Guidance Documents in the Works for 2014

CDER published its yearly Guidance Agenda today giving the industry a look at what to expect for the coming year in terms of issuance of documents.  This yearly exercise, while not guaranteeing that all of the guidance will actually be completed, provides a nice look into the important topics that CDER is planning to expound upon for the benefit of transparency.

 The Guidance documents are listed by category in the agenda; here are some of the 70 listed proposed issuances and what they may mean to industry.

There are three separate listings for internet guidance relative to Advertising that may address many of the questions that firms have been asking, and, more importantly, to address how to avoid an Untitled or Warning Letter by running afoul of Agency thinking on these topics.  It is assumed that the CDER view on these topics will assist firms navigate the increasing complexity of social media’s interplay with regulatory requirements.  

  • Internet/Social Media Platforms with Character Space Limitations: Presenting Risk and Benefit Information for Prescription Drugs and Medical Devices
  • Internet/Social Media Platforms: Correcting Independent-Third Party Misinformation About Prescription Drugs and Medical Devices
  • Internet/Social Media Advertising and Promotional Labeling of Prescription Drugs and Medical Devices – Use of Links

In addition to a revised Questions and Answers document, CDER will issue documents of interest concerning Biosimilar products to address: how interchangeability of products can be achieved, labeling issues associated with biosimilar products and reference product exclusivity.  These respond to major questions that various industry factions and FDA have been debating over the last 5 years, and include the following documents:

  • Considerations in Demonstrating Interchangeability to a Reference Product
  • Labeling for Biosimilar Biological Products
  • Reference Product Exclusivity for Biological Products Filed Under Section 351(a) of the PHS Act

Several of the documents to be issued in the Chemistry arena follow, and, while not addressing totally new issues, may nonetheless provide the answers to questions that have been coming up in CDER’s Chemistry, Manufacturing and Controls reviews for years.  For instance, while the USP does have an allowable overfill for parenteral products to assist practitioners in extracting the required quantity of drug from a vial or ampule, specific drug products that may be very toxic have proven challenging when establishing allowable excess volumes.  In addition, the topics of both compatibility protocols and NIR methods may provide additional insight on the use of these vehicles to reduce regulatory burden.  Seeing the immunogenicity guidance topic for NDAs and ANDAs (even though this document relates solely to low molecular weight heparin) is indicative of the increasing demand in the reviews of ANDAs for complex drug products.  

  • Allowable Excess Volume and Labeled Vial Fill Size
  • Comparability Protocols for Approved Drugs: Chemistry, Manufacturing, and Controls Information
  • Evaluation of Near Infrared Spectroscopy (NIR) Methods
  • Immunogenicity – Related Considerations for the Approval of Low Molecular Weight Heparin for NDAs and ANDAs

In the Quality arena, three guidance documents caught my eye.  First, the issue of computer systems validation has been somewhat of an enigma over the last few years, and now the increasing use of Cloud Computing is leading to increased scrutiny over the security and integrity of the data that comes along with the Cloud.  Compounding outsourcing facilities issues will continue to take center stage in 2014, and thus, we expect to see more FDA guidance to enhance those documents that issued last year.  And one topic that continues to trip up pharmaceutical companies is when and how to file Field Alert Reports to FDA.  Hopefully, this missive will add a level of clarity to reduce the friction between the regulators and regulated industry.   

  • GXP Consideration for Outsourced IT (Cloud Computing) Systems in Medical Product Manufacturing and Clinical Study Environments
  • Interim Good Manufacturing Practice for Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug and Cosmetic Act
  • Submission of Field Alert Reports and Biological Product Deviation Reports

Drug Safety is an area of continuing CDER concern and two of the Guidance documents for the coming year address brand naming issues and appropriate dosing of acetaminophen products in pediatric patients.  These two documents likely address the potential for medication errors that may result from confusing, sound-alike or look-alike brand names and the continued problem seen with inappropriate dosing of liquid acetaminophen OTC products in pediatric patients.

  • Best Practices in Developing Proprietary Names
  • Over-the-Counter Pediatric Liquid Drug Products Containing Acetaminophen

Lastly, in the Procedural area, these three documents jumped out of the bunch.  For years, FDA has been attempting to bring unapproved drug products under the regulatory umbrella and use of the NDC number assignment process was thought to be one tool in that effort; however, it was never really implemented in that regard.  In addition, NDC numbers are supposed to be used only on specific marketed drug products.  Could FDA be (finally) proposing to use this tool for cleaning up the drug listing process?  The issue of obtaining drug product samples for bioequivalence testing of generic products where the innovator is subject to a restricted distribution system has been a problem for ANDA applicants for years.  The proposed Guidance on submission of study protocols for certain drugs with REMS may be an FDA salvo in an attempt to break the log jam in resolving this regulatory conundrum.

  • National Drug Code (NDC) Assignment of CDER-Regulated Products
  • Submission of Study Protocols for Drug Products with Certain Risk Evaluation and Mitigation Strategies for Review by the Office of Generic Drugs
  • Use of a Master File for Shared System Risk Evaluation and Mitigation Strategies

While this review and commentary can only speculate on the purpose and impact of the proposed guidance documents listed in the 2014 Agenda, it certainly lends itself to some interesting guessing and day dreaming.  The entire list of proposed guidance documents may be viewed here.