MINUTES OF  THE MEETING  TO  FINALISE  THE  SPECIFICATIONS AND 
TEST METHOD  FOR BIPHASIC  ISOPHANE  INSULIN INJECTION
NIB, NOIDA  27 OCTOBER 2009, 2.30 p.m.

A meeting to finalize the specifications and the test method for Biphasic Isophane Insulin Injection was held under the Chairpersonship of Dr. Jotna Sokhey, Addl. DGHS & Director, NIB on 27.10.2009 at 2.30 p.m.  The representatives of leading manufacturers of Insulin, Indian Pharmacopoeia Commission, NABL expert and,  concerned officers of NIB participated in the meeting. Representative from CDSCO &  Dr. Ajmani Senior Specialist and Endocrinologist-RML Hospital did not attend. The list of participants is annexed.

Dr Sokhey welcomed the participants and said many formulations of insulin were available in the market. She said that the meeting had been convened to:

To finalize the specifications and test method for Biphasic Isophane Insulin Injection.  Method given in IP-2007, USP (method 1 & 2) and EP/BP for Soluble Insulin human content in the ratios of 30:70, 25:75 and 50:50 have differed for various manufacturers and need to be deliberated upon, for its incorporation in IP-2007 and addendum 2008 Monographs.

To incorporate “Amendment” in IP-2007 for Sterility test method for all suspensions that are Biphasic Isophane Insulin Injection, NPH, Lente, etc.

Dr. Renu Jain, SG-II & HOD of Insulin Lab made the presentation of the current status and issues required for discussion.  She said that –

1. Biphasic Isophane Insulin Injections are available for the ratio of 30:70, 25:75 and 50:50. These formulations manufactured by 6 major insulin producers of which 3 are indigenous and 3 are importers. These are  marketed   by different names viz. Wosulin, Mixtard, Huminsulin, Insuman , Recombilin, Insugen, Biosulin etc., and being  used by the end users as  anti diabetic therapeutics.

1. Specifications for testing Biphasic isophane insulin injection are  spelt out only in US Pharmacopoeia which states it as L+ 5 where L is the % of soluble insulin human stated on product label (for the ratio of 25, 30 & 50  etc.).  The range under which the sample should fall will be as per the ratio.

Specifications are not spelt out in IP wherein NIB discussed the matter of specifications on March 20, 2009 in a meeting held at NIB.

1. In the Pharmacopoeia –IP, EP, BP and USP  the test parameter has been mentioned  by the  name of  soluble  insulin human content also known  as Insulin in supernatant which is  performed by Reverse Phase  HPLC  and has variations in  the test method  in different Pharmacopoeia.

Manufacturers are sending samples of rh-Insulin for testing to NIB and some of the issues of concern are :

1. I ) Different QC protocols  of testing are submitted to NIB & the  DCG(I) office.
2. II) The label claim on the product is as per IP or EP and the test method given in manufacturer’s QC protocols have been as per USP method 1/ or 2.
4. 4.Manufacturer’s were asked to present their views.  Dr. Ashis Garg Deputy Manager- Product Quality Representative -Eli Lilly gave his presentation on the specifications and the method of Biphasic Isophane Insulin Injection to be incorporated in Indian Pharmacopoeia. Dr Shinoy– Aventis Pharma and Sh.  Krishnanada Nayak –Novo Nordisk said they shall get the comments from their Global Head quarters on the compiled information by NIB.

1. Dr Minnor Senior Manager (QC), Biocon Ltd said Test method given for Zinc estimation in IP-2007 under human insulin injection is only by chemical method wherein sensitive method by Atomic absorption Spectrometer is available in Pharmacopoeia-EP/BP and USP   and accordingly has been performed by all the producers of the insulin. Provision for this method should be incorporated in IP.
2.  

• .Dr Jai Prakash, Principal Scientific Officer- IPC informed all the participants that next revision of IP is going to be effective in Jan 2010 and any incorporations / addendum required in the monograph should be sent by Nov, 2009.

After detailed discussions, the following recommendations were made:-

1. The Representatives of insulin Manufacturer’s agreed in principal that NIB will compile information on :

Name of the Test for Biphasic isophane insulin injection to be spelt out for inclusion in the IP.  Specifications for the test of “Soluble insulin human content”.  Test method for evaluation Soluble insulin human content –ratio of 25:75, 30:70, 50:50 etc   need to be spelt out in details and be incorporated in IP under Insulin Monograph. The proposal for approval is attached. 

1. Directions to perform the Sterility test for suspensions and Method of treatment to reduce the suspensions to a clear solution.Test method to be clearly spelt   out with the requirements of Membrane filtration method.All the pertaining   details will be sent to NIB by Ms Suman, Deputy Manager QC Biocon Ltd., in the 1st week of Nov 2009.

 

1. 2.Specifications and the test method for estimation of Zinc by Atomic Absorption Spectrometer will be sent by Ms Suman, Deputy Manager QC Biocon Ltd., in the 1st week of Nov 2009.
1. 3.NIB will   finalize the information of specification and test method for Biphasic Isophane Insulin Injections,Sterility and Zinc estimation by Atomic Absorption Spectrometer after getting confirmation from the Manufacturer’s by 1st week of Nov 2009. Final proposal will be sent to Indian Pharmacopoeia Commission for its incorporation in IP-2007 and addendum 2008 under the monograph of human Insulin injection.

  The meeting ended with a vote of thanks to the Chair.

 

List of Participants

Directorate General of Health Services
Dr. Jotna Sokhey	Addl. DGHS & Director, NIB, Chairperson
Participating Laboratories
Shri Anil Puri	Associate Director, Public Affairs, Aventis Pharma Ltd., New Delhi
Ms Yasmin Shenoy	Director- Regulatory Affairs Aventis Pharma Ltd., Mumbai
Dr. Elango Minnoor	Senior Manager (QC), Biocon Ltd., Bangalore
Ms. A. N. Suman	Deputy Manager (QC) Biocon Ltd, Bangalore
Mr. R. Ranjith	Senior Executive- QC Biocon Ltd., Bangalore
Mr. Prasanth Baradhawaj	Biocon Ltd., Bangalore
Dr. Mamta Singh	Senior Manager, Regulatory Affairs, Eli Lilly & Company (India) Pvt. Ltd., Gurgaon.
Sh. Ashish Garg	Deputy Manager- Product Quality Representative   Eli Lilly & Company (India) Pvt. Ltd., Gurgaon
Sh. Krishnananda A. Nayak	Manager, Regulatory Affairs & Clinical Research, Novo Nordisk (I) Pvt. Ltd., Bangalore
Dr. Raman Shetty	Medical Director Novo Nordisk (I) Pvt. Ltd., Bangalore
Dr Anand Kumar	Associate  Vice-President-Quality, Wockhardt Pvt. Ltd., Aurangabad
NABL Expert
Dr. S. K Gaind	Professor Microbiology, &  NABL Assessor, Techno Management Consultant New Delhi
Indian Pharmacopoeia Commission
Dr. Jai Prakash	Principal Scientific Officer, Indian Pharmacopoeia Commission,  Sector 23, Raj Nagar Ghaziabad
National Institute of Biologicals -NOIDA
Dr. R. N. Prasad	Deputy Director Quality Control
Dr. Renu Jain	Scientist Grade-II & Lab Head Recombinant Product lab.
Dr. J. P. Prasad	Scientist Grade-II & Lab Head Enzyme & Hormone lab and Blood Product lab.
Sh. A. K. Sahu	Scientist Grade-III, Incharge  Sterility Test Lab.
Ms. Shalini Tewari	Scientist Grade-III,Recombinant Product lab.
Ms Gurminder Bindra	Scientist Grade-III, Recombinant Product lab.
Ms Richa Barnwal	Scientist Grade-III, Recombinant Product lab.
Sh Tara Chand	Technical Assistant, Recombinant Product lab.
Ms E. Madhu	Deputy Quality  Manager.
Ms Sudha V	Deputy  Technical  Manager.