Top Ten FDA Guidance Documents That You Should Know

There are a number of laws, regulations, and guidance documents ruling the pharmaceutical and biotechnology industries. Laws are passed by Congress and must be followed by the FDA. The Agency then publishes or issues regulations and publishes guidance documents. So what is the difference between the two?

• Regulations are developed by the FDA based on laws that are set forth in the Federal Food, Drug, & Cosmetic (FD&C) Act. FDA's regulations are federal law and are codified in the Code of Federal Regulations. In accordance with the Administrative Procedure Act (APA), when publishing a regulation, the FDA first issues a proposed regulation and allows time for public comment before the final regulation is published.
• Guidance documents "represent the Agency's current thinking on a particular subject. They do not create or confer any rights for or on any person and do not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both."

Although guidance documents are not legally binding, it is extremely important that they are not ignored. The FDA tends to rely on guidance documents as a source of informal policy making. As such, there are a number of extremely important guidance documents that we feel everyone involved in the industry should know, which include:

#10: Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects

Published about seven years ago in October 2009, this guidance document summarizes the responsibilities of investigators, which is defined as "a person who conducts a clinical investigation of a drug, biological product, or medical device."

This guidance document made our list of most important guidance documents because it clarifies FDA's expectations regarding investigators' responsibilities and helps investigators to better fulfill these responsibilities and meet the Agency's expectations.

#9: Changes to an Approved NDA or ANDA

This guidance was issued as a revised guidance document in the Spring of 2004, and provides recommendations for NDA and ANDA holders trying to make postapproval changes to their application. The document explains what FDA considers to be a major, moderate, and minor change, and is extremely helpful to all sponsors looking to alter any part of an approved NDA or ANDA – which is why it made our list of go-to guidance documents.

#8: Special Protocol Assessment

Initially released in 2002, the FDA issued an updated version of this draft guidance in May 2016, which provides detailed information on the procedures and general policies that have been adopted by both CDER and CBER for special protocol assessment (SPA).

This draft guidance made our list of most important guidance documents because it provides a number of useful recommendations and some valuable insights regarding meetings with the FDA that are held to discuss the various aspects of the sponsor's clinical trial plans. Details on this must-know document are critical for anyone preparing to go through the SPA process.

#7: Quality Systems Approach to Pharmaceutical CGMP Regulations

Published to help manufacturers with the implementation of modern quality systems and risk management approaches to meet the FDA's GMP requirements, this guidance document "describes a comprehensive quality systems (QS) model, highlighting the model's consistency with the CGMP regulatory requirements for manufacturing human and veterinary drugs, including biological drug products."

Although it is more than ten years old, this guidance document remains one of the most important that FDA has issued and is considered a necessity for anyone in the quality and compliance field.

#6: Expedited Programs for Serious Conditions – Drug and Biologics

At about two and a half years old, this guidance document helps facilitate and expedite the review of new drugs addressing an unmet medical need for a serious or life-threatening conditions. The document provides "a single resource for information on FDA's policies and procedures for these four programs."

#5: How to Comply with the Pediatric Research Equity Act

This draft guidance was released by the Agency in September 2005 in order to provide sponsors with recommendations regarding the interpretation of the Pediatric Research Equity Act (PREA) and the pediatric study requirements that accompany it. Under PREA, all sponsors or applicants of new drug applications (NDAs) and biologics licensing applications (BLAs) for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration are required to include a pediatric assessment in their submission.

The draft guidance is of utmost importance to the applicable sponsors or applicants because it clarifies how these individuals can ensure compliance with all of PREA's requirements, including the pediatric assessment, the pediatric plan (see section V.A), waivers and deferrals, compliance issues, and pediatric exclusivity provisions.

#4: Pediatric Study Plans: Content of and Processes for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study Plans

This document was issued as a draft in March of this year, and provides sponsors with information regarding the submission of initial pediatric study plans (iPSPs) as well as any amendments to an iPSP. With this draft guidance, FDA addresses the following topics:

• Who must submit an iPSP
• When a iPSP must be submitted
• What should be included in an iPSP
• What should be included in a requested amendment to an agreed iPSP

In addition, the document provides a template that should be used when developing an iPSP submission. This, in conjunction with all of the other extremely valuable information provided in the draft guidance, make this a "must have" on the desk of many drug makers involved in the preparation of an iPSP.

#3: Nonclinical Safety Evaluation of Reformulated Drug Products and Products Intended for Administration by an Alternate Route

This guidance document "provides recommendations for the nonclinical evaluation of previously approved drug substances when a new formulation or a new route of administration for a previously approved formulation is proposed by the sponsor."

Finalized by the FDA just over a year ago in October 2015, this guidance document is critical for all individuals involved in the development and review of new formulations of previously approved drug substances, making it a must-have on our list of important guidances.

#2: Labeling for Human Prescription Drug and Biological Products – Implementing the PLR Content and Format Requirements

FDA finalized this guidance document in February 2013 with the intention of assisting applicants in "complying with the content and format requirements of labeling for human prescription drug and biological products under 21 CFR 201.56(d) and 201.57."

The recommendations included in the guidance apply to applicants who are developing labeling for new prescription drugs or revising existing labeling for prescription drugs that have already received FDA approval. In addition, recommendations for developing Highlights of Prescribing Information, formatting labeling, and procedural information are also included in the guidance.

With all of this helpful information, when it came time to decide what to include in our list of most important guidance documents, this one was a no brainer.

#1: Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products

And last but not least, issued by the FDA on March 10, 2015, this draft guidance is of particular importance to anyone planning a meeting with FDA related to the development and review of a drug or biological product that is regulated by the Agency's Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). However, it is important to note that the recommendations contained in the draft guidance do not apply to sponsors of abbreviated new drug applications (ANDAs), biosimilar biological product submissions, or medical device submissions.

This document is important because it provides recommendations regarding the principles of good meeting management practices (GMMPs) and describes how sponsors or applicants should go about requesting, preparing, scheduling, conducting, and documenting such formal meetings with the FDA.

While an overview can sometimes be great, we feel that these guidance documents are so important that they deserve more details. As such, we have individual blog posts dedicated to each of these guidance documents coming over the course of the coming weeks. Stay tuned, you won't want to miss out on any of this vital information.