Download Selected Updates in Pharmacy Law

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Selected Updates in Pharmacy Law: Compounding
regulations and the Drug Quality and Security Act
Frederick M. Frankhauser, JD, MBA
Adjunct Assistant Professor
MCPHS University
+
Objectives

1. Provide an brief overview in the recent changes in
pharmacy compounding regulations

2. Describe the Drug Quality and Security Act and its impact
on pharmacy

3. Define the following: Outsourcing Facility, compounding,
Form-483, Misbranded Drug and Adulterated Drug

4. Describe the registration and reporting requirements
under the Drug Quality and Security Act
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What is Drug Compounding?

Compounding-“is a practice in which a licensed pharmacist, a
licensed physician, or, in the case of an outsourcing facility, a
person under the supervision of a licensed pharmacist, combines,
mixes, or alters ingredients of a drug to create a medication
tailored to the needs of an individual patient (fda.gov).”

A pharmacist creates their own medication for a patient’s specific
needs. Compounded drugs are not FDA approved.
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Why do pharmacists compound?
 Compounding
allows the pharmacist to work
with the patient and the prescriber to customize
a medication to meet the patient’s specific needs
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Manufacturing vs. Compounding

Section 510(g) of the Federal Food Drug and Cosmetic Act
provides that pharmacies are exempt from manufacturers if
they:

Do not manufacture, prepare, propagate, compound or process
drugs or devices for sale other than in the regular course of their
business of dispensing or selling drugs for devices at retail.
Traditional compounding by pharmacists, which is regulated by
state law, is not manufacturing.
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USP 795

USP <795>

Non-sterile compounding – products can be made without aseptic
technique due to the timing and/or type of administration being
used in patients.

The product still needs to be within a set standard but do not
need to be aseptic.

Example – suppositories
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USP 797

USP <797>

Sterile compounding – products need to made using aseptic
technique due to the timing and type of administration being
used in a patient.

Example – IV medications
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Drug
Quality and
Security
Act
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What is the Drug Quality &
Security Act?

This act was enacted on November 27, 2013

Two titles:

Title I: Drug Compounding

Title II: Drug Supply Chain Security
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What caused the enactment?

September 2012 Center for Disease Control, health departments and FDA
began to investigate multi-state outbreak of fungal meningitis and other
infections of those who received preservative-free MPA steroid injections

From New England Compounding Center in Framingham MA

Investigation included:
 Fungal Meningitis
 Localized spine or paraspinal infections
 Abscesses and arachnoiditis
 Infections in joint spaces such as knee, ankle etc.

Found Exserohilum Rostratum was the predominate fungus identified

Aspergillus Fumigatus was reported in one cases

Both funguses are found in environment however are not infectious people to
people
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Drug Quality & Security Act Title I:
Drug Compounding

“Amends the Federal Food, Drug, and Cosmetic Act with
respect to the regulation of compounding drugs. Exempts
compounded drugs from new drug requirements, labeling
requirements, and track and trace requirements if the drug is
compounded by or under the direct supervision of a licensed
pharmacist in a registered outsourcing facility and meets
applicable requirements (congress.gov).”
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The Compounding Quality Act
The Compounding Quality Act was created to ensure that
compounded medications were regulated and
pharmacists/pharmacies were using good practice when making
compounding medications to ensure patient safety.
“Under the new law, the drugs must be compounded in compliance
with CGMP by or under the direct supervision of a licensed
pharmacist in a registered facility (fda.gov).”
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Impact on FDCA

Removes certain provisions from section 503A that were
deemed unconstitutional by the U.S Supreme Court in 2002

503 A describes conditions which human drug products are
entitled to these exemptions from these three sections:


Compliance with current good manufacturing practices
(CGMP) (section 501(a)(2)(B));

Labeling with adequate directions for use (section 502(f)(1));
and

FDA approval prior to marketing (section 505).
Removing these provisions takes away the uncertainty of
validity of 503A
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Provisions to FDCA(cont.)

Created 503B


Compounder can become “outsourcing facility”
 Able to qualify for exemptions from FDA approval
requirements and requirement to label products with
adequate directions
 But NO EXEMPTIONS from CGMP requirements
Outsourcing Facilities




Must comply with CGMP requirements,
Will be inspected by FDA according to a risk-based schedule, and
Must meet certain other conditions, such as reporting adverse
events and providing FDA with certain information about the
products they compound.
Compliance with the DQSA labeling requirements for each
container
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Outsourcing Facility
Registration and Reporting

Allows an entity that compounds sterile drugs to register as an
outsourcing facility

Must meet certain requirements to be exempt from FDCA’s
approval requirements


503A

Compounded according to cGMP

Direct supervision of registered pharmacist
Report Specific information(503B3)

List of products compounded within past 6 months

Information about products (source of ingredients)

Report adverse events and labeling with certain product information
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Outsourcing Facility
Registration and Reporting
 Not
considered registered until the
establishment fee is paid
 Must
report registration electronically
unless secretary grants a wavier because
submitting electronically is not reasonable.
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Traditional Compounding

Drugs that are not registered as outsourcing facility must
meet 503 A to qualify for exemptions

MUST meet these requirements regardless of meeting above
standards

Cannot be contaminated or created in insanitary conditions

If drug does not fit the exemptions of 503A and 503B it must follow
all requirements including new approval and labeling
requirements
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Enhanced Communication with
States

Requires secretary to establish submission process from
state boards of pharmacy against compounding pharmacies
that are acting in contrary to 503 A

Implemented with National Association of Boards of
Pharmacy

State boards must be notified when secretary is notified of a
compounding pharmacy acting in contrary to 503A
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Creation of Advisory Committee

503 A and 503 B requires consultation with Pharmacy
Advisory Committee before insurances of certain regulations
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Nomination for Lists

503 A and 503 B :



contain various requirements for FDA to develop lists of drugs that
may or may not be compounded and a list of bulk substances that
may be used to compound.
Prohibits compounding drugs that are on the list of drugs that are
considered difficult to compound
503 A states a compounder may use bulk drug substances if:

The bulk drug substances comply with the standards of an applicable United States Pharmacopoeia
(USP) or National Formulary (NF) monograph, if one exists;

If such a monograph does not exist, the drug substance(s) is a component of an FDA-approved human
drug product; or
If such a monograph does not exist and the drug substance is not a component of an FDA-approved
human drug product, it appears on a list of bulk drug substances for use in compounding developed by
FDA through regulation (section 503A(b)(1)(A)(i) of the FDCA).


503 B specifies outsourcing facility may only use bulk drugs
approved on list for clinical need or on drug shortage list
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Inspection and Enforcement

Since Meningitis outbreak of 2012, FDA continues make proactive
and for cause inspections and enforcement actions are taken to
protect public health

Use Forms-483 to state the findings of inspection

”New problems continue to be identified at compounding
pharmacies across the country, and FDA intends to continue its
inspection and enforcement efforts to address these problems,
using currently available resources. For oversight of outsourcing
facilities registered under section 503B, FDA will use fees assessed
and collected from those facilities in accordance with the law to
supplement other agency resources”
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Drug Quality & Security Act Title II:
Drug Supply Chain Security

“Establishes requirements to facilitate the tracing of
prescription drug products through the pharmaceutical
supply distribution chain (congress.gov).”

The intent of this act is to be able to keep track of drugs,
properly identify drugs, and for accurate record keeping.
Regulations were set in place so in the next 10 years
dispensers, wholesalers, and pharmacies can work together
with the FDA to develop a new system (fda.gov).
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Misbranded & Adulterated Drugs

Misbranded and adulterated drugs are another component
of the Drug Quality and Security Act.

It is illegal for a pharmacy to dispense misbranded and
adulterated drugs.
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Counterfeit Drugs
Counterfeit Drugs- “A drug
which, or the container or
labelling of which, without
authorization, bears the
trademark, trade name, or other
identifying mark, imprint, or
device or any likeness thereof, of a
drug manufacturer (Pharmacy
Practice & The Law pg).”

Another part of this new act is
the prevention of counterfeit
drugs into the pharmaceutical
system.

Can be hard to decipher from
real drugs, the only way to tell
is by doing a chemical
analysis on the drug.

Other smalls signs of a
counterfeit could be slightly
different designs of the drug
logo, and packaging.
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Components of the New Act

Product Tracing

Product Verification

Product Identification

Wholesaler Licensing

Third Party Logistics
http://www.fda.gov/downloads/drugs/
developmentapprovalprocess/smallbu
sinessassistance/ucm388945.pdf
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Components of the New Act
 Product Tracing
Manufacturers, wholesaler drug distributors, repackagers, and many dispensers (primarily
pharmacies) in the drug supply chain to provide information about a drug and who handled it each
time it is sold in the U.S. market.
 Product VerificationManufacturers, wholesaler drug distributors, repackagers, and many dispensers (primarily pharmacies)
to establish systems and processes to be able to verify the product identifier on certain prescription
drug packages.
 Product
Identification-
Manufacturers and repackagers to put a unique product identifier on certain prescription drug packages,
for example, using a bar code that can be easily read electronically.
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Components of the New Act
 Wholesaler
Licensing-
Wholesale drug distributors to
report their licensing status and
contact information to FDA. This
information will then be made
available in a public database.
 Third
Party Logistics-
Third-party logistic providers, those
who provide storage and logistical
operations related to drug
distribution, to obtain a state or
federal license.
+ Instances of Pharmacy-related
Outbreaks
(Year)
y
k Cases
where
Product(s
) received
tion
Use
2001
CA
CA
Ambulatory
surgery
center
Betamethasone
Epidural,
peripheral
joint Inj.
Commercially
unavailable
(drug shortage),
off-label use
Nonsteril
e to
Sterile
Meningitis(5
), epidural
abscess (5),
hip septic
arthritis(1)
Serratia
marcescens
2002
MI
MI
Unknown
Methylprednisolo
ne
Epidural inj.
Commercially
unavailable
(drug shortage),
off-label use
Unknow
n
Mengitis (2)
Chryseomo
nas
(Pseudomo
nas )luteola
2002
SC
NC
Pain Clinic
Methylprednisolo
ne
Epidural,
sacroiliac inj.
Commercially
unavailable
(drug shortage),
off-label use
Nonsteril
e to
Sterile
Mengitis(4),
sacrolitis (1),
Lumbar
discitis (1)
Exophiala
dermatitidis
2004
FL
CT
Home
health
Heparinvancomycin
Catheter
flush
High-volume
acute care
product
Unknow
n
Bacteremia/
sepsis (2)
Burkholderi
a cepacia
20042005
MD
VA
Hospital
(inpatient)
Cardioplegia
Coronary
infusion
High-volume
acute care
product
Sterile to
sterile
Systemic
inflammatory
response
syndrome(11
)
Unknown
20042006
TX
MI, MO,
NY,SD,
TX,WY
Inpatient,
Outpatient,
Home
health
Heparin-sodium
chloride
Catheter
flush
High-volume
acute care
product
Nonsteril
e to
Sterile
Bacteremia(8
0)
Pseudomon
as species
+
Outbreak
Cases)
Date Of
outbrea
k
(Year)
+
Locations
of
Pharmac
y
Location
s of
Outbrea
k Cases
Health Care
Setting(s)
where
Product(s)
received
Contaminat
ed
Product(s)
Route(s) of
Product
Administrati
on
Response
for
Compoundi
ng/ Use
Type
of
Comp
oundi
ng
Infection
Type
(No.
Outbreak
Cases)
Organism
(s)
2005
TX
CA,MA,
NC,NJ,
NY,SD
Hospital
(inpatient)
Magnesium
sulfate
Intravenous
Inj.
High-volume
acute care
product
Sterile
to
sterile
Bacteremia(18
),
Sepsis(1)
S.
marcescens
2005
MN
D.C., MN
Ophthalmolog
y surgery
Trypan blue
Intraocular
Inj.
High-volume
surgery
product
Nonster
ile to
sterile
Endophthalmi
tis (5)
Pseudomon
as
aeruginosa
2007
MS
(suspected)
CA, MD
Hospital
(inpatient)
Fentanyl
Intravenous Inj.
High-volume
acute care
product
Unkno
wn
Bacteremia
(8)
Sphingomo
nas
paucimobili
s
20092010
TN
TN
Ophthalmolog
y clinic
Bevacizumab
Intraocular
Inj.
High-volume
surgery
product
Sterile
to
sterile
(repack
aging)
Endophthalmi
tis
(5)
Alphahemolytic
Streptococc
us
2011
AL
AL
Hospital
(inpatient)
Total
parenteral
nutrition
Intravenous
Inj.
High-volume
acute care
product
Nonster
ile to
sterile
Bacteremia
(19)
S.marcesce
ns
2011
FL
FL
Ophthalmolog
y clinic
Bevacizumab
Intraocular
Inj.
High-volume
surgery
product
Sterile
to
sterile
(Repac
kaging)
Endophthalmi
tis
(12)
Streptococc
us mitis/
oralis
Date Of
outbreak
(Year)
Locations
of
Pharmacy
Locations
of
Outbreak
Cases
Health
Care
Setting(s)
where
Product(s)
received
Contamin
ated
Product(s)
Route(s) of
Product
Administr
ation
Response
for
Compoun
ding/
Use
Type of
Compoun
ding
Infection
Type
(No.
Outbreak
Cases)
Organism
(s)
2011-2012
FL
CA,CO,IL,
IN,LA,NC,
NV,NY,TX
Ambulatory
Surgery
center
Brilliant Blue
Green(BBG)
,
Triamcinolo
ne
Intraocular
Inj.
Commercial
ly
unavailable,
off-label use
Nonsterile
to sterile
Endophthal
mitis
( Total: 47
BBG: 21;
Fusarium
incarnatumequiseti
+
Triamcinolo
ne: 26)
2012
MA
FL,GA,ID,
IL,IN,MD,
MI,NC,NH,
NJ,NY,OH,
PA,RI,SC,
TN,TX,VA
Various
Methylpred
nisolone
Spinal (e.g.,
epidural
nerve root
block),
Paraspinal
(e.g.,
Sacroiliac),
Peripheral
joint inj.
Commercial
ly
unavailable
in desired
form (i.e.
preservativ
e-free), offlabel use
Nonsterile
to sterile
Mengitis,
other
spinal/
paraspinal
infection
(e.g.,
epidural
abscess),
peripheral
joint
infection
(751)**
Exserohilu
m rostratum,
Aspergillius
, Fumigatus,
other fungi
2012
NC
NC
Hospital
(inpatient)
Fentanyl
Intravenous
Inj.
Highvolume
acute care
product
Nonsterile
to sterile
Bacteremia
(7)
B. cepacia
+
Date Of
outbreak
(Year)
Locations
of
Pharmacy
Locations
of
Outbreak
Cases
Health
Care
Setting(s)
where
Product(s)
received
Contamin
ated
Product(s)
Route(s) of
Product
Administr
ation
Response
for
Compoun
ding/
Use
Type of
Compoun
ding
Infection
Type
(No.
Outbreak
Cases)
Organism
(s)
2013
GA
GA, IN
Ophthalmol
ogy
Clinic
Bevacizuma
b
Intraocular
Inj.
Sterile to
sterile
(Repackaging)
Endophthal
mitis (5)
Granulicate
lla adiacens,
Abiotrophia
species
2013
TX
TX
Unknown
Methylcobal
amin
Intravenous
Inj.
Nonsterile
to sterile
TX
TX
Hospital
(inpatient)
Calcium
gluconate
Intravenous
Inj.
Fever, flulike
symptoms,
chills (6)
Bactermia
(15)
Unknown
2013
Highvolume
surgery
product,
repackagin
g, off-label
use
Commercial
ly
unavailable,
off-label use
Commercial
ly
unavailable
(drug
shortage)
Nonsterile
to sterile
Rhodococc
us equi
+
New Hampshire

NM H 313

Regulation of the Compounding of Drugs by Pharmacists

To Governor

Provides for regulation of the compounding of drugs by
pharmacists, provides that a licensed pharmacist shall have the
right to conduct a pharmacy for the compounding of medicines
upon physicians', dentists' and physician assistants'
prescriptions or valid order for the sale, and distribution of
drugs, requires that the compound drug product bear the label
of the pharmacy responsible for compounding and dispensing
the product directly to the patient for administration.
+
New Hampshire

Lawmakers 2013 passed new regulations for compounding pharmacies,
including new labeling requirements and limitations on the quantities of
compounded drugs that can be sent to providers.
The law also directed the pharmacy board to adopt new rules for
pharmacies that do compounding, defined as the "preparation, mixing,
assembling, packaging or labeling of a drug or device" as a result of a
practitioner's prescription drug order or "in anticipation of a prescription
drug orders based on routine ... prescribing patterns."
New Hampshire in opposition to a new federal law that created a new
category of compounding pharmacies called "outsourcing facilities." Under
the Drug Quality and Security Act (DQSA), such facilities "may elect" to
register with the Food and Drug Administration.
References

FDA, Information on Compounding,
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInform
ation/PharmacyCompounding/default.htm

Pharmacy Compounding of Human Drug Products Under Section
503A of the Federal Food, Drug, and Cosmetic Act Guidance,
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegul
atoryInformation/Guidances/UCM469119.pdf

Nadine Shaheb, Megan N. Brown, BA, Alexander J. Kallen, Joseph F.
Perz; US compounding Pharmacy-Related Outbreaks; 2001-2013:
Public Health and patient Safety Lessons Learned
www.journalpatientsafety.com