22nd Annual GMP by the Sea

Office of the Chief

Counsel Update

Marci B. Norton

Senior Counsel

Office of the Chief Counsel

U.S. Food and Drug Administration

August 30, 2017

Overview

• Recent Drug CGMP Cases

United States v. Medistat RX LLC, et al. (S.D. Ala.)

United States v. Isomeric Pharmacy Solutions, LLC,

et al. (D. Utah)

United States v. Stratus Pharms. Inc., et al. (S.D.

Fla.)

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Compounding & CGMP

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• Compounding Pharmacy

(registered under section 503B

of the FDCA as an outsourcing

facility)

• Foley, AL

• Sterile drugs: injectable

vitamins and minerals, amino

acids, hormones, steroids, and

vasodilators

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• Sept. 2014 FDA inspection

– CGMP deficiencies and insanitary conditions

– Firm promised corrective actions

• Aug.-Sept. 2015 FDA inspection

– Conducted after Rhode Island Dept. of Health notified

FDA of a Staphylococcus aureus outbreak potentially

linked to injections of Medistat’s betamethasone

– Significant deficiencies in aseptic processing practices and

drug product container/closure sterilization

• Voluntarily ceased sterile and non-sterile drug

operations on September 1, 2015

• Recalled all lots of unexpired sterile drug products

distributed since November 1, 2014

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CONSENT DECREE OF PERMANENT INJUNCTION

Defendants are enjoined from manufacturing and distributing drugs

until they correct the insanitary conditions at their facility. After FDA

authorizes them to resume operations and prior to compounding drugs

for human use as an outsourcing facility, Defendants must notify

FDA; register as an outsourcing facility; correct all CGMP violations;

hire a CGMP expert; create a work plan for the expert to inspect

Defendants’ facility, ensure that Defendants implement all corrective

actions, and certify CGMP compliance; and receive written

permission from FDA to resume outsourcing facility operations.

Defendants must also hire an auditor to analyze their ongoing

compliance with the law for 5 years after achieving initial compliance.

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• Compounding Pharmacy

(registered under section 503B

of the FDCA as an outsourcing

facility)

• Salt Lake City, UT

• Sterile drugs: injectable

hormones, injectable

corticosteroids, and ophthalmic

drops

• July 2016 FDA inspection

– CGMP deficiencies and insanitary conditions

– Firm promised corrective actions

• August 1, 2016 – voluntary recall of injectable suspension drug

due to product clumping

• Dec. 12, 2016 – FDA Warning Letter

• Feb.-Mar. 2017 FDA inspection

– Significant CGMP deficiencies in aseptic and sterilization

practices; failure to validate manufacturing processes and re-

calibrate equipment

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• Recalled all lots of unexpired sterile drug

products distributed since October 4, 2016

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CONSENT DECREE OF PERMANENT INJUNCTION

Defendants are enjoined from manufacturing and distributing drugs

until they, among other things: correct all violations; hire a CGMP

expert; create a work plan for the expert to inspect Defendants’ facility,

ensure that Defendants implement all corrective actions, and certify

CGMP compliance; and receive written permission from FDA to

resume operations. Defendants also must destroy all finished and in-

process drugs and components in their possession, custody, or control

and hire an auditor to analyze their ongoing compliance with CGMP

for 5 years after achieving initial compliance.

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FDA’s Emphasis on Enforcement

Extends Beyond Compounding

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• Stratus – FL corp. that distributes

Rx and non-Rx drugs

• Sonar – NJ corp. that contract

manufactures Rx and non-Rx drugs

for Stratus and other companies

• Stratus owns 80% of Sonar

• Various dermatological creams,

washes, gels, and lotions

• Nov.-Dec. 2014 inspection at Stratus

– CGMP deficiencies: failure to approve or reject drugs manufactured

under contract by another company; failure to review batch

production records; failure to investigate batch discrepancies and

complaints

• Feb.-Mar. 2014, Oct.-Nov. 2014, & Mar.-Apr. 2015 inspections at

Sonar

– CGMP deficiencies: used components that did not meet established

standards or specifications, failed to properly clean manufacturing

equipment and used test methods that lacked a scientific basis

• April 2015 seizure of $16 million unapproved and misbranded drugs

manufactured by Sonar and held at Stratus’s facility

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CONSENT DECREE OF PERMANENT INJUNCTION

Defendants are enjoined from manufacturing and distributing drugs

until they, among other things, establish and implement a

comprehensive quality system, correct all violations, have an expert

certify CGMP compliance, and receive written permission from

FDA to resume operations. Defendants also must destroy all non-

compliant articles of drug in their possession and hire an auditor to

analyze their ongoing compliance with CGMP for 5 years after

achieving initial compliance.

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22nd Annual GMP by the Sea

Office of the Chief

Counsel Update

Marci B. Norton

Senior Counsel

Office of the Chief Counsel

U.S. Food and Drug Administration

August 30, 2017