The document discusses various guidelines issued by the US Food and Drug Administration (FDA) regarding products regulated by the FDA, such as foods, drugs, medical devices, biologics, cosmetics, and radiation emitting products. It also provides details on FDA guidelines for toxicological studies, clinical trials, manufacturing sterile products, MRI safety, transport temperature maintenance, and clinical trial phases. Guidelines are presented for topics like food packaging, color additives, and maintaining quality control and assurance in accordance with FDA standards.

2. Introduction
 The various guidelines given by United
States Food and Drug administration
are:
 For the maintenance and for conducting the
toxicological studies
 Bioequivalence studies
 Clinical trials and
 In the field of radiology

3. Products Regulated by FDA
 Food:
 Dietary Supplements
 Nutrition
 Food Borne illness etc.
 Drugs:
 Prescription
 Over the counter
 Generic etc.
 Medical Devices:
 Contact lenses
 Hearing aids etc.

4.  Biologics:
 Vaccines
 Blood products
 Animal Feed and Drugs:
 For pets
 Cosmetics
 Safety,
 Labeling etc
 Radiation emitting products:
 Cell phones
 Lasers
 Microwaves etc.
 Combination Products

5. Guidelines
1. Manufacturing of sterile products
 Produced by the FDA in USA and published
in 1987
 FDA defines 2 areas in aseptic processing
that are of particular importance to drug
product quality
○ Critical area
 Activities that are conducted in this area include
manipulations of the sterilized materials or products
prior to and during filling or closing operations
○ Controlled area
 Packing and labeling is done

6. 2. Guidelines for Radiological Health – MRI
 Although MRI does not use ionizing radiation to
produce images, there are still some important
safety considerations which one should be
familiar with. These concern the use of;
○ Strong magnetic fields
○ Radio frequency energy
○ Time varying magnetic fields
○ Cryogenic liquids
○ Magnetic field gradients

7.  The US FDA safety guidelines states the field
strengths not exceeding 2 tesla may be routinely
used.
 People with pacemakers must not be exposed
to magnetic fields > 5 Gauss.
 The RF energy form in imaging sequence can
cause heating of the tissues in the body.
 The SAR is the limiting measure for the RF
energy
○ SAR = watts/Kg
○ SAR for the whole body must be < 0.4w/kg
○ Must be < 3.0w/kg averaged over the head

8.  Any pulse sequence must not rise the temp
by more than 1 deg C and not greater than
38 deg C in the head, 39 deg C in trunk and
40 deg C in the extremities.
 Imaging gradients do produce high acoustic
noise levels.
○ The American limits the peak acoustic noise to
200 Pascal or 140 decibels with references to
20 micropascals
○ The sounds may be due to the turning on and
off of the magnetic field gradients in various
imaging sequences.

9. 3. Maintenance of storage temperature
conditions during transport.
 Drug efficacy depends on proper temperature
management
 Uniquely patented flexible ice blanket design can be
layered over, under or wrapped around products for
a blanket of protection. This keeps the product
insulated from outside temperatures.
 While minimizing shipping damage and
contamination, many leading pharmaceutical
companies are choosing cryopak in response to the
increasing US Pharmacopeia and US FDA
involvement with cold chain management practices
and strict enforcement of the industries food
manufacturing practices.

10. 4. Food, Seafood and Perishables
 The important aspect of USFDA compliance is that
the ability to keep fragile seafood products in the
critical temperature range of 32 to 40oF during
shipping, handling and storage .
 Even after melting it continues to deliver high quality,
fresh product to customer's doorstep.
 The patented cryopak flexible pouch design is easy
to custom fit to virtually any size or type of seafood
shipment.

11. 5. Guide lines for clinical trials
 These guidelines have been evolved wih
consideration of WHO, ICH, USFDA and European
GCP guidelines as well as the ethical guidelines for
biochemical research on human subjects issued by
the Indian council for medical Research.
 They should be followed for carrying out research at
all stages of drug development, whether prior or
subsequent to product registration.
 Clinical trial is a systematic study of pharmaceutical products
on human subjects in order to discover or verify the clinical
and/or adverse effects wih the subject of determining their
safety and/or efficacy.

12. Phase-I: Human/Clinical
Pharmacology trials
 The objective is to determine the maximum
tolerated dose in humans,
pharmacodynamics effect, adverse
effect/reactions if any.
 These are often carried out in healthy
volunteers.
 At least two subjects should be used in
each dose.
 These are carried out by investigators
trained in clinical pharmacology and having
the necessary facilities to closely observe
and monitor the subjects.

13. Phase-II: Exploratory trials
 Limited number of patients are studied to
determine possible effects.
 Studied to determine possible therapeutic
uses, effective dose range and further
evaluation of safety and pharmacokinetics.
 10-12 subjects should be studied at each
dose levels.

14. Phase-III: Confirmatory
trials
 The purpose of these trials is to obtain
sufficient evidence about the efficacy and
safety of the drug in a larger number of
patients.
 Data on ADRs observed during clinical use
of the drug should be reported.
 The report on its efficacy in the prescribed
format as per USFDA guidelines should be
submitted.

15. Phase-IV
 These studies are performed after
marketing of the pharmaceutical products.
 All clinical trials should be according to the
GCP.
 Prerequisites for the study are-
 Investigational pharmaceutical product.
 Pre-clinical supporting data

16. Protocol :Relevant
components of protocol
 General Information
 Objectives and justification
 ethical considerations
 study design
 Inclusion, exclusion and with drawal of
subjects
 Handling of the products
 Assessment of efficacy and safety
 Statistics
 Data handling and management
 Quality control and quality assurance
 compensation of accidental injury

17. Clinical Trials for Vaccines
 Some Vaccines that contain active or live
attenuated organisms can possibly posses
a small risk of producing particular
infection.
 The subjects to be vaccinated should be
informed .
 Guidelines for the clinical trials of medical
devices and diagnostic agents are also
stated.

18. Data to be submitted with
application for permission to
market a new drug
 Introduction
 Chemical Information
 Pharmaceutical information
 Animal pharmacology
 Animal Toxicology
 Information about clinical trials and any other
special studies.
 Regulatory status in other countries
 Marketing information

19. Format for submission of
clinical trail reports
 Title of the trial
 Name of the investigator and institution
 Objectives of the trial
 Design of study
 Number of patients
 Treatment given
 Observations made before the trial, after the trials and
during the trials
 Results
 Discussion
 Summary

20. Animal Toxicity requirements for
clinical trails and marketing a new
drug
 Contents of the brochure:
 Species used
 Number and sex of animals in each group
 Unit dose(mg/Kg)
 Dose Interval
 Route of administration
 Duration of dosing
 Information on systemic distribution
 Duration of post exposure follow up
 Results
 Reversibility of effects
 Duration of effects
 Dose Response

21. Essential Documents for the
conduct of a clinical trial
 These documents demonstrate the
compliance of the investigator, sponsor and
monitor and with other applicable
regulatory requirements.
 The documents are of 3 types, gives the
information before the trial, after the trail
and during the trial.

22. Types of Documents
1. Before clinical trials have commenced
 Investigators brochure
 Signed protocol and amendments if any
 Information given to trial subject
 Any other written information
 Advertisement for subject requirement
 Financial aspects of the trial
 Insurance statement
 Dated documented approval of independent
ethics committee of the protocols and any
amendments, CRF informed consent form

23. 2. During clinical trials
 Medical/Lab/technical procedures/tests.
 Certificates of analysis for new batches of
investigational products.
 Signed informed consent forms
 Record of retained bodyfluids/tissue samples if any

24. 3.After clinical trials
 Completed subject identification code list
 Final trial close out monitoring report
 Clinical study report

25. Guidelines for maintenance
of quality control and
assurance
 The assurance of product quality
depends more on the responsibility of
maintaining product quality during
production than thus proper sampling
and adequate testings of various
components and finished goods.

26. The following are the
guidelines for colorants
given by FDA
Colorant Restriction on use
FD&C
Blue# 1,2
Green#2
Red#3,4
yellow # 5,6
Can be used for food, drugs and cosmetics
D&C
Blue#6
Green#5,6
Orange#5,10,17
Red#6,7,21,22,27,28
Provisional listing for use in drugs and
cosmetics
Red#8,12,19,33,36 Provisional listing for use in drugs and
cosmetics C restriction of NMT 0.75mg to be
ingested on daily basis

27. Guidelines for packing
materials
 When the FDA evaluates a drug, the agency must be
firmly convenient that the package for a specific drug
will preserve the drugs efficacy as well as its purity
identity, strength and quality for its entire shelf life.
 FDA does not approve containers as such but only
materials used in the container.
 A list of substances considered 'generally recognized
as safe '(GRAS) has been published by the FDA.
 A material which is not included under (GRAS) is
intended to be used where food must be tested by the
manufacturer and data must be subjected.

28. Item Function Test Required
High Density
Polyethylene
Containers
Containers for capsules and
tablets
Thermal Analysis
Multiple internal reflectance
extrable substances
heavy metals
Glass
TYPE I
TYPE II
Parenteral
and neutral parenteral
preparations
Light Transmission
chemical resistance
powered glass test
water attack .
TYPE III
TYPE IV
oral/topical
Elastomeric closure for
infection
Parenteral use Biologic test acute systemic
toxicity
physiochemical test
turbidity pH change
total extrac.
heavy metals