USFDA GUIDELINES

Introduction

The various guidelines given by United States Food and Drug administration are:For the maintenance and for conducting the

toxicological studiesBioequivalence studiesClinical trials and In the field of radiology

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.

Biologics: Vaccines Blood products

Animal Feed and Drugs: For pets

Cosmetics Safety, Labeling etc

Radiation emitting products: Cell phones Lasers Microwaves etc.

Combination Products

Guidelines1. 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 areaPacking and labeling is done

2. Guidelines for Radiological Health – MRIAlthough 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

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

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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

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

Animal Toxicity requirements for clinical trails and marketing a new drug Contents of the brochure:

Species usedNumber and sex of animals in each groupUnit dose(mg/Kg)Dose IntervalRoute of administrationDuration of dosingInformation on systemic distributionDuration of post exposure follow upResultsReversibility of effectsDuration of effectsDose Response

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.

Types of Documents

1. Before clinical trials have commenced Investigators brochureSigned protocol and amendments if anyInformation given to trial subjectAny other written informationAdvertisement for subject requirementFinancial aspects of the trialInsurance statementDated documented approval of independent

ethics committee of the protocols and any amendments, CRF informed consent form

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

3.After clinical trials Completed subject identification code listFinal trial close out monitoring report Clinical study report

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.

The following are the guidelines for colorants given by FDA

Colorant Restriction on use

FD&CBlue# 1,2Green#2Red#3,4yellow # 5,6

Can be used for food, drugs and cosmetics

D&CBlue#6Green#5,6Orange#5,10,17Red#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

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.

Item Function Test Required

High DensityPolyethyleneContainers

Containers for capsules and tablets

Thermal AnalysisMultiple internal reflectanceextrable substancesheavy metals

GlassTYPE ITYPE II 

Parenteraland neutral parenteralpreparations

Light Transmissionchemical resistancepowered glass testwater attack .

TYPE IIITYPE IV

oral/topical  

Elastomeric closure for infection

Parenteral use Biologic test acute systemic toxicity physiochemical testturbidity pH change

total extrac.heavy metals

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