Hatch Waxman Act And Orange Book,Purple Book, Drug Master File System In Us.

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Hatch Waxman Act And Orange Book,Purple
Book, Drug Master File System In Us.



Hatch Waxmen Act :

Introduction :

➢ The Drug Price Competition and Patent Term Restoration Act of 1984, commonly known as the Hatch-
Waxman Act.

➢ It was proposed by Orrin Hatch and Henry Waxmen.
➢ Effective since 24 September,1984.
▪ Amended the Patent laws.
▪ Amended the Federal Food, Drug, and Cosmetic Act

➢ Before 1962- new drug approved based on safety alone

➢ 1962- Proof of efficacy made compulsory for marketing approval of a new drug (Kefauver-Harris



➢ There was no provision for patent term extension prior to enactment of the Hatch Waxman Act, to make up for
the time lost out of the total patent term during the marketing approval process.

➢ Generic companies required to submit their own comprehensive NDA
▪ Costly
▪ Time consuming

➢ If drug was covered by patent
▪ Testing could not begin until patent expired

➢ To overcome the above problems an act was needed to promote generic companies.

Objectives Of The Act:
➢ Reducing the cost associated with the approval of a generic drug.
➢ Allowing Early-Experimental-Use.
➢ Compensating the branded drugs manufacturers for the time lost from the patent term because of the

regulatory approval formality.
➢ Motivating the generic drug manufacturers

“HWA strives to strike a balance between the interests of branded drug manufacturers, generic drug
manufacturers and the consumers”



Provisions Of The Act:

➢ Creation of section 505(j)
➢ Section 505(j) established the ANDA approval process
➢ The timing of an ANDA approval depends in part on patent protections for the innovator drug
➢ NDA must include any patent that claims the “drug” or a “method of using [the] drug” for which a claim of patent

infringement could reasonably be asserted
➢ On approval of NDA, FDA publishes patent information for drug in Orange Book (“Approved Drug Products

with Therapeutic Equivalence Evaluations”

The FDA maintains the list of patents in its publication, Approved Drug Products with Therapeutic Equivalence
Evaluations, commonly known as the “Orange Book.”
➢ An NDA applicant must submit the following information for each patent:
• Patent no and date on which the patent will expire.
• Type of patent, i.e. drug, drug product, or method of use.
• Name of patent owner.
• The name of an agent of the patent owner or applicant.
➢ Brand drugs listed for generics to compare with their proposed products



Four Types of Patent Certifications :

➢ When an applicant submits an ANDA to the FDA, the applicant must certify one of four things under section

• That the required patent information relating to such patent has not been filed (Para I)
• That such patent has expired (Para II)
• That the patent will expire on a particular date (Para III)
• That the patent is invalid or will not be infringed by the manufacture, use or sale of the drug for which the ANDA is

submitted (Para IV – Patent Challenge)

• An ANDA certified under paragraphs I or II is approved immediately after meeting all applicable regulatory and
scientific requirements .

• An ANDA certified under paragraph III must, even after meeting pertinent regulatory and scientific requirements, wait
for approval until the drug’s listed patent expires.

• An ANDA applicant filing a paragraph IV certification must notify the proprietor of the patent.



• The patent holder may bring a patent infringement suit within 45 days of receiving such notification.
• If the patent owner timely brings a patent infringement charge against the ANDA applicant, then the FDA must suspend

approval of the ANDA until:

(1) the date of the court’s decision that the listed drug’s patent is either invalid or not infringed.
(2) the date the listed drug’s patent expires, if the court finds the listed drug’s patent infringed or
(3) subject to modification by the court, the date that is 30 months from the date the owner of the listed drug’s patent

received notice of the filing of a Paragraph IV certification.
(4) FDA approval to market the generic drug is generally postponed for 30 months unless the patent expires or is judged to

be invalid or not infringed before that time.
(5) This 30-month postponement, commonly referred to as the “30-month stay,” gives the brand product sponsor and patent

holder a prescribed amount of time to assert patent rights in court before a generic competitor is approved and can
market the drug.



Incentives and protection:

• First generic applicant to file a paragraph IV certification is awarded a 180-day market exclusivity period by
the FDA.

• The 180-day market exclusivity period ordinarily begins on the earliest of two dates :

(1) The day the drug is first commercially marketed ; or
(2) The day a court decision holds that the patent which is the subject of the certification is invalid or not

(3) This exclusivity can be forfeited in certain situations including:
➢ Failure to market under specific time constraints.
➢ Withdrawal of the application.
➢ Amendment of the certification.
➢ Failure to obtain approval from the fda.
➢ Expiration of all patents, or the determination by the federal trade commission or the assistant attorney

general that an agreement between the brand name and generic firms violates antitrust laws.
• Subsequent applicants would not be permitted the 180-day exclusivity.
• Multiple generic firms may qualify for the 180-day market exclusivity if several anda applicants file a

substantially complete application on the same day.



Para IV Deadlines

Notification Letter: 20 DAYS

• Upon ANDA acceptance for filing, the applicant must notify the NDA holder and patent owner of the ANDA
within 20 days.

• The notice must include a detailed statement of the factual and legal basis of the opinion of the applicant that the
patent is invalid or will not be infringed.

Lawsuit: 45 Days:

• Upon notification, the NDA holder and patent owners have 45 days in which to initiate an action for patent

• If such an action is brought within 45 days, the ANDA is subject to a 30-month stay of FDA approval beginning
on the date the notification letter was received.



Patent Term Extension :
• The Hatch Waxman Act provides a patent term extension for patents covering certain products including

human drug products, that are subject to FDA approval.
• Only one extension can be granted in connection to a particular product, and it must be for a patent that

claims either a:
A) Drug product, that is, the active ingredient and any approved drug using that active ingredient.
B) Method of using that drug product.
C) Method of manufacturing a drug product.

Benefits For Branded Manufacturers:
• Orange Book provides public notice of patents .
• Allows for resolution of patent disputes prior to generic entry .
• 30-month stay of FDA approval of generic drugs.
• Patent Term Restoration
• Allows for Several Market Exclusivities:
1. Data Exclusivity
2. 5 years for New Chemical Entity (NCE) Drug.
3. 3 years for non-NCE Drug .
4. Orphan Drug (7 years).
5. Pediatric (PEDS) (6 months)



Benefits For Generic Manufacturers:

• 180-day market exclusivity for first successful challenger to Orange Book patent.
• Allows generics to challenge Orange Book patents without risk of damages.
• “Safe Harbor” rule allows generics to perform bioequivalence and other testing relating to regulatory approval

without risk of patent infringement .

• Non-patent Exclusivity:

• New chemical entity 5 years.
• New Clinical study 3 years.
• Orphan drug 7 years .
• Pediatric exclusivity 6 months.
• 180-day generic market exclusivity 180 days.



Purple Book :
❖ The Purple Book is a database that contains information about all FDA-licensed biological products regulated by the

Center for Drug Evaluation and Research (CDER), including licensed biosimilar and interchangeable products, and
their reference products.

❖ The Purple Book also contains information on all FDA-licensed allergenic, cellular and gene therapy,
hematologic, and vaccine products regulated by the Center for Biologics Evaluation and Research (CBER).

❖ Some of the information you can find in the Purple Book includes:

❑ The date on which a biological product was licensed under section 351(a) or 351(k) of the Public Health Service
Act (PHS Act).

❑ Whether a biological product licensed under section 351(k) of the PHS Act has been determined by the FDA to
be biosimilar to or interchangeable with a reference biological product (an already-licensed FDA biological

❑ The date of expiration of applicable exclusivity for a biological product if FDA has determined that the biological
product is eligible for reference product exclusivity under section 351(k)(7) of the PHS Act or first interchangeable
biological product exclusivity under section 351(k)(6) of the PHS Act, as appropriate.



❑ Patent information for certain licensed biological products required by the Biological Product Patent
Transparency section of the Consolidated Appropriations Act of 2021.

❑ The Purple Book database contains information for multiple users (e.g., patients, the general public, healthcare
providers, manufacturers, and researchers).

➢ Patients and the General Public may find the Purple Book ‘Simple Search’ useful to find information about a
biological product they are currently taking or may be prescribed and to view options for FDA-approved
biosimilar and interchangeable products.

➢ Healthcare Providers may find the Purple Book ‘Simple Search’ useful to see all associated products for a
biological product they prescribe or are considering prescribing for a patient, including biosimilars and
interchangeable products. Healthcare providers may also find the ‘Advanced Search’ useful to search using
additional terms, including strength, dosage forms, or product presentations (e.g., Autoinjector).

The ‘Product Label’ (e.g., Prescribing Information) icon/link associated with each product in the database directs
users to information a healthcare provider may find useful when prescribing a product.

➢ Manufacturers and Researchers may find the ‘Advanced Search’ useful as it allows users to view and sort all
available information in a table format, as well as download the results and information as an Excel, CSV or PDF



Drug Master File System In US:

❖ A Drug Master File (DMF) is a submission to the U.S. Food and Drug Administration (US FDA) that may be used to
provide confidential detailed information about facilities, processes, or articles used in the manufacturing,
processing, packaging, and storing of one or more human drugs.

❖ The submission of a DMF is not an FDA requirement by law or by US FDA regulation. A DMF Submission is solely
at the discretion of the DMF holder. The information contained in the DMF may be used to support an Investigational
New Drug Application (IND), a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA),
another DMF, an Export Application, or amendments and supplements to any of this submission.

❖ A DMF is not a substitute for an IND, NDA, ANDA, or Export Application. It is not approved or disapproved;
technical contents of a DMF are reviewed only in connection with the review of an IND, NDA, ANDA, or an Export

❖ US FDA will issue a DMF number to each submission. DMF number does not denote registration of the facility or

❖ US FDA is not issuing a certificate of FDA registration nor does US FDA recognize a registration certificate issued by
third party. FDA encourages foreign DMF holders to appoint a U.S. FDA Agent.



• A Drug Master File (DMF) becomes necessary when there is confidential information that a manufacturer does not
wish to share with the applicant.

• The FDA requirements for each type of DMF’s are different; Liberty Management Group’s experienced consultants
can help you to identify the FDA DMF requirements for your product.


There are five types of DMF:

Type I DMF Manufacturing Site, Facilities, Operating Procedures, and Personnel (no longer applicable).

Type II DMF Drug Substance, Drug Substance Intermediate, and Material Used in their Preparation, or Drug Product.

Type III DMF Packaging Material.

Type IV DMF Excipient, Colorant, Flavor, Essence, or Material Used in their Preparation.

Type V DMF FDA Accepted Reference Information.



DMF Submission Fees:

Type II DMF Submission from an API Manufacturer for a generic drug application need to pay FDA fees. The FDA DMF
Fees for the year 2020 is USD 57,795. There are no FDA fees for other types of DMF submissions.

DMF Submission services includes.
• Identification of test requirements (for type II DMF and III DMF).

• Identification of testing lab (for type II DMF and III DMF).

• Edit and organize DMF information.

• Submitting DMF to FDA.

• US FDA DMF Agent service.

• Communicating with FDA on behalf of our client.

• Assisting clients to issue LOA (letter of authorization) to FDA.

• Assistance with DMF Annual report submission to FDA.

• Assistance in DMF Closure request submission to FDA.

• Assistance in DMF Reactivation request submission to FDA. (for closed DMF)