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CONTENTSIntroduction.

Legislative history.

When generic drug marketed.

Approval requirement for generic drug

Bioequivalence

Clinical research for generic drugs

ANDA

Life cycle of generic drug.

Indian generic drug market.

FDA regulation for generic drug

Conclusion

References

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INTRODUCTION

A generic drug is defined as "a drug product that is comparable to brand/innovator drug in dosage form, strength, route of administration, quality and performance characteristics, and intended use.“ It should contain the same active ingredients as the original formulation.

According to the FDA, generic drugs are identical or within an acceptable bioequivalent range to the brand-name counterpart with respect to pharmacokinetic and pharmacodynamics properties.

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LEGISLATIVE HISTORY

• 1906 Pure Food and Drug Act –establishes regulation of food and drugs.

• 1938 Food, Drug and Cosmetic Act – introduced safety standards.

• 1962 Kefauver-Harris Amendments to the FDA&C Act – tightened safety standards and introduced requirements that drug must be effective i.e., proof of efficacy.

• 1984 Hatch- Waxman Act - created an abbreviated mechanism for approval of generic copies of all drugs originally approved after 1962, by stating that pre-clinical and clinical testing does not have to be repeated for generics.

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WHEN GENERIC DRUG MARKETED

After patent and exclusivity protection ends

Patent owner waives its rights

FDA requirements are met

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B R A N D N A M E D R U G

N D A R E Q U I R E M E N T

1. Labeling

2. Pharma

3. Chemistry

4. Manufacturing

5. Controls

6. Microbiology

7. Testing

8. Animal studies

9. Clinical studies

10. Bioavailability

G E N E R I C D R U G

A N D A R E Q U I R E M E N T

1. Labeling

2. Pharma

3. Chemistry

4. Manufacturing

5. Control

6. Microbiology

7. Testing

8. Bioequivalence

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A generic drug is considered to be bioequivalent to the brand name drug if :

• The rate and extent of absorption do not show a significant difference from the innovator drug , or

• The extent of absorption does not show a significant difference and any difference in rate in intentional or not medically significant .

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BIOEQUIVALENCE

CLINICAL RESEARCH FOR GENERIC DRUGS

• to demonstrate that the generic medicine is comparable to the reference medicine so that it can receive a marketing authorisation.

• to show that the generic medicine produces the same levels of the active substance in the body as the reference medicine.

• Bioequivalence studies to assure the therapeutic equivalence.

• If a generic medicine contains a different salt of the active substance to the salt used in the reference medicine

• If the medicine is a hybrid, additional tests may be required, such as the results of clinical trials that test the efficacy of the medicine.

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BE STUDY DESIGN

• Bioequivalence trials are designed to compare the release, absorption, and elimination of the active ingredient from two formulations of a product (i.e., the unmarketed generic and corresponding brand-name product) and, if successful, demonstrate similarity between both within pre-established, statistically defined, pharmacokinetic parameters.

• Appropriate study protocol including the required number of subjects and sampling intervals should be determined according to preliminary studies and previously reported data.

• Design

– Randomized crossover studies

– Parallel designs can be employed..

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RANDOMIZED CROSSOVER DESIGN

washout period

period 1

period 2

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Generic drugInnovator

drug

Patient 1

patient 2

Patient 2

Patient 1

ANDA

• An Abbreviated New Drug Application (ANDA) contains data which when submitted to FDA's Centre for Drug Evaluation and Research, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product.

• Generic applicants must scientifically demonstrate that their product is bioequivalent.

• Scientists demonstrate bioequivalence is to measure the time it takes the generic drug to reach the bloodstream in 24 to 36 healthy volunteers. This gives them the rate of absorption, or bioavailability, of the generic drug, which they can then compare to that of the innovator drug.

• The generic version must deliver the same amount of active ingredients into a patient's bloodstream in the same amount of time as the innovator drug.

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APPROVAL PROCESS FOR GENERIC DRUGS

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LIFE CYCLE OF GENERIC DRUGS

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COST EFFECTIVENESS OF GENERIC DRUGS

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INDIAN GENERIC DRUG MARKET

• U S C E N S U S B U R E A U H E A L T H & N U T R I T I O N ( 2 0 0 5 - 2 0 1 0 )

• In 2010 India’s share of the generic market is about 30% out of 71.2% and reached $100 billion.

• In late 2012 40% of DMF’s were filled by Indian market in USFDA for supplying API’s.

• Now India’s share of the generic market is about to 35%. Hence the contribution of the Indian pharmaceutical industry for the growth of generic drugs in the world is very high.

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RECENT RULES BY FDA FOR GENERIC DRUG FOR INDIA

Generic drug manufacturers would be able to independently update product labelling (also called prescribing information or package inserts) with newly-acquired safety information before the FDA’s review of the change, in the same way brand drug manufacturers do today. Generic manufacturers would also be required to inform the brand name manufacturer about the change.

All generic drug makers, including Ranbaxy Laboratories, Cipla, Dr Reddy's Laboratories and Lupin, are now required to pay a fee to the US drug regulator while seeking permission to launch their products in the world's largest drug market.

The recently enacted Generic Drug User Fee Act (GDUFA) legislation adds a $20,000-$30,000 fee at the first time the DMF is referenced in an ANDA. However, the current rates are in effect only till September 30, 2013, and will be revised every year and is likely to affect the number of DMFs filed in the coming years from India and around the world.

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CONCLUSION

After the expiry of patent or marketing rights of the patent drug, generic drugs are marketed. They are comparable to brand drug in dosage form, strength, route of administration, quality and performance characteristics, and intended use. Generic drugs are available at affordable prices with maintaining quality. These ‘Generic’ formulations balance public interest as critical disease like cancer, AIDS etc. India’s Pharmaceutical market will grew at 9.5% by 2015.

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REFERENCES

• www.ijpcbs.com/files/2106-22.pdf

• pharmaceuticals.gov.in/generic.pdf

• www.pharmacophorejournal.com/November-December2011-article1.pdf

• https://www.in.kpmg.com/pdf/Indian%20Pharma%20Outlook.pdf

• http://www.indiabioscience.org/articles/compulsory-licensing-%E2%80%93-does-it-affect-pharma-companies

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ANY

QUESTIONS

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