Data Integrity – Management’s Responsibilities

Since the initial April 2016 draft published, the pharmaceutical industry has been working to toward complying with the FDA guidance on Data Integrity and Compliance With Drug CGMP (here) which was finalized in December 2018.  One passage in the introduction of the guidance has resonated with me: “Management’s involvement in and influence on these strategies is essential in preventing and correcting conditions that can lead to data integrity problems.  

Regulatory Affairs and the CMO Factor

The use of contract manufacturers for the production of approved drug products has become more and more commonplace, particularly with the steady increase through the years of virtual pharmaceutical companies, a business model where the majority of the drug development and production work is outsourced to third parties as needed.  While the use of a contract manufacturing organization (CMO) may well be more cost efficient to a company,

Sometimes you get what you pay for; FDA joins forces with India to halt illicit drug sales

The United States Food and Drug Administration and the Indian Government join forces in “Operation Broadsword”.  No, it’s not a trailer for an action thriller, it’s a serious collaboration between two governmental entities to limit the import and sale of illicit drugs to consumers, detailed in FDA’s news release on February 18, 2020 (here).

Is your NDA a BLA?  March 23rd is Quickly Approaching….

Our own Keith Webber originally provided very detailed information and helpful hints in his August 2019 blog (here) regarding FDAs transition of certain NDAs to BLAs under the BPCI Act.

So, although this may not be “new” news, we think it’s worth a quick trip down memory lane, as the implementation date quickly approaches. 

When It Rains, It Pours; Recent Rx-to-OTC Switches

February 14, 2020 could be called a red letter day in the world of Rx-to-OTC switch.  After a long period of drought, FDA announced that they have approved the Rx-to-OTC switch of three prescription drugs. Please see the announcement here.  The three drugs are: Voltaren Arthritis Pain (diclofenac sodium topical gel, 1%) for the temporary relief of arthritis pain;

Out-of-Specification Investigations – Lessons Learned, or Not?

The FDA Guidance for Industry, Investigating Out‑of-Specification (OOS) Test Results for Pharmaceutical Production, was published in October 2006 (here).  The pharmaceutical industry has had about 14 years to learn how to comply to this guidance.  A quick survey of recent Form 483s and Warning Letters would indicate that there is still much to be learned on how to comply with the current regulatory expectations for OOS investigations. 

CBER Publishes a Boatload of New Gene Therapy Guidances


January was a gangbuster month for the FDA’s Center for Biologics Evaluation and Research (CBER) with regard to publication of gene therapy (GT) guidance documents!  A total of six final guidelines and one draft guideline on GT products were issued.  These included:

  • Chemistry, Manufacturing, and Control Information for Human Gene Therapy Investigational New Drug Applications (here)
  • Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up (here)
  • Long Term Follow-Up After Administration of Human Gene Therapy Products (here)
  • Human Gene Therapy for Rare Diseases (here)
  • Human Gene Therapy for Retinal Disorders (here)
  • Human Gene Therapy for Hemophilia (here)
  • Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations (here)

These guidances will be extremely valuable to the exploding field of gene therapeutics,

Looking at the Sentinel

FDA has announced the 12th Annual FDA Sentinel Public Workshop on April 20-21, 2020. (Please go here for the details.)  The Sentinel System is the largest multi site patient safety database in the world, and includes the Active Post-marketing Risk Identification and Analysis (ARIA) system mandated by Congress in the US Food and Drug Administration (FDA) Amendments Act (FDAAA) of 2007.  

What Is It? – Identity Testing Re-visited

In earlier blogs, we have written about specific technical items related to identity testing.  However, a review of Warning Letters published on the US FDA website for the months of December 2019 and January 2020, revealed three Warning Letters citing instances of failures to perform identity testing of active pharmaceutical ingredients prior to the manufacturing of pharmaceutical drug products.

Promoting Confidence Through Product Quality – OPQ 2019 Annual Report


 The FDA’s Office of Pharmaceutical Quality (OPQ) is the group within the FDA that defines the quality requirements for all human drugs under its umbrella (filed as NDAs, ANDAs, BLAs, 351(k)/Biosimilars, and OTC products).  The group issued its 2019 Annual Report just this month (read the full report here) that includes a look back on what OPQ has accomplished since its inception in 2015,

FDA Provides Valuable Guidance on Bridge-Building for Combination Products

Three of FDA’s Centers (CDER, CBER, and CDRH) recently published a combined draft guidance for Industry entitled Bridging for Drug-Device and Biologic-Device Combination Products  (here).  This draft guidance provides the FDA’s current thinking on what manufacturers should consider when they wish to bridge the data from one such combination product to another combination product during product development (IND-phase) or preparing an NDA or BLA.

The Importance of Sampling Plans for Uniformity of Dosage Testing

Numerous health authorities have cited companies for inadequate sampling plans of finished drug products. A recent 483 issued to a finished drug‑product firm specifically mentions the firm’s lack of a scientifically sound statistical sampling plan during production of all strengths of its drug product.  The FDA also mentions that this firm uses content uniformity results as part of its product’s release,

FDA’s Warning Letter Database – Has Any Progress Been Made Since the FDA Website Update?

Some time ago, we highlighted the issues that we had been facing searching FDA’s Warning Letter database in the new FDA website (FDA’s Website Re-Design – Did Something Get Left Behind?).  We wanted to give you an update as to where the current status of this is.

Since drafting this post,