Record Note of the Consultative Meeting for discussing the Evaluation of Biochemical Kits and Glucometers + Strips at the National Institute of Biologicals, NOIDA on Dec 09, 2010

A Consultative Meeting for discussing the Evaluation of Biochemical Kits and Glucometers + Strips was held under the Chairpersonship of Dr Jotna Sokhey, Addl DGHS and Director, NIB on 9 December 2010 at the National Institute of Biologicals, NOIDA. Dr G S Toteja, Scientist F, Division of RHN, ICMR; Dr P B N Prasad, DDC (I), CDSCO; Dr Ramesh K L, Head of Biochemistry Department, Ram Manohar Lohia Hospital; Dr Madhur Gupta, WHO Country office for India; Dr Nishant Dafale and Ms M Kalaivani, representatives of Indian Pharmacopoeia Commission; representatives of Industry and the concerned officers from NIB attended the meeting. The list of participants is given at Annexure 1.

Dr Sokhey welcomed the participants and said that the purpose of the meeting was to discuss the parameters and methodology for the quality assessment of biochemical reagents widely used for health screening and monitoring the effectiveness of treatment in the hospitals and other health settings. She said that, data had been generated at NIB for Quality assessment of glucose reagent used in automated analyzers, which would be presented. Similarly, parameters for the assessment of glucometers and strips would also be presented.

Dr Toteja said that the meeting on the quality assessment of biochemical reagents and glucometers was timely as there was a wide variety of reagents and glucometers in the market. Setting up quality standards and facilities for testing would be useful to the clinicians as well as researchers undertaking community based surveys.

Dr P B N Prasad said that as there were no pharmacopoeial guidelines, it was important that a consensus be reached on the best method for quality assessment. He said that though currently biochemical kits were not included in the critical list, this could be revised subsequently and facilities should be developed for testing.

Dr Madhur Gupta supported the desirability of agreed standards for testing as the quality of the reagents could be critical for case management of diabetic patients in case of glucose reagents. She said that she was not aware of Quality Assurance practices in other countries in the Region but would try to get information on the subject.

The presentation on Evaluation of Biochemical Kits was delivered by Ms Ajanta Sircar, Scientist Grade III, Biochemistry Laboratory. She said that the laboratory had standardized and validated a method for evaluation of Biochemical Kits using Glucose reagent. The Acceptance criterion for performance evaluation was based upon calculation of Total Error. Parameters Range, Linearity, Precision and Bias were studied as per Clinical Laboratory Standards Institute (CLSI) guidelines; CLSI EP6- A, CLSI EP5- A2 and CLSI EP9- A2. Apart from use of Calibrators and Controls, evaluation procedure involved testing of 150 patient plasma samples in various glucose concentration intervals. Ms Sircar mentioned that to undertake the tests as per the guidelines, reagents for carrying out 1200 tests was necessary and an equal quantity would be required for retests, if required and for keeping as retained samples. A total of 40 working days would be required to complete the evaluation of a Batch of reagent, since testing of each parameter as per guideline and statistical analysis of the data required following of lengthy protocols.

In the interactive session that followed, Dr Toteja appreciated the work done and wanted to know more about the sample distribution over various glucose concentration intervals. He suggested that a protocol be developed by NIB and made available. He was informed that glucose concentration levels within <50mg/dL to 500mg/dL were used as per CLSI guidelines. Further, Dr Toteja wanted to know, how batch to batch variation for a reagent would be analyzed and was told that it would be done by checking the difference between the calculated Total Error for the concerned batches.

The representatives of the industry supported the idea of setting up standards for testing so that the quality of the kits and reagents was assured. Shri. Mittal from Medsource Ozone expressed concern over the requirement of protein based calibrators since human plasma was difficult to source in India. When asked about the way Reagents meant for use on Closed Systems would be analyzed, Dr Sokhey informed that presently only reagents that were being used on open ended systems would be tested. On enquiring about the way pre-analytical variation of the clinical sample would be taken care of, Shri. Eswaran from Roche Diagnostics was told that lipemic, hemolyzed or icteric samples would be excluded. Concern was expressed by the members from the industry over the 2 months time duration required for testing of a batch of reagent as this could lead to disruption in supplies since only 3 months stocks were usually maintained by them. Apart from this, cold storage facilities at the airports were also limited. They suggested that random batches may be tested instead of all batches. They assured that necessary documents of in- house testing would be provided for all batches. On being told about the delay caused at the port of entry while getting clearance, Dr Prasad assured the industry representatives that Govt. had already initiated steps for creating a Pharma Zone at the Delhi Airport where facility for maintenance of cold chain for various products will be taken care of. He said that the concerns raised by them would be looked into by CDSCO.

The tea break was followed by the presentation on Performance Evaluation of Glucometers + Strips by Ms A Sircar, Scientist-III of NIB. She said that a method for evaluating Analytical performance of Glucometers + strips had been standardized at NIB based upon the guideline; ISO 15197. Parameters Precision and System Accuracy will be tested and Acceptance criterion adopted is as per the guideline. To overcome the limitations with respect to collection of sufficient volume of capillary blood sample (prescribed choice of sample according to guideline) for use over both measurement procedures, i.e., the laboratory reference method and the Glucometer; use of venous plasma samples spiked with O- negative RBC has been made. For evaluation of a batch of reagent strips, 40 working days and use of 10 glucometers + 1200 reagent strips will be required.

During the interactive session, noting the ISO 15197- System Accuracy requirement (95% of individual glucometer results to fall within + 15mg/ dL of the reference value for samples at glucose concentration < 75mg/ dL & 95% of individual glucometer results to fall within + 20% of the reference value for samples at glucose concentration > 75mg/ dL), Dr Toteja expressed concern over the allowable limit of + 20% of the reference value since such a broad margin would contribute to diagnostic inaccuracy. He was informed that the + 20% limit was as per the guideline and the data generated on glucometers tested at NIB show, 83.33% and 88.54% of the Glucometer results to be within + 10mg/dL and + 10% of the reference value for samples in the concentration intervals <80mg/dL and >80mg/dL respectively. Ms Seema, Quality Manager from Roche Diagnostics pointed out that manufacturers of glucometers all over the world follow the referred guideline and that these devices are only meant for self testing and management of diabetics and not for diagnostic use. She also added that FDA followed the same guideline and abided by the prescribed acceptance criterion. The discussion that followed led to the conclusion that the System Accuracy acceptance criterion may be reviewed as the results obtained from glucometers should not only protect the interest of clinicians for better patient management but also aid researchers in picking up a potential diabetic during community health surveys. Subsequently it was agreed that another meeting for discussing these aspects may be convened.

Regarding choice of sample, representatives from Morepen and Microgene Diagnostics pointed out that capillary blood was the prescribed sample in ISO15197. Ms Sircar drew attention to the fact that the adopted sampling procedure was not only practical but the results obtained show a Repeatability estimate (%Coefficient of Variation) in the range of 1.5 to 3.4 over five concentration intervals of Glucose covering <50mg/dL to ~400mg/dL. These figures were comparable to the acceptable limits for Repeatability estimates of an analyzer based method. Dr Toteja suggested that test protocols from manufacturing houses may be reviewed and a protocol may be prepared by NIB which could be circulated for review by the experts before finalization. The industry representatives were requested to share their in- house batch release/ QC protocols with NIB so that a practical and acceptable protocol could be developed. It was assured that information provided to NIB would be kept confidential. Dr P B N Prasad also reflected that establishment of a standard is a necessity. It was decided that the next meeting would be held in the middle of February 2011 to discuss the protocol for testing

Dr J P Prasad thanked the participants for their valuable comments and suggestions. The meeting ended with a vote of thanks to the Chair.

LIST OF PARTICIPANTS

S.No	Name of the participant	Position/Designation	Representing Manufacturer/ Institute
1.	Dr.Jotna Sokhey	Addl.DGHS & Director, NIB	National Institute of Biologicals, NOIDA.
2.	Dr.G.S.Toteja	Scientist-F, Division of RHN	Secretary (DHR)&DG, ICMR, New Delhi
3.	Sh.P.B.N.Prasad	DDC(I)	CDSCO, New Delhi
4.	Dr.Nishant Dafale	Senior Scientific Officer	IPC, Ghaziabad
5.	Mrs.M.Kalaivani	Pharma.Associate	IPC, Ghaziabad
6.	Dr.Madhur Gupta	NPO (Essential Drugs & Medicines)	WHO Country Office for India, New Delhi
7.	Dr.K.L.Ramesh	Senior Biochemist & Head, Biochemistry	RML Hospital, New Delhi
8.	Sh.S.Eswaran	Manager-Exports & Safety	Roche Professional Diagnostics, Mumbai
9.	Ms.Seema Nariani	Manager Quality & Customer Care Diabetes Care	Roche Professional Diagnostics, Mumbai
10.	Dr.K.Krishnan	Sr.Manager, Technical Support & QS	Ortho Clinical Diagnostics Division, Johnson&Johnson Ltd
11.	Sh.Atanu K.Sur	Retail Channel Manager, Diabetes Care	Abbott Healthcare Pvt. Ltd, Mumbai
12.	Sh.H.Sachan	Consultant, Diabetic Care	Abbott Healthcare Pvt. Ltd, Mumbai
13.	Sh.Imran Parvez	Head, Regulatory Affairs & Quality Systems	Siemens Healthcare Diagnostics Ltd, Gurgaon
14.	Sh.P.Siva Kumar	Quality Assurance	Siemens Healthcare Diagnostics Ltd, Gurgaon
15.	Sh. Anand	Quality Assurance	Siemens Healthcare Diagnostics Ltd, Gurgaon
16.	Sh.Pranav Naik	Marketing Manager	Span Diagnostic Ltd, Surat
17.	Mr.K.Sridhar	Dy.General Manager, R&D and QA,	Transasia Bio-medicals Ltd, Mumbai
18.	Sh.Rajeev Pant	Sales Manager	Morepen Diagnostics, Mumbai
19.	Sh.S.C.Kalra	Logistics Manager	Morepen Diagnostics, Mumbai
20.	Sh.Rajiv Singh	Manager, QA	SD Standard Diagnostics, Gurgaon
21.	Sh.Jyoti Bhasin	General Manager, Sales & Marketing	Microgene Diagnostic Systems Pvt Ltd,New Delhi.
22.	Sh.S.Ahuja		Microgene Diagnostic Systems Pvt Ltd,New Delhi.
23.	Sh.Prateek Mittal	Marketing Manager	Med Source Ozone Biomedicals, Faridabad.
24.	Mrs.Sumedha Mehta	Manager, QA/R&D	Med Source Ozone Biomedicals, Faridabad.
25.	Dr J P Prasad	Scientist Grade II & Head, BP Lab, E&H Lab, Biochemistry	National Institute of Biologicals, NOIDA
26.	Ms Sudha Gopinath	Scientist Grade III, Blood Products Laboratory	National Institute of Biologicals, NOIDA
27.	Dr Rajesh Sharma	Scientist Grade III, Blood Products Laboratory	National Institute of Biologicals, NOIDA
28.	Ms Shalini Tiwari	Scientist Grade III, Recombinant Products Lab.	National Institute of Biologicals, NOIDA
29.	Mr Nandagopal	Junior Scientist, Enzyme & Hormone Lab.	National Institute of Biologicals, NOIDA
30.	Ms Rashmi Shrivastav	Scientist Grade III, Enzyme & Hormone Lab.	National Institute of Biologicals, NOIDA
31.	Sh Brij Bahadur	Lab. Technician, Biochemistry Lab.	National Institute of Biologicals, NOIDA
32.	Ms Ajanta Sircar	Scientist Grade III, Biochemistry Lab.	National Institute of Biologicals, NOIDA