For Training Dr Saurav Deka MBBS MD

Medical Advisor INDIA Zydus International Division

hisaurav2007@gmail.com YeAR : 2013

PRESCRIBING INFORMATION

In the U.S., the complete label of a prescription medicine is made up of several documents that are approved and required by the Food and Drug Administration (FDA)—some professionally oriented and some intended for patients and consumers.

The first and most comprehensive of these documents is always the

• Professional Prescribing Information.

Others may include • Patient Counseling Information • A patient-oriented Medication Guide..

Prescribing information (PI)

1. Great deal of technical medical detail intended to inform health care professionals who might prescribe or dispense a medicine

2. PI is written for a professional audience.

Package insert or Prescribing information

• Manufacturers typically make the PIs of their medicines available on the Web, and must include the PI as a printed “package insert” with any medicine that is sold in a box or other type of package.

• Note that a package insert may also include other material in addition to the PI

NEWER PRODUCT PI

Must now have a two -part PI to make it easier to find and review the information.

1. The first part, titled Highlights of the Prescribing Information,

2. The second part is the full PI, with specifically labeled and numbered sections.

OLDER PRODUCT PI

Although PIs for the older products cover the same types of information as for new products, some of the sections are arranged and labeled a bit differently. For instance, in PIs of older medicines has different the topics under subsections of precautions• Interactions, • Use in Special Populations, • Patient Counseling Information.

Three topics is presented as a separate section, Warnings and Precautions section in newer PI

Indications and usage

The recognized disease or condition for which the medicine’s use is approved .Specify :I. Treat, prevent, or diagnose or to relieve the

symptomsII. Monotherapy or primary therapy or

secondary therapy or combination therapy or adjunctive therapy

III. Approved for certain subgroups of patients IV. Reserved for certain situations (refractory

cases )

INDICATIONS

Label indication : Approved indication by Regulator

Off label indication : Off-label use is the an unapproved indication or in an unapproved age group, unapproved dosage, or unapproved form of administration

The regulator does not have the legal authority to regulate the practice of the medicine, and the physician may prescribe a drug off-label.

Off label indication

Drug manufacturer Cannot promote its drug for an unapproved use, and that any such promotion is false and misleading simply because it is not FDA-approved

Many off-label uses are in fact effective and safe, as is evidenced by subsequent FDA approval of such uses for numerous drug products

However Manufacturers are now able to provide medical practitioners with publications on off-label uses of a drug, in response to an unsolicited request

CASE STUDIES

Contraindications

Medicine should NOT be taken or administered

A contraindication is a judgment by regulators—after reviewing the available medical evidence—about the benefit-risk relationship of using that medicine under specific circumstances.

The Warnings section of the PI will also include a brief mention of any contraindications (with cross-references to this section)

Contraindications Patient agePatient gender Concomitant therapy Disease state Patient hypersensitivity to the

medicine.

WARNING

The defining criterion for inclusion under Warnings is that a reasonable association must have been established between the adverse event or risk and the medicine—although a definitive causal relationship need not be established.

The Warnings section may also provide information about nonapproved uses of the medicine.

Precautions

In the old PI labeling format, actions required to make sure a medicine is properly and safely used were included under Precautions if not covered in other sections of the PI

Boxed warning

o This term refers to a specially formatted warning that is the strongest level of safety warning that may be required by the FDA for an approved medicine.

o Specifically, a boxed warning gives a brief explanation of any contraindications or serious warnings that may be associated with death or serious injury, with a cross-reference to more detailed information covered in the Warnings and/or Contraindications sections of the PI.

o If a boxed warning is required, it will be found at the beginning of the PI, with the text surrounded by a thick black border.

INFORMATION FOR PATIENTS/PATIENT COUNSELING INFORMATION

Note that this section may have different titles and locations within the product label according to when the medicine and/or its labeling was approved. Whether in the newer or older format, however, the same types of information are provided.

• Information for Patients is found in PIs for older medicines.You will find it as a subsection under the Precautions section near the middle of the PI.

• Patient Counseling Information, on the other hand, is a separate section at the very end of the PIs for newer medicines.

Patient counseling information

Prescribing Information

Discussion

• Is it legal to copy paste innovator PI ?

• Can you use all the indications ?

• How to prepare the Generic drug PI ?

• Do Innovator has patent protection on it’s data ?

Is it legal to copy paste innovator PI ?

If the generic product proves that it is bioequivalent to the innovator product, the Waxman-Hatch act allows the generic company to claim the exact labeling content as the innovator product.

The most recent Reference Listed Drug (RLD) package insert is available on the FDA web site “Drugs@FDA”, where the most recently approved package insert, the original package insert and all the subsequent amendments/changes to the current package insert can be found.

Can you use all the indications ?

The different indications of the RLD may have different patent expiration dates or exclusivity dates so that some indications may still be protected under patent or exclusivity. If this is the case, the generic company can market the drug only if they “carve out” the patent/exclusivity protected indication and relevant information from the RLD labeling.

The generic company must not only carve the patent or exclusivity protected indication(s) from the INDICATIONS section of the package insert, they must carve out all clinical trials data and any other text that makes any reference to the protected indication.

Case Study

For example, the RLD product Risperdal® (risperidone) originally had the indications of Schizophrenia, Bipolar Mania Irritability associated with autistic disorder (paediatric)

Schizophrenia and Bipolar Mania have patent dates and exclusivity dates that will expire much sooner than that of the pediatric indication. Thus, in order for a generic company to submit an ANDA and market the generic risperidone, they must “carve out” any reference to the pediatric indication.

Which format ?

The proposed package insert document is usually created in Microsoft Word and submitted as part of the final labeling folder.

The package insert is also submitted in PDF and SPL format.

Although prior FDA labeling submission requirements have been in the MS Word and PDF formats, the FDA now requires the package insert portion of the labeling folder to also be submitted in SPL format.

Check list for preparation Generic label

1. Innovator Package insert with last updated date 2. Indications ( patent exclusivity check )3. Formulation check ( same or not )4. Country any deviation (dosage and strength

indications )

Resource FOR Generic PI

The DailyMed website has the most updated package insert in SPL format used by the RLD manufacturer

Micromedex Innovator website Regulatory website (eg : US –FDA)

Apply Your Knowledge

True or False

Enteric-coated tablets can be crushed and

mixed with food.

All capsules may be opened and mixed with food.

Parenteral forms of drugs includes transdermal and inhalants.

T

F

F

This would allow the drug to be absorbed sooner than intended.

Some capsules should be swallowed whole.

Innovator Name in Generic PI

• Generic company does not want to put innovator brand name .

• Replace innovator brand name with generic name

• Do not replace with own brand name

Cross Check Formulation

Cross Check Innovator Name With Generic Name

Conclusion

• Prescribing information is an important regulatory document

• Prescribing information also a legal document • Only approve indications should be shared here • Off label indication may lead to legal problems • It should be update periodically as per latest

update or ruling by regulatory

THANKS