Category Archives: quality assurance

Generic Drugs | A Guidance on FDA Guidance

by Barbara Unger, GMP Quality Expert, and GMP Regulatory Intelligence Editor-in-Chief

On November 1, 2017, we published a blog that addressed a large collection of newly issued guidance for the generic drug industry.  With this post, we continue with another three generic drug guidance that were issued recently.  Consistent with the previous collection, many of these find their roots in GDUFA legislation.  This time we address three guidance documents.  Regulatory affairs departments should carefully read the first two that include detailed specifics on who needs to pay what and when.  The last guidance addressed here should be read carefully by groups who develop filing strategy.  It appears most problematic and may not provide the relief or speed as it may have intended.

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Recent Generic Drug Guidance

by Barbara Unger, GMP Quality Expert, and GMP Regulatory Intelligence Editor-in-Chief

October has so far seen a flurry of guidance publications focused on generic drugs.  It’s unusual to see so many guidance on one kind of product published almost simultaneously — though the device area seems to be making the same effort!  Many of the generic drug guidance are published to implement requirements in the Generic Drug User Fee Act (GDUFA I or II).  Two of the guidance documents are final, and one is a MAPP; the others are drafts available for comments that the FDA will consider prior to finalizing.  In addition, the FDA published thirty-two (32) new draft bioequivalence guidance and nineteen (19) revised guidance to assist in the development of generic drugs.  We won’t cover the bioequivalence guidance here, but if you operate in the generics area, please look at them.  Let’s take each of the others in turn to briefly see what they cover.

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The Heightened Importance of Contract Manufacturing Organizations

by Barbara Unger, GMP Quality Expert, and GMP Regulatory Intelligence Editor-in-Chief

One of the most thought-provoking presentations at the recent PDA / FDA meeting in Washington DC was given by Guy Villax, CEO of Hovione Pharmaceuticals.  Hovione Pharmaceuticals offers a range of contract services including but not limited to, product development, manufacturing of API and drug products, and analytical support.  Guy’s presentation was one of two on the opening day that addressed ‘Current Quality Challenges for Pharmaceutical Executives.’  He began his talk by saying that 60% of small molecule APIs for new NDAs are made by contract manufacturers.  I was surprised by the figure.  This is clearly different than practices of 15-20 years ago and, according to Guy, represent a migration of CMC knowledge to CDMOs.  That alone calls for us to re-evaluate the relationship between CDMO and sponsor firms, particularly for the virtual firms.

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New FDA GMP Inspection Model

by Barbara Unger, GMP Quality Expert, and GMP Regulatory Intelligence Editor-in-Chief

While the drug GMPs haven’t changed much, if at all, in recent years, the FDA is planning for significant changes in how drug GMP inspections are scheduled and conducted.  The FDA recently made available a description of their new operating model that will ensure integration of review and inspection activities for human drugs.  This model continues the FDA’s efforts to refine inspection operations as described in their recent reorganization of the Office of Regulatory Affairs (ORA).   It aligns and supports the New Inspection Protocol Program.  The MRA between the EMA and FDA allows health authorities to maximize their abilities to focus inspection efforts on high risk sites and rely on each other’s inspection outcomes.  Taken together, these changes will permit:

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FDA Sent These 11 Warning Letters for Pharma Companies | August 2017

We took a snapshot of the 11 warning letters the FDA sent to pharmaceutical companies last month.  Drug manufacturing violations ranged from failing to keep drug product infestation free to failing to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the proper education, training, and experience.

From pharmaceuticals in China, Georgia, and more, here they are (starting with the most recent):
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Summer Enforcement Actions for Compounding Pharmacies and Outsourcing Facilities

by Barbara Unger, GMP Quality Expert, and GMP Regulatory Intelligence Editor-in-Chief

July and early August 2017 saw another uptick in FDA actions associated with compounding pharmacies/outsourcing facilities.  In the past few years, the FDA has placed a disproportionate effort towards enforcement actions for these facilities.  We have addressed this focus and the history of these facilities in a previous blog.  The FDA published twenty-one (21) 483s and six (6) warning letters issued to these facilities in July 2017.  It’s clear that FDA’s extreme focus on these facilities continues and the compliance problems for these facilities have not been appropriately addressed. And, more problematic for me, is that firms do not appear to be learning from the enforcement actions taken against others in this area.   In addition, there have been several recalls of unexpired products and notices to healthcare professionals regarding adverse events apparently associated with these products and two consent decree agreements. Let’s look at these in turn:

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US-EU Mutual Recognition Agreement of 2017

A Long Time in the Works

by Barbara Unger, GMP Quality Expert, and GMP Regulatory Intelligence Editor-in-Chief

Implementation of the Mutual Recognition Agreement (MRA) for drug GMP inspections between the US FDA and the European Union (EU) inspectorates has been in the development since 1998 and was formalized this year. This agreement was driven by the reality of the changes in sites of drug manufacturing over the last decades. No longer is drug manufacturing primarily a ‘domestic’ function, either in the US or European countries.  The current supply chains are global with significant proportions of manufacturing performed across the globe, most significantly in India and China.  Both the FDA and EMA inspectorates have limited personnel and budgets and have been working to leverage their expertise and minimize where the two inspectorates visit facilities that their partner recently inspected, thus increasing their efficiency.  This allows each inspectorate to take a more risk-based approach to inspections and concentrate on those facilities that are in developing regions and provide a large percentage of either APIs or finished products that are prescribed and sold in the US and EU.

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FDA Sent These 9 Warning Letters for Pharma Companies | July 2017

We took a snapshot of the 9 warning letters the FDA sent to pharmaceutical companies last month.  Drug manufacturing violations ranged from “adulterated and misbranded drug products” to sites “failing to sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination.”

From pharmaceuticals in Italy, Tennessee, and more, here they are (starting with the most recent):
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CHINA DRUG INSPECTIONS, 2016

by Barbara Unger, GMP Quality Expert, and GMP Regulatory Intelligence Editor-in-Chief

China published their annual report of drug inspections for 2016 on June 2, 2017.  The 31-page document reports on a variety of inspection types including but not limited to: pre-approval inspections, GMP certification inspections, and GMP follow-up inspections.  The report is accompanied by tables and figures.  For the most part, it is easily understood, but where discrepancies seem to appear between the various values and terminology, I’ve highlighted the uncertainty.  Some types of inspections are absent here, but the report provides specific details on the inspections and the deficiencies identified.

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