Drug Utilization in a regulated Enviorment

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

DRUG UTILIZATION

ABSTRACT: Tracking drugs across the supply chain in a regulated environment. This white paper brief on would be

drug utilization approach of Life Science Industry.

This white paper is just a step forward to show future life science industry process automation

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

INTRODUCTION Track & trace solutions are top of the agenda for pharmaceutical industry, following the passing of the Drug Quality, regulation & compliances. Supply chain traceability has long been a hot topic for pharmaceutical industry. Given the very real risks to patient safety, keeping a close eye on shipments goes far beyond protecting revenue streams. Manufacturers need to remain on high alert, ensuring their product integrity isn't compromised and doing all they can to forestall the chance of counterfeiting.

Industry trends

Globalization

o From sourcing to new markets in emerging countries

o Global price regulation and reduced reimbursement

Complex global regulatory environment

o Innovation while managing current offerings.

Global collaboration

o Changing business models

- Controlling quality, compliance, governance and risk

Pharmaceutical supply chains are

global and any one chain will need to be able to comply with

multiple national standards.

Within the pharmaceutical industry, the top

issues will be ensuring the highest levels of both patient

safety and brand protection.

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

DRUG UTILIZATION

Drug Utilization Reviews (DUR), also referred to as Drug Utilization Evaluations (DUE) or

Medication Utilization Evaluations (MUE), are defined as an authorized, structured, ongoing review

of healthcare provider prescribing, pharmacist dispensing, and patient use of medication. DURs

involve a comprehensive review of patients' prescription and medication data before, during, and

after dispensing to ensure appropriate medication decision making and positive patient outcomes.

Classification of Drug Utilization:

COMPLIANCE AND PERSISTENCE, LOT, LTV, LIFETIME VALUE OF A PATIENT

Poor adherence to medications is a major problem and is estimated to cause deaths .A new study

has found that an average pharmaceutical brand loses its sales to non-adherence issues, and,

according to industry estimates, it costs the pharmaceutical industry in lost revenues. With such a

well-identified and significant clinical and financial challenge, pharmaceutical manufacturers need

to improve the approaches they use to improve patient adherence to their therapy. The potential

for improving adherence is clear: improved outcomes and higher lifetime patient value.

To improve adherence program now pharmacy companies use compliance packaging. This includes

blister cards with pill specific calendars and directions for use and patient-friendly inhalers that

record the number of doses taken. Patient education and communication has been an integral part of

and involves the dissemination of information on the drug, disease and other relevant aspects.

As a part of compliance lot of different attempts are being made to combat drug counterfeiting, e.g.

applying seals to the packaging to prevent unauthorized repackaging or special holographic labels.

As another consequence governments throughout the world have established or will establish

legislation to enable seamless tracking and tracing of each single pack of medication from the

• Evaluation of a patient's therapy before medication is dispensed

Prospective

• Ongoing monitoring of drug therapy during the course of treatment

Concurrent

• Review of therapy after the patient has received the medication

Retrospective

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

manufacturer to the point of dispensing the drug to a patient. This will be achieved through

serialization of each individual packaging unit. Ultimately a consumer or pharmacist should have the

ability to take a single package of any drug, scan it and get the information whether this package is

genuine.

The Drug Quality and Security Act (DQSA - H.R. 3204) which was signed by President Obama on

Nov. 27 has pre-empted any state laws incl. California ePedigree and the existing Florida legislation.

Item level serialization will be pushed to 2017 but lot level tracking is required stating Jan 2015.

o India has established legislation for all products exported from India. There are currently no

requirements for government reporting but manufacturers have to keep the serialized data to

be able to verify single packages on request.

Today, the lifetime value of a patient is pretty high.

A hospital or medical practice can’t afford to lose patient goodwill – and the potential revenue it represents – nor can they afford to let those accounts turn into bad debt.

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

CONCOMITANCY, DOSING, TITRATION, MONO VS COMBO THERAPY, PATH OF THERAPY

In many patients, several drugs are given concomitantly in order to increase the treatment efficiency

or to treat diseases occurring simultaneously. In such cases, pharmacokinetic interactions between

drugs may occur and the therapeutic efficacy or the toxicity of the drugs implied may be affected.

Improper or lack of association among Adverse Events , Concomitant Medications and Medical

History pose a risk to obtaining a clear study endpoint.Sponsors should review how the associations a

re designed, managed and enforced in the study.

When dealing with complex and multiple data associations between adverse~events and concomitant

medications many challenges and obstacles can arise when associations are manually managed. Life

Science~companies can improve data quality by using EDC products with built-in

association features.

Life Science organizations are always looking for ways to safely accelerate their drug development.

The ability to obtain clean data faster is a key to a study’s success.

Challenge

When dealing with sick patient populations, the list of pre~studies adverse events and concomitantmedications can be large. It is critical to understand what new adverse events are generated and howt

he concomitant medications are related after the subject enrolls and starts the study.

However, when so many data points exist, it is possible that intervening medications for the AE are

not recorded in the concomitant medication list. Also, for a particular concomitant medication, if an

AE association is needed, the process should support the association or highlight when the associati

on is not made.

If a study has 4000 adverse events of which 2000 have an intervening medication listed, we should

expect at least 2000 medications in the concomitant medication list, not less. By not addressing this

critical association up front, organizations may be left with inadequate information to determine

the safety profile of their new product.

Approach

To solve the problem, companies have used the following approach:

o Select an Electronic~Data~Capture system that natively supports the association of AEs

with concomitant medications.

o Use the EDC system’s native association to perform edit checks for logical integrity within

the system. Study specific examples may include:

- For an AE form, if “intervention medication” is selected, ensure a concomitant

medication is associated.

- Ensure the medication start date is on or after the AE start date.

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

- Ensure associated medications have a start date after the patient’s study start

date (e.g. consent date).

- If a concomitant medication is given for “new condition”, ensure an AE is asso

ciated.

- Inherent system AEconcomitant medication associations not only allow data t

o be associated cleanly but also enable the monitoring and data management

teams to query and follow up when information is missing or inaccurate. The

se features assure better data consistency at the study endpoint.

Results

Leveraging the AE and concomitant references and associated edit checks, firms are better able to e

nsure data is collected properly. This process leads to cleaner data more quickly. Benefits of the sol

ution include:

o Eliminates missing data by ensuring medications are associated when medication interventi

on is specified on the AE form

o Speeds data entry

o Accelerates data cleaning

o Reduces number of queries

o Improves data quality by enabling users to make the association of data without a complex

and problematic numbering scheme

Dosing & Path of therapy

Dosing Regimen: The objective of drug therapy is to bring plasma concentration within the

therapeutic window. The dosage regimen is the modality of drug administration that is chosen to

reach the therapeutic objective. This depends on the drug used, the condition to be treated, and the

patient's characteristics.

The decisions defining dosage regimen are about:

o Route of administration

o Galenic formulation

o Unit dose

o Frequency

o Loading dose

o Length of treatment

Dosing regimen implications:

For most drugs, a usual dosage regimen is proposed by the manufacturer and approved by registration authorities. This regimen should suit the average patients needs. As a principle, individualization of the dosing regimen should be considered systematically, leading in selected cases to apply unusual dosing decisions in order to tailor the treatment to a patient condition.

Loading Dose

Maintainance Dose

Dosing Interval

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

For example, the standard regimen must be adapted to the patient's characteristics (e.g. weight and age) and to the presence of comorbidity that affects the drug's pharmacokinetics (e.g. renal failure, liver disease).

After the initiation of therapy, individualization of the dosage regimen, with regard to the response, can be necessary to better adapt the treatment to the patient's condition.

Dosage Individualization

"Adaptation of the dosage regimen in function of the clinical characteristics of the individual, aiming to achieve the best possible therapeutic efficiency at the lowest risk of unwanted effects."

The objective of drug therapy is to produce, the desired therapeutic effect, with the highest chance and minimum toxic effects.

As described, the dosage regimen must be first adapted to the patient's characteristics and comorbidities. This initial adaptation realizes a priori individualization. After initiating therapy, the patient's response to the drug must be evaluated and the dosage regimen further adapted in case of ineffective therapy or appearance of undesirable effects. In selected circumstances, the follow-up of an effect marker may improve the monitoring of treatment. Adaptation in response to such feedback information realizes the a posteriori individualization.

The reasons for failure of drug treatment can drive from physiological inter-individual variation of pharmacokinetic parameters, which cannot always be evaluated prior to initiation of drug therapy (e.g. genetic metabolic differences). Other causes of treatment failure are variation in response due to inter-individual differences in pharmacodynamics (e.g. sensitivity towards the drug), including drug tolerance (diminished pharmacologic responsiveness to the drug). Disease states can further alter the response to drugs, and draw attention to dosage individualization.

Dosage Individualization implications:

A priori individualization must be considered each time a drug treatment is introduced. After initiating drug therapy, the desired response (e.g. analgesia) and the appearance of undesirable effects (e.g. sleepiness) should be evaluated for each patient. If these features are not satisfactory, an alteration of the dosage regimen should be discussed.

For some drugs, it is standard practice to monitor surrogate markers (e.g. prothrombin time) for evaluating the effectiveness of therapy.

Dosage Titration

Titration is used in a medical sense to figure out drug dosages in at least two ways:

o The goal might be to take as little of a drug as possible to get the desired effect like keeping your blood pressure or cholesterol in check.

o Another goal might be to see how much of a drug your body can handle before the side effects outweigh the benefit of the drug, which is normally only done in the early stages of clinical trials. This type of titration is seen most with chemotherapy drugs. A trial

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

participant is given progressively more of a drug over a period of time while the researchers test to see if it's killing the cancer cells it's supposed to be killing.

Mono vs Combo Therapy

Combination therapy or polytherapy is the use of more than one medication or other therapy

(vs. monotherapy, which is any therapy taken alone). Typically, these terms refer to using multiple

therapies to treat a single disease, and often all the therapies are pharmaceutical (although it can

also involve non-medical therapy, such as the combination of medications and talk therapy to treat

depression). 'Pharmaceutical' combination therapy may be achieved by prescribing/administering

separate drugs, or, where available, dosage forms that contain more than one active

ingredient (such as fixed-dose combinations).

Off Label & Source of Business

Good medical practice and the best interests of the patient require that physicians use legally

available drugs, biologics and devices according to their best knowledge and judgment. Although

off-label drug use is a complex issue and is not synonymous with inappropriate drug use, a high

rate of unlicensed/off-label drug use was found and was also associated with an increased risk of

adverse drug reactions. More efforts are needed to increase rational drug use in children.

Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved

age group, unapproved dosage, or unapproved form of administration. Both prescription

drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although most study of off-

label use centers on prescription drugs. Off-label use is generally legal unless it violates specific

ethical guidelines or safety regulations, but it does carry health risks and differences in legal

liability.

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

SOLUTION ON DRUG UTILIZATION:

TRACKING OF DRUGS ACROSS SUPPLY CHAIN IN REGULATED ENVIRONMENT

Supply chain optimization can happen in any industry only when there would be a regulation and

technology adoption. Recently government have work out many regulations for pharmaceutical &

food industry, because the criticality of their business.

In recent years the complete process would be digitalized. This will give visibility towards proper

drug utilization.

Drug Packaging Process:

o Packaging of each drug packet with unique barcode with batch number, expiry date along

with dosage indications.

o Point to be in consideration, if the barcode can be encrypted then the chances of delicacy

can be reduced.

Supply Chain Traceability:

o Digitalize the complete supply chain process will optimize the process and helps to improve

process excellency.

Drug Manufacturing

• Excellency in QC

• Unique ID of each drug

• Manufacturing & expiry details

• Dosage indications

• Visibility in Supply chain

Supply Chain Tracability

• Tracking in Supply Chain

• Managing FIFO Process

• Procure as per demand VS supply forecast

• Storage in control temp.as per regulation.

Doctor Prescription

Creation of patient profile

Electronic Data Capture of each patient prescription

Digitilize Hospital Retail Inventory

Hospital Retail Chain/Chemist

Retail will receive all the patient profile

Patient will provide lists of retail attender

Attender will enter patient ID in the system

System will generate bill of materials as per doctor directions

Patient profile

• Patient profile

• Patient medical history

• Unique ID of each patient

Tracking drugs across supply chain in regulated environment

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

Doctor prescription

Patient Consumption

Pharmacist/

Chemist

o This will decrease the level of error and will follow regulation guidelines.

o Clean logistics warehouse and storage temperature to be maintained across supply

processes.

o Working on process re-engineering to achieve excellency.

Visibility in Drug Utilization:

Drug Utilization Reviews help pharmacists/healthcare fulfill their professional responsibility and ensure that medication is dispensed safely. It also assists in monitoring compliance with the doctor‘s intended drug regimen. When possible harmful drug interactions are detected, alternative drug therapies may be recommended after discussions with the prescribing physician. This may take the form of dosage adjustments, alteration of medication administration and/or additional patient monitoring.

Drug Utilization help ensure patient health, safety and compliance. Control pharmacy costs with automated clinical support; with ever-increasing medication costs, appropriate use means more than ensuring patient safety.

With Drug Utilization Review (DUR) solutions program can promote clinical safety, therapeutic

efficacy and appropriate drug use more efficiently. Electronic Data Capture solutions review and

analyze prescriptions in real time against predetermined clinical criteria, helping healthcare

improve adherence.

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

Doctor Prescription:

The doctor will use computer/laptop/tablet to enter the details of patients. The details of patients

will be entered in columns. The doctor can also visit the patient medical history in case of some

relevant information is required.

Doctor will have to login to the HIS system.

Chemist Supply:

Based upon doctor prescription report the patient will got to the chemist/pharmacist. The

pharmacist will login to his system.

In case of titration process the chemist or lab in charge to capture data of all FG drugs details in

system with reference to patient ID.

Enter patient ID in the system. The system will automatically generate bill of materials of medicines

with quantity. The pharmacist will also have an option to take the printout from the system.

In case of big retail outlet: The BOM will be downloaded on the mobile computer of the picker. The

picker accordingly picks the materials and an auto bill will be raised from the system.

At the back end the doctor will also get informed that the patient had purchased the right

prescribed medicine from said outlet. HIS will be linked with Supply chain system which helps to

forecast PO to the vendors according to the analytical data of demand and supply.

Patient Login Screen:

The patient will not bond to any retail outlet or healthcare. He can visit any of the healthcare who is

availing this HIS system. There would be a HIS-CRM provider or any healthcare would run this

application. The patient can login into the system using a login id and password.

Patient Disease

Tracking drugs across the supply chain in a regulated environment.

Alok Anand [email protected] 0091 9560639947

The patient can any time see the doctor report and also download those reports for his kind

reference.

According to dosage prescription the patient can also receive sms on what medicine he/she has to

take at what time. E.g. The patient have to take beta medicine tablet at 8 ‘o clock morning and he

shall get an sms alert at 7.45 as an reminder. This will improve the efficiency of medical practice’s

/healthcare and will also improve drug dose utilization of patient.

Report:

o Analytical report

o Dashboard for monitoring the patient report card

Benefits:

o Tracks and identifies over-consumption and under-consumption o Prevention of medication errors: ensuring patient safety through the administration of right

medicines to the right person in the right dosage at the right time through the right route of the administration.

o Product authentication: enabling authentication of individual packages, cases or pallets of medical supplies.

o Tracking medical products: enabling tracking and tracing of medical equipment’s, medicines etc. in the health care Supply Chain by using The Global Traceability Standard for Healthcare (GTSH) as a foundational framework, which describes the traceability process and defines minimum requirements for all stakeholders, independent of technologies, organization size or operational sophistication.

o Freeing up healthcare professionals: allowing healthcare professionals to spend more time caring for patients by reducing time spent on paperwork and other manual processes like data processing and ordering and counting.