Author Archives: Barbara Unger

The End of Homeopathic Products’ Free Pass

Homeopathic Products:  What Are They and Why Should You Care?

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

Among the unique enforcement actions in fiscal year 2017 are a cluster of warning letters and recalls of homeopathic products.  2017 saw as many warning letters issued to these firms as were issued between 2009 and 2013.  This is a marked change from previous years beginning in 2009 with one warning letter in this category, 2011 had 2 such warning letters, 2012 had 1, 2013 had 2, and 2014 through 2016 had no warning letters issued to homeopathic manufacturers.  But, suddenly, 2017 saw 6 warning letters issued to these firms.  This information is presented in Table 1 below.

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Is the FDA Now Shifting its Focus to South Korea?

FDA Enforcement Actions Against Firms in South Korea

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

Several years ago, the FDA began, in earnest, to take more enforcement actions against sites outside the US than they did against sites within the US.  This was simply because the majority of drugs and APIs are produced outside the US.  If we look at warning letters, we initially see a distinct focus on dosage form and API sites in India followed by a similar focus on sites in China.  Now we see the FDA focusing warning letters and import alerts against multiple sites in the Republic of (South) Korea.

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Novel Medicinal Products Part II (The EMA’s Guidance)

The EMA and GMPs for Advance Therapy Medicinal Products

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

Manufacturing and testing of Advance Therapy Medicinal Products (ATMPs) is generally significantly different from processes used in chemical synthesis of small molecules or cell-based production of recombinant DNA therapeutic products.  The novelty and complexity of these new products prompted the need for rules to ensure that these products were safe/efficacious and that they could move within the markets of the European Community.  To this end, the European Commission adopted the 88-page Guideline on Good Manufacturing Practice Specific to Advanced Therapy Medicinal Products on November 22, 2017 to which manufacturers must comply no later than May 22, 2018.  Further, they developed an Action Plan on ATMPs to promote the development and use of these products.  The Guideline on GMPs is now the first document in the new Part IV of the EU Guide on Good Manufacturing Practice for Human and Veterinary Drugs.  More documents will follow governing ATMPs and will be collected in this Part.

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Novel Medicinal Products Part I (The FDA’s Guidance)

The FDA and Its New Guidance on Regenerative Medicine Drugs

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

The four guidance we address here are part of the FDA’s announced ‘comprehensive regenerative medicine policy framework and support implementation of provisions in the 21st Century Cures Act.  The FDA is actively supporting the development of stem cell and other types of regenerative therapies and attempting to differentiate them from the hundreds of stem cell clinics that make broad and unfounded claims of safety and efficacy.  The FDA has issued several warning letters in the past year to clinics that deliver services and products of this type where the FDA determined they posed an immediate safety risk to the public.  At issue regarding enforcement appears to be the definitions of “minimal manipulation” and “homologous use” — both of which are defined in the guidance.  The NYT also reports the story with their perspective.  Below, we address each of the four recent guidance, beginning with the two that are final and following with the two that are drafts available for comment:

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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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Deep Pockets | Does the FDA Get Tougher if the Owner Gets Richer?

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

Acquisition of one pharmaceutical firm by another is preceded by due diligence efforts in many functional areas.  Let’s talk about activities in the GMP area.  Firms may not be able to fully rely on past inspections by the FDA to predict the extent of remediation that might be necessary in the manufacturing and testing of the firm’s products.  We provide five recent examples where the FDA appears to increase their enforcement intensity when an acquiring firm with perceived ‘deep-pockets’ enters the game.

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New CDRH Guidance in October

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

The FDA has been on a bit of a tear in publishing guidance for devices and generic drugs.  Here we address the CDRH guidance issued between September 29th and October 25th 2017 and provide summaries of their content.  Seven guidance listed below are final, and one is published for comment.  Many are associated with requirements in the Medical Device User Fee legislation, MDUFA.  Expect more of these moving forward into the MDUFA IV era.

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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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