Setting initial Expiry Date of an IVD per BS EN 23640:2015

Ronen E

Problem Solver
Staff member
Moderator
#11
Nevertheless, like in any validation, there is probably an expectation for statistical rigor. Not in terms of “lots” but in terms of number of individual samples, analysis methods etc.

The requirement for 3 lots in (manufactured) raw materials stems from the assumption that the product is expected to be uniform (which is obviously not the case with biological samples). As we all know, in reality the product is never 100% uniform - there is variation within-specification and there is noise (variation in uncontrolled variables), and the 3 lots requirement is supposed to (minimally) account for such real-life variation.

I am confident that if you analyse 30 individual samples (not from the same source) per treatment, you will be well-positioned for a rigorous statistical analysis (assuming you are analysing variables and not attributes - the latter will require much larger sample sizes). If samples are difficult to obtain, 20 might do; 15 would be marginal. Below 10-15, statistical distribution determinations become questionable; below 6, standard deviation falls and below 3 even the mean may not be seen as representative.
 
Elsmar Forum Sponsor
E

EthanLoh

#12
Specimen stability studies are always a tricky issue.

Firstly, there are no defined requirements. Unlike reagents stability we can used US FDA or EN standards. Most IVD manufacturers do not even conduct such studies.

Secondly, certain specimens are different to obtain. E.g. SARs, Ebola, etc....
Most of the time, IVD manufacturer need to collaborate with external hospitals or research laboratories for performance evaluation.

Thirdly, different reviewers (US FDA vs EU Notified Bodies) may have different opinions.

When I was working as a regulatory affairs of an IVD company, I removed the portion of specimen storage in the IFU and replaced it with refer to individual clinical laboratory specimen storage procedure.

Hope it help :)
 
K

Karen747

#13
Ronen E said:
Nevertheless, like in any validation, there is probably an expectation for statistical rigor. Not in terms of “lots” but in terms of number of individual samples, analysis methods etc.

The requirement for 3 lots in (manufactured) raw materials stems from the assumption that the product is expected to be uniform (which is obviously not the case with biological samples). As we all know, in reality the product is never 100% uniform - there is variation within-specification and there is noise (variation in uncontrolled variables), and the 3 lots requirement is supposed to (minimally) account for such real-life variation.

I am confident that if you analyse 30 individual samples (not from the same source) per treatment, you will be well-positioned for a rigorous statistical analysis (assuming you are analysing variables and not attributes - the latter will require much larger sample sizes). If samples are difficult to obtain, 20 might do; 15 would be marginal. Below 10-15, statistical distribution determinations become questionable; below 6, standard deviation falls and below 3 even the mean may not be seen as representative.
Specimen stability studies are always a tricky issue.

Firstly, there are no defined requirements. Unlike reagents stability we can used US FDA or EN standards. Most IVD manufacturers do not even conduct such studies.

Secondly, certain specimens are different to obtain. E.g. SARs, Ebola, etc....
Most of the time, IVD manufacturer need to collaborate with external hospitals or research laboratories for performance evaluation.

Thirdly, different reviewers (US FDA vs EU Notified Bodies) may have different opinions.

When I was working as a regulatory affairs of an IVD company, I removed the portion of specimen storage in the IFU and replaced it with refer to individual clinical laboratory specimen storage procedure.

Hope it help :)
Thank you both, you have been a great help!! I find it's really beneficial to get other peoples opinions on topics that are quite subjective. :):):)
 
Thread starter Similar threads Forum Replies Date
J Setting accuracy limit for a read out General Measurement Device and Calibration Topics 4
B Setting flexible packaging specification limits ISO 14971 - Medical Device Risk Management 4
I Setting action completion dates Nonconformance and Corrective Action 3
S Qualification question - ISO 13485 - Setting up a small lab Reliability Analysis - Predictions, Testing and Standards 2
S Heat Sealers Upper and lower limit setting during OQ for Heat Sealer Qualification and Validation (including 21 CFR Part 11) 0
Ed Panek GDPR in Urgent Healthcare Setting Other ISO and International Standards and European Regulations 1
M Setting deadlines (ex. 45 days) for Document Registration & Review Cycle Document Control Systems, Procedures, Forms and Templates 3
Ashok sunder What are the criteria for setting a target KPI value against a quality objective? Benchmarking 7
K Setting Quality Objectives (for the first time) AS9100, IAQG, NADCAP and Aerospace related Standards and Requirements 17
R ISO 11137 Gamma sterilization validation, dose setting, dose audit Other Medical Device Related Standards 1
M Best Practice for setting tolerances on a Drawing Inspection, Prints (Drawings), Testing, Sampling and Related Topics 8
T Setting up a quality department in an Engineering Firm Quality Management System (QMS) Manuals 11
B Software for setting up New Warehouse Manufacturing and Related Processes 0
S Setting up the process - First piece inspections Statistical Analysis Tools, Techniques and SPC 3
A Add-On software for VMC to calculate setting time, Idle Time, OEE etc.. Manufacturing and Related Processes 2
G Setting Up a Basic Quality Lab for a small manufacturing company General Measurement Device and Calibration Topics 2
A Setting up an LLC as a Consultant Paid Consulting, Training and Services 27
Q Setting Quality Objectives with a Timeframe ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 4
Proud Liberal Setting up Prolink's QC-Gage to a Keyence IM-6225 Vision System Statistical Analysis Tools, Techniques and SPC 2
P Setting Acceptance Quality Limits (AQL) for New Medical Devices ISO 13485:2016 - Medical Device Quality Management Systems 4
Hami812 Cpk Setting Tolerance - Cart before the Horse? (Wifi Routers) Capability, Accuracy and Stability - Processes, Machines, etc. 3
K Bioburden 0 cfu for Dose Setting using the VDmax25 Other Medical Device Related Standards 9
A New company, no employees, Setting up a QMS ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 5
F Setting up a new sterilization unit in a new facility 21 CFR Part 820 - US FDA Quality System Regulations (QSR) 6
C ISO 14001 Recertification without setting Targets ISO 14001:2015 Specific Discussions 3
T Guidance - Setting up an integrated quality & environmental management system Career and Occupation Discussions 12
M Setting up a M1003 QA Program for the AAR Various Other Specifications, Standards, and related Requirements 2
A Setting up a Medical Device Distributor in Malaysia Other Medical Device Regulations World-Wide 16
R Irradiation Sterilization Dose Setting and Dose Audit Flow Charts ISO 13485:2016 - Medical Device Quality Management Systems 0
J Setting Up New QMS - New US Location ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 2
A Setting air gauging outside of a part tolerance Capability, Accuracy and Stability - Processes, Machines, etc. 2
S Target Setting - Internal metric(s) to drive Internal Processes Six Sigma 1
S MSA Help or guidelines - Plastics - Setting up an MSA on a multi cavity fixture Gage R&R (GR&R) and MSA (Measurement Systems Analysis) 2
G Setting up a corporate umbrella QMS ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 4
T Setting Quality Objectives ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 10
W Setting up from scratch - Looking for help (ISO9001 / ISO13485) ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 4
F Setting up a New QMS for Certification when ISO 9001 is about to Change ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 23
P New to AS9100 Rev. C - Setting KPIs and FAI Reports AS9100, IAQG, NADCAP and Aerospace related Standards and Requirements 14
B Setting Lower Control Limit on Attributes Charts Statistical Analysis Tools, Techniques and SPC 9
J Lean 5S - Setting Min/Max Inventory Levels Lean in Manufacturing and Service Industries 3
V Setting Specification Limits for UOD (Uniformity) for Live Bacteria or Spores Pharmaceuticals (21 CFR Part 210, 21 CFR Part 211 and related Regulations) 4
D How do I make the Corporate QMS work in the manufacturing setting? ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 9
J Setting Quality Objectives for Service, Repair and Sales ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 4
Q Setting Specification Limits Quality Tools, Improvement and Analysis 11
C Mitutoyo SJ210 Settings - Is there an Industry Standard Surface Measurement Setting? General Measurement Device and Calibration Topics 4
W Setting up a Zmike for Pin Gage Calibration General Measurement Device and Calibration Topics 3
W Zero setting of correlation graph when plotting best fit linear regression Statistical Analysis Tools, Techniques and SPC 7
G Setting up a 3 Factor, 2 Level,2 response DOE in Minitab Using Minitab Software 7
B Quality Goals and Improvements in a Bioanalytical Laboratory Setting Quality Tools, Improvement and Analysis 1
N Setting up MSA system in a machine shop environment. Gage R&R (GR&R) and MSA (Measurement Systems Analysis) 5

Similar threads

Top Bottom