FDA Clarifies Human Subjects Protection Expectations

A new guidance from the U.S. Food and Drug Administration (FDA) provides welcome direction to sponsors, investigators, and institutional review boards (IRBs) on human subjects protection.

The guidance is one of the agency’s follow-ups to its revisions of the “Common Rule” (Federal Policy for the Protection of Human Research Subjects), which became effective in July 2018. General compliance for the revised Common Rule is mandated to begin in January 2019. The purposes of the Common Rule are to promote “uniformity, understanding, and compliance with human subject protections and to create a uniform body of regulations across federal departments and agencies,” FDA explains in the new guidance.

The requirements contain several new areas of informed consent, including changes relating to the content, organization, and presentation included in the consent form. It also clarifies the process to facilitate a prospective subject’s decision about whether to participate in research. FDA is clarifying the provisions to help sponsors and investigators develop, and IRBs implement, two separate informed consent forms.

The guidance also follows up on earlier FDA rules which allowed IRBs to use expedited review procedures for certain kinds of research involving “no more than minimal risk.” The new guidance includes a list of categories that may qualify for the fast track, while it also makes clear that, as appropriate, IRB reviewers must find that the research on the list involved no more than minimal risk.

FDA Adds Device Scenarios to Final GMP Guidance for Combo Products

In the finalized guidance on GMP requirements for combination product manufacturers, the FDA clarified how to comply with certain device requirements with compliance examples for prefilled syringes, drug-coated mesh and drug-eluting stents. This final version reiterates that combination product manufacturers have two options for compliance: satisfy all drug and device GMPs, or implement a streamlined quality system that focuses primarily on one but incorporates elements of the other GMP systems. This guidance details which GMPs are applicable to a product, general methods for how to implement them, key definitions, and how to make post-market changes to a product’s quality system. 

Read the guidance here.

FDA Guidance for Pharmaceutical CMO Quality Agreements

Quality agreements are critical to ensure you and your contract manufacturer define each other’s roles and responsibilities with respect to quality. On November 22, 2016, the FDA released the finalized guidelines that specify what should go into quality agreements between pharmaceutical companies and outsourced contract manufacturers.

This guidance applies to commercial manufacturing for human drugs, veterinary drugs, certain combination products, biological and biotechnology products, finished products, APIs, drug substances, in-process materials, and drug constituents of combination drug/device products.

It does not apply to Type A medicated articles and medicated feed, medical devices, dietary supplements, or human cells, tissues, or cellular or tissue-based products regulated solely under section 361 of the Public Health Service Act and 21 CFR part 1271.

Download the guidance here.

Quality Metrics – New Guidance from FDA

Quality metrics are used throughout our industry to drive continuous improvement efforts in manufacturing. Collecting the right quality metrics is critical to ensure compliance. Quality metrics can also help the FDA in developing compliance and inspection policies and procedures by allowing the FDA to:

  • Use a risk-based inspection scheduling of drug manufacturers
  • Improve ability to predict and possibly mitigate future drug shortages
  • Encourage the pharmaceutical industry to implement state-of-the-art, innovative quality management systems for manufacturing.

The revised draft guidance includes an explanation of how the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) intend to utilize submitted data and quality metrics to help ensure that their policies and practices continue to support continuous improvement and innovation.

FDA is initiating a voluntary reporting phase of the FDA quality metrics reporting program where they expect to learn more about a limited set of quality metrics, associated analytics, and improve the FDA quality metrics reporting program.

During the voluntary phase of the reporting program, FDA will accept voluntary submissions of data from drug manufacturing firms involved in the manufacture, preparation, propagation, compounding, or processing of finished dosage forms (FDF) or active pharmaceutical ingredients (API) used in the manufacture of “covered drug products.”

For more information and to download the guidance, click here.

FDA Requires Use of eCTD Format and Standardized Study Data in Future Regulatory Submissions

FDA will now require that certain regulatory submissions conform to the electronic Common Technical Document (eCTD) format. In addition, study data will have to be submitted in standardized format for certain studies.  The eCTD has been the standard format for submitting applications, amendments, supplements, and reports to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) since 2008 and makes it easier for FDA to review data, approve new drugs, and monitor drugs after they go on the market. It also simplifies the process for submitters, because the CTD format is used by drug regulatory agencies in many countries.

Starting on May 5, 2017, eCTD will be required for applications submitted to CDER and CBER for the following:

  • New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs), Biologics License Applications (BLAs), and all subsequent submissions to these types of applications, including amendments, supplements, and reports, even if the original submission was filed before the requirements went into effect.
  • Master files, such as Drug Master Files (DMFs), which are considered to be submissions to an IND, NDA, ANDA, or BLA.
  • Combination products (if CDER or CBER is designated as the lead center).

Download the guidance here.

For a complete listing of all documents and supportive files needed in order to submitelectronically, refer to the eCTD Web page at http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/



Guideline on Process Validation for Manufacturing of Biotechnology-Derived Active Substances

Are you up to date on process validation requirements for the manufacture of biotechnology-derived active substances and data to be provided in the regulatory submissions for the EU?  Process validation is the documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an active substance or intermediate meeting its predetermined specifications and quality attributes (ICH Q7).

The EMA just published a new guideline that addresses the data requirements for process characterization and verification for submission of a marketing authorization application or variation.

These principles apply to recombinant proteins and recombinant polypeptides, their derivatives, and products of which they are components (e.g. conjugates). This guideline discusses process characterization and process verification requirements.  It also includes points to consider such as evaluation and verification of the upstream and downstream processes, issues related to single use equipment and multiple harvests, reprocessing, hold time, storage, transportation, and multi-facility production.

Download the full guidance here.

Comparability Protocols for Human Drugs and Biologics: Guidance for Industry

How do you handle post-approval changes to your products?  New draft FDA guidance document establishes a framework to ensure you effectively use your product and process knowledge and understanding to prepare a Comparability Protocol that employs the tools in ICH Q8 to Q11.  It also provides guidance on a robust control strategy, incorporates risk management over the product’s life cycle and describes elements of an effective pharmaceutical quality system.

Learn more and download the guidance here.