Regulatory Pathways and Designation Flashcards
Pure Food and Drug Act, 1906
Banned foreign and interstate traffic in adulterated or mislabeled food and drug products
Directed the U.S. Bureau of Chemistry (pre-FDA)to inspect products and refer offenders to prosecutors
Required that active ingredients be placed on the label of a drug’s packaging and that drugs could not fall below purity levels established by the United States Pharmacopeia or the National Formulary.
NOTE: NO safety or efficacy data reporting requirements
Definition of Drugs:
(a)articles recognized in the US Pharmacopeia, official Homeopathic Pharmacopeia, of the US or official National Formulary, or any supplement to them;
(b)articles intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease in man or other animals;
(c)articles (other than food) intended to affect the structure and function of the human body of man or other animals; or
(d)articles intended for use as a component of any article specified in clauses (a), (b), or (c)
Biologics Act of 1902
Careless errors were made during early biologics manufacturing
In St. Louis, a horse contaminated with tetanus was used to produce antitoxin; 5 children died from contaminated product
In New Jersey, a contaminated smallpox vaccine killed 9 children
The Act established licenses for those who wanted to manufacture vaccines and antitoxins
Licenses were renewed annually; manufacturers were subject to inspection, and revocation of licenses was possible punishment
Products were subject to certification prior to release
Definition of Biologics:
Biological products include a wide range of products: vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins.
Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues.
Biologics are isolated from a variety of natural sources - human, animal, or microorganism - and may be produced by biotechnology methods and other cutting-edge technologies.
FOOD Drug & Cosmetic (FD&C) Act of 1938
The New Drug Application (NDA)Pathway is regulated by this ACT
Chemically synthetized drugs
Classically fermented antibiotics
Chemicals of a natural origin
All Hormone Proteins and peptides
Some Enzyme proteins (natural-sourced and rDNA derived)
Public Health Service (PHS) Act of 1944
Defines a biological product
Defines Pathway for a Biologics License Application(BLA)
Grants FDA the authority to immediately suspend licenses
Emphasizes manufacturing control and adherence to processes
Prescription Drug User Fee Act (PDUFA) Background
DRIVER: Before 1992, timeliness of FDA drug review was a big concern PDUFA
User fees added resources for more review staff to eliminate the backlog of overdue applications and improve review timeliness
FDA agreed to meet specific performance goals
Result: More predictable, streamlined process
Average clinical development time has dropped 10% and average time to approval dropped nearly 60% *
Patients gain earlier access to over 1500 new drugs and biologics approved since 1992
PDUFA also applies to Biologics
Curent Fee Structure
Established at start of PDUFA in 1993
Total target revenue is collected via 3 equal components
Full-Application-Equivalents
Establishment fees
Product Registration fees
Application with clinical 4,048,695
No clinical 2,024348
PDUFA I: 1993-1997
Added funds for pre-market review; reduce backlog and set predictable timelines (goals) for review action
PDUFA II (FDAMA): 1998-2002
Shorten review timelines, add review goals; add process and procedure goals; some added funding
PDUFA III (BioTerrorism Preparedness & Response Act): 2003-2007
Significant added funding; increase interaction in first review cycle (GRMPs); allow limited support for post-market safety
PDUFA IV (FDAAA): 2008-2012
Increased and stabilized base funding; enhanced pre-market review; modernize post-market safety system
PDUFA V (FDASIA): 2013-2017
Small increase to base funding; review enhancements increase communication with sponsors; strengthen regulatory science & post-market safety; electronic data standards
PDUFA VI (FDARA): 2018-2022
Ensure effective review process incorporating patient perspective, focus on rare diseases and breakthrough therapies, strengthen drug safety surveillance, explore use of real-world evidence and promote staff hiring and retention
PDUFA VII (FDORA) – 2023 – 2027
efforts are aimed at modernizing the U.S. regulatory and drug development paradigm and addressing new areas such as digital health technologies, cell and gene therapies, and manufacturing
Generic Drugs (GDUFA)
Congress first enacted GDUFA in 2012, following negotiations between the FDA and industry and with input from public stakeholders.
Ensures patients have access to safe, high-quality, and affordable generic drugs
Biosimilars (BSUFA)
Congress first enacted BSUFA in 2017
Biosimilar biological products represent an important public health benefit, with the potential to offer life-saving or life-altering benefits at reduced cost to the patient
FDA dedicates these fees to expediting the process for the review of biosimilar biological product applications, including postmarket safety activities
Therapeutic Biologics
Therapeutic biologics requirements for commercialization are the same as those for drug products
Follow IND (21 CFR 312) and NDA (21 CFR 314) regulations as well as BLA (21CFR601)
Same reporting and documentation requirements
IND amendments, safety reports, annual reports; post-marketing requirements
Additional post-marketing reporting requirements
505(b)(1) application
505 refers to the section of the Food, Drug and Cosmetic Act
used for novel drugs that have not previously been studied or approved.
Requires the Sponsor to conduct all studies needed to demonstrate the safety and efficacy of the drug.
505(b)(2) application
the investigations the applicant relied on for approval were not conducted by or for the applicant and
the applicant has not obtained a right of reference or use for the investigations (21 U.S.C. 355(b)(2)).
Section 505(b)(2) expressly permits FDA to rely, for approval of an NDA, on data not developed by the applicant - such as published literature or the agency’s finding of safety and/or effectiveness of a previously approved drug product
505(b)(2) Eligibility
Changes in dosage form, strength, formulation, dosing regimen or route of administration
Repurposed or repositioned drug products
A new combination product, including substitution of an active ingredient
A modified active ingredient (i.e. – salt, chelate, ester, complex, etc.)
New indications for previously approved drugs (RLD)
Over-the-counter switch of an approved prescription drug
(b)(1) vs (b)(2) Content Reviews
505(b)1
Labeling
Chemistry, Manufacturing and Controls
Pharm/Tox – animal studies
Human Studies – bioavailability, efficacy and safety
505(b)2
Labeling
Chemistry, Manufacturing and Controls
Pharm/Tox – only for new dosage form/route of admin
Human Studies – BA/BE, Efficacy and Safety only for new indications
For Novel ([505(b)(1)] the Process is…
LONG
10 to 15 years by the FDA.
RISKY
Less than 12% of the candidate medicines that make it into Phase I clinical trials are approved
EXPENSIVE
Expedited Regulatory Pathways
Breakthrough Therapy Designation
Fast Track Designation
Accelerated Approval
Priority Review
