Category Archives: biopharma


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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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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6 Key Take-Aways from the 2016 EMA Annual Report

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

The EMA published their Annual Report for 2016 in May 2017, and it provides highlights of their work in partnership with the national health authorities.  Christa Wirthumer-Hoche, chair of the EMA Management Board, provides the Forward to the report, and Guido Rasi, the EMA Executive Director, provides the Introduction.  The report identifies important activities in 2016 and how they advance public health.  It also holds a collection of graphics from a variety of areas including human and veterinary medicines, the European regulatory network, and inspections/compliance. The report also identifies 22 Annexes that may be found on the Agency’s website but are not included in the report.  

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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

What Does Getting a 483 or Warning Letter Really Cost You?

“Forget about actual warning letters. The cost of us receiving a moderately bad 483 is roughly $250,000.”

I heard this from a reputable Head of Manufacturing of one of the largest biopharma companies in the world.  While most pharma and med device companies seems to learn quickly from everyone else’s mistakes, companies still occasionally get a “moderately bad” 483.  And then what happens after that? Continue reading

Data Integrity cGMP FDA draft guidance

FDA Draft Guidance on Data Integrity and Compliance With CGMP

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


The FR announced availability of the long awaited 10-page FDA draft Guidance on Data Integrity and Compliance with CGMP for comment.  I include links to the MHRA guidance HERE and the draft WHO guidance HERE for comparison.  The guidance is structured in a Q&A format with a total of 18 questions.  This guidance focuses heavily on identifying and citing the predicate rules as they apply to electronic records and data integrity, and for this it is an excellent reference.  In my opinion, though, the excessive citation of regulations detracts from the content and provides little insight into FDA’s intent and actual expectations in this area.

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