Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2021 7
of Federal Regulations (CFR)] Part 4 provides rudi-
mentary guidance about which elements of either
the drug code or device code in the CFR should
be integrated, but it is not as easy as it sounds (4).
PharmTech: What are some best practices when
developing combination products?
Lambert (Pharmatech Associates): Developing a robust
target product profile, design specification, and risk
assessments early on in the development of the com-
bination product lifecycle is critical to minimizing
risk as the product moves from the bench to market
authorization. Clearly defining drug performance,
device performance, and product performance qual-
ity attributes, with tests early on, enable the develop-
ment of robust manufacturing processes and help
to ensure consistency and quality of the manufac-
tured product, for product that has a higher degree
of safety and quality. I have worked on a number
of products that, while approved, were difficult to
manufacture. Because of this, a significant number
of batches failed to meet release specifications and
caused significant losses in revenue and time. Also,
ensuring that you have a clear framework for using
design controls is essential to support the data pro-
vided in your submission.
PharmTech: What kind of experts from the medi-
cal device side should be involved with the drug
development team?
Lambert (Pharmatech Associates): Device develop-
ment verification and validation engineers—and
toxicologists specializing in medical device de-
velopment—should closely interact with the drug
development team. Specific verification/validation
requirements and toxicological risk assessments
are critical to understand early in the development
of a combination product. A failure to properly
address device-related biological compatibility and
verification validation studies could delay approval
of combination products significantly.
Trends
PharmTech: What do you see as trends in combina-
tion products?
Lambert (Pharmatech Associates): A considerable
number of auto-injection devices are in develop-
ment, such as prefilled syringes, cartridge systems,
and pens. Auto-injection devices allow improved
compliance and simplify the administration of the
therapeutic, because patients can easily administer
many of these products. It can be problematic for a
patient with a chronic condition to consistently get
to appointments for administration of the thera-
peutic, so the option for self-administration can
improve the patient quality of life and outcome.
Combination products are themselves big driv-
ers for the development of new formulations.
Drug/biologic/device interactions, drug delivery/
performance, and drug/biologic/device stability
are parameters that impact the formulation con-
siderations for the combination product. By mov-
ing a drug from an intravenous infusion that must
be performed at the physician's office or at a clinic,
to an injection administered at home dramati-
cally expands the potential patient base for a drug
therapy. In particular, opportunities for biologics
have expanded due to innovations in combination
product solutions, including the development of
personalized healthcare.
References
1. CFR Title 21, 3.2(e)
2. FDA, "Combination Product Definition Combination Product
Types," fda.gov (Feb. 15, 2018).
3. EMA, EMA/CHMP/QWP/BWP/259165/2019, Guideline on
Quality Documentation for Medicinal Products When Used
with a Medical Device, July 22, 2021.
4. CFR Title 21, 4
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