A sensors used recently like three-dimensional printing based



Medicine or customized
Medicine refers to the fitting of remedial treatment to the individual quality
of every patient. It doesn’t mean the formation of medications or therapeutic device
that are one of a kind to a patient, however the capacity to group patients
into subpopulations that vary in their reaction to a particular treatment. Helpful
appeal can be focused on those patients who will profit, saving cost and no

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right patient with the right drug at the right dose at the right time” PERSONALIZED MEDICINE

With the growth of the pharmaceutical and
medical device industries in the 20th century came the rise of
genetics, imaging and data mining. But the differences in response to drugs in
the variations of human genome served as the foundation of pharmacogenetics.

At the turn of 21st century, A set
in motion for the transformation of personalized medicine to from an idea to

Generally, the patient’s doctor makes a
decision about the medication based on only general information for the
disease. This trial and error approach can lead to patient dissatisfactions,
adverse drug responses and drug interactions and poor adherence to treatment

The main goal of personalized medicine is
to reduce healthcare costs by improving our ability to quickly and reliably
select effective therapy for a given patient while minimizing costs associated
with ineffective treatment and avoidable adverse events. Stratification is a
core element of personalized medicine.

is an investigation of varieties of DNA and RNA characteristics as related to
drug response is the most important area in personalized medicine.

Personalized medicine generally involves two medical products:

1. Diagnostic device (invitro tests) &
(in vivo tests)               

2. Therapeutic product

Many medical device therapies have been
tailored to specific patient characteristics include patient anatomy,
physiology and environment of use.

Additional physiological sensors used
recently like three-dimensional printing based on image of a patient’s anatomy.

Before the inlet of personalized medicine,
there exit a situation in which everyone gets the same dose of a drug,
regardless of genotype.

Thus, after the approach of personalized
medicine in which the dose of the drug is selected based upon Geno typical and
therefore phenotypical, variability of the metabolizing enzyme.

Responsibilities of FDA:

FDA’S aim is to protect and promote the
health of all Americans through assuring the safety, efficacy, security of
drugs, biologics and medical devices.

Each year, Americans consumes 20 cents of
every dollar of FDA- regulated products.

main job of FDA:

 1. Is
to determines that products are safe and effective before marketing after a
certain evaluation of benefits and risks.

 2. It
must also require manufactures to follow quality manufacturing practices and
process and must conduct post-market surveillance.

 3. The
main thing in which the FDA strives to advance the public health by helping to
speed access to innovative medical products.


The mission of FDA is a series of
institutional responsibilities that are key to the emergence and direction of
the field of personalized medicine which includes:

The main responsibility
is to carefully consider the benefits and risks during the evaluation of
medical products into the innovative product while assuring proper patients

The new advances of
science facts and technology must be stay along to produce an innovative
medical product.

In order to increase the
new development of medical product, they must encourage to provide clarity
& predictability and guidance to industry.

The latest information of
science, technology and facts must be used appropriately and rationally to
inform clinical trial design, drug and device development and clinical

To evaluate and validate
new diagnostics and therapeutics, FDA must work together with university
scientists, government agencies, including NIH, companies, standards
organizations, practicing physicians and patients.

New safer and effective
drugs and medical devices are streamlined for regulatory process and advancing
the science and tools that will help drive innovation.


Every medical product has inherent risks, but FDA’s
job is to determine if the benefit exceeds the risk in the targeted populations
as a whole.

It can be approved as “safe and effective” only when
that product has some scientific evidence during the clinical trials to the
certain group of patients who has same diseases with similar characteristics.

But the response varies from one individual to the
next as a result of genetic and environment factors, as well as the interaction
of these factors.


As a result, from this information the drugs must not
be used for every patient based on only the general information, thus improving
the safety and efficacy of drugs by specifying the populations in which they
must be used.


When the targeted populations were given
certain drugs to the targeted disease or condition based on only the general
information have different rates of efficacy as follows:

Depression -38%


Cardiac Arrythmias-40%







Thus, with the help of personalized
medicine, the healthcare management paradigm will focus on prevention, moving
from illness to wellness, and from treating disease to maintaining health and
improving the success rates.


As many drugs needs to be developed, NCTR
(national center for toxilogical research) has reorganized that works as a cross
functional teams on NCTR research projects. The reorganization formed three new
branches within the Division of systems biology and has better positioned NCTR
to support the larger personalized medicine efforts of the agency.

The three new branches the division of
systems biology are:

(1) Biomarkers and alternative methods

(2) Innovative safety and technologies

(3) Personalized medicine


The program aim is to provide a framework
for scientic development and regulatory acceptance of biomarkers for use in
drug development and and integrating the qualified biomarkers in this
regulatory review process and encourage for the new identification and emerging

CDER developed the process for qualifying
biomarkers for use in drug development. Once it has been qualified, a biomarker
can be used by drug developers in the context of use in investigations and
marketing submissions without requesting the relevant agency.


Microarrays and next generation sequencing
represent core technologies in pharmacogenomics, toxic genomics, and
personalized medicine. Implemented, organized and run by NCTR scientists, the
FDA-led MAQC/SEQC project seeks to advance translational and regulatory
sciences by assessing technical performance and practical utility of emerging
molecular technologies for clinical application and safety evaluation. This
collaborative effort wil help to ensure that the field of personalized medicine
will benfit from high quality diagnostic tests.


Human leukocyte antigen system is a large
number of genes and protein products that are related to immune system function.
It is a process of testing the patient or donor blood and other tissue samples
for the HLA antigens, and to determine the compatibility between the HLA

Molecular –based typing methods are used
to improve transplant outcomes for the precise HLA matching and especially
critical for bone marrow transplant, where the poor matches result in
catastrophic health consequences. For the ambiguous results,” gold standard”
DNA-based HLA typing methods, and also due to the variability and complexity of
the HLA genes. CBER scientists, along with others by using a high-resolution
HLA typing methods to achieve the results without ambiguities.


CDRH have made major advances in the
underlying of heart disease and used new methods for them using the analysis of
the electrocardiogram to predict which patient benefit from the cardiac
resynchronization therapy. This diagnose the electrical conduction problems and
to quantify the scar tissue in the heart, but the women benefit it more than
the men due to the certain criteria. This explains why the efficacy and safety
of medical products differs in patients and can be used to design more
efficient clinical trials.


It is a clinical trial to select the
patients for whom therapy is most likely to provide a benefit. FDA is working
to address the issues like missing data’s, multiple endpoints, patient enrichment,
and adaptive designs due to the development of targeted therapeutics. FDA is
most probably used for clinical trials for oncology drug development. Generally,
the cancer is heterogeneous in which each with their own specific genetic
makeup and thus respond differently to therapies with different people. The
I-SPY 2 trial, a highly collaborative initiative developed under a unique
public-private partnership and involving the participation of more than 20
centers are recruiting and treating the patient.


In the early stage, multiple drugs were
removed because of the increased fatal abnormal heart rhythm called “torsade de
poites”. This increases a measurement on the electrocardiogram called the “QT
interval”. However not all drugs cause torsade de pointes. Some effective drugs
are prevented in the market. Thus, CDER and CDHR is assessing new device based
algorithms and biomarkers that distinguishes benign (not harmful) from
malignant(harmful)drug-induced QT prolongation.

Recombinant protein therapeutics, which
are the fastest growing segment in the pharmaceutical industry are mainly used
for the complex medical conditions.

At 2010, 38% of drugs are approved for
efficacy, safety and pharmacokinetics.

At 2011, personalized medicines have been
increased to 12, which is 51%.

In 2013, it has been decreased from 117%
to 67% due to the design of more drugs to the small populations. Such
approaches can dramatically shorten overall drug development and review times.

most significant challenge in personalized medicine:

Limited understanding of
the intrinsic biology of diseases.

Common conditions
involving multiple gene.

An outdated disease
classification system.

Lack of infrastructure.

Investment uncertainties.

Access to personalized



The FDA is committed to
work improving the personalized medicine by advancing the science and tools
that will provide clarity and guidance to industry in order to provide more
drugs to the market.





Personalized medicine promises to enhance
medical products development by improving the probability of success.

The combined products seek to reduce the
burden of disease by targeting prevention and treatment more effectively.

It raises a number of regulatory, policy,
sponsor coordination and reviews management challenges.

FDA’s mission is to protect and promote
the health assuring the safety, efficacy, and security of drugs, biologics, and
medical devices. In addition, FDA strives to advance the public health by
helping to speed up the innovative medical products.

The FDA’s three medical product review
centers are:

Center for devices and
Radiological Health (CDRH).

Center for drug
evaluation and Research (CDER).

Center for biologics
Evaluation and Research (CBER).

Office of special medical
programs(OSMP)-It accomplishes these goals by the experts from innovative
products and the regulatory industry to develop guidance documents and
regulations to assists the developers.


These centers took steps to begin to put
into place regulatory processes and policies to meet the challenges of
regulating these complex products and coordinating their review and oversight.


Over the past decade, there have been some
significant advances in the development of new pharmacological options.
Nevertheless, there is a widespread recognition that the rate of introduction
of new drugs has been disappointingly slow, and that many drugs do not provide
benefits to a sufficient percentage of patients who receive the therapy. Other
drugs have stumbled because of adverse events.

The regulatory regime that was expressly
designed to cover these products could simplify the regulatory process both for
companies and agency.

The agency has issued a number of guidance
documents and regulations to seek to clarify requirements, overview of
premarket reviews, delineate the activities and responsibilities of the
different centers.

Using the guidance and policies:

Designing clinical trials
to incorporate biomarker data.

cross-labeling activities.

pharmacogenomics data.

Demonstrating companion
diagnostic test performance.

The laws and regulations play a large role
in determining the pace of personalized medicines development and adoption of
the following are:

on PG Data submissions concept paper on drug-diagnostic Co-development.

this year 2005, pharmacogenomics data are submitted based on:

When to submit it during
the product development and review process.

What format and content
to provide for submissions

How and when the data
must be used in the regulatory decision making.

(1) Guidance on Pharmacogenomics tests and genetic tests for heritable markers:

It is used to increase the progress in
this field to shorten the development and review timelines and transfer of new
technology to the clinical laboratory.

Both the manufacturers and scientific
reviewers must provide a common baseline to operate it.

Statistical Guidance on reporting results from studies evaluating diagnostic

Reporting the qualitative results from
different studies and identifies the common inappropriate practices by
evaluating diagnostic tests.

Definitions for genomic biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic
Data and Sample Coding Categories.

Using the key terms, it is used to develop
harmonized approaches to drug regulation.

on Qualification Process for Drug Development tools (draft guidance) Drug
development tools are once qualified by the drug developers for the qualified
context in new submissions which helps to speed up the therapy development and evaluation.

(1) Guidance on clinical PG: Premarketing evaluation in early phase clinical

Both the industry and agency must submit
the premarket clinical performance studies to focus on critical elements of
safety and effectiveness for the approval.

Guidance on clinical trial designs employing enrichment designs.

In the clinical trials, to support the effectiveness
and safety of new drug and biologic license applications consists of three
enrichment strategies:

1.    Practical
enrichment 2. Prognostic enrichment 3. Predictive enrichment

The Clinical Pharmacogenomics guidelines by FDA: A before stage of clinical
study by evaluating the premarket for label recommendations. This
direction will help by, how the new medication improvement in assessing the
varieties in the human genome strikes concentrate on the standards of study
plan, information accumulation and information examination in early-stage
trials. It additionally gives proposal to naming.

In the current years, the customized pharmaceutical
of demonstrative and remedial items is as of now to help shepherd items through
the survey procedure and screen their security and post-advertise.



Even though we belong
to the same specie we are not designed in the same manner when it comes to
genetic level. the 3 billion base pairs present in us are responsible for
20,000-25,000 protein coding genes. And as a result of this we need to group
the population based upon some similarities and dissimilarities. In order for a
personalized medicine to work on a selected group of population or individual
we have to first know if this is the right drug for the right person. And to do
that we need a reliable diagnostic test which gives a low number of false
positive or false negative results. since a diagnostic test is the very first
approach in determining if an individual has a problem or not. it needs to be
constantly updated and monitored. This job is being done by the FDA’s medical
device authority.

They check the
values of the devices based on 

validity:- specific test is suitable for its intended use

validity :- to check if the patient truly has the documented condition

utility:- usefulness of the test in improving the patients outcome

The diagnostic tests
used in personalized medicine are mostly IVD’s

which checks if the
individual has altered biomarkers. and the presence/absence of genetic
susceptibility biomarkers. IVD’S are marketed into IVD kits developed by a
conventional device manufacturer and sold to labs, hospitals and physicians
offices and LDTs are those that are designed, manufactured, and used by a
single laboratory. However the FDA has control over the regulation of the LDT’S
so that they give accurate measurement values even when made by different
manufacturers. The product interdependency plays a vital role in personalized
medicine making sure the therapeutic intervention and the therapeutic product  are beneficial to the user and not harm them.
In cases where a test is essential for the safe and effective use of a
corresponding therapeutic product, it is termed a “companion diagnostic.”

companion diagnostics
are useful in when new medicine or new diagnostic devices are made usually
these 2 are made by different organizations such things are termed as
co-development. Development of companion diagnostics
together with therapeutics should allow for more efficient studies with smaller
patient populations while also leading to more focused therapies that offer
better outcomes, less toxicity, and fewer treatment delays.

Clinical trials take place before a drug
is being marketed to the targeted population. These trails are in accordance
with the FDA’s “Enrichment Strategies for Clinical Trials” which is a draft
introduced in 2012 to choose the right people for the clinical trials so there
won’t be any bias. development.
co-developments are regulated by Shepard programs by the FDA so that they stay
in constant communication with the sponsors for tailoring to the needs of the

Through such
strategies Vemurafenib is a drug for treating late
stage melanoma which was approved by FDA in near record time (3.6 months)
through this process as a result the outcome for the prognosis for this disease
was better.

After the medicine is made it is labeled
scientifically so that the prescribing physician can give the dosage depending
on the factors such as age region and race. And drug is constantly updated
whenever any new changes are made listing out the side effects and the
contraindications of the drugs. In order to prevent any mishap for the

Whenever the drug is updated after a new
study the labeling is also updated so that it can carter to the needs of the

Pharmacogenomics information can appear in
different sections of the labeling Therapeutic Indications, Warnings and

A guidance table is made which contains
information of the time of approval of the drug, the disease which it treats
and the biomarker which Is related to the disease is also given so that the
physician can confirm if the concerned person has the disease before initiating
the treatment.

post marketing surveillance is done after the medicine is being released into
the market this collects the long-term data of the effects of the medication on
different population living in different sub continents and all the data is
being collected and sent to the FDA. This data includes the electronic data of
the patient and what they were afflicted with before and after treatment. This
is one in case if the marketed drug causes some adverse effects in the long
run. Even though clinical trials and studies are conducted before approving the
medication by the FDA. These trails have been only undergone in a small group
of people in each phase when compared the huge population to whom this
medication is marketed to.

So, the FDA has developed a sentinel
system via FDA’s Mini-Sentinel pilot program, a large-scale working model of
the eventual full-scale System.

The Mini-Sentinel System provides secure
access to the electronic health care information of more than 125 million
patients, provided by 17 data partners nationwide. 

The objective of FDA for medicinal Equipment
post- advertise observation is
the production of a national system that serves four primary functions:

1) Communicates timely, accurate,
systematic, and prioritized assessments of the benefits and risks of medical
devices throughout their marketed life using high quality, standardized,
structured, electronic health-related data

2) Identifies potential safety signals in
near real-time from a variety of privacy protected data sources

3) Reduces the burdens and costs of
medical device post-market surveillance

4) Facilitates the clearance and approval
of new devices, or new uses of existing devices.

is pursuing four key proposed actions to help fulfill the vision for a National

1) Establish a unique device identifier
(UDI) system and promote its incorporation into electronic health information.

2) Promote the development of national and
international device registries for selected products.

3) Modernize adverse event reporting and

4) Create and utilize new techniques for
prove age, union, and evaluation.

The patient follow-up registry will help
the in keeping track of events that take place over the long-time due to action
of medication these things will be noted down and appropriate alterations will
be made to the personalized drug.