|
Navigating Regulatory
Landscapes:
Drug-Device Combination Products In The EU And USA?
|
Anil Chaudhari,
Founder
Operon Strategist |
What are combination
products?
Combination product is a
product composed of any combination of a drug and a
device; a biological product and a device; a drug and
a biological product; or a drug, device, and a
biological product.
These products can be
composed of two or more components, each of which
would typically be classified as a drug, a device, or
a biological product individually. These products
combine therapeutic agents with medical devices to
improve patient outcomes and treatment adherence. The
combination of these components into one single
product is intended to provide a more effective
treatment or diagnostic tool than if each component
were used separately. Examples include prefilled drug
syringes, Dose Inhalers, drug-eluting stents, insulin
pumps and certain diagnostic test kits that include
reagents and instruments. |
In this article we will discuss what are challenges
manufacturers of combination product may face when
seeking regulatory approval for their integral
combination product and what are requirements for EU and
US markets.
Regulatory Framework for Market Access and
Commercialization in Europe and US
Combination products are regulated by health
authorities such as United States (FDA) and European
Union (EMA) under specific regulatory frameworks that
address the unique challenges and requirements posed by
their combined nature.
EU regulations for Drug-device combination products
Obtaining a Notified Body Opinion (NBOp) will require a
significant investment of time and regulatory knowledge
and resources. If it is not addressed correctly, the
process may directly impact the costs and time to
approval. Manufacturers of Drug Device combinations have
to opt for Notified Body Opinion (NBOp) to get their
regulatory approvals for device components.
What is Notified Body Opinion?
According to Article 117 of MDR, Integral drug-device
combination products DDCs regulated as a medicinal
product and NB Opinion (NBOp), is required for those
products to obtain marketing authorization for a
medicinal product which forms a single integral product
with an any medical device. The Marketing Authorization
Holder is, if a NBOp is applicable, required to submit
the NBOp in conjunction with the Marketing Authorization
Application (or variation application) to the Drug
Competent Authority.
NBOp Technical file of integral Drug-Device Combination
(DDC) products need to follow stringent regulatory
requirements and technical documentation.
What should be included in NBOp submission file?
Manufacturers needs to identify all the relevant and
applicable GSPRs for their combination product with
sufficient level of evidence to meet requirements. A
significant amount of documentation for device
components are required for an NBOp which shall be
prepared and maintained by manufacturer.
● Documentation shall focus on General description
device and components making direct or indirect contact
with the human body, Mode of Action, Key Functional
Elements.
Description of variants and configurations, Accessories,
Technical specifications, features, dimensions and
performance attributes
● Comprehensive Design History File, user instructions,
product inserts, and packaging details provide essential
guidance for safe application. Harmonized standards and
common specifications backed by documents offering
robust evidence of conformity.
● Manufacturer shall not only focus on the device part,
but also on the device part´s interoperability and
compatibility with other devices, products or
substances, Threshold analysis Report and bench testing
data with RLD.
● A thorough GSPR checklist identifies and justifies
applicable regulatory requirements, while methods to
demonstrate conformity include comprehensive summaries
of results, supported by raw data and original test
report. Technical documentation shall also be supported
by detailed clinical evaluation or clinical
investigation (If applicable) inconsideration to device
type and risk category.
What is Role of Notified body?
Notified Body sets the assessment based on Article 117
(Regulation (EU) 2017/745 on medical devices (MDR)), and
Issues and opinion on the conformity of the device as
apart of drug device combination.
Points to be considered for selecting a Notified Body
to issue your NBOp
- Do they have experience with providing NBOps?
- Any existing relationships between NB and
manufacturer?
- How much charges to provide the NBOp, and is it within
your budget?
- What are the NBs’ proposed timelines for complete
process?
Post market requirements for Drug device combination
products.
Drug device combination (integral) regulated as a
medicinal product, device vigilance requirements for MDR
are not applicable but is recommended that manufacturer
has the technical knowledge and processes built into
their Quality Management System (QMS) for handling,
evaluating and investigating, where necessary, all
device-related complaints. Manufacturers should review
their pharmacovigilance agreements with suppliers to
ensure that they take into consideration additional data
that may need to be collected and communicated, such as
device malfunctions and device-related events.
Labelling and Unique Device Identification (UDI)
As integral Drug device combinations regulated as
medicinal products, the labelling and UDI requirements
under MDR are not applicable. When labelling, the
integral DDC manufacturer should follow the labelling
requirements for a medicinal product.
US regulations for Drug-device combination Products
Background
A provision in the 21st Century Cures Act enacted in
December 2016 (PL 114-255) amends section 503(g) of the
Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 USC
353(g)), which addresses combination products (21 USC
353). The amendments aim to enhance clarity, efficiency,
predictability, and consistency in premarket regulatory
expectations for combination products. This ensures that
the FDA’s components and staff coordinate appropriately on
premarket review of the combination products and that the
agency’s stakeholders are in harmony in conducting these
reviews. |
