availability of essential medicines in the czech ...

March 15th, 2017

AVAILABILITY OF ESSENTIAL MEDICINES IN THE CZECH REPUBLIC

Publication date: March 15, 2017

ARETE-ZOE, LLC Registered office: 1334 E Chandler Blvd 5A-19, Phoenix 85048 AZ, USA T: +1-480-409-0778 (24/7) | +1-631-791-8129 E-mail: [email protected] | Website: http://www.aretezoe.com/

Availability of Essential Medicines in the Czech Republic

2017

Executive Summary This report analyzes availability of essential medicines as defined in the World Health Organization (WHO) Essential List Medicines (Report of the WHO Expert Committee) in the Czech Republic. The WHO list of essential medicines contains most effective and safe medicines needed to meet the most important needs in health systems, and is frequently used by countries to create their own national lists. Without these drugs, some conditions will not be able to receive optimal therapy. Availability gap represents serious public health concern. Expert Committee of the World Health Organization selects Essential Medicines Lists in accordance with approved procedures. The Committee evaluates the scientific evidence on the basis of the comparative effectiveness, safety and cost–effectiveness of the medicines. Both lists (adult and pediatric) went through major revisions in 2015, as the Committee considered 77 applications, including 29 treatment regimens for cancer, hepatitis C and tuberculosis (The Selection And Use Of Essential Medicines. Report Of The WHO Expert Committee, 2015). Local availability is expressed as registration, in the form of total number of licensed products, and number of marketed products, i.e. products that were on the market in Q3 2016. Of the total number of 13,256 individual registrations for essential medicines, only 2,110 (14%) were actively marketed in Q3 2016. Total number of licensed and marketed product equals all strengths, formulations and dosage forms counted separately. The dataset is current as of December 30, 2016. Any revisions to the database made in the period between data download and publication of this report are not considered. Locally available products were compared to the WHO list of essential medicines. The material is presented in graphs and summary tabulations as listed in the table of contents.

Of the 427 essential drugs, 311 are registered in the Czech Republic, 292 were registered and marketed in Q3 2016, 19 were registered but not marketed, and 135 (32%) were unavailable. Most affected classes are antibacterials, antituberculars, antiretrovirals, antiparasitics, and dermatologicals. Essential medicines availability gap overlaps significantly with drugs that are in shortage globally. The report provides overview of the situation in the Czech Republic. Essential medicines availability gap represents both public health concern and risk of harm to individual patients. Substitute and second line therapies are often less effective, more toxic, or more expensive. Improvisation and the use of less familiar medicines are more likely to lead to medication errors. Mitigation of shortages and creation of shared contingency supplies puts additional strain on understaffed hospitals, in addition to human toll inflicted by social stress. Drug shortages make it impossible to follow evidence-based practice guidelines, and force decisions to prioritize certain group of people over another. Public health concerns arise due to inability to prevent and treat contagious diseases such as tuberculosis. Significant resources have to be dedicated to overseeing and managing the situation at government and supranational level. Of the 427 essential medicines, 311 are registered. Of these, 292 essential medicines showed active marketing in Q3 2016 and 19 were registered but not marketed. 116 (27%) were not registered, and therefore not available, rather than in shortage locally. Availability gap amounts to 135 (32%) essential medicines for both unregistered and not marketed essential medicines. However, essential medicines that are not available locally significantly overlap with medicines that are in periodic or chronic global shortage. Examples of the most significant global shortages of essential medicines are presented in the context of local availability gap. The Czech Republic is a small market with complex regulatory environment and inconsistently applied and enforced rules that often change in response to political demand. Alternative sources currently include parallel import from other EU countries. Attempts to obtain essential medications from alternative sources provide opportunity for the introduction of counterfeit, falsified and substandard drugs into clinical practice. ARETE-ZOE, LLC 1334 E Chandler Blvd 5A-19, Phoenix 85048 AZ USA

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2017

SYNOPSIS

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Essential medicines are mainly generic formulations that are relatively inexpensive to buy but not necessarily cheap to make.

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Problematic availability of essential medicines affects all countries around the globe, not just the Czech Republic.

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Most affected drugs are parenteral nutrition components, sterile injectables, antibacterials, anti-tuberculars, anti-retrovirals, tuberculin, vaccines, oncology drugs, anesthetics, anti-malarial drugs, anti-parasitics and others.

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Most drugs in shortage are difficult or impossible to replace, and workaround solutions are usually less effective, more toxic, and/or more costly.

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Main causes of drug shortages are consolidation of the industry, lack of competition, low profit margin of some generic drugs, production issues, raw material availability, business decisions and regulatory actions.

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Additional issues include sudden price hikes following acquisition and rebranding of old generic products as well as for-profit adulteration (heparin).

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Counterfeit, falsified and substandard drugs reach both hospitals and individuals through illegal supply chains. Common findings include cancer drugs, anti-retrovirals, anti-malarials and anti-tuberculars.

ARETE-ZOE, LLC 1334 E Chandler Blvd 5A-19, Phoenix 85048 AZ USA

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2017

About ARETE-ZOE ARETE-ZOE, as a consultancy, provides solutions to complex problems in the high stakes and high consequence environment of Global Pharmaceuticals, including clinical research, healthcare informatics, and public health. We blend established, Pharma sector methodologies, innovation, and adaptations/transfers from other sectors to identify and resolve consequential practices that pose risk and often result in avoidable patient casualty. However, we are specifically, not a patient advocacy group but believe in optimizing organizational effectiveness and that smart business is agile, competitive and profitable, while intrinsically safe, secure, and resilient. We work within a global context because transnational interests influence national circumstances and choices at point of prescription. ARETE-ZOE provides full spectrum organizational and operational risk management consultancy. Our published materials provide a glimpse of some aspects of our services to demonstrate both knowledge and ongoing participation within the Pharmaceutical Industry. Our analysis and consultancy includes all channels of misuse, diversion, counterfeiting and illicit exploitation of pharmaceuticals, medical devices, and precursor chemicals. Our advisement is to manufactures, jurisdictional entities, insurers, legislators, litigators, patients, and health care providers. This scope also frequently segues into the nexus of crime and terrorism as significant influencers that undermine sector integrity differentiated from other criminal activity. Obviously, vulnerability assessment, information collection management and intelligence production supporting decision-making for risk reduction and interventions are routinely within the scope of our services as well as design and implementation of operational control measures.


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Availability of Essential Medicines in the Czech Republic I.

2017

Situation in the Czech Republic

Focus of the following analysis is on essential medicines that are not available in the Czech Republic, and evaluation of the situation in the context of global drug shortages. Czech Republic, as a small market with low prices levels, may have difficulty securing access to essential medicines that are in short supply globally. The World Health Organization (WHO) considers 427 drugs essential for health systems. Of these, 311 are registered in the Czech Republic, 292 were on the market in Q3 2016, and 135 (32%) are currently unavailable. Availability gap in the Czech Republic amounts to 135 (32%) essential medicines for both unregistered and not marketed essential medicines. Worst affected groups include anti-parasitic drugs and antiinfectives, especially drugs for the treatment of tuberculosis and HIV/AIDS, and dermatologicals. The data is presented in detail in appendices. 

Appendix 1 – Availability of essential medicines in the Czech Republic shows summary table and summary graph of total number of essential medicines by their generic names and their availability in the Czech Republic by organ class. The series of graphs shows detailed breakdown of all system organ classes by availability of essential drugs.

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Appendix 2 – Essential medicines unavailable in the Czech Republic lists all essential medicines not available in the Czech Republic, organized by organ class. The table includes information about number of registrations and number of marketed products.

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Appendix 3 – Essential medicines unavailable in the Czech Republic: Global context lists all essential drugs unavailable in the Czech Republic in a summary table by organ class, adds information on patent status of the drug and main indication, and makes mention of major shortages of the products worldwide.

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Appendix 4 – Essential medicines available in the Czech Republic: Registration and marketing compares the share of actively marketed products and products that are registered but not marketed.

Alimentary tract and metabolism There are 34 medicines listed on the World Health Organization (WHO) list of essential drugs, of which 25 are currently approved for marketing and available to patients. As of December 29, 2016, 9 (26%) were unavailable in the Czech Republic. The highest share of approved and marketed drugs was found for glucose lowering agent metformin (657 approvals/54 marketed), gastric ulcer medication omeprazole (430/52), fast-acting insulin (153/17) and oral hypoglycemic agent gliclazide (144/13). Unavailable medications include motion sickness drug hyoscine (scopolamine) hydrobromide, docusate sodium – drug for the treatment of constipation, intestinal anti-infective paromomycin, ready to use formulations of oral rehydration therapy salts, hydrocortisone for topical rectal use, vitamins nicotinamide and riboflavin, zinc sulfate and sodium fluoride. Significant number of medicines for the treatment of alimentary ailments is only available in very limited number of registrations, making the system vulnerable to disruption: calcium gluconate (1/1), pyridoxine (2/2), thiamine (2/2), glibenclamide (2/1), atropine (2/2), retinol (3/3), sulfasalazine (3/3) and others. Most of these products are subject to continuing or periodically emerging global shortages that affect many off-patent drugs and especially sterile injectables and parenteral nutrition components. None of the essential medicines is available through European centralized procedure. With the exception of paromomycin, Portugal is the only EU country, where these essential medicines are currently obtainable. For details, see Graphs 2 to 6 in Appendix 1; Table 2 in Appendix 2 and Table 16 in Appendix 3.


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2017

Availability of Essential Medicines in the Czech Republic APPENDIX 1 Availability of essential medicines in the Czech Republic

TABLE 1 - Summary (table): Availability of essential medicines by organ class WHO Essential Medicines

Availability (number of registrations)

Availability (marketed registrations)

Not registered

Availability gap

Percentage unavailable

A – Alimentary tract and metabolic diseases B – Blood and blood-forming organs C – Cardiovascular system D – Dermatologicals G - Genito-urinary system, sex hormones H – Hormones

34 30 25 21 19 11

25 23 22 10 12 10

25 23 22 9 12 10

9 7 3 11 7 1

9 7 3 12 7 1

26% 23% 12% 57% 37% 9%

J – Anti-infectives L – Anti-neoplastic agents, immunomodulants

119 45

90 40

80 39

29 5

39 6

33% 13%

M – Musculoskeletal system N – Nervous system P – Anti-parasitics, repellents R – Respiratory system S – Sensory organs V - Various TOTAL

6 37 36 10 13 21 427

5 35 9 9 9 12 311

5 33 6 9 9 10 292

1 2 27 1 4 9 116

1 4 30 1 4 11 135

17% 11% 83% 10% 31% 52% 32%

System organ class


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2017

Availability of Essential Medicines in the Czech Republic GRAPH 1 – Summary (graph): Availability of essential medicines by organ class 140

WHO Essential Medicines 119

120

Availability (number of registrations) Availability (marketed registrations)

100

Unavailable

90 80

80 60

45

40

39

34

30

25 25

20

25

23 23 9

7

22 22

21

37 35

36

33

30 21

19 10 9 12

3

40 39

12 12

7

11 10 10 1

6

6 5 5

1

4

0


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9

6

13

10 9 9 1

9 9

12 10 11 4

2017


GRAPH 32 - Antimycobacterials (J04) – Tuberculosis: Aminosalicylic acid and derivatives (J04AA), Antibiotics (J04AB), Hydrazides (J04AC) and thiocarbamides (J04AD) Availability (number of registrations) Availability (marketed registrations) 2

3 2 1

1

1 1

capreomycin

isoniazid

protionamide

ethionamide

0 0

rifapentine

0 0

rifabutin

0 0 rifampicin

0

1

cycloserine

0

1 1

p-aminosalicylic acid

3,5 3 2,5 2 1,5 1 0,5 0

J04AA01

J04AB01

J04AB02

J04AB04

J04AB05

J04AB30

J04AC01

J04AD01

J04AD03

GRAPH 33 - Antimycobacterials (J04) – Other antituberculars (J04AK) and combinations (J04AM), drugs for the treatment of leprosy (J04B) 4

Availability (number of registrations) Availability (marketed registrations)

2

2

0

0 0

0 0

0 0

0 0

delamanid

rifampicin and isoniazid

ethambutol and isoniazid

rifampicin, pyrazinamide and isoniazid

rifampicin, pyrazinamide, ethambutol and isoniazid

0 0 dapsone

0

clofazimine

0 0

bedaquiline

1

terizidone

1 1

ethambutol

1 1

pyrazinamid

4,5 4 3,5 3 2,5 2 1,5 1 0,5 0

J04AK01 J04AK02 J04AK03 J04AK05 J04AK06 J04AM02 J04AM03 J04AM05 J04AM06 J04BA01 J04BA02


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2017

Availability of Essential Medicines in the Czech Republic APPENDIX 2 Essential medicines unavailable in the Czech Republic TABLE 8 - Antiinfectives for systemic use (J) ATC Code

Active ingredient

Available (number of registrations)

Available (marketed registrations)

0 0 0 0 0 0 0

0 0 0 0 0 0 0

0

0

Antibacterials J01CF02 J01DB01 J01EC02 J01FA01 J01GA01 J01GB04 J01XX04

Cloxacillin Cephalexin Sulfadiazine Erythromycin Streptomycin Kanamycin Spectinomycin Antimycotics

J02AX01

Flucytosine

J04AA01 J04AB01 J04AB05 J04AD01 J04AD03 J04AK03 J04AK05

p-aminosalicylic acid Cycloserine Rifapentine Protionamide Ethionamide Terizidone Bedaquiline

1 1 0 0 0 0 2

0 0 0 0 0 0 0

J04AK06 J04AM02 J04AM03 J04AM05 J04AM06 J04BA02

Delamanid Rifampicin + isoniazid Ethambutol + isoniazid Rifampicin, pyrazinamide and isoniazid Rifampicin + pyrazinamide + ethambutol + isoniazid Dapsone Antivirals Valganciclovir Saquinavir Lopinavir + ritonavir Stavudine Nevirapine Lamivudine + nevirapine + zidovudin Efavirenz + emtricitabine + tenofovir Lamivudine + nevirapine + stavudine Ombitasvir + paritaprevir + ritonavir

4 0 0 0 0 0

0 0 0 0 0 0

0 2 0 9 15 0 2 0 0

0 0 0 0 0 0 0 0 0

Antimycobacterials

J05AB14 J05AE01 J05AE30 J05AF04 J05AG01 J05AR05 J05AR06 J05AR07 J05AX66


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APPENDIX 3 Essential medicines unavailable in the Czech Republic: Global context TABLE 29 - Various (V) Active ingredient

Status

Main indications

Major reported shortages

Reasons

Edentates

Generic

None

n/a

Generic

Chelation therapy: mercury and lead poisoning Cyanide poisoning and pityriasis versicolor Cyanide poisoning

Thiosulfate (Reg.)

Generic

Sodium nitrite Dimercaprol Methylthioninium chloride (methylene blue) (Reg.)

Generic

USA, 2012, resolved

n/a n/a

Heavy metal poisoning

Global, past resolved USA, past, resolved

Generic

Methemoglobinemia

USA, global, current

Manufacturing delays

Acetylcysteine

Generic

Acetaminophen overdose

USA, current

Manufacturing delays, shipping delays

Fomepizole

Generic

Ethylene-glycol and methanol poisioning

USA, Fomepizole Injection, current

Generic

Tuberculosis

USA, global, past

Generic Generic

Disinfection X-ray contrast medium

None

Generic

X-ray contrast medium

Tuberculin, purified protein derivative (PPD) - BCG Technical disinfectants Diatrizoic acid Iotroxic acid

None None


Manufacturing delays

Discontinued, higher demand on remaining suppliers Manufacturing delays, higher demand n/a n/a n/a

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APPENDIX 4 - Essential medicines available in the Czech Republic: Registration and marketing GRAPH – 63 – Essential medicines available in the Czech Republic: Availability gap by organ class 140

Not registered

120

Registered but not marketed in Q3 2016

100

Registered and marketed in Q3 2016

80 60

40 20 0


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