This document defines combination products and medical devices and discusses their classification and regulatory requirements. Combination products involve two or more regulated products combined in a single package. Medical devices are instruments or articles used for diagnosis, prevention, monitoring or treatment of disease. The document outlines the classification of medical devices into Classes I-III based on risk and the regulatory pathways of 510(k), reclassification, product development protocol, de novo review, and premarket approval.

1. PREPARED BY
AKASH
M.PHARMA 1ST SEM.
(PHARMACEUTICS)

2.  Two or more separate products packed
together in a single package or as a unit
comprised of drug and device products,
device and biological products or biological
and drug products.
 i.e. Drug or biologics with applicator/delivery
devices.
 Monoclonal antibody combined with a
chemotherapeutic drug.

3.  Prefilled syringes
 Patches for transdermal drug delivery
 Wound dressings whose primary purpose is
to deliver a drug
 Red blood cell processing solutions
 Contrast media

4.  Drug impregnated devices
 Injectable collagen
 Wound dressing (act as a barrier)
 Blood bags containing anticoagulant
 Drug coated devices such as catheters, shunt
sensors or pacemaker leads

5. According Therapeutic Goods Act 1989, it is
defined as any instrument apparatus, appliance,
material or other article (whether used alone or in
combination and including the software necessary
for its proper application) intended to be used for
human being for:
 Diagnosis, prevention, monitoring, treatment or
alleviation of diseases.
Investigation, replacement or modification of the
anatomy or of a physiological process.

6. Intended use and device
characteristics
Classification
Regulatory requirements
Regulatory submission
process

7. Legislation Effective date Comment
Federal Food And
Drug Act
1906 Did not include medical devices
Food, Drug And
Cosmetics Act
1938 Extended control to cosmetics and
medical devices
New Drug
Amendments
1962 The Kefauver-Harris Amendments
requiring efficacy prior to
marketing, post-marketing
surveillance, and adverse event
reporting
Medical Device
amendment
1976 Devices divided into 3 categories
with defined approvals processes
Safe medical
devices act
1990 Additional reporting and tracking
rules with emphasis on class III
devices

8. The Food & Drug
Administration
Modernization Act
1997 Allowed accelerated reviews,
regulation of advertisements, and
reauthorized for additional 5 years,
with certain technical improvement
Medical Device User
Fee & Modernization
Act
2002 Multiple reforms to medical device
regulations, authorization of user fees,
and establishment of the office of
combination products (OCP)
The Food & Drug
Administration
Amendment Act
2007 Reauthorization of medical device user
fees, new pediatrics devices provisions,
and clinical trial registry for 510(K) and
PMA eligible products
The Food & Drug
Administration
Safety & Innovative
Act
2012 Reauthorization of the medical device
user fee act (MDUFA III) for another 5
years and implementation of about 3
dozen medical device provision

9. Classification Comments
Class I Low risk of harm to user, registration only
unless 510(K) clearance required, compliance
with general controls
Class II Moderate risk of harm to user,510(K)
clearance unless waived, compliance with
general controls and special controls
Class III High risk of harm to user, often requires
premarket approval (PMA), compliance with
general controls and PMA
Combination Product Depending on the primary mode-of-action
(PMOA), may be reviewed by multiple
interagency divisions

10.  In India, the medical devices are regulated by
the Drug Controller General of India (DCGI)
within the Central Drugs Standard Control
Organization (CDSCO) under the Drug &
Cosmetics Act 1940 and Drugs & Cosmetics
rules of 1945.
 CDSCO include bone cements, heart valves,
blood component bag, condoms, cardiac
stents, disposable hypodermic needles and
orthopedic implants.

11.  Medical classification by the EU, Canadian
Drugs and Health Products (DHP), Japanese
Pharmaceuticals and Medical Devices Agency
(PMDA), Russian Roszdravnadzor (RZN) and
Australian Therapeutic Goods Act (TGA) are
subdivided into four categories as class I
through IV and Class I, IIa, IIb and III for EU,
RZN and TGA.
 The four levels of classification is based on
low, Low-moderate, moderate-high and high
risk to patients.

12.  Depending on the device, several regulatory pathways are
available to the applicants including 510(K) premarket
notification, reclassification, product development protocol
(PDP), de novo review, and premarket approval (PMA)
application.
 A 510(K) filing, the device is “cleared” if it is substantially
equivalent (SE) to an already marketed device referred as a
“predicate device”
 Reclassification process could include a petition to the
USFDA to classify the device at a lower than originally
requested, in order to receive permission for marketing.

13.  PDP’s aim is to design preclinical and clinical
studies by working closely with the USFDA in
advance of any testing.
 The de novo review or so-called automatic
reclassification is for those class I and II devices
that have no predicate device after receiving a not
substantially equivalent (NSE) response.
 PMA for higher-risk sustaining devices, often class
III that requires a major commitment by the
sponsor to conduct preclinical and clinical studies.