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FDA Deeming: Beyond the Sticker Shock - The Hidden GMP Requirements

by Chris Ford May 08, 2016

FDA Deeming: Beyond the Sticker Shock - The Hidden GMP Requirements

Immediately following FDA's announcement last week, bringing e-liquids containing nicotine and e-cigarettes under the Federal tobacco regulations, changing vaping as we've come to know it, industry was left with severe sticker-shock. Fixated on the $1 Million price tag, the volumes of data required, and the hope that this is all just a bad dream, most manufacturers haven't absorbed the full implications of the FDA requirements and the hidden meaning behind the "regulatory speak" that makes ambiguous reference to the Agency's expectations.

What you don't know and what you can't see CAN cripple you. 

In its Draft Guidance for Industry, Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems, FDA specifies the requirements for the information that you provide in your PreMarket Tobacco Application (PMTA) as a general bullet-listed description. What many manufacturers may not have noticed, is the real meaning behind FDA's ambiguous requirements that, on the surface, seem black and white.

FDA requires manufacturers to include manufacturing descriptions showing how the product is made to conform with the product information provided in the PMTA. On the surface, that seems simple enough. Maybe a few paragraphs, describing the manufacturing process and equipment with a flow chart and a list of tests?


FDA requires  “a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and packaging of the new tobacco product, including e-liquids and aerosolizing apparatus.”

Section VI, Content of a PreMarket Tobacco Product Application for ENDS Products, lays out the eight sections of the PMTA. The last section of the PMTA, H. Scientific Studies and Analyses actually lists the items you should have in place before even beginning the application process. 

What you need

You need to provide a listing of all FDA manufacturing, packaging, and control sites, including the facility names and addresses, and a contact name and telephone number for each facility. This includes co-packers and contract manufacturers.

FDA expects a written narrative description, accompanied by a list and summary of all standard operating procedures (SOPs). This should be in the form of a full system descriptive document, such as a Quality Management System Manual. 

In addition to describing the overall processes, you will need to establish the following procedures to satisfy the filing requirements in Section H of your PMTA.

  1. Production Control SOP, including requirements for the work environment and equipment
  2. Management Responsibility SOP
  3. Training SOP
  4. Formulations Processes SOP
  5. Packaging and Labeling SOP
  6. Supplier Selection and Monitoring SOP
  7. Supplier Corrective Action SOP
  8. Purchasing Controls SOP
  9. Incoming Inspection / Test SOP
  10. Product Identification and Traceability SOP
  11. Product Acceptance Testing SOPs (including acceptance criteria)
  12. Production Release Testing SOP
  13. Product Storage and Handling SOP
  14. Shipping SOP
  15. Process Validation SOP
  16. Equipment Calibration SOP
  17. Preventive Maintenance SOP
  18. Complaint Handling SOP
  19. Risk Analysis SOP
  20. Adverse Event Reporting SOP
  21. Recall SOP
  22. Corrective and Preventive Action SOP
  23. Control of Nonconforming Product SOP
  24. Internal Audit SOP

In addition, you'll need to provide examples of the relevant forms and records associated with all of these SOP's, including a completed hazard analysis that details the correlation of the product design attributes with public health risk, and any mitigations for identified hazards that have been implemented.

As if the EU/TPD2 hurdles weren't enough... now THIS

There is a bit of a silver lining here. The GMP requirements that FDA spells out in the draft Guidance aren't really different from TPD2 (aside from the obvious, massive difference in the submission package), with the exception of specialized requirements for reporting adverse effects. So, if you've already been hard at work, implementing the new procedures you need in place for EU/TPD2 this month, don't worry - you can use them for your U.S. business, as well which means you're already ahead of the curve.

Manufacturers should take a Process Approach, toward establishing the SOPs necessary to fulfill FDA requirements, such as that described in the ISO 9001:2015 quality management standard. 

A certified quality management system by a reputable, accredited certification body will go a very long way in your PMTA submission. Based on the strategic direction of your company, Top Management should consider the extent and impact of the FDA Tobacco Products Regulation and the EU/TPD2 requirements that are relevant to the company’s purpose and strategic direction and the short and long term solutions that can be implemented to reduce the burden. The Quality Management System should be implemented based on how you’ll address these issues. Establish processes and objectives that support the scope of your business, and from there, you’ll develop the Standard Operating Procedures and records you need to show you’re in compliance with the requirements.

Chris Ford
Chris Ford


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