www.biopharminternational.com March 2020 BioPharm International eBook 5
South Korea, Germany, Australia,
Trinidad and Tobago, and Mexico.
T he r eg u l ator y i s s ue s c ite d
during these inspections include
failure to inspect or test compo-
nents or materials from suppliers,
inadequate batch records, lack
of supplier oversight, inadequate
quality control units, inadequate
control of computer systems, lack
of laboratory controls, lack of writ-
ten procedures, failure to validate
the reliability of a supplier's mate-
rials, failure to conduct release
testing, and failure to use appropri-
ately designed, sized, located, and
maintained equipment (3).
These citations are t y pical of
past violations. Now, the global
p a nde m ic broug ht on b y t he
COVID-19 coronavirus adds fur-
ther uncertainty to the quality of
drugs for patients in the US.
A NEW NORMAL FOR QUALITY?
The rapid spread of COVID-19 has
stressed FDA's resources to pro-
tect US patients while monitoring
a global supply chain. The agency
took a number of actions such as
issuing emergency use authoriza-
tions to accelerate diagnostic test-
ing and sending warning letters to
seven companies for selling fraudu-
lent COVID-19 products (4). Its over-
sight role was disrupted, however, as
travel bans forced the postponement
of inspections.
O n M a r c h 18 , 2 0 2 0 , F DA
announced that the agency was
temporarily postponing all domes-
t ic rout i ne su r ve i l la nce fac i l-
ity inspections, those conducted
every few years based on a risk
analysis (5). In a statement, FDA
Commissioner Stephen M. Hahn
said the agency will evaluate all
dome st ic for- c au se i n sp e c t ion
assignments and "will proceed if
mission-critical." On March 10,
2020, FDA announced a postpone-
ment of foreign inspections (4).
"From our experience across
the agency, we also believe FDA-
regulated firms understand and
appreciate their shared responsibility
to ensure the integrity of the sup-
ply chain and we will continue to
communicate with them during this
time to underscore this partnership,"
Hahn said in the statement (5).
While store shelves were emptied
of cold medicines and other sup-
plies, FDA also said it was monitor-
ing the supply chain. The agency
has identified drugs that may be
susceptible to shortages due to sup-
ply chain disruptions to ingredients
and finished drug products and was
committed to assist manufacturers
with potential shortages.
The positive progress made by
the bio/pharma industry—includ-
ing innovation and rapid approval
of therapies—will be tested in the
coming months as the bio/pharma
industry and regulators adjust to
a "new normal" of supply chain
disr uptions, travel restr ictions,
economic upheaval, and health
threats to the workforce.
FROM NDA TO BLA
I n ot he r ac t ion, t he r e g u l a -
t o r y a p p r o v a l p a t h w a y f o r
certain protein-based drug prod-
ucts—including insulin and insulin
analogs, human growth hormone,
pancreatic enzymes, and repro-
ductive hormone—will transition
from FDA approval as a "biological
product" under section 505 of the
Federal Food, Drug, and Cosmetic
Act (FD&C Act) to a biologics license
application (BLA) under section 351
of the Public Health Service Act (PHS
Act) effective March 23, 2020 (6).
As specified in the Biologics Price
Competition and Innovation Act of
2009 (BPCI Act), proposed prod-
ucts submitting a marketing appli-
cation after March 23, 2020—that
previously could have been submit-
ted under section 505 of the FD&C
Ac t—must submit a market ing
application under section 351 of the
PHS Act as a 351(a) "stand-alone"
BLA or a 351(k) BLA for a proposed
biosimilar product or a proposed
interchangeable product.
In addition, nearly 100 drugs
previously approved under a new
drug application (NDA) as a "bio-
logic product" will transition to
biologic license application status
on March 23, 2020. This change to
the approval pathway for certain
biologic drugs can pave the way for
marketing applications for products
that are biosimilar to the approved
originator drug, FDA notes.
T h e F u r t h e r C o n s o l i d a t e d
Appropriations Act, 2020, enacted
on December 20, 2019, f urther
amended the definition of a "bio-
logical product" in the PHS Act to
include chemically sy nthesized
products that fall within the inter-
pretation of "protein" to be within
the definition of "biological prod-
uct" and subject to the statutory
transition. The legislative change
does not affect polymers composed
of 40 or fewer amino acids.
F DA has publ ished a l ist of
affected drugs, a final rule on the
definition of the term "biological
product," as well as answers to com-
mon questions about the imple-
mentation (6).
REFERENCES
1. FDA, "Office of Pharmaceutical Quality,
2019 Annual Report, One Quality Voice,"
February 2020.
2. FDA, "Recalls, Market Withdrawals, &
Safety Alerts," www.fda.gov, accessed
March 16, 2020.
3. FDA, "Warning Letters," www.fda.gov,
accessed March 16, 2020.
4. FDA, "Coronavirus Disease 2019
(COVID-19)," www.fda.gov, accessed
March 16, 2020.
5. S.M Hahn, "Coronavirus (COVID-19)
Update: FDA Focuses on Safety of
Regulated Products While Scaling Back
Domestic Inspections," Statement,
www.fda.gov, March 18, 2020.
6. FDA, "'Deemed to be a License' Provision
of the BPCI Act," www.fda.gov. ◆
Regulatory Sourcebook Regulatory Update
