Category Archives: FDA

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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STARTING MATERIALS SELECTION and JUSTIFICATION

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

The EMA published a reflection paper on July 3, 2017, that addresses ‘the requirements for selection and justification of starting materials for the manufacture of chemical active substances.’  The intent of the reflection paper, prepared by the Quality Working Party, is to clarify expectations outlined in ICHQ11, Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological / Biological Entities).  This document covers both human and veterinary medicinal products.  ICH issued a Q&A regarding the selection and justification of starting materials, and the most recent draft is dated October 13, 2016. This reflection paper provides additional granularity on expectations of the EU regulatory authority beyond what is found in the ICH Q&A. Taken together, the reflection paper can be summarized as being ‘all about impurities’, both known and unknown. It also targets catalysts, solvents, and regents that are used in manufacturing starting materials and how they are controlled to ensure consistent manufacturing of the active substance.

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FDA Sent These 5 Warning Letters for Pharma Companies | June 2017

*August 3 update: we added 2 additional warning letters that were released by the FDA after we published this post on July 12, 2017.*

We took a snapshot of the 5 warning letters the FDA sent to pharmaceutical companies last month.  Drug manufacturing violations ranged from “misbranded products” to sites “failing to investigate the unexplained discrepancy.”

From pharmaceuticals in China, Texas, and more, here they are (starting with the most recent):
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The FDA Re-Org Has Begun. What Does it Mean for You?

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

BACKGROUND:

The FDA began a plan to align the Office of Regulatory Affairs (ORA) into a ‘program based structure’ in 2013.  This reorganization is now being implemented. The ORA is the lead for all FDA field activities including inspections of regulated products and their manufacturers, and review of imported products.  Effective May 15, 2017, we enter the transition phase as the FDA moves to reorganize the ORA structure and function to align with the agency’s centers. The FDA provides information on each of the areas, including a ‘fact sheet’ and a ‘boundary map’ for these offices.

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When Will the FDA Move On from Data Integrity?

The FDA has been writing up companies on data integrity since the year 2000. Even after all the horror stories, and even after billions of dollars of market cap have been erased from it, here we are in 2017, still talking about it.

Here is some troubling text from recent Warning Letters that cite data integrity:

“…our investigator observed your warehouse supervisor tearing out pages from your firm’s annual report and placing the pages into his pocket.”

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Why is No One Talking About This? 2016 was the Year the FDA Exploded on China

New data synthesized by FDAzilla has revealed several dramatic shifts with FDA inspection and enforcement activity.

The FDA issued 15 pharma GMP-related warning letters to manufacturing sites in China in 2016 – a 5-fold increase from years prior. China averaged 2.7 Warning Letters per year from 2013 to 2015.  This explosion was led mostly by infamous FDA investigator, Peter Baker, who performed 17 inspections in China in 2016, leading to 13 FDA Form 483s and 4 Warning Letters. Continue reading

Delay, Denial, or Limiting of Inspections Since 2008

Delay, Denial, or Limiting of Inspections Since 2008

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

In October 2014, the FDA published a final Guidance for Industry, Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection. Publishing this guidance was a requirement of section 707 of the Food and Drug Administration Safety and Innovation Act (FDASIA).  Section 707 of FDASIA adds 501(j) to the Food, Drug, and Cosmetic Act (FD&C Act) to deem a drug adulterated if it “has been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection.”  Before that time and since, the FDA cited instances where firms have delayed inspections or denied investigators access to areas or documents that they should be able to view.

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