differentiation between food supplements and drugs: how to ......differentiation between food...

Differentiation between Food Supplements and Drugs:

How to set-up a respective Market Control System

1’st International Food Supplement and Nutrition Conference

Ankara-November 23, 2017

Dr. Gert Krabichler

Dr. Gert Krabichler - Ankara - 23.11.2017

Content

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1 Definition of Food Supplements and Medicinal Products

Differentiation between Food Supplements and Medicinal Products

Co-Existence of Food Supplements and Medicines having the identical API

How to ensure Safety for Consumers of Food Supplements given by an example of a well working Market Control System


Differentiation between Foods and Medicinal Products

Definition of Food / Food Supplements (1)

Foods / Food Supplements Food Supplements are Foods

WHO - Codex Alimentarius Definition of Food Supplements

1 Definition

Vitamin and mineral food supplements for the purpose of these guidelines derive their nutritional relevance primarily from the minerals and/or vitamins they contain. Vitamin and mineral food supplements are sources in concentrated forms of those nutrients alone or in combinations, marketed in forms such as capsules, tablets, powders, solutions etc., that are designed to be taken in measured small-unit quantities, but are not in a conventional food form and whose purpose is to supplement the intake of vitamins and/or minerals from the normal diet.






2 Selection of Vitamins and Minerals

Vitamin and mineral food supplements should contain vitamins/provitamins and minerals whose nutritional value for human beings has been proven by scientific data and whose status as vitamins and minerals is recognised by FAO and WHO.






3 Contents of Vitamins and Minerals

Maximum amounts of vitamins and minerals in vitamin and mineral food supplements per daily portion of consumption as recommended by the manufacturer shall be set, taking the following criteria into account:

(a)upper safe levels of vitamins and minerals established by scientific risk assessment based on generally accepted scientific data, taking into consideration, as appropriate, the varying degrees of sensitivity of different consumer groups;

(b) the daily intake of vitamins and minerals from other dietary sources.


Foods and Medicinal Products

Definition of Foods / Food Supplements (2)


Definition of Food / FS (EU Regulation)

1 For the purposes of this Regulation, ‘food’ (or ‘foodstuff’) means any substance or product, whether processed, partially processed or unprocessed, intended to be, or reasonably expected to be ingested by humans.

2 Food shall not be placed on the market if it is unsafe Food by definition has to be safe

3 ‘food supplements’ means foodstuffs the purpose of which is to supplement the normal diet and which are concentrated sources of nutrients or other substances with a nutritional or physiological effect, alone or in combination, marketed in dose form, namely forms such as capsules, pastilles, tablets, pills and other similar forms, designed to be taken in measured small unit quantities;


Medicinal Products • Prescription Medicines • OTC Medicines incl. Traditional

Herbal Medicines

Foods and Medicinal Products

Definition of Medicinal Products

Definition of Medicinal Products (EU)

1 (a) Any substance or combination of substances presented as having properties for treating or preventing disease in human beings; or

2 (b) Any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.

3 Medicines are

either prescribed by doctors or given under supervision of a Health Care Professional (HCP) e.g. OTC medicines


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Different regulatory philosophies – Comparison (1)

Food Supplements Consumers Medicinal Products Patients

Health Claim (Function Claim): Maintenance of Health or a Health Status Reduction of a Disease Risk

Indication: Curing, treating or prevention of a disease

Ingredients (nutritional): Regulated list of ingredients (positive or negative lists)

Active Pharmaceutical Ingredient: Open, dossier requirement for each API, drug substance part

Safety driven: Risk Assessment for long term use by international government bodies like EFSA (EU) or IoM (US)

Risk – Benefit driven: Benefit has to outweigh the risk, but can be a potentially harmful substance. Short term use during treatment period.

Additives: Positive list of Food Additives with proven long term safety

Excipients: Excipients are part of the risk-benefit assessment during drug development

Market authorization: Many markets allow simple notification procedure, no registration (depending on market surveillance by natl. authorities)

Market authorization: Always pre-market authorization required, always registration with natl. authorities, dossier requirements may differ between Rx and OTC Medicines




Food Supplements Consumers Medicinal Products Patients

Quality Management: HACCP concept (EU), risk based quality management, lower requirements on single ingredient testing

Quality Management: GMP System approach (qualification and validation) independent of the individual risk of a product

Tolerances: Wider range of tolerances (+50% to -20%) as they are less critical regarding safety

Tolerances: Usually +/- 5% deviation allowed. Larger deviations could already pose a serious risk.

Monitoring of Safety: Either no monitoring required or Nutrivigilance System (national requirements)

Monitoring of Safety: Pharmacovigilance system, regular product update safety reports (PSURs)

Stability and Validation: Often no mandatory testing, but manufacturer is responsible to fulfill labelled content throughout shelf-life

Stability and Validation: Mandatory proof via stability batches, climatic zone requirements, continuous monitoring throughout shelf-life

Product documentation: No (drug) substance part required, but raw material specifications to be available on request

Product documentation: Full CTD dossier (or equivalent) required


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Drug Legislation Food Legislation

Has to be safe by definition, maximum levels to be set for nutrients or “other” substances.

Maintaining Health or a Health Condition, health claim based on general benefit analysis for nutrients, either based on generally accepted data or by authority (e.g. EFSA)

Reduction of a disease risk (EU via EFSA)

Clear certification requirements (e.g. GMO, TSE, allergens, Nano, …)

Based on benefit-risk ratio, contra indications, user instructions

(patient leaflet), warnings

Curing or treating of a disease, medicinal claim based on product specific indication justified by clinical data on efficacy.

Prevention of diseases

Controlled processes (CTD dossier)


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Legislative principles– Comparison (4)

Drug Legislation Food Legislation

Ingredients are highly regulated

Nutrients have to be food components

Use of nutrients is limited

Positive list of nutrients

Levels (max.) are regulated

Positive list of food additives

Levels of additives are regulated

No registration

Great freedom to act within the frame given by the regulation e.g. multi-component products

Process and principle highly regulated

APIs can be newly created

Excipients can be used according to the required property of the drug

Registration required (dossier requirements, e.g. CTD format, ICH guidelines)

Great freedom to act in a controlled process to choose the API and excipients, restrictions on combinations



Legislative principles– Comparison (5)

2 1 Drug Legislation

Almost unlimited space

Food Legislation

Clearly defined space

FOOD

Safety based

PHARMA

Benefit / Risk

based

Food Business Operator (FBO) is fully

responsible to ensure safety


What is appro-priate for FS?

All substances used in FS have to be safe. Safety is a pre-condition for food! Would you register a salat?

Notification vs. Registration for Food Supplements

Comparison of processes (1)

Notification

1. Fast and un-bureaucratic process

2. Process according to the low risk posed by food supplements to consumers

3. No renewals of registration

4. Lower level of control from the authority perspective

5. Theoretically, higher number of products may enter the market

6. Post market control is the key element to ensure consumer safety

7. Strong food control agency has to be in place

Registration

1. Time consuming process

2. Process according to products posing certain and potentially high risk to patients

3. Renewals of registration optional or mandatory

4. Full control for the authorities?

5. Due to registration the number of products in the market might be significantly lower (but less consumer choice)

6. Post market control is also required for registered products

7. Lower burden for the control agency


What is appro-priate for FS?

All substances used in FS have to be safe. Safety is a pre-condition for food! Would you register a salat?

Notification vs. Registration for Food Supplements

Comparison of processes (2)

Notification

Shift of workload

from

“Registration Agency”

to

“Control Agency”

Full Responsibility is with Food Business Operator

Registration

Large workload

with the

“Registration Agency”

but still

post-market control needed

Also registered products can be falsified!

Aim of the applied strategy for consumers:

• Protection of consumers by providing a maximum of safe choices for consumers

• Control / ban resp. ban of incompliant manufacturers / marketers

• Control of “falsified” supplements or illegal products to ensure that they don’t contain illegal “pharmaceutical” substances (no difference to falsified medicines!)


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Co-Existence of Medicine and Supplement with an identical active

The different philosophy of Nutrition and Medicines

Purpose of Good Nutrition

1. Supplying the body with all key nutrients which are needed to keep the organism in a healthy status

2. Nutrient levels have to be based on safety even when consumed daily and life-long

3. No supervision of a Health Care Professional (HCP) is needed

4. Side effects are not accepted. Levels have to be at levels below any risk

Health Maintenance

Purpose of a Medicine

1. Fast restoration of the body for treatment of a deficiency syndrome or treating a disease

2. Sort-term treatment to bring the body back into a healthy status even dosages which may pose long-term a risk

3. Always given under the supervision of a Health Care Professional

4. Side effects are accepted and are managed by adaptation of the therapy

Treatment of a Disease

Co-Existence

2 different philosophies: 1. Continuous

sufficient supply with all key nutrients

2. Treatment (repair) to cure a disease



Examples (1)

Vitamin C

Medicine: 1000mg of Vitamin C for the treatment of Scurvy

Food: 1000mg of Vitamin C for the maintenance of a normal healthy immune system

Vitamin D

Medicine: 1000 I.U. of Vitamin D for the prevention of Osteoporosis

Food: 1000 I.U. of Vitamin D for the maintenance of healthy or normal bones

Co-Existence

The claim or the presentation of the product creates the differentiation between a medicine and a food



Examples (2)

Iron

Medicine: 30mg of Iron for the treatment of Anemia

Food: 30mg of Iron for the maintenance of a normal formation of red-blood cells

Gingko biloba

Medicine: 120mg Gingko-biloba leaf extract for the symptomatic treatment of brain-induced mental impairments

Food: 100mg of Gingko-biloba leaf extract, no claim, but showing the leaf. Claims made on permitted Vitamin claims for cognition

Co-Existence




Examples (3)

Probiotic LGG

Medicine: For the treatment of Diarrhea of Babies and small children

Probiotic LGG

Food: Food Supplement with freeze-dried life bacteria of Lactobacillus rhamnosus GG Co-Existence




Examples (4)

Saccharomyces cerevisiae

Medicine: For the treatment of acute Diarrhea of adults, adolescents, and children

Saccharomyces cerevisiae

Food: Food Supplement to support the gut flora with probiotic cultures 20mg

Co-Existence


Ingredients: Maisstärke, Oligofructose, Inulin, Vitamin C, Zinkgluconat, Saccharomyces cerevisae mit Betagluconan, Lactobacillus acidophilus, Natriumselenit in Calciumcarbonat; Kapselmaterial: Hartgelatine; Trennmittel: Magnesiumsalze von Speisefettsäuren


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How to ensure Consumer Safety Elements used for Market Control Systems

Law Enforcement and Control

Legislative

Structural

Food Legislation

FS included

with all consequences

Risk Assess-ment Body

Risk Manage-ment Agency

Regular inspections

Knowing “the critical players”

Notification

as a consequence

Anti-fraud law

(as responsibility is with FBO)

Clear line of responsibilities

High level expertise in all institutions

Control Bodies

Well coordinated

Alert system!

Located closely to the Food Business Operators (FBOs)

Focus on critical topics, e.g.:

Adulteration

Falsified products


Consumer Safety: Food & Food Supplements

Example: Germany

Ministry BMEL

Risk Assement BfR

Risk Management BVL

1 2 3

Ministry responsible for Food Policy and Safety Legislation

Several institutions “report” into the BMEL:

BfR Risk Assessment

BVL Risk Management

MRI Nutrition Research

Institute responsible for Risk Assessment

Additional Tasks:

Focal point to EFSA

Risk Communication

Research

Tasks for the BMUB (Fed. Ministry for Environment)

Agency responsible for Risk Management and Control System

Notification body for Food Supplements

Distribution of information to local control agencies


National Inspection Authorities: Germany

Organization of Market Control Systems (1)

Source: BfR: EU Food Safety Almanac http://www.bfr.bund.de/en/publication/EU/_almanac-192693.html

http://www.bfr.bund.de/en/publication/EU/_almanac-192693.html




Fed. Rep. of Germany (FRG) (and GDR)

Germany (GER)

Federal Ministry of Health (BMG)

1949 1990 1994 2001/2002 2013

Federal Ministry of Nutrition & Agriculture (BML) BMVEL BMEL

(BGA) Fed. Health Agency

BfArM

Split of BGA into:

BgVV

Split of BgVV into:

BfR (Risk Assessment)

BVL (Risk Management)

EU Reg. 178/2002


History




The Ministry










The Risk Assessment Institute








The Risk Management Agency







Source: BfR: EU Food Safety Almanac http://www.bfr.bund.de/en/publication/EU/_almanac-192693.html BVL presentation, see below

The Regional / Local Authorities

Local:

Over 400 cities and districts (Counties)

Responsible for:

Inspection of Companies

Taking of samples

Inforcement of actions

Regional:

35 Inspection Offices, Labs (specific inspection agencies)

Responsible for:

Sample testing

Reports

Food Inspection System Regional, City and County Authorities







Notification of a Food Supplement

Food Supplement Manufacturer / Marketer

The BVL informs the Ministry and the Competent Federal States Authorities for Food Control. This ensures an effective supervision of food products.

Notification to BVL

How does this work in detail, how is it managed? See the following slides gratefully provided by BVL!

Food supplements Notification procedure and legal

provisions in Germany

Federal office of consumer protection and food safety (BVL)

Gratefully provided by Dr. Evelyn Breitweg-Lehmann, BVL, Head of Department 101

19. September 2014 Bund-Länder-Aktivitäten

BVL: Koordination

bundesweit,

Datenauswertung,

Berichte

Koordination bundesweit,

Gesetzgebung,

Datentransfer ans BVL

Probenahme,

Inspektion, Vollzug

16 Bundesländer

Over 400 rural districts

and cities

35 Untersuchungsämter

Untersuchung,

Gutachten

Food surveillance system in Germany

Specific

Inspection

Agencies

Sampling,

Inspection of

companies

and stores,

Enforcement

Sample testing,

Reports 16 Federal States

http://www.bvl.bund.de/cln_007/nn_495478/DE/Home/homepage__node.html__nnn=true

06. November 2014

Federal Ministry of Nutrition and Agriculture (BMEL)

• Competent authority for food safety and [sanitary?] consumer protection

• Cooperation with European Commission

• Communication

Federal Office of Consumer

Protection and Food Safety

(BVL) • Risk management

• Communication

• Coordination of activities on

regional, national and EU level

e.g.

NOTIFICATION PROCEDURE

FOR FOOD SUPPLEMENTS

Federal Institute for Risk

Assessment (BfR)

• Risk assessment

• Risk communication

Cooperation

Scientific

advice

Data

Data

Scientific

advice

Risk assessment in Foodstuffs


Notification procedure of food supplements

According to paragraph 5 NemV

https://apps2.bvl.bund.de/nem/form/main.do

• Application form - online

– First Notification,

– Second notification or

– Notification of amendments

– Compulsory and voluntary

information to provide

– In German language, only

https://apps2.bvl.bund.de/nem/form/main.do

According to paragraph 5 NemV

Random

assessment

by competent

local authorities

Automatic

receipt

Electronic

submission of a

notification

Notification procedure of FS

Receipt of your message is hereby confirmed.

This is NOT a certification of marketability.

Forwarded

to the

German

Länder

authorities

Automatic reply

to the applicant


Notification Procedure for Food Supplements

Process: Key elements

Summary

1. Notification by the Applicant (FBO: Marketer / Manufacturer) to BVL

• Automatic receipt of notification to Applicant (but no legal check of the product)

2. Automatic storage of application in a BVL databank

1. Databank is protected and not externally accessible therefore extracted copy is used for information to others 2. Information to Ministry 3. Information to all local Federal States Authorities

3. Control: random assessment of FBOs by local competent authority

4. Feedback from local authorities to BVL (in case of findings)

5. BVL coordination of necessary actions (e.g. alert, recall, consumer info, etc.)

19. September 2014 Bund-Länder-Aktivitäten

BVL: Koordination

bundesweit,

Datenauswertung,

Berichte

Koordination bundesweit,

Gesetzgebung,

Datentransfer ans BVL

Probenahme,

Inspektion, Vollzug

16 Bundesländer

Over 400 rural districts

and cities

35 Untersuchungsämter

Untersuchung,

Gutachten

Food surveillance system in Germany

Specific

Inspection

Agencies

Sampling,

Inspection of

companies

and stores,

Enforcement

Sample testing,

Reports 16 Federal States


20. Oktober 2017

Non-harmonized substances

Vitamins Minerals

Amino acids

other substances

Ayurvedic

products

Fat ingredients

Bacteria

Pla

nts

Other substances as food (ingredients)

• (Usually,) no authorisation of food or food ingredients necessary

(exemptions possible, e.g. novel food)

• no lists with allowed or forbidden substances (in Germany)

• no specific regulations for the use of other substances as food (ingredients)

• no specifications or standardizations e.g. of plant extracts

• no maximum levels for substances or

• no maximum levels for non-desired (chemical) by-products

• (usually) no minimum levels

Legal framework

List of substances - Category Plant and Plant parts

Novel food

Safe food

Medicinal

product

? ?

Unsafe food

Reg. (EC) No.

178/2002

Reg. (EC) No.

1925/2006

Reg. (EC)

No. 278/97

Reg. (EC) No. 1331/2008 -

1334/2008

Directive

2002/46/EC

Labelling;

Hygiene;

Residues

Contaminants etc.

Medicinal

law

Law on

narcotics

Classification – legal basis


Other substances as food (ingredients)

Case-by-case assessment by FBO and surveillance authorities of the

German Länder

Case-by-case assessments are time-consuming and inefficient

But: General food law is applicable


• Classification as (safe) food

• Unsafe food (ingredients) are forbidden

• Novel food (ingredients) have to be authorized

19. September 2014 Dr. Evelyn Breitweg-Lehmann

Contact:

Bundesamt für Verbraucherschutz

und Lebensmittelsicherheit

[email protected]

www.bvl.bund.de

Thank you for your attention !

mailto:[email protected]

http://www.bvl.bund.de/

Dr. Gert Krabichler

Food-PharmaOTC Consult, Founder & Owner

IADSA Company Council Representative for Merck CH

Formerly, Director Global Regulatory Policy & Intelligence

and Head Global Regulatory Affairs

Merck Consumer Health, R&D

[email protected]

Mob.: +49 160 97279831





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