Pakheim International Pharma (Pvt) Ltd, 28-Km, Ferozepur Road, Lahore. (Private Limited firm)

Decision of CLB:

The Board considered and approved the change of title of M/s Zakfas Pharmaceuticals (Pvt) Ltd, Multan, License No. 000603 by way of (Formulation) as per Form-29 of SECP as under:

Title and legal status of the firm at previous renewal of DML as per Form-1A	Title and legal status of the firm at Current renewal of DML as per Form-1A & Form-29
M/s Pakheim Pharma, 28-Km, Ferozepur Road, Lahore. (Partnership firm)	M/s Pakheim International Pharma (Pvt) Ltd, 28-Km, Ferozepur Road, Lahore. (Private Limited firm)

Proceedings of Licensing Division in compliance to the decision of Central Licensing Board:

In the aforesaid minutes of Central Licensing Board the name of the firm was inadvertently typed as M/s Zakfas Pharmaceuticals (Pvt) Ltd, Multan, License No. 000603 by way of (Formulation) Instead of M/s Pakheim Int’l (Pvt) Ltd, 28-Km, Ferozepur Road, Lahore under DML No. 000492 by way of formulation.

Proceedings and Decision of Central Licensing Board in 259^thmeeting

The Board considering the case and approved the correction.

QUALITY ASSURANCE CASES
Case No. 1: M/s Eros Pharmaceuticals (Pvt) Ltd, Karachi

Background of the case:

Dr. Abdur Rashid, Additional Director (QA<), Dr. Najam-us-Saquib, Area FID, Karachi, Dr. Muhammad Kashif, AD, Karachi and Dr. Krishan, AD, Karachi conducted inspection of the firm M/s Eros Pharma (Pvt) Ltd, Karachi on 04.04.2017 to verify GMP compliance / production activities of the firm. The panel noticed critical observations and rectification. Accordingly show cause notice / suspension of production order was issued to the firm on 01.06.2017.

The firm was served letter for personnel hearing in the 255^th Meeting of CLB, wherein Mr. Asif Iqbal, Director, M/s Eros Pharmaceuticals (Pvt) Ltd, Karachi along-with his brother Mr. Abid Iqbal, Director, M/s Eros Pharmaceuticals (Pvt) Ltd, Karachi appeared before the Board for personnel hearing. The Central Licensing Board has decided as under:-
Decision of the 255^th Meeting of CLB
After thorough discussion / deliberations, considering all the pros and cons of the case, keeping in view the available record, the Board decided to:-

1. 
   De-seal the firm by Area FID so that the firm can start rectifying the deficiencies pointed out by the panel.
   
2. 
   The firm will complete all the renovation work within one month time after de-sealing and a panel inspection will be conducted by the following members on approved format under Schedule-B-II of Drugs (LR&A) Rules, 1976.
   

1. 
   Mr. Syed Muid Ahmed, member CLB
   
2. 
   Chief Drug Inspector, Sindh
   
3. 
   Area FID, DRAP, Karachi
   

3. 
   The panel will also submit report in tabulated form indentifying the previous observations and the current status.
   
4. 
   The production will remain suspended during this period and orders for resumption of production will be issued by CLB bases upon the findings / recommendations of the inspection panel.
   
5. 
   Area FID will be asked to submit his reply as to why detailed report and sealing memo was not forwarded in time and inspection report was not signed by one of the members of the panel. Further, CLB will also be intimated about the approval of composition of the panel for conducting said inspection.
   

Accordingly decision of the CLB was conveyed to the firm and quarters concerned vide letter No.F.8-4/2017-QA (M-255-CLB) dated 05.10.2017.

Dr. Najam-us-Saquib, Additional Director, DRAP, Karachi vide letter dated 23.01.2018 informed that post of the Chief Drug Inspector, Sindh is vacant at present and requested that further necessary directions may kindly be given for the inspection of the firm. In the meanwhile, Syed Kalbe Hassan has been posted as Chief Drug Inspector, Sindh.

Updated Status

The panel conducted inspection of the firm on 26.03.2018 and concluded as

“M/s Eros Pharmaceuticals (Pvt) Ltd, situated at plot No. 94-95/23, Korangi Industrial area Karachi, was inspection by the panel as constituted vide DRAP letter No.F.8-4/2017-QA (M-255-CLB) dated 05.10.2017 for observing the improvements made and up-gradation carried out by the firm after the inspection of the firm by the panel conducted on 06.04.2017, wherein the firm was sealed then after central licensing board in its 255^th meeting ordered to de-seal the premises and allowed the firm to rectify the deficiencies pointed out by the panel.

Based on the observation made, documents reviewed and the finding of inspection, panel is of opinion that M/s Eros Pharmaceuticals, Karachi has attended almost all the shortcomings as noticed by the panel during last inspection (dated 04.04.2017) and up-graded the facility by providing the HVAC system, epoxy flooring and segregating the ware-housing facility for raw materials, packaging materials and finished goods and premises observed maintained at a good level of sanitation and hygiene.

Keeping in view the above stated fats panel recommends the resumption of the production in the following sections:

Tablet (General)

Capsule (General)

Syrup Oral (General)

Ointment / Cream “

Proceeding of the 259^th meeting of the CLB

The case was placed before the board in the light of the decision of 255^th meeting of CLB and recommendations of the panel of experts in its report dated 26.03.2018.

Decision of the 259^th Meeting of CLB
After thorough discussion/deliberations, considering all the pros and cons of the case, recommendation of the panel of experts its report dated 26.03.2018, the Central Licensing Board decided to resume the production activities of the firm M/s Eros Pharma (Pvt) Ltd, Karachi in Tablet Section (General), Capsule Section (General), Syrup Oral Section (General) and Ointment / Cream Section.

CASE NO. 2: M/S REX PHARMA, KARACHI
CHANGE OF PANEL DUE TO DEATH OF ONE OF THE HONORABLE MEMBER DR. KIFAYAT ULLAH, CDC, GILGIT, BALTISTAN
Background of the case

Inspection of the firm M/s Rex Pharmaceutical Pakistan, Karachi was conducted on 06.03.2013 by Mr. Abdul Rasool Sheikh, FID, Karachi. During inspection the FID pointed out a number of serious/critical shortcomings in all sections. Accordingly showcause notice/stop production order was issued on 23.04.2013. The case was presented before CLB in its 232^nd meeting held on 29&30^th July 2013. The Board had decided as under:-

1. 
   The case was deferred by Central Licensing Board till its next meeting as per your request that the Director of the firm had gone to Saudi Arabia for performing Umrah and requested to defer the case till next meeting of CLB.
   

2. 
   The production will remain stopped / suspended till the final approval for resumption of production by the Central Licensing Board.
   

2. The case was again presented before the 233^rd Meeting of CLB, wherein the CLB had decided as under:-

“After thorough discussion and deliberations, considering the background of the case and facts on record, Board unanimously decided to suspend the DML of the firm for period of three months under Rule 13 of Drugs (Licensing, Registering and Advertising) Rules, 1976. The Board further decided to issue show cause notice and personal hearing to the firm and advised for market survey of production manufactured by firm.”
3. The decision of the CLB was conveyed to the firm on 24.02.2014.The firm vide letter No. Nil dated 02.04.2014 replied that they have removed all the shortcomings and ready for inspection. The Area FID visited the firm on 18.11.2014 and recommended for cancellation of DML. The case was placed before the CLB in its 245^th Meeting held on 30.12.2015.
Proceedings of the 245^th Meeting of CLB:

The firm was provided opportunity of personal hearing before the Board, but no representative appeared before the CLB, on behalf of firm. The Board showed displeasure on such non serious attitude of the company.

Decision of 245^th Meeting of CLB:

The Board after thorough discussion, keeping in view the available record, observations of the FID in its inspection conducted on 06.03.2013, track record and non serious attitude of the firm, and report of the FID dated 18.11.2014 which categorically stated that “The DML of the firm may be cancelled in larger public interest”, has decided to suspend the DML of the firm M/s Rex Pharmaceuticals Pakistan, Karachi for a period of 06 months, under Rule 12 of the Drugs (LR&A) Rules, 1976.

4. The decision of the CLB was conveyed to the firm on 09.02.2016.

Inspection conducted by Area FID, Karachi on 06.01.2017

Mr. Abdul Rasool Shaikh, FID, Karachi vide letter dated 24.01.2017 informed that the firm was inspected on 06.01.2017 and found non-operational, no one was there except watchman who told that factory is closed since 2011 and owners are reported to be living in USA now days. Based on the current conditions of the firm it is recommended that their DML by way of formulation may be cancelled in larger public interest.

Proceedings of the 252^nd Meeting of CLB

The Board was informed by the Deputy Director (QA) that the firm was served letter for personal hearing on 08.03.2017 and the area FID was also informed to send the letter to the firm. But no representative of the firm appeared before the Board for personal hearing under section 41 under the Drug Act 1976, read with rule 12 of the Drugs (L, R & A) Rules 1976.

Decision of the 252^nd Meeting of CLB

After thorough discussion/deliberations, considering all the pros and cons of the case, recommendations of the Federal Inspector of Drugs in its letter dated 24.01.2017, in which the FID recommended to cancel the DML of the firm in the larger public interest, casual attitude of the firm towards GMP compliance, track record of the firm and nonappearance of representatives of the firm before the Board to defend the case, the Board decided to cancel the Drug Manufacturing License of the firm M/s Rex Pharmaceutical Pakistan, Karachi, under Section 41 of the Drugs Act, 1976 read with Rule 12 of the Drugs (L,R&A) Rules, 1976, from the date of issuance of decision of the 252^nd meeting of CLB.

5. Decision of the CLB was conveyed to the firm and quarter concerned on 15.03.2017.
Decision of Appellate Board in its 147^th Meeting

M/s Rex Pharmaceutical Pakistan, Karachi filed an appeal against the decision of the CLB regarding cancellation of DML. The case was considered in 147^th meeting of the Appellate Board held on 28.08.2017, wherein the appellate board decided to suspend the operation of impugned order of CLB dated 15.03.2017 communicated on 24.04.2017 and remand the appeal back to the CLB. The appellate board constituted a panel of following panel to inspect the premises of the appellant who shall submit its report within 30 days from the date of communication:-

1. 
   Dr. Kifayat Ullah, CDC, Gilgit, Baltistan
   
2. 
   Prof. Dr. Maqsood Ahmed, Ripah International University, Lahore
   
3. 
   Syed Muied Ahmed, Expert in Manufacturing, Karachi
   

The report of the panel will be placed before the CLB in its forthcoming meeting. Meanwhile the production of the firm will remain suspended till recommendations by the panel for the resumption of production and approval thereof by the CLB.

Panel inspection on the decision of the Appellate Board:-

The panel inspected the firm on 12.12.2017 and noticed following observation which still needs rectification:-

General:-

• 
  Layout of the facility was approved by DRAP in 1997. Panel noticed number of changes in the facility as compared to the approved layout of 1997.
  

Dry Powder injectables (Cephalosporin)

• 
  There was not status labeling for clean down quarantine and passed material storage areas
  
• 
  There was not air conditioning in cold store area.
  
• 
  No temperature monitoring or recording in raw material stores area
  
• 
  No designated area for material sampling.
  
• 
  No provision of HVAC in change room and main corridor of ceph manufacturing area
  
• 
  No HVAC in vial washing room
  
• 
  Plain water, deionized water and distilled water lines were provided in the vial washing room but no status labeling on these lines.
  
• 
  No provision was seen for water for injection loop in vial washing room
  
• 
  Dry heat sterilizer and autoclave installed in washing room were very old and no evidence was available for their qualification / validation
  
• 
  Magenhelic gauge outside the sterile vial filling area showed zero pressure, meaning there was no pressure differential in the room.
  
• 
  Dry powder vial filling line was very old and no evidence of qualification / validation.
  
• 
  No temperature monitoring in finished goods store area.
  

Liquid injectables (ampoule) section

• 
  Common change room for liquid injectable and cephalosporin dry powder injectable sections. Male and female staff enter and come out of both the above sections through the same change room.
  
• 
  No proper change room for ampoule washing room
  
• 
  No proper HVAC in ampoule washing room
  
• 
  Ampoule washing machine was very old and almost manual.
  
• 
  No clarity on quality of water used for ampoule washing. No provision was seen for water injection loop in ampoule filling machine.
  
• 
  No manometer installed to demonstrate air pressure differential in ampoule filling room.
  
• 
  No connection of water for injection loop in ampoule manufacturing area. No mixer for making solutions. No means for pressure filtration of solutions.
  
• 
  Autoclave for filled ampoule sterilization was very old and no evidence of qualification / validation.
  
• 
  No provision for ampoule leak testing.
  

Veterinary injectables section

• 
  Clean down and quarantine area is common
  
• 
  No temperature control in raw material store.
  
• 
  No sampling and dispensing booth
  
• 
  No status label on water lines
  
• 
  No filter assembly was available for filtration of injectable solutions.
  
• 
  No laminar flow on injectable filling machine
  
• 
  No HVAC in sterile cool down area and vial washing area.
  
• 
  No autoclave was available in veterinary injectable area
  

Eye drop section:

• 
  No proper change facility for sterile eye drop section
  
• 
  No HVAC in washing area
  
• 
  No status labeling on water lines
  
• 
  No filter assembly for eye drop solution filtration.
  
• 
  One old filling machine was installed in a room, without any provision for stopper inserting and capping. No laminar flow on filling machine.
  

Eye ointment section

• 
  There was no equipment in ointment manufacturing
  
• 
  No service lines or drain lines in the room
  
• 
  There was not any room for ointment filling and no filling machine was available.
  

Dry powder (cephalosporin)

• 
  No status labeling in stores
  
• 
  No HVAC in change room
  
• 
  HVAC was not working in powder mixing room
  
• 
  Cephalosporin powder filling room is next to non-cephalosporin tablet compression room and non-ceph tablet coating room with a door in between. Chances of cross contamination were evident.
  
• 
  No provision of bottle cleaning
  
• 
  No dust control or extraction in powder filling area.
  
• 
  A blister cutting and a strip cutting machine were lying in a small room. Both were very old and looking out of order.
  
• 
  An old capsule filling machine was lying in a small room in cephalosporin area.
  

Oral liquids section

• 
  HVAC supply and return duct were on the same wall of the liquid filling room. Therefore chances of quality air not reaching to the other end of the room
  
• 
  No transfer pump or filtration assembly seen in the liquid manufacturing room.
  

Tablet section

• 
  No positive or negative air pressure differential in tablet compression rooms.
  
• 
  Entry to one table compression room is through another tablet compression room; therefore chances of cross contamination.
  
• 
  Solvent coating is carried out in open pans. No exhaust system for solvent vapors.
  
• 
  No proper HVAC ducting. Supply and return on the same wall.
  
• 
  Granulation area very noisy due to air coming from the air supply duct. Seems problem in air balancing. No positive or negative air pressure differential in granulation room.
  

Veterinary oral liquid & powder section.

• 
  No proper manufacturing vessel in liquid manufacturing area.
  
• 
  No proper liquid filling machine.
  
• 
  Powder blender was available in one room but not powder filling machine.
  
• 
  No exhaust system or air pressure differential were available.
  

The panel further concluded and recommended that:-
The panel observed a number of shortcomings in building, production machinery, HVAC system, documentation etc. Therefore, based on the areas inspected, the people met and documents reviewed and considering the findings of inspection the panel recommends that the Drug Manufacturing License may be granted to M/s Rex Pharmaceuticals Pakistan, Karachi, for two sections only namely Oral Liquids and Tablet (after addressing the observations in this report).
Decision of 257^th Meeting of CLB:-
The case was placed before the Central Licensing Board in its 257^th Meeting held on 24-25 Jan, 2018 and decided as under:-
“After thorough discussion/deliberations, considering all the pros and cons of the case, recommendations of the panel of experts in its report dated 12.12.2017 decided to
i. Re-inspect the firm M/s Rex Pharmaceutical Pakistan, Karachi by following panel of experts, constituted by the Appellate Board in its 147^th Meeting:-

1. 
   Dr. Kifayat Ullah, CDC, Gilgit, Baltistan
   
2. 
   Prof. Dr. Maqsood Ahmed, Ripah International University, Lahore
   
3. 
   Syed Muied Ahmed, Expert in Manufacturing, Karachi
   

ii. The panel shall submit the detailed report alongwith rectification status of the observations in the Tablet Section and Liquid Syrup Section noted by the panel in the report dated 12.12.2017. Further more the panel will also submit detailed report regarding the quality control laboratory and storage facilities of the firm. The report shall be placed in the forthcoming meeting of Central Licensing Board for consideration.

The Decision of the 257^th meeting of CLB was conveyed to the firm and quarters concerned on 06.03.2018.
Updated status:-

The firm vide letter No. Nil dated 20.03.2018 received on 27.03.2018 informed that they have rectified the observations recommended by the panel. In the meanwhile one of the respected panel member Dr. Kifayat Ullah, CDC, Gilgit passed away.

Proceedings of the 259^th meeting of the CLB

The case was placed before the board in the light of request of the firm M/s. Rex Pharmaceutical Pakistan, Karachi regarding death of one of worthy panel member Dr. Kifayatullah, Chief Drug Controller, Gilgit Baltistan.

Decision of the 259^th Meeting of CLB

After thorough discussion / deliberations, considering all the pros and cons of the case and intimation of the firm regarding death of the worthy panel member Dr. Kifayatullah, Chief Drug Controller, Gilgit Baltistan, the Central Licensing Board decided to replace name of deceased member Dr. Kifayatullah, Chief Drug Controller, Gilgit Baltistan with Additional Director, Karachi, other members of the panel shall remain same.