Tests on finished formulation is given here

1. 1. i.Identification
   2. ii.Potency
   3. iii.Purity
   4. iv.Safety and
   5. v.Physical Quality

    

2. Tests   for characterization of human insulin API is given here

   i.    Peptide mapping for protein identification
   ii.    Purity for Related proteins
   iii.   Purity for Higher molecular weight proteins

   1. Tests are carried out as per the requirements given in is given here 
   2. i.Indian Pharmacopoeia-2007,
   3. ii.European and British Pharmacopoeia
   4. iii.US Pharmacopoeia

    

   Quantity of samples required for testing

   The quantity has been calculated on the basis of tests required for complete batch testing and the quantity to be retained. Accordingly the requirement is based on pack size of formulations available in the market. The number of Vials or Prefilled syringes-PFS   that should be sent for testing are:

   Packing	Quantity required		Total
   	Test	Retained
   Vials-10 mL	14	14	28
   PFS-3 mL	28	28	56

    

3. Scrutiny of Protocols details are here

4. 
      Information required to be submitted for evaluation of  QC tests on formulations and human insulin bulk have been prepared .The format on which the information should be sent is available on the web site.

   1. Preparation of Reference Standards Participation in Inter laboratory Collaborative study

    

   1. NIB has taken up a program for Preparation of insulin National Reference Standard through Inter laboratory comparisons. The study assist in the evaluation of competence of laboratories to meet the Proficiency program complying with the NABL 162 Guideline Issue No: 04 2008.The Purpose of the study is:
   1. i.To determine the performance characteristics of a method, by identifying inter laboratory differences.

    

5. ii.To assign property values to human insulin Active Pharmaceutical Ingredient- API and assess their suitability by measurement method   based on Calibration hierarchy of the highest metrological order.see callibration Hierarchy

6.  

   1. The aim of the Collaborative study is to set out the criteria in which collaborators must meet to be recognized as competent to supply Reference standard of stated property for human Insulin. This applies to:
   1. i.Manufacturer’s, Regulatory bodies. The samples provided to each participant laboratory shall remain   homogenous so that any results later identified as extreme should not be attributed to any significant sample variability.

    

   1. ii. The study possesses comparison of test results obtained by 5 testing laboratories. NIB as one of the participating laboratories is a controlling and coordinating the functions of calibration performances and characterizations by means of inter-laboratory comparison. It consists of two parts viz.

   Part-I Calibration forPotency as per requirements laid down in IP-2007.

   1. The test is performed on Insulin human Active pharmaceutical ingredient (API) purchased from the Manufacturer’s. After completion of the Potency test the results are returned to the coordinating body and compared with the assigned values stated in the Certified Standard.
   2. Calibration for potency determination is done as per Assay by HPLC method. In Each performance the coded sample is used as Analyte and calibrated against the Certified Standard of human Insulin to determine the potency value.   Property value in IU/ mg is calculated on as such basis to give an indication of the performance of the individual laboratories. The method for  calculation  is  attached in the study Protocol

   Part-II   Characterization of the human insulin- API as per requirements laid down in IP-2007:

   1. Identification of proteins  by Peptide mapping  using HPLC
   2. Impurity for related proteins by HPLC assay
   3. Impurity for Higher molecular weight  proteins by HPLC assay
   
   

   Participation in the Inter laboratory Collaborative study.

       Nature and the purpose of the program;

   1. i.Indian Pharmacopoeia-IP-2007 has a Monograph on human Insulin. However the National Reference Standard on insulin with any metrological trace ability is not available so far and need is felt.
   3. ii.The certificate of Analysis   on Insulin working standard also varies from one Manufacturer to another as there  have been  no guidelines and Recommendations laid down for National Reference  standard.
   1. iii.International biological standards are the “Primary standards” against which Secondary standards are calibrated. Secondary standards may be –   a) National standard   b) Regional standard, c) Working Reference material.

    

   Procedure for the manner in which the participants are selected.

   1. i.NIB organized a meeting of Insulin Manufacturer’s in March 20, 2009 to discuss the modalities for preparation of Insulin National reference standard. All the Manufacturer of insulin, indigenous and whose product is being imported in the country were invited to participate in the meeting. The meeting was attended by Dr. G.N. Singh, Secretary-cum-Scientific Director, Indian Pharmacopoeia Commission, Ghaziabad, and the representatives of Drug Controller General (India); M/s Wockhardt Ltd.; M/s Biocon Ltd.; M/s Novo Nordisk and concerned officers of NIB. 

    

   1. ii.The representatives of the manufacturing institutions agreed to participate in the study as availability of national reference standard was a felt need. Minutes of Meeting along with Power point presentation  were  communicated  (details are here)
   1. iii.Manufacturers were sent letters to confirm the cost of insulin bulk and confirmation of their participation in the collaborative study. The responses were obtained from the Manufacturers confirming their participation and the cost of material. Next meeting scheduled to be held on October 27, 2009 to discuss the study protocol and time lines of the study.

    

   The Participant laboratories involved in the program are from the Manufacturing facility and National Control Laboratory:

   S. No	Name of the Participant lab
   1	M/s Biocon- Biopharmaceuticals Pvt. Ltd., Bangalore
   2	M/s M . J. Biopharm- Navi Mumabi
   3	M/s Novo Nordisk- Pvt. Ltd- Bangalore  Parent company -Sweden
   4	M/s Wockhardt Ltd., Aurangabad
   5	National Institute of Biologicals NOIDA

   There are advisory panel for various functions which includes experts from:

   1. Indian Pharmacopoeia Commission

   Dr G. N. Singh, Director Cum Secretary
   Sector 23, Raj Nagar Ghaziabad
   E mail: ipclab@vsnl.net

   1. Dr Vishwanath Malkar

   CEO, Reliance Life Sciences
   Mumbai
   E mail: vishwanath_malkar@relbio.com
   Fax: 022-67678099

   1. Drugs Controller General  of India or his representative 

   FDA Bhawan, New Delhi
   E mail: dci@nb.nic.in

    

   Expansion of activities
   
8.  Institute has expanded its activities by taking up the QC evaluation of other recombinant
   DNA derived Biologicals. The Biologicals taken up in phase manner as per requirements of IP, EP/ BP, USP are:
   1. i.Interferon alpha 2b
   2. ii.Granulocyte colony stimulating factor ,G-CSF
   3. iii.Granulocyte macrophage colony stimulating factor , GM-CSF
   4. iv.Insulin  Analogs –Aspart and Lispro

    

   1. To maintain a repository of cell lines traceable to ATCC-USA. Cell lines Madrin Darby kidney and NSF-60 are required for Potency test Interferon alpha 2b, G-CSF and GM-CSF for which the national repository bank will be maintained at NIB. 

    

9.   Scientific Links:
   
10. Name of organization / Instt/ body-National or International

    1.  Secretary-cum-Scientific Director,
    Indian Pharmacopoeia Commission,
    Raj Nagar, Sector 23,
    Ghaziabad
    E mail: ipclab@vsnl.net

    1.  2. Drugs Controller General (I),

    First Floor, CHEB Campus,
    Room No. 111, FDA Bhawan,
    New Kotla Road,
    New Delhi-110001
    E mail: dci@nb.nic.in

    3.National Institute for Biological Standard and Control (NIBSC),

    Blanche Lane, South Mimms,
    Potters Bar, Hertfordshire EN6 3QG,
    United Kingdom
    E Mail: enquiries@nibsc.hpa.org.uk
    Fax: +44(0)1707641050

    1. 4.United States Pharmacopoeia (USP)

    12601 Twinbrook parkway, Rockville,
    Maryland 20852-1790. USA
    E Mail: foreigncontrol@usp.org

    1. 5.European Directorate for the Quality of Medicines & Health Care (EDQM)

    Council of Europe, 7allée Kastner, CS 30026, F-67081,
    Strasbourg, France
    E Mail: Through www.edqm.eu
    Fax: +33(0)388412771

    1. 6.American Type Culture Collection (ATCC)

    P. O. Box No. 1549, Manassas, VA 20108.
    USA
    E Mail: tech@atcc.org
    Fax: 703365-2750

    6(a)American Type Culture Collection (ATCC)
    LGC Prochem India Pvt. Ltd., Unit No. 401-402,
    Model Export Bhavan, Plot No. 488B, VITC,
    14th Cross, 2nd stage, Peenya,
    Bangalore-560058 India
    E Mail: KVS@usp.org, AD@usp.org, RKI@usp.org, GM@usp.org
    Fax: +91-4023480088

    Manufacturer’s –National or International

    M/S. Wockhardt Pvt. Ltd. Biotech Park, H-14/2, MIDC Waluj, Aurangabad-431126 Tel. 91-240-6626444, 2563361 Fax : 91-240-6626333	M/S. M.J. Biopharm Pvt. Ltd. L-7, MIDC Area, Taloja, Navi Mumbai, Dist. Raigad (M.S.) Tel. 91-22-27402331, 27410956/0770 Fax : 91-22-27402311 E.mail : hpandit@mj-india.com
    Novo Nordisk (I) Pvt. Ltd. Plot No. 32, 47-50, EPIP Area, Whitefield, Bangalore-560066. e.mail : Krin@novonordisk.com Fax : 91-80-41123518	M/S. Aventis Pharma Ltd. Unit No. 5&6, 4th Floor, D-2, Southern Park, Saket District Centre, New Delhi-110017 e.mail : anil.puri@sanofi-aventis.com Fax : 91-11-26539223
    M/S. Biocon Biopharmaceuticals Pvt. Ltd. 20th KM Hosur Road,Electronics City, Bangalore-560100. e.mail : personalgroup@gmail.com Tel. 91-80-28523434 Fax: 91-80-2852	Eli Lilly & Company (India) Pvt. Ltd. Plot No. 92, Sector 32, Institutional Area, Gurgaon. e-mail : singh_mamta@lilly.com Fax : 91-124-4753013
    Reliance Life Sciences Pvt. Ltd. R282, TTC Area, MIDC Rabale, Thane Belapur Road, Navi Mumbai-400701. e.mail : vishwanath_malkar@relbio.com Fax No. 022-67678099

         

    Scientific Documents for References

    1. i.ISO guide G-34; 2000:  General requirements for competence of Reference material producers.

     

    1. ii.ISO guide 17511; 2000: in vitro diagnostic medical devices –Measurement of quantities in biological samples –Metrological traceability of values assigned to calibrators and control materials.
    2. iii.ILAC-G12; 2000: Guidelines for the requirements  for the competence of Reference material producers (available on site)

     

    1. iv.Guidelines for Proficiency testing program for testing and calibration  laboratories , NABL 162 issue No 4:  24.03.2008 
    1. v.Guidelines for  inter laboratory comparison for Calibration laboratories where formal PT programmes are not available,  NABL 164 issue  No 01: 28.04 2005

     

    1. vi.Pharmacopoeias: Indian Pharmacopoeia-2007, European Pharmacopoeia 6.0 and United State Pharmacopoeia 32
    
    

      UPDATES

    1. Update on Insulin Monograph

     

    1. i.Inter-laboratory collaborative study for preparation of human insulin National Reference standard. Meeting shall be held on Oct 27, 2009 at NIB
    2. ii.Meeting of Insulin manufacturer’s for incorporation of specifications and method on biphasic Isophane insulin preparations.  Meeting to be held on Oct 27, 2009 at NIB.

     

11. iii. Invited participants  for the meeting are:

    1. a.Indian Pharmacopoeia commission
    2. b.Drugs Controller General  (India) 
    3. c.M/s Aventis Pharma-Delhi
    4. d.M/s Biocon Ltd., Bangalore
    5. e.M/s Eli-Lilly-Gurgaon
    6. f.M/s MJ Biopharm-Navi Mumbai
    7. g.M/s Novo Nordisk-Bangalore
    8. h.M/s Wockhardt –Aurnagabad

     

    1. FORTHCOMING EVENTS

    The monograph for Insulin Analogs Glargine, Aspart and Lispro and are not available in Indian Pharmacopoeia which is a need felt in the country and this need to be incorporated. This will be taken up in coordination with the manufacturer of Insulin Analogs and the Indian Pharmacopoeia commission. 

     

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