INTRODUCTION:

The term Nutraceutical is defined any food or any food part which provides health benefits. They are found in the way of Pills, capsules and powders. They act by preventing or treating diseases¹.

According to Health Canada which was then defined as an isolated product. Dispensed in the form of medicine and they are not inter related with food. They provide prevention against chronic disease^{1, 2}

These products can range from specific diets to genetically engineered foods, nutrients in the isolated form, dietary form of supplements and also includes foods like beverages. With these technological improvements in the cellular level medical practitioners and Nutraceutical agents are now implementing new form of templates for searching and updating the knowledge by conducting clinical studies^{3, 4}

NUTRACEUTICAL CLASSIFICATION: FOOD AS MEDICINE:

Dietary Supplement:

A dietary supplement is a type of preparation administered by the oral route, which is meant for supplementing the diet, it consists of dietary ingredients and the product label must state that it is a dietary form of supplement⁵.

These supplements is a product (other than tobacco) which contains "dietary ingredients" which may include

· Mineral

· Vitamin

· Other botanical or Herbal

· These substances are meant for improving the level of dietary intake in the human body.

A good manufacturing practice (GMP) is regulated by the FDA for dietary supplements so it helps to ensure their purity, identity, composition and strength. For safety and labeling of their products the firm is only responsible which is necessary to evaluate their product prior entering the market in order to ensure that the products fulfill all the requirements of FDA and DSHEA (Dietary Supplement Health and Education Act) regulations.

The action will be taken by FDA incase if there is any adulteration or misbranding these preparations⁶.

Functional Food:

A functional food which is being used can be identical, or maybe, a conventional food, which can be either taken as a normal diet form⁷. Nutraceutical are enriched with micro or macronutrients.

Examples:

· Yogurts which is used as probiotics in intestinal health

· Omega-3 eggs with added omega-3 fatty acids, produced by feeding flaxseed to hens, to improve brain health

· Prebiotics–oligofructose for controlling intestinal flora

· Bran, lignin, oats for treating heart disease and colon cancer

Current scenario in USA:

In the USA, the FDA governs dietary supplements according to the Dietary Supplement Health and Education Act (DSHEA) 1994⁸. This act includes a measure for safety and guidance on good manufacturing practice (GMP). Under DSHEA, manufacturers are responsible for marketing the very safe and properly labeled products, but the main fact is that FDA bears all the burden of providing a product which is unsafe and improperly labeled. Public Health Security and Bioterrorism Preparedness & Response Act (2002), they are responsible for taking essential methods for protecting the people in actions related to United States food related issues

Figure1: Global Nutraceutical Market

Public Health Security and Bioterrorism Preparedness & Response Act (2002), they are responsible for taking essential methods for protecting the people in actions related to United States food related issues⁹.

Registration of Food Facility:

Details Needed:

FDA requires that firm have to submit the below mentioned details for facility registration.

· Phone number, Name of the facility, emergency contact number and address

· Company holders name, Phone number and other necessary details if required

· Name, owner address and contact number and address of the owner, agent in charge or operator

· The U.S. agent email information is to be provided in case if it is a foreign type of facility

· Food product categories which is applicable in form

Required Information–Optional:

· Owner or Operator email information & fax number

· Facility-Fax number

· In case there is difference from that of the facility then other mailing address is to be given

· If possible the email information & fax number of the holder company required

· Operation date of the facility

· In case of any holding facility then type of storage

Procedure for registration:

· FDA allows registrants for submitting their registrations on paper by FAX or mail. These submissions are entered into its registration system as soon as possible. FDA usually recommends an electronic type of submission.

· Registration should contain regarding the contact information & the name of its parent company and facility. The trade names of the classified food products as available in 21 CFR 170.3. Contact details of the person who holds the company and also ensuring that the details which is submitted is very exact.

· If it is a foreign facility then the contact information and name for the facilities U.S. agent which also includes contact information¹⁰.

21 CFR 170.3:

FDA ensures that for a food facility one have to submit registration containing that the general food category as mentioned in 21 CFR 170.3 to the FDA. This part also contains other classifications of food categories appropriate by FDA.

Additional categories of Food Product for Foods for Human Requirement

· Dietary Supplement Categories: Fats, Proteins, Amino acids, Lipid Substances

· Baby Food Preparations including (Infant and Junior)

· Vegetable Juice and Fruit, Concentrate Products

· Cheese Product categories cheese¹¹.

Facility Registration:

How to Register Facility

The form 3537 is to be used by registrants to register, update a registration, or to renew. The registration form is available only in form of paper and also in online. If there are a multiple facilities then they can also apply on CD-ROM.

· Once if the order received then the FDA will process CD-ROM and Paper submissions.

· FDA generally doesn’t accept registration done in person

Online Registration:

· Online at http://www.access.fda.gov/can be used to register. This site provides online help and it works 24 hours a day & also in working days.

· From 7:00 AM until 11:00 PM U.S. For helping Eastern Standard Online Registration Desk is available for helping you.

Fax

Fax Questions to 301-436-2804

Phone

Other than the U.S.: Call 301-575-0156

Within the U.S.: Call 301-575-0156 or 1-800-216-7331

http://www.fda.gov/Food/GuidnceRegulation/FoodFacilityRegistration/ucm2006832.htm& fill it

Registration by using Paper:

1. Register using Form 3537. The form mentioned below DHHS/FDA Form No. 3537: (available in PDF).

2. On the form any information is left blank or if it is not clear enough to read when FDA receives the form, then the FDA will return the form for revision. During returning for clearance, FDA will send it by the mail or fax through which it received the form.

3. FDA first completely enter and mail legibly

4. Then the FDA will mail which is mentioned on the registration application or through the address mentioned.

5. The information which was submitted previously was not in a correct form during reporting in such cases immediately you have to update your facility's registration as mentioned in the final rule §1.234

· DHHS/FDA Form No: 3537 (available in fill-in PDF for printing).

· Food Facility Registration Form for cancellation Form No: 3537a (available in fill-in PDF for printing)

To Request the Paper Form
Phone (7:00 a.m. to 11:00 p.m. U.S. Eastern Standard Time)	Call 301-575-0156 or 1-877-216 7331
mail	Write to: U.S.Food and Drug Administration Food Facility Registration HFS-681 5001 Campus Drive College park, MD 20993 USA

Paper registration is not more recommended rather than the online registration. Because the time taken for receiving the confirmation status will be longer for registration by paper. In case if there is any an error or deletions then the FDA will resend the form for correcting it meanwhile the FDA will not register your facility which leads to delay in the process of registration.

Registration by using CD-ROM:

1. Goto http://www.fda.gov/Food/Guidance Regulation Regulation/Food Facility Registration /ucm073728.htm

2. Then Form No: 3537 have to be downloaded in PDF format and need to be filled in a separate copy of the form electronically for each facility

3. Then by using the same preferred mailing address for each facility.

4. After that save the form for each facility under a different file name:

· Use the first part of the file name to identify the parent company

· The file name can be up to 32 characters long

5. Copy the files to a CD-ROM with ISO 9660 (CD-R or CD-RW) data format.

6. The certification statement that appears on the registration form Box 13 is to be enclosed

7. CD-ROM is the finally mailed to the FDA.

If any above mentioned information is not in accordance then the duty of the FDA is to resend it without further processing so it results in delayed registration.

Registration Confirmation:

Once if the registration is processed then the FDA will issue the registration number and confirm the registration.

Registration	Registration Confirmation
Fax	Fax
Online	Electrically
CD-ROM or by Surface mail	By Surface mail

Updating Registration Information:

· If there is any correction in the submitted registration information then in cases the operator, owner, or may be an authorized individual need to inform the FDA within the period of 60 days.

· The changes can be submitted through online or means of paper or on CD-ROM.

· In order to update the changed information then on online visit http;//www.access.fda.gov/.In case by means of CD-ROM then enters the changes on CD-ROM. In case by paper forms then use the paper procedure.

· In terms of new ownership then the former owner need to cancel the registration of the facility within the time period of 60 days.

Registration cancellation:

Registration can also be cancelled in the stipulated time period of 60 days by means of 3537a cancellation form¹⁰.

FDA requirements–Dietary Supplements imported into the USA:

· Dietary Supplement Manufacturers (both domestic and foreign) must register their establishment with the FDA. (Bioterrorism Act of 2002)

· Foreign facilities require a U.S. agent

· It is necessary that FDA have to give some prior notice on shipments of imported food

· Dietary supplement manufacturers must be in compliance with Current Good Manufacturing Practice.

· A New Dietary Ingredient Notification must be sent to the FDA 75 days before marketing your Dietary supplement that contains the NDI

· Dietary Supplement Labeling Regulations is to be followed during labeling of the products^{12, 13}.

Food Safety Modernization Act (FSMA):

The FSMA enacted on January 4, 2011, amended the Federal Food section 415, Drug, and Cosmetic Act (FD&C Act), in relevant part. Main purpose is to provide the facilities which are involved in the process of manufacturing, packaging, processing or holding, or consumption in the United States must submit additional registration information to FDA that must include a statement that at any time the FDA has a right to inspect the facility as mentioned in the FD and C Act. Food Drug and Cosmetics Act, as amended by FSMA, which also requires food facilities needed to be registered with FDA to renew such registrations every other year, and provides FDA with authority for suspending the registration of a food facility in certain circumstances^{14, 15}.

How Registration is affected:

If the facility is in one of the below mentioned food facility sectors then you have to register your facility with the FDA. Facility that contains manufactures, processes, holds or packs which contains only a pesticide or food meeting substance is not necessary to be register with the FDA.

Affected Food Facility Sectors

· Foreign and Domestic packers

· Foreign and Domestic manufactures or processors

· Foreign and Domestic Storage Operations

Foods maintained by more than one foreign facility

If	Then
Only if minimal activity is performed by the second foreign company, such as putting on a label	Both the facility have to be registered
If a foreign facility processes, manufactures, packs or holds the food sends the it to the another foreign facility for proceeding the further manufacturing or processing before the food is exported into the US	The second foreign facility is only to be registered with respect to that food
If any foreign facilities holds or packs food after the last foreign processor of the food	The foreign holder or packer must register

Food included in the Regulation:

As defined in 21 CFR 1.227 registrations is pertained only to facilities that manufacture, processes, hold or pack of food which is used for consumption by animals or humans in U.S. If the facility contains any of the following foods then it must have to be registered.

Excluded Foods	Included Foods
Pesticides	Dietary supplements and Dietary ingredients
Food contact substances	Vegetables and Fruits
	Seafood and Fish
	Frozen foods and Canned
	Shell eggs and Dairy products
	Infant Formula
	Snack food, Bakery goods and Candy
	Beverages (bottled water & alcoholic beverages)¹⁶

The Safety Reporting Portal:

The role is to (manufacturer, health care professional, researcher, the public health official, or concerned citizen), while submitting a safety report through this Portal, you need to make a vital contribution to the safety of America's medicines, food supply, and other products that touch us all. In this website, only some parts have been translated from English into Spanish. Pages that have been translated have an "En Espanola" link in the upper right part of the Page. You have to click this link to see the page in Spanish (Espanola). Click "In English" to see the page in English. In the case of any discrepancy in meaning, the English version is considered official. Currently, report questions are only in English and reports should only be submitted in English¹⁹.

Who should submit a safety report?:

· Food Manufacturers, Processors, Packers, and Holders

· Researchers

· An applicant for an approved drug product or a manufacturer, distributor or packer listed on the label of any drug product

· Drug Manufacturers

· Dietary supplement manufacturers, packers, and distributors¹⁶

CONCLUSION:

The usage to medical foods has been growing steadily since the introduction of Lofenalac over 40 years ago. Just within the last few years, however, the medical food market has prolifically expanded. In the U.S. and globally, there have been 100 new medical food product launches annually since 2009. In 2011, global sales were projected at just less than 59 billion, but the lack of industry association and scarcity of public data have made it difficult to estimate medical food revenue in the U.S. The recent publication of the FDAs Revised Draft Guidance, coupled with the issuance of two warning letters in 2013 regarding the definition of medical food, indicates that the agency may be acknowledging the need for stricter enforcement of its medical food regulations.

ACKOWLEDGEMENT:

The author acknowledges the management of SRM College of Pharmacy, SRM Institute of Science and Technology for their valuable support.

CONFLICT OF INTEREST:

The author does not declare any conflict of interest

REFERENCES:

1. Food Research International. Nutraceuticals: a piece of history, present status and outlook. Available from: URL: http://www.sciencedirect.com/science/article/pii/S096399690100179X.

2. Brower V. Nutraceuticals: poised for a healthy slice of the healthcare market? Nat Biotechnol. 199;16:728-731.

3. Eskin N A M and Tamir S Dictionary of Nutraceuticals and Functional Foods, CRC Press, Boca Raton, USA. 2006.

4. Zeisel SH. Regulation of Nutraceuticals Science. 1999:285:185-186.

5. D’Alberto A, Kim A. Regulation of the herbal medicine in the UK and Europe. An Interview with Micheal McIntyre- Chair of EHPA. Chinese Medicine Times-Volume 1 Issue 5–October 2006.

6. Dietary Supplements Available from: URL: https://www.fda.gov/Food/Dietary Supplements/default.htm.

7. Available from: URL: Nutraceuticals/Functional Foods and Health Claims on Foods.

8. Dietary Supplement Health and Education Act (DSHEA) Available from: URL: http://www.anh-usa.org/dshes/

9. Available from: URL: http://www.fda.gov/oc/bioterrorism/bioact.html.

10. Available from: URL: https://www.fda.govFood/Guidance Regulation/Food Facility Registration/default.htm

11. Available from: URL: https://www.fda.gov?food?guidancere gulation?foodfacilityregistration/ucm073728.htm#forms

12. Available from: URL: http://www.fda.gov/Food/Dietary Supplements/ucm109764.htm

13. FDA 101: Dietary Supplement Available from: URL: https://www.fda.gov/For Consumers? Consumer Updates? ucm050803.htm.

14. FDA Food Safety Modernization Act. Available from: URL: https://www.fda.gov/food/guidanceregulation/fsma/.

15. Available from: URL: https://www.fda.gov/food/ guidanceregulation/fsma/default.htm

16. Available from: URL: https://www.safetyreporting. hhs.gov/SRP2/en/Home.aspx?sid=e05fae18-0d47-418

Received on 08.04.2018 Modified on 31.05.2018

Research J. Pharm. and Tech 2018; 11(10): 4744-4748.

DOI: 10.5958/0974-360X.2018.00864.8