21BM3022

MEDICAL ETHICS AND

SAFETY
Module 4:Medical Devices Standards
1. Medical Standards and Regulations
2. Device classification
3. Registration and listing –CE, UL standards, ICMED regulations
4. Investigational Device Exemptions
5. Institutional Review Boards – IDE format
6. Good laboratory practices
7. Good manufacturing practices.
Medical Standard and Regulations in
India
• In India, medical devices are governed by CDSCO(Central Drugs
Standard Control Organization). It is regulated by Directorate General
of Health Services , Ministry of Health and Family Welfare and
Government of India.
• CDSCO is the only government body which regulate the medical
devices.
Medical Device Regulatory Structure
• Ministry of Health and welfare
• Drug controller general of India
• Central drugs standard control organization(CDSCO)
Medical Device Regulatory Structure
• The Ministry of Health and Family Welfare is an Indian government
ministry charged with health policy in India. It is also responsible for
all government programs relating to family planning in India.
• The Drug Controller General of India (DCGI) is the key official within
the CDSCO. The DCGI is responsible for the approval of the
manufacturing of certain drugs (vaccines, blood products, r-DNA
derived), specific medical devices, and new drugs.
• The Central Drug Standards Control Organization (CDSCO) is India’s
main regulatory body for pharmaceuticals and medical devices.
IMDRA
• Medical devices in India are regulated under the Medical Device Rules
• IMDRA - Indian Medical Devices Regulatory Act come in force
December 31, 2009
• The composition of the committee is represented by:
Central Government
Eminent Jurist
Two eminent medical practitioners
Two eminent medical technologists
Secretary General Quality council
IMDRA ESSENTIAL PRINCIPLES
• Should not compromise health and safety
• Design and manufacture of devices must conform with safety
principles
• Long term safety should be ensured
• Benefits of the devices must outweigh any side effects
• Medical devices should be useful for the intended purpose
IMDRA OBJECTIVES
• Provide notification of essential principles
• Provide for risk based classification of devices
• Notify standards and guidelines
• Provide mechanism of conformity
• Provide a post market surveillance system
• Provide for enforcement
IMDRA regulation
• Design and manufacturing requirements
• Performance evaluation
• Demonstration of device standards, testing and compliance
• Regulation of post marketing follow up
• Regulation of recalls
• Principle of safety
IMRDA classification
• Class A – Devices involving low risk levels
• Class B – Devices involving low to medium risk
• Class C – Devices involving moderate to high risk
• Class D – Devices involving high risk.
Device Classification System
 DEVICE
CLASSIFICATION

https://www.greenlight.guru/blog/medical-device-regulatory-classification
https://asiaactual.com/india/medical-device-classification/
https://www.qualio.com/blog/fda-medical-device-classes-differences – Details about Class 1,2 and 3 devices into market
A medical device is
• Section 201(h) of the FDCA defines, “A Medical Device as any
product that does not achieve its purposes by chemical action or
metabolization”.
– As simple as a tongue depressor
– As complex as robotic surgery devices
• WHO defines, “A Medical Device can be any instrument, apparatus,
implement, machine, appliance, implant, reagent for in vitro use,
software, material or other similar or related article, intended by the
manufacturer to be used, alone or in combination for a medical
purpose”.
Classification History
• May 28, 1976 – Medical Device Amendments
• Section 201(h) of Federal Food, Drug & Cosmetic Act (FD&C Act) –
Provides definition of a medical device
• FDA classification panels conducted initial classification of pre-
amendments medical devices, i.e., Class I, II, III
• Initial classification completed in mid-1980s
Medical Device Regulatory
• The rules that apply to your medical device depend on how your product is
classified by the regulatory agencies. Each regulatory agency has defined several
different classifications for medical devices.
• The classifications are, for the most part or as a general rule, related to the
perceived risk of the product type.
• Medical device manufacturers selling internationally need to familiarize
themselves with the applicable regulations of those markets. This is easier said
than done and can be a challenge for most manufacturers. The US has its set of
rules, while Canada adheres to another, and Europe another one still.
• Fortunately, there are many parallels between international medical device
regulations and standards. This guide is designed to show you how to classify
your device in different markets around the world.
Importance of Classification
• Knowing how your medical device is classified matters for the
following reasons:
1. Product classification will determine what you have to do before you
can sell your product.
2. Product classification will help you establish requirements during
the product development phase, specifically design controls.
3. Product classification is an important component in determining
how much it will cost to bring your device to market and give you
some idea of how long it will take.
Classification “Terms”
• Classified – Formally classified by FDA classification panel or FDA,
– Example: 21 CFR 880.2910 - Clinical electronic thermometer –
Class II 510(k)
• Un-classified – Preamendments device pending formal classification
with regulation, i.e., Class III 510(k)
• Not Classified – Postamendments device under application review
Preamendments device refers to devices legally marketed in the US by a
firm before May 28, 1976 and which have not been significantly
changed or modified since then and for which a regulation requiring a
PMA(Premarket Approval)application has not been published by FDA.
Examples of Class I Devices
• Electric Toothbrush
• Tongue Depressor
• Oxygen Mask
• Reusable Surgical Scalpel
• Bandages
• Hospital Beds
• Non-electric wheelchair
Bringing Class I Medical Devices to Market
• Class I devices are the fastest and easiest to bring to market since they
present the lowest amount of risk to the patient and are rarely critical
to life-sustaining care. The majority of Class I devices are exempt
from FDA requirements for Premarket Notification (510k) and
Premarket Approval (PMA).

• Class I devices are not exempt from FDA general controls, a series of
commands which applies to Class I, II, and III medical devices.
Examples of Class II Medical Devices
• Catheters
• Blood Pressure Cuffs
• Pregnancy Test Kits
• Syringes
• Blood Transfusion Kits
• Contact Lenses
• Surgical Gloves
• Absorbable Sutures
Bringing Class II Medical Devices to Market
Controls vary depending on the device, but according to the FDA, can include:
• Device performance
• Post-market surveillance
• Patient registries
• Special labeling requirements
• Premarket data requirements
• Guidelines

The majority of Class II devices are FDA approved for the market through the
Premarket Notification, or 510(k) process.
Examples of Class III Medical Devices
• Breast implants
• Pacemakers
• Defibrillators
• High-frequency ventilators
• Cochlear implants
• Fetal blood sampling monitors
• Implanted prosthetics
Bringing Class III Medical Devices to Market
• Class III devices are subject to all FDA General Controls and the FDA
Premarket Approval (PMA) process. The FDA writes, "due to the level
of risk associated with Class III devices, FDA has determined that
general and special controls alone are insufficient to assure the safety
and effectiveness of Class III devices".
• The PMA is the most intensive type of device marketing application
required by the FDA. Some FDA Class III devices are exempt and
may qualify for a 510(k) filing, but the majority are expected to gain
Premarket approval.
Medical Device Classification in the United
States
• In the United States, medical devices are regulated by the Food &
Drug Administration, or FDA. The specific branch within the FDA is
the Center for Devices & Radiological Health (CDRH).
• The mission of CDRH is to protect and promote public health. In other
words, ensure medical devices are safe. In the U.S., medical devices
are either Class I, Class II, or Class III. The FDA CDRH classification
is based primarily on risk the medical device poses.
• Class I medical devices are generally deemed low risk and Class III
medical devices are seen as the highest risk. The types of controls
required is dependent on your product’s classification.
Medical Device Classification in the United
States
• Classification is directly related to intended use and indications for
use. The distinction between these terms is a bit confusing.
• Intended Use is the general purpose of the medical device or its
function (what you “claim” the medical device does).
• Indications for Use describe the disease or condition the medical
device will diagnose, treat, prevent, cure, or mitigate, including a
description of the target patient population.
• Remember, the intended use and indications for use of your medical
device convey the reasons you developed this new medical device in
the first place.
Path to market in the U.S.
• FDA defines three regulatory controls for each medical device class:
1. Class I medical device (low to moderate risk): General Controls
2. Class II medical device (moderate to high risk): General Controls
and Special Controls
3. Class III medical device (high risk): General Controls and Premarket
Approval (PMA)
Medical device classification in Europe -
European Commission (EC)
• The regulations for a medical device in the European Union (EU) are
established through EU MDR 2017/745 by the European Commission
(EC).
• On 26 May 2021, EU MDR became applicable in the European Union.
The regulation amends Directive 2001/83/EC, Regulation (EC) No
178/2002 and Regulation (EC) No 1223/2009 and repealing Council
Directives 90/385/EEC and 93/42/EEC.
• The path to market in Europe is to obtain a CE marking. The requirements
to obtain CE-marking is based on the EU classification of your medical
device. The European Union’s medical device regulation (EU MDR)
includes the necessary information to determine your device class.
Medical device classification in Europe -
European Commission (EC)
• You will need to determine if your medical device is:
• Non-Invasive- Any device which does not penetrate the body through an
orifice or the surface of the body. These devices are typically Class I;
however, certain rules and exceptions apply that could make them Class
II devices or higher.
• Invasive- Any device which, in whole or in part, penetrates inside the
body, either through a body orifice or through the surface of the body.
• Active- Any device whose operation depends on a source of energy other
than that generated by the human body for that purpose, or by gravity,
and which acts by changing the density of or converting that energy.
Path to market in Europe
• The European Union has a similar product classification system as the
U.S.:
• In accordance with the European Medical Device Directive 93/42/EEC:
1. Class I = Low risk
2. Class Im (measuring device) = Low risk
3. Class Is (sterile device) = Low risk
4. Class IIa = Medium risk
5. Class IIb = Medium to high risk
6. Class III = High risk
Medical Device Classification in Canada -
Health Canada
• The medical devices regulations in Canada are established by the
Government of Canada and regulated by Health Canada.
• Like the U.S. and EU, to sell into the Canadian marketplace, you must
first determine the medical device classification under Canada’s
regulation.
• Similar to the requirements outlined in EU MDR, Health Canada
provides a fairly straightforward and easy to follow Guidance on the
Risk based Classification System for Non-In Vitro Diagnostic Devices
for medical device manufacturers to use when selling into this market.
Medical Device Classification in Canada -
Health Canada
• Health Canada defines four groups of non-in vitro diagnostic medical
devices:
1. Invasive Devices (Rules 1 - 3)
2. Non-Invasive Devices (Rules 4 - 7)
3. Active Devices (Rules 8 - 12)
4. Special Rules (Rules 13 - 16)

• For each of the broad categories, there are a set of rules which apply.
These rules are what manufacturers should follow in order to determine
the risk classification of their device.
Path to market in Canada
• There are four levels of medical device classifications in Canada:
1. Class I
2. Class II
3. Class III
4. Class IV
• Prior to going to market in Canada, you must first apply for a medical
device license. Class I medical devices do not require a license.
Manufacturers can reference the Health Canada guidance document,
which walks you through this process.
India Medical Device Classification
• The Indian classification system is based on the MDR 2017 Guidance
and are dependent on the intended use, level of risk, delivery method,
and the degree of invasiveness in the human body.
• The Indian regulatory system is currently in a transition period and only
a specified list of product types requires Import Licenses. All other
medical devices can be submitted Voluntarily during the current grace
period.
• After this voluntary period, all class A and B non-Regulatory medical
devices will have 12 months (i.e., by October 1, 2022) to obtain an
Import License. Class C and D devices will have 24 months (i.e., by
October 1, 2023) to meet the same requirement.
Path to market in India
• Products are classified into one of the following, from lowest to
highest risk:
1. Class A
2. Class B
3. Class C
4. Class D
Inference
• Whether you are submitting to the EU, FDA, Health Canada, or others,
your path to market and steps to success are determined by your
classification and requirements.
• By knowing how your device is classified, you can streamline your path
to market approval by understanding the processes and documents which
are likely to be required by the FDA.
• The differences between medical devices classified as Class I, II, or III by
the FDA is mostly risk, amount of contact with a patient and their internal
systems, and whether a device is critical to sustaining life.
• Once you’ve determined your FDA medical device class, you’ll need to
monitor your quality closely.
CE STANDARD:
• CE(Conformite Europenne) means that the product meets the
European Union's safety standards and other requirements for
sale.
• Products used in E.U are CE Listed.
What is CE Marking for Medical Device?
• To sell medical devices in the European Union (EU), you must obtain
CE Marking for your product.
• CE Marking indicates that your medical device complies with
applicable EU regulations, and enables the commercialization of your
products across all EU member states.
• As a legal medical device manufacturer, you are responsible for
maintaining regulatory compliance and securing CE marking for your
product.
How to obtain CE Marking?
• CE is not a quality mark, but compliance with the EU Medical Devices Regulation (MDR 2017/745) requires
you to meet specific standards of performance, quality, safety, and efficacy for your product type. However, the
basic process follows these steps:
1. Determine whether your product meets the definition of a medical device according to the MDR.
2. Determine the classification of your device.
3. Implement a Quality Management System, if applicable to your device. Most companies use ISO 13485 to meet
the requirements.
4. Prepare a CE Marking Technical File or a Design Dossier.
5. Prepare a Clinical Evaluation Report (CER) according to MDR.
6. Select and appoint a European Authorized Representative (EC REP) to act on your behalf within the EU if you
have no physical location in Europe.
7. Have your Technical File/Design Dossier audited by a Notified Body, unless your device is Class I, is not
sterile, and has no measuring function.
8. Obtain CE Marking and ISO 13485 certificates from your Notified Body.
9. Prepare a Declaration of Conformity (DoC), which states that your device complies with the MDR.
UL STANDARD:
• UL(Underwriters Laboratories) means the product meets the
standards of Underwriters Laboratories, a private safety testing
organization.
• Products used in U.S are UL Listed.
What is UL Marking for Medical Device?
• UL certifies products with the intent to make the world safer for
consumers and workers.
• Along with product safety testing, UL sets the industry standards for
companies to follow during the process of innovating new products.
• UL continually checks products to ensure they meet standards and are
constructed properly for the highest level of safety.
• For instance, UL testing will review whether devices can handle the
proper amount of current and whether wire sizes are correct.
UL Marked Equipments Category:
• Equipment that UL addresses tends to fall into the following categories:
• IT
• Appliances
• Cable and wire
• Signaling alarms
• Electronic equipment
• Electrical components
• Equipment to be used in hazardous areas
• Fire suppression and protection equipment
UL Marking:
• This UL listing mark is most often seen on:
• Heaters
• Furnaces
• Life jackets
• Smoke detectors
• Sprinkler systems
• Electrical appliances
• Bullet-resistant glass
• Computer equipment
• Carbon monoxide detectors
How to obtain UL Marking?
UL will help manufacturers maintain certifications and identify and close gaps in regulation. So how do you get
UL listed? A manufacturer can obtain,
• Facility certification : UL can evaluate how well an operation adheres to the applicable healthcare safety
standards and regulations. UL will review plans, conduct checks for safety issues, assess the performance of
components and products and perform on-site evaluations.
• Process certification: UL can also work with you to make sure business processes meet the applicable
requirements and standards.
• Personnel certification: UL’s personnel certification can help empower practitioners with qualifications
needed to effectively and safely perform their work.
• System certification : UL offers system certification to evaluate how individual processes and products
work together.
• Product certification: A product certification from UL can demonstrate that a product has been tested and
meets applicable standards.
 What is ICMED?
• In order to enhance patient safety, provide enhanced consumer protection, eliminate trading
of sub-standard products or devices of doubtful origins, independent third party voluntary
certification system to assure quality of medical devices manufactured in the country
has been rolled out.

• To help address this gap, the Association of Indian Medical Device Industry (AIMED) in
collaboration with the Quality Council of India (QCI) and the National Accreditation Board
for Certification Bodies (NABCB) established a voluntary quality certification scheme for
medical devices in India, ICMED 13485.
https://www.youtube.com/watch?v=lRFwcnpYYXw
https://www.youtube.com/watch?v=WXesC2ajDfA

• It was commenced on 2016 https://www.corpzo.com/indian-certification-for-medical-devices-icmed-9000icmed-13485

https://qcin.org/indian-certification-for-medical-devices-icmed-scheme
 Objectives:
• To fill the regulatory vacuum in quality certification space for medical devices in the
country.

• To enhance patient safety, and provide enhanced consumer protection.

• To provide much needed product credentials to manufacturers for installing

confidence among buyers.

• To significantly eliminate trading of sub-standard products or devices of doubtful

origins, a widespread and injurious phenomenon in the Indian market
• To bring down the substantial time and cost-run to obtain globally
accepted quality certification for Indian companies.

• To eliminate the malpractices of sub-standard or fraudulent certification

or quality audits.
 Significance
• With the recent announcements from the government for focusing "Atma Nirbhar
Bharat" self-reliant India, emphasis is on Indian products.

• Indian medical device industry is required to fulfill Indian regulatory requirements of

ICMED.

• This scheme is focused on assessment of specific Indian regulatory requirements and

enhances the compliance level.
Components
The Scheme has been launched with two levels of certification:

➲ ICMED 9000 (an ISO 9001plus additional requirement)

This certification is for low-risk medical devices

➲ ICMED 13485 (an ISO 13485 plus additional requirement)

This certification is for medium or high-risk devices.
ICMED Scheme
 Features
• The scheme has been designed to integrate the quality management system
components and product-related quality validation processes
• It involves witness testing of products with reference to the defined product standards
and specifications.
• This scheme is an end-to-end quality assurance scheme for the medical devices sector
in India.
• The scheme provides the much-needed institutional mechanism for assuring product
quality and safety.
• It will assist the procurement agencies to tackle the challenges relating to the menace
of counterfeit products and fake certification.
Procedure
• File application form along with required document and fees
• The certifying body will raise a query if any within 7 working days from the receipt
of application
• The applicant will respond to that raised query in the prescribed format
• Audit program
For ICMED 9000 & ICMED 13485 the audit cycle shall include:
• Initial certification audit in two stages (Stage 1 and Stage 2) as per ISO 17021:2011
for ICMED 9000 and ICMED 13485
• Recertification audits (before end of 3-year validity)
• Granting of certification
 Device Description and Product Specification
The manufacturer shall define and document a device description, with following details:
• General description including its generic name, model name, model no., materials of
construction, intended use, indications, instructions for use, contraindications, warnings,
precautions and potential adverse effects
• The intended patient population and medical condition to be diagnosed or treated and other
considerations such as patient selection criteria
• Principle of operation or mode of action
• An explanation of any novel features
• A description of the accessories, other medical device and other product that are not medical
device, which are intended to be used in combination with it and it shall also be clarified
whether these accessories or device are supplied as a system or separate components
• A description or complete list of the various configurations or variants of the device that will be made
available
• A general description of the key functional elements, e.g. its parts or components (including software if
appropriate), its formulation, its composition, its functionality and where appropriate, this will include:
labelled pictorial representations (e.g. diagrams, photographs, and drawings), clearly indicating key parts
or components, including sufficient explanation to understand the drawings and diagrams
• A description of the materials incorporated into key functional elements and those making either direct
contact with a human body or indirect contact with the body, e.g., during extracorporeal circulation of
body fluids. Complete chemical, biological and physical characterization of the material (s) of the medical
device
• For medical devices intended to emit ionizing radiation, information on radiation source (e.g.
radioisotopes) and the material used for shielding of unintended, stray or scattered radiation from patients,
users and other persons shall be provided
Accreditation for certification
In order to be able to offer certification the certification bodies shall need to be accredited by
NABCB (The National Accreditation Board for Certification Bodies) as per the following
requirements:
• For offering certification for ICMED 9000 and ICMED 13485, the certification body shall
need to be accredited as per ISO 17021-1:2015 for ISO 9001 and ISO 13485 respectively
along with additional requirements specified in this document by NABCB.
• The certification body shall have been witnessed for ICMED 9000 and/or ICMED 13485
audit, as applicable, by NABCB.
• For certification to ICMED 13485 Plus, the certification body shall need to be accredited
against ISO 17021-1:2015 for ISO 13485 and ISO 17065: 2012 with additional requirements
specified in this document and shall have undergone a witness assessment by NABCB in last
one year one year in scope sector 19 (DL33.1) for ISO 13485 .
Documentation required for certification

• Organization registration certificate

• Organization detail (Manufacturing/importer)
• Organization authorized signatory detail (ID and Address proof)
• Medical equipment detail
• Holding ISO certificate
• Importing company detail and exporting company detail (in case of import)
 Use of Certificates and Certification and
Accreditation Marks – ICMED Specific
• The certified client shall abide by the logo use rules as appropriate while using the certification
mark(s)/certificate(s) and for providing information about their certification status.

• The client shall ensure that the certificate is used only with reference to specific manufacturing
facility. Accordingly, the Certification Mark shall be put on the product (also refer Labelling
guidelines, F103-28 MED ICMED -Labelling Checklist) carrying reference to the supplies made
by the certified manufacturing facility and shall carry the following information as minimum: a)
Certification Mark (Under certification mark, ICMED-001/2016, and certificate no. will be
marked) b) CB Logo (Optional)

• Certification mark shall be put only on the products included in the scope of certification as
mentioned on the certificate issued by Intertek.
 Criteria which may result in Suspension of
certification in instances when not adhered to
Intertek shall issue instructions to the certified organization for suspension of certification when
a) the major NCs issued are not closed in timelines prescribed
b) repeated major NCs are raised in consecutive surveillance assessments
c) there is failure to organize a surveillance audit within the specified time period
d) there is non payment of outstanding dues
e) any major changes have taken place in the legal status, ownership, name etc without prior information to the CB
f) any wilful misuse of the logo of the Scheme is detected
g) any wilful false declaration in the application form or otherwise is detected
h) excessive or serious complaints against the certified organization management system are recieved and are found to be
valid
i) the certified organization voluntarily requests a suspension.Such request must be submitted in writing to the CB along with
the reasons. The CB may decide to accept the request but may not allow the client to revoke suspension on its own
Non conformance (NC) is an ISO 9000 audit designation indicating the quality management system or a portion of it does not
meet the requirements established by ISO 9000.
 Criteria which may result in Withdrawal of
certification in instances when not adhered to
Intertek shall withdraw the certificate when

• Certified organization contravenes the terms and conditions of certification and provisions of the ICMED
scheme

• The certified organization is not conforming to the requirements of the Certification Criteria and the corrective
actions taken are not ensuring compliance

• The proposed plan for corrective actions will take a considerable time beyond 6 months for implementation;

Intertek shall withdraw the certificate at the request of the certified plant, if the operation(s) in the certified
organization can no longer be carried due to reasons of natural calamities such as flood, fire, earthquake etc, lock
out declared by the management, or closure of business operations etc .
INSTITUTIONAL REVIEW BOARDS –
IDE FORMAT- INTRODUCTION
• Experimentation on human being is subject to ethical standards that
promote respect for all and protect their health and rights.
• Research requiring ethical review:
• Research involving living human subjects and use of their medical
records.
• Research involving human remains, cadavers, biological fluids,
tissues, embryos, fetuses and etc.
Investigational Device Exemptions

• Investigational device exemption (IDE) is a phase in clinical trials for new

medical devices. IDE allows sponsors to test their devices for safety and efficacy
in multiple patient centers. IDE is granted by the FDA.
• Innovations in spine procedures relying on devices, rather than pharmaceuticals,
can be tested in patient populations sooner under IDE. Pharmaceuticals must go
through longer trial periods before approval is received for testing in human
patients.
• IDE refers to the regulations under 21 CFR 812. An approved IDE means that the
IRB (and FDA for significant risk devices) has approved the sponsor’s study
application and all the requirements under 21 CFR 812 are met.
Investigator :
Investigator is an individual who actually conducts a clinical investigation, i.e., under
whose immediate direction the investigational device is administered, dispensed to, or used
involving a subject. In the event of an investigation being conducted by a team of individuals,
"investigator" refers to the responsible leader of that team.
Sponsor :
Sponsor is a person or other entity that initiates but does not actually conduct the
investigation. An entity other than an individual (e.g., a corporation or an agency) which uses one or
more of its own employees to conduct an investigation that it has initiated is considered to be a
sponsor, not a sponsor-investigator, and the employees are considered to be investigators. The
sponsor of an IDE must be located in the United States (see 21 CFR 812.18).
Clinical Trial Definition

• A clinical trial is a scientific research study that is typically designed to test the
safety and effectiveness of a new drug, device or treatment on humans.
• A clinical trial is conducted with voluntary patients who qualify according to set
inclusion/exclusion criteria which are usually based on age, gender, type or stage
of disease, treatment history and other medical conditions.
• Participants in clinical trials can potentially gain access to new treatments before
they are available to the public and obtain expert medical care. However, many
trials are "randomized," which means that participants are randomly assigned to
receive either the new treatment or the control group (e.g. current standard of care
or placebo) treatment, so not all participants will receive the drug or device being
studied.
• Also, participants run the risk of serious or life-threatening side effects to any new treatment.
In the United Statues, clinical trials are conducted under the direction of the Food and Drug
Administration (FDA) before being made available for general clinical use in healthcare.
Preclinical Studies Definition
• Preclinical studies refer to the testing of a drug, procedure or other medical treatment in
animals before trials may be carried out in humans. During preclinical drug development,
the drug’s toxic and pharmacological effects need to be evaluated through in vitro and in
vivo laboratory animal testing.
• The FDA requires sponsoring companies to develop a pharmacological profile, determine
toxicity in at least two species of animals and conduct short-term toxicity studies. Various
preclinical requirements exist for different kinds of laboratory animals. Information gathered
in preclinical studies are used as evidence and support in FDA applications for the approval
of new drugs and medical procedures
IDE Responsibilities

• Responsibilities of Sponsors for Significant Risk Device Studies

• Responsibilities of Sponsors of Nonsignificant Risk Device Studi
es
• Responsibilities of Investigators for Significant Risk Device Stud
ies
• Responsibilities of Investigators for Nonsignificant Risk Device
Studies
• Responsibilities of Monitors
Responsibilities of Sponsors for Significant Risk Device Studies

General responsibilities
Sponsors are responsible for selecting qualified investigators and providing them with the
information that they need to conduct the investigation properly. They must also ensure proper
monitoring of the investigation and IRB review and approval, submit an IDE application to FDA for
significant risk device studies, and inform the IRB and FDA promptly of any significant new
information about the investigation.
FDA and IRB approval
A sponsor cannot begin an investigation or any part of an investigation until an IRB and
FDA have both approved the application or supplemental application.
Selecting Investigators
A sponsor is responsible for selecting investigators qualified by training and experience to
investigate the device.
Investigator Agreements
A sponsor must obtain a signed agreement from each participating investigator that includes:
• the investigator's curriculum vitae,
• a statement of the investigator's relevant experience, including the dates, location, extent, and type of experience,
where applicable.
• An explanation of the circumstances that led to termination of a study if the investigator was involved in an
investigation or other research that was terminated, a statement of the investigator's commitment to:
• conduct the investigation in accordance with the agreement, the investigational plan, the IDE and other
applicable FDA regulations, and conditions of approval imposed by the reviewing IRB or FDA,
• supervise all testing of the device involving human subjects. and
• ensure that the requirements for obtaining informed consent are met.
• sufficient accurate financial disclosure information to allow the sponsor to submit a complete and accurate certification
or disclosure statement as required under 21 CFR 54, Financial Disclosure by Clinical Investigators. The sponsor shall
also obtain a commitment from the clinical investigator to promptly update this information if any relevant changes
occur during the course of the investigation and for one year following completion of the study. (The financial
certification or disclosure is submitted in the PMA or Premarket Notification 510(k) application. It should not be
submitted in the IDE application.)
Informing investigators
A sponsor must supply all investigators participating in the investigation with copies of the investigational plan
and a report of prior investigations of the device.

Monitoring
Securing Compliance: A sponsor who discovers that an investigator is not complying with the signed
agreement, the investigational plan, the IDE requirements, any other applicable FDA regulations, or any
conditions of approval imposed by the reviewing IRB or FDA must promptly either secure compliance, or
discontinue shipments of the device to the investigator and terminate the investigator's participation in the
investigation. A sponsor must also require that the investigator dispose of or return the device, unless this action
would jeopardize the rights, safety, or welfare of a subject.
Unanticipated Adverse Device Effects: The sponsor must immediately conduct an evaluation of any
unanticipated adverse device effect. A sponsor who determines that an unanticipated adverse device effect
presents an unreasonable risk to subjects must terminate all investigations or parts of the investigations
presenting that risk as soon as possible. Termination must occur no later than 5 working days after the sponsor
makes this determination and no later than 15 working days after the sponsor first received notice of the effect.
Resumption of Terminated Studies: For significant risk device investigations, a sponsor may not resume a
terminated investigation without IRB and FDA approval. For a nonsignificant risk device investigation, a
sponsor may not resume a terminated investigation without IRB approval. If the nonsignificant risk study was
terminated for unanticipated adverse device effects, the sponsor must also obtain FDA approval.

Sponsor records
The sponsor must maintain accurate and complete records relating to the investigation. These records include:
• all correspondence including required reports,
• records of shipment of the device,
• records of disposition of the device
• signed investigator agreements including financial disclosure information,
• records concerning complaints and adverse device effects whether anticipated or not,
• any other records that FDA requires to be maintained by regulation or by specific requirement for a category
of investigation or a particular investigation.
Sponsor Reports

The sponsor must provide the following reports in a timely manner to FDA, the IRB's, and/or the
investigators.

• Unanticipated Adverse Device Effects

• Withdrawal of IRB Approval
• Withdrawal of FDA Approval
• Current List of Investigators
• Progress Reports
• Recalls and Device Disposition
• Final Report
• Informed consent
• Significant Risk Device Determination
• Other Reports
Labeling
Under §812.5 an investigational device or its immediate package must bear a label with the following information:
• the name and place of business of the manufacturer, packer, or distributor;
• the quantity of contents, if appropriate; and
• the statement, "CAUTION ­Investigational device. Limited by Federal (or United States) law to investigational use.“
Promotion of Investigational Devices (§812.7)
Under §812.7, a sponsor, investigator, or any person acting for or on behalf of a sponsor or investigator cannot:
• Promote or test market an investigational device, until after FDA has approved the device for commercial distribution.
• Commercialize an investigational device by charging the subjects or investigators a higher price than that necessary to
recover costs of manufacture, research, development, and handling.
• Unduly prolong an investigation. If data developed by the investigation indicate that premarket approval (PMA) cannot be
justified, the sponsor must promptly terminate the investigation.
• Represent that an investigational device is safe or effective.
Responsibilities of Investigators for Significant Risk Device
Studies

• The investigator is responsible for protecting the rights, safety, and welfare of subjects. An investigator
must conduct the investigation in accordance with the signed agreement with the sponsor, the
investigational plan, the IDE regulations and other applicable FDA regulations, and any conditions of
approval imposed by an IRB and FDA. (§812.100)
• While awaiting approval of an IDE application, an investigator may determine whether or not potential
subjects would be interested in participating in an investigation, but cannot request written informed
consent or allow any subjects to participate before obtaining IRB and FDA approval.
Informed Consent
• An investigator is responsible for obtaining informed consent under 21 CFR Part 50.
Supervision of device use (§812.110)
• An investigator can permit use of the investigational device only with subjects under his/her supervision
and cannot not supply an investigational device to any person not authorized under the IDE regulations
to receive it.
Financial Disclosure
The clinical investigator must disclose to the sponsor sufficient accurate financial information to allow the
IDE applicant (or sponsor) to submit certification or disclosure of financial interests under 21 CFR 54. The investigator
must update the information if any relevant changes occur during the course of the investigation and for one year
following completion of the study.
Device Disposal
Upon completion or termination of a clinical investigation or the investigator's part of the investigation or at
the sponsor's request, an investigator must return to the sponsor any remaining supply of the device or dispose of the
device as the sponsor directs.
Records (812.140)
• The investigator must maintain accurate and complete records relating to the investigation. These records
include:
• all correspondence including required reports,
• records of receipt, use, or disposition of the investigational device,
• records of each subject's case history and exposure to the device,
• the protocol and documentation (date and reason) for each deviation from the protocol,
• any other records that FDA requires to be maintained by regulation or by specific
requirement for a category of investigation or a particular investigation.
• See Records for additional information on recordkeeping requirements.
Investigator Reports
• The investigator must provide the following reports in a timely manner to the sponsor
and/or the IRB.
• Unanticipated Adverse Device Effects
• Withdrawal of IRB Approval
• Progress Reports
• Deviations from the Investigational Plan
• Failure to obtain Informed Consent
• Final Report
Responsibilities of Monitors

• The sponsor is responsible for selecting monitors qualified by training and experience to monitor
the investigational study. Monitors may be employees of the sponsor or an organization contracted
by the sponsor to perform the duties of the study monitor.
• The monitor is responsible for securing compliance with the requirements of the IDE regulations
(§ 812.46). The monitor must assure that the investigators are complying with the signed
agreement, the investigational plan, the IDE requirements, any other applicable FDA regulations,
or any conditions of approval imposed by the reviewing IRB or FDA.
• The IDE regulation requires that the sponsor identifies the name and address of the monitor and
provide written monitoring procedures [§812.25(e)]. While the IDE regulations do not specify the
content of the written monitoring procedures, FDA has published the following guidance
documents to assist sponsors in the development of such procedures.
IDE Informed Consent :

• No clinical investigator may involve a human being as a subject in research unless the investigator
has obtained the legally effective informed consent from the subject.
• Informed Consent is a written notification to human subjects involved in clinical investigations
that provides them with sufficient opportunity to consider whether or not to participate in the
study.
• The informed consent document must include all the basic elements of informed consent (outlined
below) or it may be a short form written consent document stating that the elements of informed
consent have been presented orally. If the short form method is used, there must be a witness to the
oral presentation.
Additional elements of informed consent. When appropriate, one or more of the following elements
of information must be provided to each subject:
• A statement that a particular treatment or procedure may involve risks to the subject (or to the
embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable.
• Anticipated circumstances under which the subject’s participation may be terminated by the
investigator without regard to the subject’s consent.
• Any additional costs to the subject that may result from participation in the research.
• The consequences of a subject’s decision to withdraw from the research and procedures for
orderly termination of participation by the subject.
• A statement that significant new findings developed during the course of the research which
may relate to the subject’s willingness to continue participation will be provided to the
subject.
• The approximate number of subjects involved in the study.
IDE Application
Protocols involving an exception to the informed consent requirement under
this section must be performed under a separate investigational device exemption
(IDE) that clearly identifies such protocols as protocols that may include subjects
who are unable to consent.
The submission of those protocols in a separate IDE is required even if an IDE for
the same device already exists.
Applications for investigations under this section may not be submitted as
amendments to an approved IDE
CFR - Code of Federal Regulations Title 21

• Sec. 812.1 Scope

The purpose of this part is to encourage, to the extent consistent with the
protection of public health and safety and with ethical standards, the discovery and
development of useful devices intended for human use, and to that end to maintain
optimum freedom for scientific investigators in their pursuit of this purpose.
This part provides procedures for the conduct of clinical investigations of
devices.
An approved investigational device exemption (IDE) permits a device that
otherwise would be required to comply with a performance standard or to have
premarket approval to be shipped lawfully for the purpose of conducting
investigations of that device.
Sec. 812.7 Prohibition of promotion and other practices.
A sponsor, investigator, or any person acting for or on behalf of a sponsor or investigator
shall not:
(a) Promote or test market an investigational device, until after FDA has approved the
device for commercial distribution.
(b) Commercialize an investigational device by charging the subjects or investigators for a
device a price larger than that necessary to recover costs of manufacture, research,
development, and handling.
(c) Unduly prolong an investigation. If data developed by the investigation indicate in the
case of a class III device that premarket approval cannot be justified or in the case of a class
II device that it will not comply with an applicable performance standard or an amendment
to that standard, the sponsor shall promptly terminate the investigation.
(d) Represent that an investigational device is safe or effective for the purposes for which it
is being investigated.
Sec. 812.10 Waivers.

(a) Request. A sponsor may request FDA to waive any requirement of this part. A waiver request, with
supporting documentation, may be submitted separately or as part of an application to the address in §
812.19.
(b) FDA action. FDA may by letter grant a waiver of any requirement that FDA finds is not required by the
act and is unnecessary to protect the rights, safety, or welfare of human subjects.
(c) Effect of request. Any requirement shall continue to apply unless and until FDA waives it.

Sec. 812.18 Import and export requirements.

(a) Imports. In addition to complying with other requirements of this part, a person who imports or offers
for importation an investigational device subject to this part shall be the agent of the foreign exporter with
respect to investigations of the device and shall act as the sponsor of the clinical investigation, or ensure
that another person acts as the agent of the foreign exporter and the sponsor of the investigation.
(b) Exports. A person exporting an investigational device subject to this part shall obtain FDA's prior
approval, as required by section 801(e) of the act or comply with section 802 of the act.
 Subpart B - Application and Administrative Action- Sec. 812.20 Application
(a) Submission.
(1) A sponsor shall submit an application to FDA if the sponsor intends to use a significant risk device in an investigation,
intends to conduct an investigation that involves an exception from informed consent under § 50.24 of this chapter, or if FDA
notifies the sponsor that an application is required for an investigation.
(2) A sponsor shall not begin an investigation for which FDA's approval of an application is required until FDA has approved
the application.
(3) A sponsor shall submit a signed "Application for an Investigational Device Exemption" (IDE application), together with
accompanying materials in electronic format, to one of the addresses in § 812.19, and if eCopy by registered mail or by hand .
Subsequent
. correspondence concerning an application or a supplemental application shall be submitted in electronic format
and if eCopy by registered mail or by hand.
(4)(i) A sponsor shall submit a separate IDE for any clinical investigation involving an exception from informed consent
under § 50.24 of this chapter. Such a clinical investigation is not permitted to proceed without the prior written authorization
of FDA. FDA shall provide a written determination 30 days after FDA receives the IDE or earlier.
(ii) If the investigation involves an exception from informed consent under § 50.24 of this chapter, the sponsor shall
prominently identify on the cover sheet that the investigation is subject to the requirements in § 50.24 of this chapter
b) Contents. An IDE application shall include, in the following order:

(1) The name and address of the sponsor.

(2) A complete report of prior investigations of the device and an accurate summary of those sections of the
investigational plan described in § 812.25(a) through (e) or, in lieu of the summary, the complete plan. The
sponsor shall submit to FDA a complete investigational plan and a complete report of prior investigations of
the device if no IRB has reviewed them, if FDA has found an IRB's review inadequate, or if FDA requests
them.
(3) A description of the methods, facilities, and controls used for the manufacture, processing, packing,
storage, and, where appropriate, installation of the device, in sufficient detail so that a person generally
familiar with good manufacturing practices can make a knowledgeable judgment about the quality control
used in the manufacture of the device.
(4) An example of the agreements to be entered into by all investigators to comply with investigator
obligations under this part, and a list of the names and addresses of all investigators who have signed the
agreement.
(5) A certification that all investigators who will participate in the investigation have signed the agreement,
that the list of investigators includes all the investigators participating in the investigation, and that no
investigators will be added to the investigation until they have signed the agreement.
• A list of the name, address, and chairperson of each IRB that has been or will be asked to review the
investigation and a certification of the action concerning the investigation taken by each such IRB.
(7) The name and address of any institution at which a part of the investigation may be conducted that has
not been identified in accordance with paragraph (b)(6) of this section.
(8) If the device is to be sold, the amount to be charged and an explanation of why sale does not constitute
commercialization of the device.
(9) A claim for categorical exclusion under § 25.30 or § 25.34 or an environmental assessment under §
25.40.
(10) Copies of all labeling for the device.
(11) Copies of all forms and informational materials to be provided to subjects to obtain
informed consent.
(12) Any other relevant information FDA requests for review of the application.
Additional information. FDA may request additional information concerning an
investigation or revision in the investigational plan. The sponsor may treat such a
request as a disapproval of the application for purposes of requesting a hearing under
part 16.
d) Information previously submitted. Information previously submitted to the Center for
Devices and Radiological Health, the Center for Biologics Evaluation and Research, or
the Center for Drug Evaluation and Research, as applicable, in accordance with this
chapter ordinarily need not be resubmitted, but may be incorporated by reference.
Sec. 812.2 Applicability.

This part applies to all clinical investigations of devices to determine safety and
effectiveness, except as provided in paragraph (c) of this section.
Sec. 812.5 Labeling of investigational devices.
(a) Contents. An investigational device or its immediate package shall bear a label with the
following information: the name and place of business of the manufacturer, packer, or
distributor (in accordance with § 801.1), the quantity of contents, if appropriate, and the
following statement: "CAUTION - Investigational device. Limited by Federal (or United
States) law to investigational use."
The label or other labeling shall describe all relevant contraindications, hazards, adverse
effects, interfering substances or devices, warnings, and precautions.
(b) Prohibitions. The labeling of an investigational device shall not bear any statement that
is false or misleading in any particular and shall not represent that the device is safe or
effective for the purposes for which it is being investigated.
(c) Animal research. An investigational device shipped solely for research on or
with laboratory animals shall bear on its label the following statement: "CAUTION
- Device for investigational use in laboratory animals or other tests that do not
involve human subjects."
(d) The appropriate FDA Center Director, according to the procedures set forth in §
801.128 or § 809.11 of this chapter, may grant an exception or alternative to the
provisions in paragraphs (a) and (c) of this section, to the extent that these
provisions are not explicitly required by statute, for specified lots, batches, or other
units of a device that are or will be included in the Strategic National Stockpile.
INTRODUCTION - IRB

• The “Institutional Review Board” (IRB) is a local administrative body

established to protect the rights, safety, and well-being of human research
subjects recruited to participate in a clinical research.
• The IRB has the authority to approve, require modification in, or
disapprove all research activities that fall within its jurisdiction.
• The IRB provides assurances to research subjects that every reasonable
attempt has been made to protect their rights and safety as subjects.
 CONSTITUTION OF IRB
The IRB should consist at least SEVEN members, who collectively have the
qualifications and experience to review and evaluate the science, medical aspects, and
ethics of the proposed trial.
• Chairperson – Appointed (who is
from outside the institution)
• 1-2 basic medical scientists
• 1-2 clinicians from various institutes
• One legal expert or retired judge
• One social scientist
• One philosopher or ethicist
• One lay person from community
• Member secretary – Appointed
QUARUM OF IRB
For reviewing and making decision on each protocol the quorum
of IRB should be atleast FIVE members with the following
representations:

1. Basic medical scientists (preferably one pharmacologist)

2. Clinicians
3. Legal expert
4. Social scientist / Representative of non-governmental voluntary
agency / Philosopher / Ethicist / Theologian or a similar person
5. Lay person from the community
QUARUM OF IRB

• In any case, the IRB must include

• at least one member whose primary area of interest / specialization is
nonscientific
• at least one member who is independent of the institution / trial site
• Besides, there should be appropriate gender representation on the IRB.
• If required, Subject experts may be invited to offer their views. Further, based
on the requirement of research area, e.g. AIDS, genetic disorders etc. specific
patient groups may also be represented in the IRB.
FUNCTIONS AND OPERATIONS OF IRB

• Only those IRB members who are independent of the clinical trial and the
Sponsor of the trial should vote / provide opinion in matters related to the
study.
• Only members who participate in the IRB/IEC review and discussion should
vote/provide their opinion and/or advise.
• The IRB should perform its functions according to written standard operating
procedures, should maintain written records of its activities and minutes of its
meetings, and should comply with GCP and with the applicable regulatory
requirement(s).
 Cont….
.
• The investigator may provide information on any aspect of the trial, but
should not participate in the deliberations of the IRB or in the
vote/opinion of the IRB.
• The IRB should establish, document in writing, and follow its procedures,
which should include.
• Determining its composition (names and qualifications of the members).
• Scheduling, notifying its members of, and conducting its meetings.
• Conducting initial and continuing review of trials.
• Determining the frequency of continuing review, as appropriate
 Cont…..

• Specifying that no subject should be admitted to a trial before the IRB

issues its written approval / favorable opinion of the trial.
• Specifying that no deviations from, or changes of, the protocol should be
initiated without prior written IRB approval / favorable opinion of an
appropriate amendment, except when necessary to eliminate immediate
hazards to the subjects or when the change(s) involves only logistical or
administrative aspects of the trial.
 Cont…
..
• Specifying that the investigator should promptly report to the IRB.
• Deviations from, or changes of, the protocol to eliminate immediate
hazards to the trial subjects.
• Changes increasing the risk to subjects and/or affecting significantly the
conduct of the trial. All adverse drug reactions (ADRs) that are both
serious and unexpected.
• New information that may affect adversely the safety of the subjects or
the conduct of the trial.
 Cont….
.

• Ensuring that the IRB promptly notify in writing the

investigator/institution concerning.
• Its trial-related decisions/opinions .
• The reasons for its decisions/opinions.
• Procedures for appeal of its decisions/opinions.
RESPONSIBILITIES OF IRB
• An IRB should safeguard the rights, safety, and well- being of all trial
subjects.
• The IRB should obtain the following documents.
• Trial protocol(s)/amendment(s) Written informed consent form(s).
Subject recruitment procedures (e.g.: Advertise).
• Written information to be provided to subjects.
• Investigator’s Brochure (IB).
• Available safety information.
• Information about payments and compensation. Investigator’s current
curriculum vitae.
• Any other may need to fulfill its responsibilities.
 Cont….
.
• The IRB should review a proposed clinical trial within a reasonable time and document its views in
writing, clearly identifying the trial, the documents reviewed and the dates for the following.

• Approval / favourable opinion.

• modifications required prior to its approval / favourable opinion;

• disapproval / negative opinion.

• Termination / suspension of any prior approval / favourable opinion

• The IRB should consider the qualifications of the investigator for the proposed trial, as documented by
a current curriculum vitae and / or by any other relevant documentation the IRB requests.
 Cont…..
• The IRB/IEC should conduct continuing review of each ongoing trial at intervals appropriate to the degree
of risk to human subjects, but at least once per year.

• The IRB may request more information than is given to study subjects when, in the judgement of the IRB
the additional information would add meaning to the protection of the rights, safety and/or well-being of the
subjects.

• The IRB should review both the amount and method of payment to subjects to assure neither compulsion
nor undue influence on the trial subjects.

• Payments to a subject should be prorated (day basis) and not wholly contingent on completion of the trial
by the subject.

• The IRB should ensure that information regarding payment to subjects, including the methods, amounts,
and schedule of payment to trial subjects, is set forth in the written informed consent form and any other
written information to be provided to subjects.
IRB REVIEW PROCESS
ETHICAL REVIEW PROCESS
IRB DECISION FLOW CHART
MEETING OF COMMITTEE

Initially, the Board will meet every other month and review all applications

• As the need arises, the Board will meet monthly.

• The schedule for the meetings for the entire year will be circulated on the
first of August the prior year.

• Additional meetings, as the need arises, will be announced as needed.

 DUTIES OF THE IRB
• Review and have authority to approve, require
modifications, or disapprove all research
activities involving humans
• Review and approve informed consent from the
research subjects.
• Continuing review of approved research not less
than once per year
• Review and approval in accordance
with the three Belmont principles of
• Autonomy(Respect of person)
• Beneficence
• Justice
• Prepare and maintain adequate
records and documentation of IRB
activities
RESEARCH NOT REQUIRING IRB
APPROVAL
• Research of existing literature
• Quality assurance studies whose goal is the improvement of
care at the institution
• Interviews of individuals with questions focusing on things
and not people ;an example would be questions focusing on
policy
• In case of confusion regarding the need for IRB review, the
Board can be contacted on a phone number to be assigned
soon.
 GOOD LABORATORY PRACTICE

• GLP is an FDA regulation.

• GLP is a formal regulation that was created by the FDA (United states food and drug
administration) in 1978.
• In the early 70’s FDA became aware of cases of poor laboratory practice all over the United States.
• They discovered a lot fraudulent activities and a lot of poor lab practices.
• Examples of some of these poor lab practices found were
1. Equipment not been calibrated to standard form , therefore giving wrong measurements.
2. Incorrect/inaccurate accounts of the actual lab study.
3. Inadequate test systems.
• GLP embodies a set of principles that provides a frame work within which laboratory studies are
planned, performed, monitored, and archived and reported.
Purpose of GLPs:

• GLP is to certify that every step of the analysis is valid or Not.

• Assure the quality & integrity of data submitted to FDA in support of the safety of
regulated products.
• GLPs have heavy emphasis on data recording, record & specimen retention.
GOOD LABORATORY PRACTICES PRINCIPLES:
1. Test Facility Organisation and Personnel.
2. Quality Assurance Programme(QAP).
3. Facilities.
4. Apparatus, Material and Reagents.
5. Test systems.
6. Test and Reference Substances.
7. Standard Operating Procedures(SOP).
8. Performance of The Study.
9. Reporting of Study Results.
10. Storage and Retention of Records and materials.
 Continue…

1.Test Facility Organization and Personnel Responsibilities

Should have the Knowledge of the GLP principles.
 Access to the study plan and appropriate SOP’s.
 Comply with the instructions of the SOP’s.
 Record raw data.
 Study personnel are responsible for the quality of their data.
 Exercise health precautions to minimize risk.
 Ensure the integrity of the study.
2.Quality Assurance Program Responsibilities of the QA Personnel
Access to the updated study plans and SOP’s.
Documented verification of the compliance of study plan to the GLP principles.
Inspections to determine compliance of the study with GLP principles.
Report the inspection results to the management.
3.Facilities
Suitable size, construction and location.
Adequate degree of separation of the different activities.
Isolation of test systems and individual projects to protect from biological hazards
4. Apparatus, Materials and Reagents
Apparatus of appropriate design and adequate capacity.
Documented Inspection, cleaning, maintenance and calibration of apparatus.
Apparatus and materials not to interfere with the test systems.
Chemicals, reagent and solutions should be labelled to indicate identity, expiry
and specific storage instructions.
5. Test Systems
 Physical and chemical test systems.
 Biological test systems.
 Records of source, date of arrival, and arrival conditions of test systems.
 Proper identification of test systems in their container or when removed.
 Cleaning and sanitization of containers.
6. Test and Reference Items
 Receipt, handling, sampling and storage
 Characterization.
 Known stability of test and reference items.
7.Standard Operating Procedures (SOP)
Written procedures for a laboratories program.
They define how to carry out protocol- specified activities.
Most often written in a chronological listing of action steps.
They are written to explain how the procedures are suppose to work
Actions to be taken in response to equipment failure.
Keeping records, reporting, storage, mixing, and retrieval of data.
8. Performance of the Study

 Prepare the Study plan.

 Content of the study plan.
 Identification of the study.
 Records.
 Dates.
 Reference to test methods.
 Information concerning the sponsor and facility.

 Conduct of the study.

9. Reporting of Study Results
Information on sponsor and test facility.
Experimental starting and completion dates.
A Quality Assurance Program Statement.
Description of materials and test methods.
Results.
Storage (samples, reference items, raw data, final reports) etc.
10. Storage and Retention of Records and Materials
The study plan, raw data, samples.
Inspection data and master schedules.
SOPs.
Maintenance and calibration data.
If any study material is disposed of before expiry the reason to be justified and
documented.
Benefits Of Good Laboratory Practices.
• It will give better image of company as a Quality producer in Global market.
• Provide hot tips on analysis of data as well as measure uncertainty and perfect
record keeping.
• Provide guideline for doing testing and measurement in detail.
• Provide guidelines and better control for maintenance of instruments, environment
control, preservation of test records etc
INTRODUCTION
• Good Manufacturing Practices (GMP) is that part of Quality
Assurance, which guarantees that products are regularly produced
and controlled to the quality standards suitable to their intended use.
• GMP is intended mainly at diminishing the risk characteristic in any
pharmaceutical production. Such risks are essentially of two types:
1. Cross-contamination (in particular, with unexpected
contaminants)
2. Mix-ups (for example, false labelling).
Cross Contamination
• Cross contamination is defined as the contamination of a starting
material, intermediate product or finished product with another
starting material, intermediate product or finished product is called
cross contamination.
• Preventive measures: To prevent cross contamination the personnel
should be taught of gowning practices and maintaining of personal
hygiene. The personnel should wash their hands regularly. Penicillin
like sensitive products should be handled carefully as they may cross
contaminate and cause fatal effects. Filters should be cleaned
regularly pipes should be sanitized as per the written procedures.
Mix Up
• Mix up is the contamination of one product with another product by
human errors or inadequate process or plant design. Mix ups occur
during labelling, packing, line clearance problems or receipting.
• Preventive measures: Physical segregation of the products with
proper labelling and identification details proper design for the flow
of materials packing should be done in compliance with the written
procedures.
Good Manufacturing Practices To Avoid
Contamination and Mix Up
• Procedures should be clear and should be followed to achieve the
objective of quality for the product.
• All the procedures regarding materials and products regarding their
receipts, sampling, storage, cleaning, labelling, quarantine and
dispensing should be in accordance with written procedures.
Guidelines by Different Authorities
Worldwide, there are different official regulatory statements and guidelines, both
national and international, for GMP for pharmaceutical (or ‘drug’ or ‘medicinal’)
products.
• In United States they follow Current Good Manufacturing Practices for Finished
Pharmaceuticals regulations.
• In European Union there is European Commission Guide to Good Manufacturing
Practice for Medicinal Products.
• The ICH Q7 guidelines are there for Good Manufacturing Practice Guide for Active
Pharmaceutical Ingredients.
• In India, Good Manufacturing Practices guidelines come under Schedule, The
Drugs and Cosmetics Act and Rules, 1945
DOCUMENTATION
• Documentation is the key to GMP compliance and ensures traceability
of all development, manufacturing, and testing activities.
• Documentation provides the route for auditors to assess the overall
quality of operations within a company and the final product.
GOLDEN RULES OF GMP
Get the Facility Design Right from the Start
• It is the responsibility of the manufacturer to design the layout for facilities
and equipment right from the start.
• Facility layout: Lay out the production area to uniform the sequence of
operations. The main focus is to reduce the chances of cross contamination
and to avoid the mix-ups and errors during manufacturing process.
• Environment: It is important to control the lighting, ventilation, air, water,
temperature, and humidity within a plant so that it does not impact
product quality.
• Equipment: Design and install equipment in an area where it can be easily
cleaned and Suitable for its intended use. Equipment’s must be calibrated
at defined intervals and clearly labelled.
Validate Processes
• Consistent performance is the key to maintaining safety and
effectiveness of every product and enhances a company’s status for
quality and trustworthiness.
• Validation usually involves:
 Installation Qualification, which is testing to verify that the
equipment is installed correctly.
 Operational Qualification, which is testing to verify that the
equipment operates correctly.
 Performance Qualification, which is testing to verify that product
can be consistently produced to specification.
Writing Good Procedures
• Plan the task before you begin writing the procedure.
• Generate a brief breakdown of the important steps and key points related to
the task; a flow chart is a useful tool.
• Remember that people don’t usually read processes from start to end; they
have a habit of to scan the document for key words.
• It’s better to break the procedure into portions and use like; Headings, tables,
bullet points and diagrams.
• It is a GMP requirement to frequently review documentation to ensure that
it’s up to date. Most companies have a three-year review cycle for their
documents however this can be set according to the possibility of change in
the procedure that the document relates to.
Following Procedures
There are two main reasons for this:
1. Many shortcuts may create pitfalls that can be costly in the end.
2. Each step in a procedure has been included for a purpose.
Identify Who Does What
All employees should clearly understand what they have to do each
day. It avoids misunderstandings and minimizes the risk to product
quality.
There must be a job description for each role to define:
1. job title
2. job objective
3. duties and responsibilities
4. Skill requirements.
Keep Good Records
• Good records empower you to track all activities those are performed
during the manufacturing of batch from the receiving of raw
materials, to the final product release; they provide a history of the
batch and its supply.
• It is a vital part of GMP to keep truthful records because this will help
during an audit; it also helps to convey that you are following the
written procedures.
• It also reveals that procedures are known and under control.
Train and Develop Staff
• To meet GMP necessities it’s essential to have the right people to do
the precise job. It is very important that employees have the abilities
and awareness to complete their job.
• Training: It is our responsibility to provide training for all employees,
whose duties take them into production areas or laboratories, and
whose activities can affect the quality of the product.
• Demonstrating Job Competence: Employees must demonstrate their
job ability every day by manufacturing quality products in a safe and
well-organized manner.
Practice Good Hygiene
• Personnel hygiene plays a vital role in any manufacturing company. It
is not just putting sanitization program, so with that you can reduce
contamination. Develop a program to meet the standards of
cleanliness necessary for the product. The fight against contamination
is a constant battle and is one that requires the attention of every
single employee, every day.
• It’s necessary to aware the staff against the importance of washing
their hands after toileting, ask the microbiology department to take
fingerprint samples from each operator after they have washed their
hands.
Maintain Facilities and Equipment
• It is necessary to have a maintenance schedule for facilities and
equipment. Consistent equipment maintenance averts equipment
breakdowns, which can be costly.
• It also helps to reduce the risk of contamination and maintains the
‘validated state’ of the facility or equipment. Sometimes an
unexpected event may affect the facility or equipment and under
such circumstances, you need to carry out repairs immediately.
• It’s also a GMP requirement to have a maintenance schedule in place
with the frequency determined by the criticality of the equipment.
Design Quality into the Whole Product
Lifecycle
• By working in the, drug, and medical device industry you know that
the health and safety of the customer depends on the quality of the
product.
• The Quality control department can only inspect for quality so it’s
critical that you build quality into the product lifecycle.
• Every step in the product lifecycle requires effective controls to assure
product quality.
Perform Regular Audits
Audits must be conducted to evaluate whether you are following the
GMP guidelines. External bodies such as the Food and Drug
Administration (FDA) or the Therapeutic Goods Association (TGA), will
conduct these audits.
I. It is important to carry out in-house audits, or self-inspections, to
ensure GMP compliance.
II. It’s a good practice to undertake a self-audit a few times a year and
to target different manufacturing areas and departments each time.
Thank You