1. FDA standards for IVDs. Why does FDA need them?
Mehis Pold, M.D.
July 9, 2010
What is a standard?
Put at its simplest, a standard is an agreed, repeatable way of
doing something. It is a published document that contains a
technical specification or other precise criteria designed to be
used consistently as a rule, guideline, or definition.
1

2. The U.S. FDA – The United States Food and Drug
Administration
Title 21 CFR Part 820 – Title 21 of Code of Federal
Regulations, Part 820
• Title 21 describes the rules of FDA
• Part 820 contains the quality system regulation (QSR) for
medical devices including In Vitro Diagnostic Devices (IVDs).
2

3. Part 820 in a nut shell:
Design, production, and distribution of medical
devices including IVDs must be carried out in a
transparently controlled and documented
environment by an appropriately trained staff in
order to meet the established quality and
performance characteristics.
3

4. PART 820 QUALITY SYSTEM REGULATION
Subpart A -- General Provisions
Subpart B -- Quality System Requirements
Subpart C -- Design Controls
Subpart D --Document Controls
Subpart E -- Purchasing Controls
Subpart F -- Identification and Traceability
Subpart G -- Production and Process Controls equipment.
Subpart H -- Acceptance Activities
Subpart I-- Nonconforming Product
Subpart J -- Corrective and Preventive Action
Subpart K -- Labeling and Packaging Control
Subpart L -- Handling, Storage, Distribution, and Installation
Subpart M -- Records
Subpart N -- Servicing
Subpart O -- Statistical Techniques
4

5. HISTORY of IVD STANDARDS:
The Clinical Laboratory Improvement Amendments of
1988: IVDs needed regulations to unify their performance & quality
characteristics in order to better serve the public.
What is and IVD standard? IVD standard is a published document
that contains a technical specification or other precise criteria designed
to be used consistently as a rule, guideline, or definition. They are
created by bringing together the experience and expertise of all
interested parties including the manufacturers, users, and regulators of
IVDs.
Definition of IVD: IVDs are products that employ reagents,
instruments, and systems intended for use in diagnosis of disease or
other conditions, including a determination of the state of health, in
order to cure, mitigate, treat, or prevent disease or its sequelae. Such
products are intended for use in the collection, preparation, and
examination of specimens taken from the human body.
5

6. What happens if you developed a novel technology for
which FDA simply does not have rules?
Are you doomed?
Certainly not!
(1) Time
(2) Patience
(3) Dialogue
Pre-IDE: The "pre-IDE" process is an informal "pre-submission" process. It may involve:
sending analytical or clinical protocols to FDA for review and comment before
proceeding with studies, or meeting with FDA to discuss protocols and/or possible
regulatory pathways. The term "pre-IDE" has been used for this process so that FDA can
assign it an official tracking number, just as numbers are assigned to 510(k)s and PMAs.
This does not mean that manufacturers are required to subsequently submit an IDE
application.
6

7. R&D Manufacturing FDA regulatory filing
Stable prototype = Fully Full Part 820-compliance
established performance possible only if fully established
characteristics performance characteristics exist.
Otherwise there is nothing to
compare the QC results to!
Evaluation of Precision Performance of Quantitative Measurement Methods EP05-A2
Evaluation of the Linearity of Quantitative Measurement EP06-A
Interference Testing in Clinical Chemistry EP07-A2
Method Comparison and Bias Estimation Using Patient Samples EP09-A2
User Protocol for Evaluation of Qualitative Test Performance EP12-A2
Evaluation of Matrix Effects EP14-A2
7

8. FDA values tradition and clarity. Therefore, Title 21
CFR 820 compliance must support clarity.
Without the IVD standards, FDA would not know how to properly go about
the approval process. The IVD standards equip not only the FDA but also
the inventors and manufacturers with useful technical information that
promotes the quality of clinical tests. Without the IVD standards, we would
be back to the pre-CLIA 88-period that witnessed the deficiencies in
laboratory testing due to the lack of clear standards.
8

9. Title 21 CFR 820 CONCLUSIONS:
Title 21 CFR 820-compliance is essential for
successful FDA filing.
Full Title 21 CFR 820-compliace is enabled by
complete R&D based on IVD standards
agreed upon with FDA during pre-IDE.
Full 820-compliance is facilitated by pre-IDE
process. Especially when IVD stems from
novel technology.
The U.S. FDA is a partner for IVD companies.
9