On FDA’s Latest FSMA Guidance

The Food and Drug Administration recently issued three new guidance documents to help simplify compliance with Food Safety Modernization Act (FSMA) regulations and programs.

On November 7, the agency released new draft guidance on registration of food facilities. The expanded registration introduced by FSMA is a key change that underpins all other FSMA requirements and I would encourage you to read the new draft as it includes substantive information in a useful question-and-answer format, including details on the timing of the biennial registration renewals and other new information. For example, it is not necessary to wait until after October 1 to renew registration.

On November 10, FDA released final guidance on compliance with the Voluntary Qualified Importer Program (VQIP). The eligibility criteria for taking part in this voluntary, fee-based program include compliance with the Foreign Supplier Verification Program (FSVP). But the VQIP importer may be located either inside or outside the U.S., whereas the designated importer under the FSVP must be U.S.-based, the agency says.

In addition, the VQIP importer may be, but need not be, the importer of record listed with U.S. Customs and Border Protection (CBP). CBP defines the importer of record for a food as the person or firm responsible for making entry and payment of import duties, fees, and taxes for the food. So there is some potential for confusion of the various roles. Willingness to participate in the VQIP program may depend on such practical issues of eligibility and compliance, as well as on the bottom line analysis of the program’s costs and benefits.

On October 31, the agency released final guidance for small entities on compliance with the Preventive Controls for Human Foods (PCHF) rule. Because the guidance is designed for companies that may not have in-house expertise in the fundamentals of hazard analysis and current good manufacturing practices (cGMPs) it takes nothing for granted and is a useful introduction to the rule’s requirements, whether or not a company is a “small entity.”

One PCHF requirement that is likely to be a challenge for all sizes of companies is the required risk-based supply chain program for raw materials and other ingredients for which a hazard has been controlled before receipt.

If a registered facility identifies a hazard that requires a control and that control is applied in the supply chain before receipt, the facility must have a supply-chain program, FDA explains. Food facilities covered by the regulation must ensure raw materials and other ingredients for their products are received “only from approved suppliers, or — if received on a temporary basis from unapproved suppliers — ensuring those materials are subject to verification activities before being accepted for use,” the agency says.

If an applied control is applied by an entity other than the receiving facility’s supplier, the receiving facility must either verify the applied control or obtain verification documentation from another entity, the agency explains. Supplier verification activities can include onsite audits, testing of raw materials and other ingredients, review of the supplier’s food safety records, as well as other appropriate supplier verification activities. What’s appropriate will depend on the risk associated with the raw material or ingredient and on the supplier’s performance, the agency says.

The compliance dates for the supply chain program will depend on the size of the receiving facility and the status of the supplier. For example, if a facility is not a small or very small business and its supplier will not be subject to the human preventive controls rule or the FSMA produce safety rule, the compliance date is March 17, 2017. If the receiving facility is a small business and its supplier will not be subject to the human preventive controls rule or the produce safety rule, compliance is required by September 18, 2017.

If the supplier will be subject to the human preventive controls rule or the produce safety rule, the compliance date will be six months after the supplier is required to comply with the applicable rule.

So many registered facilities covered by the PCHF and produce rules have another round of compliance deadlines to look forward to in 2017.

Drug Master File Submissions – An Overview

(This article summarizes a White Paper on DMF submissions prepared by EAS Independent Consultant Albert Yehaskel.)

Drug Master Files (DMFs) are detailed submissions to the Food and Drug Administration (FDA) that may be used to provide confidential details about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. Submitted solely at the discretion of the holder, the information contained in the DMF may be used to support drug applications, supplements to applications, export applications or other DMFs.

Prior to creating and submitting a DMF, FDA requires the drug firm to request a Pre-Assigned Application Number. Once the number is assigned, the DMF may be pDrug Master File Submissions – An Overviewrepared and submitted to FDA. The file must include five core modules providing quality and manufacturing details pertinent to chemistry, manufacturing and controls (CMC) and non-CMC related information (facilities, manufacturing, processing, packaging, and storage requirements) of the drug constituent. Additional items to be included are Letters of Authorization (LOAs) for who may reference the DMF, a user fee form demonstrating proper payments have been made for the submission of the DMF and administrative information, such as contacts within the filing firm and assignment of a U.S. agent. It is important that all required information is accurate and current for the DMF to be active. Also, the holder must provide an annual report on the anniversary date of the original submission to maintain the DMF’s active status. To be accepted for consideration in the New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) in which it is referenced, the DMF must be current at the time of review.

DMFs are neither approved nor disapproved but are reviewed by FDA to determine whether the information contained is adequate to support a particular application which references it. Although the submission of a DMF is voluntary it can be a very important business tool, as it allows FDA to review claims of safety and quality of the constituent without revealing proprietary manufacturing information to another company using that constituent to manufacture a drug product. DMFs also accelerate FDA’s review process for Investigational New Drugs (INDs), NDAs, ANDAs and New Animal Drug Applications (NADAs). For this reason, the DMF must be continuously maintained and current at the time of FDA review and is an essential element in achieving a successful drug application, which can represent a multi-billion dollar profit potential for the drug product applicant.

Manufacturers with a large number of DMFs are often considered to be more reliable in terms of quality, regulatory standards, and capability to meet Current Good Manufacturer Practice (cGMP) requirements.

Effective May 5, 2017, FDA will require all DMFs to be submitted electronically through an Electronic Common Technical Document (eCTD) process submitted through FDA’s Center for Drug Evaluation and Research (CDER) Electronic Submissions Gateway (ESG). More details on the eCTD process can be found in the EAS white paper on DMF submissions as well as a previous EAS-E-News Issue of the Month article and background information on the EAS webpage. Should you or your company have questions on DMF submissions, LOAs or converting documents to the required eCTD process, please contact EAS to discuss your specific regulatory needs.