The Medical Device Validation Handbook
1
Introduction
Countless US Food and Drug Administration
(FDA) warning letters and inspectional obser-
vation forms are issued by the agency each
year, with many citing a failure to ensure that
processes were validated or revalidated. While
it is true that corrective and preventive action
(CAPA), complaint handling, production and
process controls, and design controls are also
violations cited frequently by the FDA, process
validation is the most challenging to address.1
Process validation was sixth on the list of
reasons for issuing FDA Form 483s. Inadequate
process validation was cited 86 times in 2022,
or three out of the 10 most-cited violations.2
The problem may lie in the definition of “valida-
tion” in the agency’s Quality System Regulation
(QSR), 21 CFR Part 820. Section 820.75 of
that rule explains that validation is confirmation
by examining and providing objective evidence
that the requirements for a specific intended
use can be consistently fulfilled. The QSR also
divides process validation and design validation
into two separate entities: “Process validation
means establishing by objective evidence that a
process consistently produces a result or product
meeting its predetermined specifications.”3 The
rule further says that “design validation means
establishing by objective evidence that device
specifications conform with user needs and
intended use(s).”4
The definitions lack specificity, and compa-
nies must interpret the regulation independently.
Even more head-scratching is that “process
validation” is defined differently in a 2011
FDA guidance document as the “collection and
evaluation of data, from the process design stage
through the commercial production, which estab-
lishes scientific evidence that a process is capable
of consistently delivering a quality product.”5
The FDA’s 2011 guidance updated a 1987
process validation guidance from the agency.
Thus, the 2011 document replaces the 1987 ver-
sion, but only for human drugs, veterinary drugs,
biological and biotechnology products, finished
products and active pharmaceutical ingredients
(APIs or drug substances), and the drug con-
stituent of a combination product. The 2011
guidance does not cover medical devices rather,
guidance for devices was provided in coopera-
tion with the Global Harmonization Task Force
(GHTF), the precursor to the International
Medical Device Regulators Form (IMDRF).6
Regulatory Basics of Process
and Design Validation
Robert Falcone, Ph.D., FRAPS, FTOPRA
1
1
Introduction
Countless US Food and Drug Administration
(FDA) warning letters and inspectional obser-
vation forms are issued by the agency each
year, with many citing a failure to ensure that
processes were validated or revalidated. While
it is true that corrective and preventive action
(CAPA), complaint handling, production and
process controls, and design controls are also
violations cited frequently by the FDA, process
validation is the most challenging to address.1
Process validation was sixth on the list of
reasons for issuing FDA Form 483s. Inadequate
process validation was cited 86 times in 2022,
or three out of the 10 most-cited violations.2
The problem may lie in the definition of “valida-
tion” in the agency’s Quality System Regulation
(QSR), 21 CFR Part 820. Section 820.75 of
that rule explains that validation is confirmation
by examining and providing objective evidence
that the requirements for a specific intended
use can be consistently fulfilled. The QSR also
divides process validation and design validation
into two separate entities: “Process validation
means establishing by objective evidence that a
process consistently produces a result or product
meeting its predetermined specifications.”3 The
rule further says that “design validation means
establishing by objective evidence that device
specifications conform with user needs and
intended use(s).”4
The definitions lack specificity, and compa-
nies must interpret the regulation independently.
Even more head-scratching is that “process
validation” is defined differently in a 2011
FDA guidance document as the “collection and
evaluation of data, from the process design stage
through the commercial production, which estab-
lishes scientific evidence that a process is capable
of consistently delivering a quality product.”5
The FDA’s 2011 guidance updated a 1987
process validation guidance from the agency.
Thus, the 2011 document replaces the 1987 ver-
sion, but only for human drugs, veterinary drugs,
biological and biotechnology products, finished
products and active pharmaceutical ingredients
(APIs or drug substances), and the drug con-
stituent of a combination product. The 2011
guidance does not cover medical devices rather,
guidance for devices was provided in coopera-
tion with the Global Harmonization Task Force
(GHTF), the precursor to the International
Medical Device Regulators Form (IMDRF).6
Regulatory Basics of Process
and Design Validation
Robert Falcone, Ph.D., FRAPS, FTOPRA
1