Regulatory Aspects of Food and Nutraceuticals : "Nutritional Labeling And Clinical Investigation And Evaluation Of Medical Devices And IVDs Recommended Dietary Allowances in Europe "

1. Regulatory Aspects of Food and Nutraceuticals
Topic: Nutritional Labeling And Clinical
Investigation And Evaluation Of Medical
Devices And IVDs Recommended Dietary
Allowances in Europe
Name: 1)Gaurav Patil
2) Shubham Kumavat
3) Manish Sahane
Class: M. Pharm (RA)

2. CONTENTS
Nutritional Labeling In Europe
• Introduction
• Purpose of Nutritional Labeling of Food.
• Purpose of Nutritional Labelling.
• Nutrition labeling regulations.
• Offences and Penalties Regarding Nutritional Labeling.
• Health claims.
• Nutrition/Functional claims.
• Key parts of the food label.
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3. Clinical Investigation And Evaluation Of Medical Devices
And IVDs In Europe
• Introduction
• Classification
• Factors needing consideration in study protocols include
• Final study-Report
• Clinical Investigation of Medical Devices
• Clinical Investigation Objective
• How it is conducted ?
• Essential Principle applicable to all Medical Device and IVDS
• Why Clinical Evaluation important?
• Data or document required for the clinical evaluation
• General principle for conducting investigation
• What is the process? And Clinical Research Report
3

4. Recommended Dietary Allowances
• What is the Recommended Dietary Allowances?
• History of RDA
• RDA chart for Europe
• Calculations for RDA
• Uses of RDA
• References
4

5. Nutritional Labeling
 Food labeling is a primary means of communication
between the producer, seller and consumer of food.
 Nutrition label is considered as an ideal vehicle for
conveying dietary guidance/information about the
nutrition attributes of food (Nusrath Nasir, 2013).
 Nutrition labeling law starts working from December,
2007 for all prepackaged foods.
 Nutrition Facts "Nutrition labeling become mandatory".
Bringing India in line with the developed world, all
processed food made or sold in India have to carry the
nutritional Labeling [Health minister, Govt. of India].
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6. PURPOSE OF NUTRITIONAL LABELLING
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7. Purpose of Nutritional Labeling of
Food
How do I use the nutrition information of food labels in a healthy eating
context ?
• Nutritional food label gives you information about which nutrients are in the
food.
• Food labels don't suggest what foods to eat - that's your decision. But labels
can help you make your "personal best" food choices.
• Nutritional labeling make significant impact on consumer health through
declarations of certain nutrients such as; Polyunsaturated fatty acids, omega-
3, fiber, trans fats, cholesterol, sodium etc.
7

8. Nutrition labeling regulations.
The regulations stipulate the requirements for 3 different types nutrition information on
food labels Nutrition Facts table
 Nutrient content claims:
e.g. low in saturated fat, low in sodium.
 Diet-related health claims:
e.g. reduce risk of high blood pressure, heart disease.
Are there any exemptions to mandatory nutrition labelling?
Fresh fruit and vegetables
 Raw meat, poultry and fish, seafood.
Alcoholic beverages.
Foods sold at road-side stands, craft shows, fairs.
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9. Offences and Penalties Regarding
Nutritional Labeling
• It is very easy to notice the defect in labeling through visual inspection.
• Faulty nutritional claims:
1 . If the food product is not labeled in accordance to the regulations.
2. it does not provide the required complete information or
3. the food product is promoted for sale with false, misleading or deceptive claims.
Penalties are –
1. Misbranded food up to 3 lakh rupees penalty
2. Misleading advertisement up to 10 lakh rupees
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10. Health claims
• General claims about benefits to overall good health, such as 'healthy' or 'good for you',
will only be allowed to be used if accompanied by an approved claim.
This means that have an explanation of why the food is 'healthy’
.Labels are not allowed to claim that food can treat, prevent or cure any disease of medical
condition. These sorts of claims can only be made of licensed medicines.
Examples of health claims include:
• Calcium is important for normal growth and development of bones.
• Beta-glucans from oats help to reduce cholesterol.
• Xylitol in some sugar-free chewing gum helps to neutralise plaque acids.
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11. Nutrition/Functional claims
• A nutrition claim describes what a food contains (or does not contain) or
contains in reduced or increased amounts.
• Examples include:
• Low fat (less than 3g of fat per 100g food) Symbol
• High fibre (more than 6g of fibre per 100g food) Symbol
• Reduced sugar (30% less than the original product) Symbol
• Zero transfat Symbol X.
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12. Key parts of the food label
1] Principal display panel (PDP)
• Portion of label most likely to be seen by consumer at time of purchase
Principal display panel must contain
• Net quantity of content (amount of food in package)
2) Information Panel-
Panel to the immediate right of (PDP)
Principal information panel must contain.
1] Name and address of manufacturer.
2) Ingredient list.
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13. • As per USFDA-An instrument, apparatus, implement, machine, contrivance, implant,
invitro reagent or other similar or other article, including a component part, or accessory
which is recognized in the official National formulary or USP or any supplement to them
, intended for use in diagnosis of disease or other condition or in the intended, or
prevention of other diseases in men and animals or intended to affect structure or any
function of the body of man or other animal.
• Which does not achieve any of it's primary intended purpose through chemical action
within or on the body of man or other animal which is not dependent being metabolized
for the achievement of any of its primary intended purposes
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Clinical Investigation And Evaluation Of Medical Devices
And IVDs

14. • IVDS,- Definition: In vitro diagnostic products are those reagents,
instruments, and systems intended for use in diagnosis of disease
or other conditions, including a determination of the state of
health, in order to cure, mitigate, treat, or prevent disease or its
sequelae. Such products are intended for use in the collection,
preparation, and examination of specimens taken from the human
body. [21 CFR 809.3]
• IVDs are devices as defined in section 201(h) of the Federal
Food, Drug, and Cosmetic Act, and may also be biological
products subject to section 351 of the Public Health Service Act.
Like other medical devices, IVDs are subject to premarket and
post market controls. IVDs are generally also subject to
categorization under the Clinical Laboratory Improvement
Amendments (CLIA '88) of 1988.
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15. CDSCO (IMRDA) & MDD risk based
classification
Class A (Class-1)-Devices involving low risk
levels(Thermometer)
Class B (Class-2a)-Devices involving low to
mediumrisk (Hypodermic needle)
Class C (Class 2b)-Devices involving moderate
to highrisk (Lung ventilator)
Class D (Class 3)-Devices involving high risk
(Heartvalve, Implantable devices)
15

16. By USFDA,
Class-1 (low risk)-Elastic bandages, examination
gloves, adult incontinence pad
Class-2 (Medium risk)-Catheter gloves, adult
syringe , needle
Class -3 (High Risk)-Pacemakers, dental lasers,
heart valves
Classification
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17. • Clinical Investigation of Medical Devices
• Clinical Investigation
A clinical investigation is defined as any systematic investigation or study in or on one or
more human subjects, undertaken to assess the safety, clinical performance and/or
effectiveness of a medical device. The undertaking of a clinical investigation is a scientific
process that represents one method of generating clinical data.
• Clinical Investigation Objective
The objective of a clinical investigation is to assess the safety, clinical performance and/or
effectiveness of a medical device for a particular indication or intended use Clinical
Investigation
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18. • How it is conducted ?
ISO 14155: 2011
Clinical Investigation of Medical Devices for Human Subjects
- Good clinical practice details the requirements for the conduct of clinical
investigations. Clinical investigations must take into account scientific principles
underlying the collection of clinical data along with accepted ethical standards
surrounding the use of human subjects.
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19. Essential Principle applicable to all Medical Device and IVDS
When should Clinical Investigation conducted?
Clinical investigations are necessary to provide data not available
through other sources (such as literature or nonclinical
testing)When considering the need for a clinical investigation,
one should consider whether there are new questions of safety,
clinical performance and/or effectiveness for the particular
medical device and intended use that need to be addressed in a
clinical investigation.
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20. • General principle for conducting investigation
1. Be based on the results of the clinical evaluation process
2. Follow a proper risk management procedure to avoid undue risks
3. Be appropriately planned, conducted, analyzed and reported
4. Be compliant with all relevant legal and regulatory requirements
5. Follow appropriate ethical principles.
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21. • Factors needing consideration instudy protocols include
1. Clear statement of objectives
2. Minimization of risk to subjects and those involved withthe conduct of the
investigation0 Adverse event definitions and reporting
3. Study endpoints
4. Appropriate subject population(s) Minimization of bias (e.g.randomization
blinding/masking, concealment of allocation)
5. Identification of confounding factors (e.g.concurrent therapies, co-
morbidities)
Final study-Report
The outcome of a clinical investigation should be documented in a final study
report. This then forms part of the clinical data that is included in the clinical
evaluation process andultimately becomes integrated into the clinical evaluation
report
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22. Ethical consideration
for conducting
investigation
• It should generate new data and answer specific
safety, clinical performance, and effectiveness
questions that remain unanswered by the
current body of knowledge
• The desire to protect human subjects from
unnecessary or inappropriate experimentation
must be balanced with the need to protect
public health through the use of clinical
investigations where they are indicated.
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23. Clinical Evaluation of Medical Devices and IVDs
• Clinical Evaluation
• Clinical evaluation is a set of ongoing activities that use scientifically sound methods for
the assessment and analysis of clinical data to verify the safety, clinical performance
and/or effectiveness of the medical device when used as intended by the manufacturer.
• When is Clinical Evaluation undertaken?
• It is first performed during the development of a medical device in order to identify data
that need to be generated for regulatory purposes and will inform if a new device clinical
investigation is necessary, together with the outcomes which need to be studied.
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24. • Why Clinical Evaluation important?
• When placing a medical device on the market, the manufacturer must have
demonstrated through the use of appropriate conformity assessment procedures
that the medical device complies with the Essential Principles of Safety and
Performance of Medical Devices.
• Generally, it is expected that the manufacturer has demonstrated the medical
device achieves its intended performance during use according to its labelling
(i.e. information supplied by the manufacturer)and the that known and
foreseeable risks are minimised and acceptable when weighed against the
benefits
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25. • General principle for Clinical Evaluation
• The clinical evaluation is based on a comprehensive analysis of available pre- and post-
market clinical data relevant to the intended use of the device in question, and/ or
performancelinical safety, including effectiveness data .
• There are any design features of the medical device or Target Treatment that populations
that Requires specific attention.
• Whether data from comparable devices can be used to and/or performance clinical
safety,the support effectiveness of the device in question.
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26. Data or document required for the clinical evaluation
• The clinical investigation plan
• Clinical investigation plan amendments and the rationale forthese
changes
• The relevant Ethics Committee documentation, opinion(s)
andcomments for each investigation site, including a copy of
theapproved informed consent form(s) and patient
• information documents;
• Case report forms, monitoring and audit records
• Regulatory Authority approvals and associated correspondenceas
required by applicable regulations
• The signed and dated final report
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27. • What is the process?
• To conduct a clinical evaluation, a manufacturer needs to:
1. Identify the Essential Principles that require support from
relevant clinical data
2. Identify available clinical data relevant to the medical device
and its intended use
3. Evaluate (appraise and analyses) clinical data in terms of its
suitability and contribution to demonstrating the safety, clinical
performance and/or effectiveness of the medical device in
relation to its intended use
4. Generate clinical data needed to address remaining questions of
safety, clinical performance and/or effectiveness
5. Bring all the clinical data together to reach conclusions about
the safety, clinical performance and/or effectiveness of the
medical device 27

28. • CLINICAL RESEARCH REPORT
• At the completion of the clinical evaluation process a report should be compiled that
outlines the scope and context of the evaluation; the inputs(clinical data).
• The appraisal and analysis stages; and conclusions about the safety and performance of
the device in question The clinical evaluation report should contain sufficient information
to beread as a stand alone document by an independent party (e.g. regulatory authority or
notified body).The technology on which the medical device is based, the intended use of
the device and any claims made about the device's clinical performance or safety The
nature and extent of the clinical data that has been evaluated; and How the referenced
information (recognized standards and/or clinical data)demonstrate the clinical
performance and safety of the device in question.
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29. What is the Recommended Dietary Allowance?
 Recommended Dietary Allowances (RDAs) are the levels of
intake of essential nutrients that, on the basis of scientific
knowledge, are judged by the Food and Nutrition Board to be
adequate to meet the known nutrient needs of practically all
healthy persons.
 The first edition of the Recommended Dietary
Allowances (RDAs) was published in 1943 during World War II
by Lydia J. Roberts , Hazel Stiebeling , and Helen S. Mitchell with
the objective of “providing standards to serve as a goal for good
nutrition.
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30.  The European Food Safety Authority (EFSA) refers to
the collective set of information as Dietary reference
value, with Population Reference Intake (PRI) instead of
RDA, and Average Requirement instead of (Estimated
Average Requirement) EAR.
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31. History of RDA
 The committee was renamed the Food and Nutrition Board in
1941, after which they began to deliberate on a set of
recommendations of a standard daily allowance for each type
of nutrient.
 The standards would be used for nutrition recommendations
for the armed forces, for civilians, and for overseas population
who might need food relief.
 Roberts, Stiebeling, and Mitchell surveyed all available data,
created a tentative set of allowances for "energy and eight
nutrients", and submitted them to experts for review
31

32.  The final set of guidelines, called RDAs for Recommended Dietary
Allowances, were accepted in 1941.
 The allowances were meant to provide superior nutrition for civilians
and military personnel, so they included a "margin of safety.
 Because of food rationing during the war, the food guides created by
government agencies to direct citizens' nutritional intake also took food
availability into account.
 The Food and Nutrition Board subsequently revised the RDAs every
five to ten years.
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33. Recommended Dietary Allowances chart
33

34. Calculations for RDA
The equations used to calculate the RDA are as follows:
If the standard deviation (SD) of the EAR is available and the
requirement for the nutrient is symmetrically distributed, the
RDA is set of two SDs above the EAR:
RDA=EAR+2SD(EAR)
If data about variability in requirements are insufficient to
calculate an SD, a coefficient of variation (CV) for the EAR of
10 percent is assumed, unless available data indicate a greater
variation in requirements. 34

35.  If 10 percent is assumed to be the CV, then twice that amount
when added to the EAR is defined as equal to the RDA. The
resulting equation for the RDA is then
RDA=1.2EAR
This level of intake statistically represents 97.5 percent of the
requirements of the population.
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36. Uses of RDA
 For interpreting food consumption records of individuals and
populations.
 For establishing Standards for the national feeding programmes
implemented by the Governments for its vulnerable population.
For planning and procuring food supplies for population groups.
36

37. Comparison of individual intakes to the RDA allows an estimate
to be made about the probable risk of deficiency among
individuals.
Modifying nutrient requirements in clinical management of
diseases.
To help public health nutritionists to compose diets for schools,
hospitals, prisons etc.
For health care policy makers and public health nutritionists to
design, develop nutrition intervention programmes and policies.
For evaluating the adequacy of food supplies in meeting national
nutritional needs. 37

38. References
1. https://en.wikipedia.org/wiki/Dietary_Reference_Intake.
2. https://www.ncbi.nlm.nih.gov/books/NBK234926/#:~:text=Recommended%20
Dietary%20Allowances%20(RDAs)%20are,of%20practically%20all%20health
y%20persons.
3. https://www.efsa.europa.eu/sites/default/files/assets/DRV_Summary_tables_jan
_17.pdf
4. GHTF SG1/ NO44:2008 Role of Standards in the Assessment of Medical
Devices.
5. GHTF SG1/ N071:2012 Definition of the Terms 'Medical Device' and 'In Vitro
Diagnostic(IVD) Medical Device.
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39. 6. IMDRF GRRP WG/N47 FINAL: 2018 Essential Principles of Safety and Performance
of Medical Devices and IVD Medical Devices .
7. GHTF/SG1/N45:2008 Principles of In Vitro Diagnostic Medical Devices
Classification.
8. https://www.fda.gov/training-and-continuing-education/cdrh-leamn/overvlew-
regulatory.tequirements-medical-devices29/12/20227.
9. https://cdsco.gowin/opencms/opencms/en/Medical-Device-Diagnostics
10. https://cdsco.cov.in/opencms/export/sit@s/CDSCO_WEB/Pdfdocuments/IVD/
FAQS/FAQ IVD MDR-2017_ 2.pdf
11. GHTF SG1/ N78:2012 Principles of Conformity Assessment for Medical Devices.
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