Regulatory requirements for orphan drugs delivery

Regulatory Requirements for Orphan Drugs Delivery

Dr. Basavaraj K. Nanjwade M.Pharm., Ph.D

Professor of PharmaceuticsKLE University, Belgaum, IndiaE-MAIL: [email protected] No: 00919742431000

mailto:[email protected]

What is an Orphan Drug?

A drug to test a rare disease or condition affecting <200,000 people in the U.S.

A vaccine, a preventive drug, or a diagnostic drug to be administered to <200,000 persons per year

A drug with no expected profitability within years even if prevalence > 200,000 people in the U.S.

02/03/2010 2BIOBIO-2010, Hyderabad

Orphan Drug Act Incentives

Marketing Exclusivity-7 years

Tax Credits-50% of Clinical Investigations Expenses

Exemption from PDUFA Application Fees

Protocol Assistance in Drug Development Process


Orphan Drug Act Incentives

Grant Support-Medical Foods and Medical Services also

Open Protocols to increase drug availability for patients

Establish DHHS orphan products board


Orphan Drugs

Among orphan drugs, 15-20% are for diseases only affecting children, 55% for diseases affecting both adult and children

Orphan drugs receive 10 years of market exclusivity in EU

Orphan drugs must submit a Pediatric investigation plan

Orphan drugs can get 2 additional years of exclusivity when they comply with PIP



Paediatric Investigation Plan (PIP)

Paediatric investigation plan proposed by company

By end of phase 1 for new products Plan is discussed, modified, and

agreed/refused by paediatric committee

Followed by EMEA decision Binding on company


Paediatric Investigation Plans

Define necessary data on Quality, Safety and Efficacy for use in the paediatric population (0 – 18 years)

No explicit link with adult indication Specify development timelines, including

deferral of studies Define age-appropriate formulation Results according to agreed plan serves

as basis for approval02/03/2010 8BIOBIO-2010, Hyderabad

PIP Waivers/Deferrals

On request from applicant or initiative of Paediatric Committee, for all or part of the paediatric population:

Waiver of development for ‘classes’ of indications, or for a specific product

Deferral of initiation of studies and/or completion

Development is most often a combination of a plan with deferrals and waivers (population subset)


Life cycle of a Paediatric Investigation Plan

1

Phase 1 Phase 2 Phase 3 Post Approval

Modifications

MAPIP

Compliance

Paediatric Committee

Non-clin


Life cycle of a Paediatric Investigation Plan

1

Non-clin Phase 1 Phase 2 Phase 3

ComplianceModifications

MAPIP With deferral

Paediatric Committee

Post Approval


Applications and Indications

Each PIP corresponds to an active substance (or a combination) from a company

Each PIP usually covers more than one indication (e.g. high grade glioma and neuroblastoma)


PIP Therapeutic areas (%)

- CNS 6- Cardiovascular 10- Oncology 14- Anti-infectives 10- Endocrinology/metabolism 21- Immunology/vaccines 11- Other 28


Tips for Applying for Orphan Product Designation

1. The required information to be included in the application is found under 21 CFR 316.20(b), shown as (9) items.

- Number the items in your application 1 though 9 and respond to the nine items as described.

- Creative numbering is not helpful02/03/2010 14BIOBIO-2010, Hyderabad


2. While all nine items will be reviewed, the application will be reviewed most critically in two areas: scientific rationale (Item 4) and population prevalence (Item 8).

- Do not confuse prevalence with incidence

- They are different entities and can’t be substituted for one another



3. Information provided by the sponsor relating to Item 7 is often incomplete

- Provide the IND or NDA/BLA numbers if they are available to you



4. Format your application so that it is user friendly

- After addressing the nine required items, provide a bibliography displayed in a related fashion as shown in the text of your document.

- Usually references within the application are cited numerically with superscripts



5. Submit the original and one photocopy of the application in separate binders or report covers to the office of Orphan Products Development

- The photocopy needs to be an exact duplicate of the original application.



- If there is a cover letter with the original, there needs to be a copy of the cover letter with the duplicate

- No correspondence should arrive loose or out of the binder or report cover

- They are inexpensive and readily available, plus they fit in standard filing cabinets nicely



6. Submit the application (one original and one photocopy) for orphan designation to:

Director, Office of Orphan Products DevelopmentFood & Drug Administration, HF-355600 Fishers Lane, Room 6A55Rockville, MD 2085702/03/2010 20BIOBIO-2010, Hyderabad

How to Apply for Designation as an Orphan Product

(a)A sponsor that submits a request for orphan drug designation of a drug for a specified rare disease or condition shall submit each request in the form and containing the information required in paragraph (b)

(b)A sponsor shall submit two copies of a completed, dated, and signed request or condition that contains



1. A statement that the sponsor requests orphan drug designation for a rare disease or condition, which shall be identified with specificity



2. The name and address of the sponsor; the name of the sponsor’s primary contact person and/or resident agent including title, address, and telephone number; generic and trade name



3. A description of the rare disease or condition for which the drug is being or will be investigated, the proposed indication or indications for use of the drug, and the reasons why such therapy is needed



4. A description of the drug and a discussion of the scientific rationale for the use of the drug for the rare disease or condition

- Copies of pertinent unpublished and published papers are also required



5. Where the sponsor of a drug that is otherwise the same drug as an already approved orphan drug seeks orphan drug designation for the subsequent drug for the same rare disease



6. Where a drug is under development for only a subset of persons with a particular disease or condition, a demonstration that the subset is medically plausible



7. A summary of the regulatory status and marketing history of the drug in the US and in foreign countries, e.g., IND and marketing application status and dispositions



8. Documentation, with appended authoritative references, to demonstrate


An orphan disease has an incidence fewer than 5 patients per 10,000 population (EU) or <200,000

patients (US).



THANK YOU


Healthcare

Regulatory requirements for orphan drugs delivery