Internet Drug Sellers:

What Providers Need to Know

A program sponsored by the Federation of State Medical

Boards and the Alliance for Safe Online Pharmacies

Accredited for CME and CPE

Program Faculty

• Tim K. Mackey, MAS, PhD, University of California at San

Diego

• Dr. Ilisa Bernstein, PharmD, JD, Deputy Director, Office of

Compliance, Center for Drug Evaluation and Research,

U.S. Food and Drug Administration

• John Horton, JD, President, LegitScript

• Jon V. Thomas, MD, MBA, Immediate Past Chair, FSMB

Risks of Online Pharmacies:An overview of patient safety and public health risks

associated with illicit online pharmacies

Tim K. Mackey, MAS, PhD

UC San Diego

ASOP CME

September 2014

Sub headlineAGENDAPRESENTATION AGENDA

• Background:

Emergence of eHealth, the e-patient and illicit online pharmacies

• Characteristics of an Online Pharmacy:

What does an online pharmacy look like, what are the risks?

• Examples of Clearly Dangerous Drugs Online

What have we found for sale online and why is it dangerous?

• Marketing to your Patient

Methods and sophistication of multi-channel direct-to-consumer marketing

Committee Members

Background: Emergence of Digital

Health (eHealth)

• By end of 2014 ITU estimates that

there will be 3 billion Internet users

globally

• 72% of Internet Users in Pew survey

looked for health information online

within the last year. More than 1/3rd

self-diagnose online.

• FDA survey found that 23% of adult

Internet users purchased prescription

drugs online

• “No Rx”: Use of misleading marketing,

including “no prescription” offers and

online scripts.

• Cybercrime: Associated with fraud,

spam, phishing, viruses, malware, and

spyware.

• Vulnerable Consumers: Target

vulnerable patient populations including

elderly, teens, uninsured/underinsured,

low SES, low health literacy.

• Illicit Activity: Sell counterfeit, falsified,

substandard, and adulterated product

direct to patient w/out healthcare

professional oversight.

Key Risk Factors

Sub headlineThe Problem: Illicit Online Pharmacies

Variety of drugs including lifestyle, essential, pain relief, weight loss, pet

meds, etc.

FAQ does not require Rx for dispensing, “medical

questionnaire” is taken at point-of-sale

Extremely low pricing compared to legal sources and various sales specials

Multiple languages, worldwide coverage

Common Characteristics

Example: Illicit Online Pharmacy

Sub headlineCounterfeit/Falsified/Fraudulent Medicines

What “medicine” will you get?

•Global Public Health Challenge: Part of

global problem of transnational criminal

trade in counterfeit medicines

•Authenticity?: Since it may not be from

the authorized manufacturer, who knows

who made it and if quality standards were

met

•Quality?: Drug could have some or no

active ingredient, could be adulterated, or

could have toxic chemicals.

•Harm?: Patients get no treatment since

the drug is not effective; worse, there’s a

risk to patient’s life from taking a drug that

contains toxic ingredients. Consumers can

also suffer financial fraud.

Can you tell which one of

these are fakes?

Sub headlineRecognized Public Health Hazard

Recent GAO Report

•Title: “Most Rogue Sites Operate from

Abroad, and Many Sell Counterfeit Drugs”

published Feb 27.

•Scope: Highlights report by LegitScript that

over 36,000 “rogue” Internet pharmacies in

operation as of Feb 2013.

•Challenges: Difficult to prosecute, in

multiple jurisdictions, use several methods to

disguise themselves, and are often part of a

complex global criminal operation.

•Marketing: Use of sophisticated marketing

methods to appear legitimate and confuse

consumers.

WHAT HAS BEEN FOUND ONLINE

• Digital social media, youth, and nonmedical

use of prescription drugs: The need for

reform. JMIR (2013).

• Suspect online sellers and contraceptive

access. Contraception (2012).

• Online availability and safety of drugs in

shortage: a descriptive study of internet

vendor characteristics. JMIR (2012).

• Vaccine shortages and suspect online

pharmacy sellers. Vaccine (2012).

Published Research

CLEAR AND PRESENT DANGER: Marketed as Available Online!

Drugs not

approved

Narrow Therapeutic

Index Drugs

Drugs subject to

Global Recall

NARROW THERAPEUTIC INDEX DRUGS

• Danger: Narrow proximity between therapeutic

and toxic amounts requires close professional

oversight and precise manufacturing.

• Challenges: Switching can entail risks arising

from variable active ingredient bioavailability.

Acceptable list of NTI drugs not well defined.

• Availability: Actively marketed for sale. Core list

13/14 (92%, digitoxin available on Alibaba.com);

Including Expanded list 24/26 (92%).

• Implications: Higher risk of adverse event

associated with NTI patients; no physician

monitoring; manufacturing processes need to be

precise and rely on originator information for BE.

Citation

Primary Findings

Liang BA, Mackey TK, Lovett KM. Illegal “no prescription”

internet access to narrow therapeutic index drugs. Clin Ther.

35(5): 694-700 (2013)

DRUGS NOT APPROVED

• Danger: Obesity is global health crisis. Belviq

(lorcaserin HCI, S-IV CS) approved by FDA but

was not legally marketed by manufacturer. Weight

loss drugs previously identified as being

counterfeited.

• Opportunity: Research was conducted after FDA

approval but prior to DEA scheduling.

• Availability: Actively marketed for sale by “no

prescription” online vendors (e.g.,

buybelviqonline.com) and Alibaba.com.

• Implications: Drug was not approved, consumers

could be sourcing anything. Could be other weight

loss products or counterfeit.

Citation

Primary Findings

Liang BA, Mackey TK, N Archer-Hayes A, Shinn LM. Illicit

online marketing of lorcaserin before DEA scheduling. Obesity.

21(5): 861-864 (2013)

DRUGS SUBJECT TO GLOBAL RECALL

• Danger: Drugs subject to equivalent of FDA class

I recall may cause serious adverse health

consequence or even death. There may also be no

“authorized” manufacturing of drug.

• Challenges: There is no central list of globally

recalled drugs (2002-2012). We had to construct

such a list for this research from multiple sources.

• Availability: Total of 16 (12 oral/4 injectable)

identified. 50% marketed for sale “no rx” online.

• Implications: Despite efforts to remove from

market, many recalled drugs are marketed online.

Consumers do not know what they will receive,

and even if it is authentic, could carry serious risks

for patients especially in absence of clinical

oversight.

Funding Source

Preliminary Findings

Part of larger grant through Canadian Social Sciences and

Humanities Research Council on counterfeit drugs. Authors:

Mackey TK, Liang BA, Aung PS. Work in progress.

Use of Social Media

Marketing Direct-to-Patient

Multiple Actors – Legitimate and Illegitimate

Internet Pharmacy Ecosystem

• Rise of the e-Patient

Patients/consumers are increasingly going online for health information. Illicit online pharmacies

are exploiting this change and aggressively marketing dangerous medical products to patients.

• Risks to Patients

Patients/consumers can suffer adverse consequences associated with illegally purchasing

medicines online. Clinicians should be aware of these risks and possible ramifications.

• Education and Awareness

Physicians can act as important stakeholders in the process of educating and raising awareness

to the public and patient safety risks of illicit online pharmacies. We need your help!

Illicit Online Pharmacies and e-Marketing

BY PRESENTER AND CO-AUTHORS…

Tim K. Mackey & Bryan A. Liang. Pharmaceutical Digital Marketing and Governance: Illicit Actors and Challenges to Global Patient Safety and Public Health, GLOBALIZATION AND HEALTH

(2013), 9(1):45.

Tim Mackey & Bryan A. Liang, The Global Counterfeit Drug Trade: Patient Safety and Public Health Risks, 100(11) JOURNAL OF PHARMACEUTICAL SCIENCES 4751-4579 (2011).

Tim K. Mackey, Bryan A. Liang, Steffanie A. Strathdee. Digital Social Media, Youth and Non-Medical Use of Prescription Drugs: The Need for Reform, 15(7) JOURNAL OF MEDICAL INTERNET

RESEARCH e143 (2013), doi:10.2196/jmir.2464.

Tim K. Mackey & Bryan A. Liang, Global Reach of Direct-to-Consumer Advertising Using Social Media for Illicit Online Drug Sales, 15(5) JOURNAL OF MEDICAL INTERNET RESEARCH e105, doi:

10.2196/jmir.2610 (2013)

Bryan A. Liang, Tim K. Mackey, Kimberly M. Lovett, Illegal “No Prescription” Internet Access to Narrow Therapeutic Index Drugs, 35(5) CLINICAL THERAPEUTICS 694-700 (2013)

Bryan A. Liang, Tim K. Mackey, Ashley Archer-Hayes, Linda M. Shinn, Illicit Online Marketing of Lorcaserin Before DEA Scheduling, 21 OBESITY 861-864 (2013).

Kimberly M. Lovett & Tim K. Mackey, Online Threats to Senior Safety: The Direct-to-Consumer Medical Marketplace and eElder Abuse, 9(1) NATIONAL ACADEMY OF ELDER LAW ATTORNEYS

JOURNAL 91-113 (2013) [law review].

Tim K. Mackey & Bryan A. Liang, Separating Online Piracy from Counterfeit Medicines: The Need for Policy Reform and a Call to Action, 1(3) HEALTH POLICY & TECHNOLOGY 120-122 (2012)

Bryan A. Liang, Tim K. Mackey, Kimberly Lovett, Suspect Online Sellers and Contraceptive Access, 86(5) CONTRACEPTION 551-556 (2012).

Bryan A. Liang, Tim Mackey, and Kimberly Lovett, Emerging Dangers from Direct Botulinum Access and Use, 9(1) JOURNAL OF HOMELAND SECURITY AND EMERGENCY MANAGEMENT (2012):

doi:10.1515/1547-7355.1973

Bryan A. Liang & Tim Mackey, Online Availability and Safety of Drugs in Shortage: A Descriptive Study of Internet Vendor Characteristics, 14(1) JOURNAL OF MEDICAL INTERNET RESEARCH e27

(2012) doi:10.2196/jmir.1999

Bryan A. Liang & Tim Mackey. Vaccine Shortages and Suspect Online Pharmacy Sellers, 30(2) VACCINE 105-108 (2012).

Bryan A. Liang & Tim Mackey, Prevalence and Global Health Implications of Social Media in Direct-to-Consumer Drug Advertising, 13(3) JOURNAL OF MEDICAL INTERNET RESEARCH e64 (2011)

doi:10.2196/jmir.1775

Tim Mackey & Bryan A. Liang, Promoting Online Drug Safety: Using Public-Private Partnerships to Deter Illicit Online Drug Sales, 17(3) JOURNAL OF COMMERCIAL BIOTECHNOLOGY 266-271

(2011)

Bryan A. Liang & Tim Mackey, Direct to Consumer Advertising with Interactive Internet Media: Global Regulation and Public Health Issues, 305(8) JOURNAL OF THE AMERICAN MEDICAL

ASSOCIATION 824-825 (2011)

Bryan A. Liang & Tim Mackey, Searching for Safety: Addressing Search Engine, Website, and Provider Accountability for Illicit Online Drug Sales, 35(1) AMERICAN JOURNAL OF LAW & MEDICINE

125-184 (2009). [law review].

OTHERS:

Fittler A, Bősze G, Botz L. Evaluating aspects of online medication safety in long-term follow-up of 136 Internet pharmacies: illegal rogue online pharmacies flourish and are long-lived. J Med

Internet Res. 2013;15(9):e199.

Orizio G, Rubinelli S, Schulz PJ, Domenighini S, Bressanelli M, Caimi L, et al. “Save 30% if you buy today.” Online pharmacies and the enhancement of peripheral thinking in consumers.

Pharmacoepidemiol Drug Saf. 2010 Sep;19(9):970–6.

Jena AB, Goldman DP, Foster SE, Califano JA. Prescription medication abuse and illegitimate internet-based pharmacies. Ann Intern Med. American College of Physicians; 2011 Dec

20;155(12):848–50.

Forman RF (2003) Availability of opioids on the Internet. JAMA 290: 889. doi:10.1001/jama.290.7.889.

List of Peer-reviewed Studies (Bibliography)

Dangers of buying medications

over the Internet:

FDA perspective

Ilisa Bernstein, PharmD, JDDeputy Director, Office of Compliance

Center for Drug Evaluation and Research

U.S. Food and Drug Administration

• Due to high cost of Rx drugs, many seek ways to find cheaper drugs -- - INTERNET

• Involves importing drugs from outside the U.S.

• Illegal under current law

• The Food, Drug, and Cosmetic Act

– Drugs must be approved before marketed

– Approval is manufacturer-specific, product-specific, FDA-inspected facility

– Stringent regulation of manufacturing

Therefore, anything coming from foreign sources (without FDA approval) are unapproved drugs and illegal

Overview of the problem

Drugs sold illegally on the Internet

• Counterfeit

Rx Drugs

• Counterfeit

OTC Drugs

“Supplements” sold illegally on Internet

• Over 150 adverse event reports related to:

• Weight Loss Products

• Zi Xiu Tang Bee Pollen

• Fruta Planta

• Pai You Guo

• Botanical Slimming

• Erectile Dysfunction Products

• Black Ant

• Stiff Nights

• Libigrow

• Vitalikor

• Pain and Inflammation Products

• Reumofan Plus

Compromised integrity:

Recent supply chain threats

• Counterfeit

Avastin

• Counterfeit

Altuzan

• Other

CounterfeitCounterfeit

26 26

BeSafeRx (www.fda.gov/BeSafeRx)

• Awareness about the risks of buying medicines online

• Red flags for identifying a fraudulent online pharmacy

• State licensure

Know Your Source (www.fda.gov/KnowYourSource)

Protect your patients from

unsafe drugs

• Beware of offers too good to be

true

• Check for signs that a prescription

drug may be unsafe, ineffective or

fake

• Ensure you receive FDA-approved

prescription drugs

• Buy only from wholesale drug

distributors licensed in your state

• Pay close attention to patient

feedback

FDA outreach

• Consumer Alerts

• Health Care Provider Alerts

• FDA Statements

• Doctor Letters

– Over 1800 “informational” letters sent to

doctors

• To educate about safe purchasing

practices and public health risks when

products are bought from outside the

legitimate supply chain

• Copied Medical Boards

• Posted on FDA webpage

• Presentations

• Messaging on social media

New Drug Supply Chain Security Act

“Track and trace law” (enacted 11/27/2013)

• Beginning 1/1/2015 - trading partners must be “authorized”

• Authorized Trading Partners

– Manufacturers and Repackagers: valid registration with FDA

– Wholesale distributors: valid State or Federal license and compliance with

reporting requirements

– Third-party logistics provider: valid State or Federal license and compliance

with reporting requirements

– Dispensers: valid State license

What does this mean for you?

– Dispensers (including doctors, pharmacists, clinics, pharmacies, etc.)

can only purchase from authorized trading partners

Final thoughts…..

1. Prescription drugs are being sold illegally all over the Internet and

put your patients’ health at risk

2. Be aware that your patients may be taking drugs purchased from

fake online pharmacies and consider their effect when evaluating a

patient’s response to therapy or making other medical decisions.

• Please report all adverse events and drug quality issues to FDA’s

MedWatch program at www.fda.gov/medwatch/report.htm.

3. Educate your patients on the dangers of purchasing drugs on the

Internet

4. Purchase medications only from licensed and authorized drug

distributors in the U.S.

THANK YOU!

For more information:

http://www.fda.gov/Drugs/Drug

Safety/DrugIntegrityandSupplyChainSecurity/default.htm

Please send comments or questions to:

FDAInternetPharmacyTaskForce-CDER@fda.hhs.gov

References• “Drug Supply Chain Integrity.” Drugs. U.S. Food and Drug Administration, 9 Oct. 2014. Web. 16 Oct.

2014. <http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/default.htm>.

• “FDA Operation Reveals Many Drugs Promoted as ‘Canadian’ Products Really Originate From Other Countries.” News & Events. U.S. Food and Drug Administration, 16 Dec. 2005. Web. 16 Oct. 2014. <http://www.fda.gov/newsevents/newsroom/pressannouncements/2005/ucm108534.htm>.

• “Altuzan (bevacizumab): Counterfeit Product - Contains No Active Ingredient.” Safety. U.S. Food and Drug Administration, 23 May 2012. Web. 16 Oct. 2014. <http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm298583.htm>.

• “February 16, 2007: FDA Alerts Consumers to Unsafe, Misrepresented Drugs Purchased Over the Internet.” Inspections, Compliance, Enforcement, and Criminal Investigations. U.S. Food and Drug Administration, 16 Feb. 2007. Web. 16 Oct. 2014. <http://www.fda.gov/iceci/criminalinvestigations/ucm280218.htm>.

• “BeSafeRx: Know Your Online Pharmacy.” Drugs. U.S. Food and Drug Administration, 19 Nov. 2013. Web. 16 Oct. 2014. <http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/BuyingMedicinesOvertheInternet/BeSafeRxKnowYourOnlinePharmacy/default.htm>.

• “Know Your Source: Protecting Patients from Unsafe Drugs.” Drugs. U.S. Food and Drug Administration, 23 Sept. 2014. Web. 16 Oct. 2014. <http://www.fda.gov/Drugs/ResourcesForYou/HealthProfessionals/ucm389121.htm>.

• “Drug Supply Chain Security Act (DSCSA).” Drugs. U.S. Food and Drug Administration, 7 Oct. 2014. Web. 16 Oct. 2014. <http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/DrugSupplyChainSecurityAct/default.htm>.

LegitScript

Is it telemedicine…or an

illicit Internet pharmacy?

Program sponsored by the Alliance for

Safe Online Pharmacies and Federation of

State Medical Boards

By LegitScript: Making Sense of the Online Healthcare Products

Market

How Big Is the Internet Pharmacy Problem?

LegitScript

• At any time, there are roughly 35,000

- 50,000 active Internet pharmacies

worldwide, plus thousands of websites

selling tainted dietary supplements

and psychoactive substances like

“bath salts” and “spice"

• The vast majority of online drug

sellers fail to comply with applicable

laws and regulations (97%).

• Rogue Internet pharmacies can make

millions of dollars in sales each month

95.0%

0.5%

4.5%

The Internet Pharmacy

Marketplace

Rogue Legitimate Potentially Legitimate

About 97% of Internet Pharmacies Operate Illegally

LegitScript

A “rogue” Internet pharmacy sells prescription drugs in a way that violates drug and patient safety laws and regulations where the drugs are dispensed from or where they are offered to be shipped to.

Three common violations:

1. Selling prescription-only medicines without a valid prescription

2. Selling unapproved, adulterated, misbranded, or counterfeit drugs

3. Lacking required pharmacy licenses in the jurisdictions it ships drugs to

LegitScript

Become a 33 Drugs affiliate:

E.g. DrugRevenue.com

Affiliate websites – run by others – collect and fill drug ordersk2med.com, rxvalid.com, 33-drugs.com, Alwaysdrugs.com, creativedrugs.com, Fulldrugstore.com,

Dealpharmacy.com, Cleografik.com, chemists-shop-us.com, Cheapmedsinc.com, cheapeasyfast.info,

Cheapamericandrugs.com, Cheap-meds-rx.com, Capcarbonnow.com, Canadian-rx-store.com, Canadasme

All payments

33Drugs.com

Supplies

Operations

Affiliate Recruiting

How affiliate networks work

Rogue networks sometimes recruit

doctors to write mass prescriptions,

so they can say “there’s a real Rx” –

and call it telemedicine.

Are these really telemedicine websites?

NO. They are Non-Compliant Internet Pharmacies.

Red Flags: Legitimate Telemedicine Website

vs.

Non-Compliant Internet Pharmacy

Potentially LEGITIMATE Likely NON-COMPLIANT

Physician is licensed in state

where patient resides

Physician is not licensed

where patient resides, or

website provides no

information about licensure

Physician has legitimate,

typically prior, relationship

with patient

Prescription is solely based

on an online consultation or

questionnaire

Website is not affiliated with a

pharmacy/does not ship drugs

directly to patient

Website ships drugs to

patient directly, or via an

“affiliated” pharmacy

No guarantees or quid

pro quos.

Website ties payment to

receipt of prescription drugs.

Patient Harms

LegitScript

Marcia Bergeon:

• Sister; Died from

heavy metal poisoning

found in fake drugs

bought online

Lorna Lamden:

• Paramedic; Died

due to complications

from sleeping pills

bought online without a

physical exam

Steve Kovacs:

• Student; Died from

prescription drugs

bought online without a

prescription, no

medical supervision

Regulatory Risk: Not Just Controlled Substances

LegitScript

• Dr. John E. May of New York: convicted and sentenced to 12 months in prison for issuing prescriptions via the Internet without seeing patients (July 2014)

• Nurse Ali Lovins of Florida: charged, along with six others, for multiple counts related to operations of an illegal Internetpharmacy scheme (May 2014)

• Dr. Miles Jones of North Dakota: lost medical license for issuing prescription-only medicines without a proper medical evaluation (2005)

Three Things to Remember:

1. If the deal from an Internet pharmacy seems too

good to be true, it is.

2. If all you’re doing is reviewing Internet forms and

writing prescriptions, you are a target of

indictment, even if the drugs are not controlled

substances.

3. If the rogue pharmacy is willing to operate like a

pill mill, it may also be willing to cut corners and

offer misbranded drugs not approved by the FDA.

Bibliography

• Slides 2-6 (36-40 overall):

• LegitScript’s own analysis and research

• Slide 7 (41 overall) (“Patient Harms”):

• Alliance for Safe Online Pharmacies

• Slide 8 (42 overall) (“Regulatory Risk”):

• Re John May:

http://www.fda.gov/ICECI/CriminalInvestigations/ucm406704.htm

• Re Ali Lovins:

http://www.fda.gov/ICECI/CriminalInvestigations/ucm400366.htm

• Re Miles Jones: http://www.ndcourts.gov/court/opinions/20040161.htm

RECAP: KEY TAKEAWAYS

FOUR KEY RESOURCES

IF YOU REMEMBER ONE THING…

FIVE TAKEAWAYS

Type in a URL

Get results

Go to: www.Legitscript.com

LegitScript also offers a list of legitimate Internet pharmacies

and a healthcare product verification tool

#1: LegitScript URL Verification Tool

#2: NABP’s VIPPS List and AWARxE

Search “NABP VIPPS list”

or go to

http://www.nabp.net/prog

rams/accreditation/vipps/

find-a-vipps-online-

pharmacy/

Search for “FDA BeSafeRx”

#3: FDA’s BeSafeRx

Fact sheets, data, and educational videos

#4: Alliance for Safe Online Pharmacies’ website

Go to www.safeonlinerx.com

ASOP provides:

• Links to FDA,

NABP, FSMB,

LegitScript

other credible

sources

• Short videos;

• Fact sheets;

• Newsletter;

• Data; and

• Reports;

Do You Know Where They Go?

• Do you know where your PATIENTS go to get medicines?

• Do you know where your KIDS go to get medicines?

• Do you know where your FRIENDS go to get medicines?

Do YOU know where they go?

ASK

Key Takeaways1. Warn patients not to purchase healthcare products online

– unless they do so from a reputable source

2. When evaluating a patient’s response to medication,

remember that the drug may have been purchased online

-- report any issues to FDA’s MedWatch

3. Direct patients to the top four resources listed

4. Don’t write prescriptions for Internet pharmacy operations

5. Ask patients where they got their medicine; Do you know

where they go?

Questions for

Dr. Mackey

Questions for

Dr. Bernstein

Questions for

Mr. Horton