What Has the FDA Been Focusing on for the Month of August?

We took a snapshot of the 13 warning letters the FDA sent to pharmaceutical companies last month.  Drug manufacturing violations ranged from failing to “maintain written records” to failing to wear “clothing appropriate to protect drug product.”

From pharmaceuticals in Brazil, India, China, and 6 US states, here they are (starting with the most recent):
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FDA cGMP Quality News Briefing: August-September

We’ve compiled August and September’s most relevant, important news for anyone concerned with Pharmaceutical Industry GMP and FDA inspections. Our top 12 picks are listed chronologically by publication date. Happy reading!

  1. 25 JulyAfter scandal, China begins vaccine inspections nationwide– Discovery of a blackmarket vaccine ring earlier this year was the impetus for China’s nationwide campaign to inspect vaccine purchasing. The $90 million scheme involved illegal purchase and distribution of non-refrigerated vaccines. — China has cracked down on their enforcement of sourcing and distribution, launched an investigation into the scandal, and added random checks to their regularly vaccine inspections, which will be overseen by China’s NHFPC.
  2. July/AugustThe Real Cost of Poor Data Integrity in Pharmaceutical Manufacturing (PDF) — In this whitepaper from Lanchman, James Davidson, PhD, explains just how much data integrity issues can cost your company. After this, he outlines and defends a “proactive approach to the assessment of risks to data reliability.” This is an important read for anyone in the pharmaceutical industry.
  3. 17 AugustFDA sends warning letters to 12 medical device companies — It’s important to note the incredible variety and uniformity simultaneously at work in this story. Violations were found at plants across a wide geographical spread: Italy, Germany, China, the Philippines, Argentina, the U.K., France, and the U.S.  Products made by these firms include items as diverse as surgical devices and dental floss. The takeaway? First, that violations can happen in any company, regardless of plant location or product type. Second: No matter how simple or complex the device, FDA inspectors will enforce the rules.
  4. 18 AugustWhat Does Getting a 483 or Warning Letter Really Cost You? — One Head of Manufacturing estimates that even a “moderately bad” warning letter costs his company $250,000, and we can understand why. Correcting from a 483 can include internal teams, external consultants, process redesign, and hundreds or thousands of hours dedicated to the recovery. All of those processes add up. Unfortunately, Warning Letters are even more costly — exponentially so: corrections run in the hundreds of millions of dollars, and that’s not to mention the hits companies take to reputation, drug approvals, and competitive response. 
  5. 30 AugustTheranos Halts New Zika Test After FDA Inspection —  The FDA inspected Theranos earlier this month in response to the company filing for emergency clearance on a Zika virus blood test called minilab. Sadly, it seems that Theranos by-stepped some important procedures in their rush to develop their new product. Inspectors found that some of the supporting data had been collected without implementing protocol approved by an IRB (Institutional Review Board). In response to these findings, Theranos volutnarily withdrew their request for clearance. They plan to collect additional data — this time under properly reviewed protocols — and resubmit their application. For their sake, let’s hope this round will involve a more dedicated attention to detail. The takeaway? Even for an emergency clearance, the FDA does not budge on patient safety. 
  6. 31 AugustFDA finds China manufacturing plant full of holes, chipped paint, and insects –Words like “lizards”, “falsified”, and “mold” catch the eye, but the keyword here is “management.” This article covers two instances of plants owned by Chinese companies receiving FDA enforcement action for violations of the most fundamental GMP standards. The problems stated here are so serious they are almost unbelievable. Stories such as these are significant in today’s global market. Remember: China controls 50% of the API market globally, and exports from China to the US grew 4% in just the last year. You can read the warning letter issued to one of the two companies here
  7. 31 AugustPharmaceutical Compounding: The FDA Is Not The Problem – Some concerning statistics: 65% of the 43 states that responded to a PEW survey indicated that they “did not mandate specific expectations for specialized training.” In 60% of these states, pharmacies are not required to report “serious adverse events or reactions related to sterile compounding.” 30% do not require a pharmacist license to work in pharmaceutical compounding. Given these facts, it might not surprise you to hear that the FDA is requesting more jurisdiction over the preparation of sterile drugs. The last section of the article outlines three recommended reforms for compounding pharmacy. 
  8. 1 SeptemberSterility Assurance and Cross Contamination – In this article, GMP Quality Expert Barbara Unger will guide you through 6 examples of 483s whose observations note problems with sterility assurance and cross contamination. This overview will help you understand the scope of these issues and the enforcement actions that can be linked to non-compliance. The main point? “FDA observations regarding problems in SA & CC include facility design and operations issues, training of operating staff, and deficiencies in media fill exercises.” Good to know.
  9. 7 SeptemberCDMO Pharmaceutics International gains $93M investment, new president — A consortium of investors, including Athyrium Capital Management, HIldred Captial Partners, and Pharmascience, signed a deal with Pharmaceutics International worth $93 million. In exchange, they will receive equity stake and debt refinancing. The article outlines how Pharm Int. will use these extra funds — they plan to focus on manufacturing and formulation. You can read a statement on these plans here. The company’s new executive is Michael Bogda. 
  10. 12 September: No expectations for China or India to join Inspection Co-operation Scheme — PIC/S currently has 49 members, 4 new applicants, and 3 pre-applicants. Many other nations —  including Armenia, Bulgaria, Nigeria, Saudia Arabia, Uganda, Vietnam, and Zimabwe — are showing interest in joining. Despite the importance of international cooperation and the fact that they supply most of the world with pharmaceuticals, officials say it is unlikely that either China or India will be joining PIC/S or the International pharma regulatory schemes (ICH) any time soon — But China has exhibited markedly more interest in joining than India. For China, obstacles to joining the PIC/S arise from administrative and political complications. Chinese politicians, not the CFDA, would have to make the decision to apply. In India, hesitation centers on the expensive of joining. Some argue that if India were to follow GMP standards in manufacturing, local patients in India would be unable to afford medication.
  11. 15 September: New Bills Would Require Drug Companies to Justify Price Hikes of More than 10% – The FAIR Drug Pricing Act, proposed by Tammy Baldwin, John McCain and Rep. Schakowsky, hopes to “expose the profiteering of drug corporations” by requiring increased transparency. If passed, the proposed bills would require manufacturers to submit a transparency and justification report 30 days before increasing the price of certain drugs by more than 10% of the current cost. The act would not keep companies from increasing prices, but would hopefully highlight problems leading to price gouging. The required reports would include info on net profits from the drug in question, marketing-advertisement spending, a justification of price increase, manufacturing, research, and development costs. All of this information would be made available to the public online within 30 days. You can find text of the bill  here.
  12. 22 September: FDA May Push Back Release of Biosimilar Interchangeability Draft Guidance – Have you been waiting for the FDA to finalize their definition of “interchangeability”? If so, you might be disappointed — the final publication year is now expected to be 2019 or 2020, and the FDA says the first draft will be produced by 31 December 2017. The article lists the FDA’s timeline for the publication of guidance drafts on other related topics, as well.

Is there a story we missed? How do you keep up with your industry’s news? Let us know in the comments!

Learn more about how FDAzilla can help you achieve your quality and inspection preparation goals: get 483s, Inspector Profiles, Enforcement Analytics, and GMP Regulatory Intelligence. Any questions? Contact me at


3 Key Learnings from the PDA/FDA Joint Conference

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

OVERALL:  This is the 25th anniversary of the PDA/FDA conference and many of the presentations provided evidence of the significant progress made in research and medicine during this time.  It was fascinating to stand back for a few moments to see just how far we’ve come.  The overall conclusion I take from the two days of the conference that I attended are:

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Sterility AssuranceandCross Contamination

Sterility Assurance and Cross Contamination

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

Forms 483 Addressing Sterility Assurance and Cross-Contamination 

Along with data integrity, deficiencies in sterility assurance and the potential for product or API contamination identified during FDA inspections often lead to warning letters. Also many product recalls are based on lack of sterility assurance or less frequently on potential cross contamination.  Here we take a look at six forms 483 that include observations associated with sterility assurance and potential cross contamination.  These are certainly not meant to provide an all-inclusive view of the topic, but rather represent recent inspection observations in these areas to demonstrate the broad scope of the topic.  FDA’s flurry of inspections and enforcement actions against compounding pharmacies and outsourcing facilities focuses heavily of requirements associated with expectations regarding aseptic manufacture of sterile drug products. These sites are often also cited for the potential for cross contamination. Lack of sterility assurance and the potential for cross contamination, particularly by high potency compounds or sensitizing agents both have potentially serious consequences for patient safety.   Many compounding pharmacies and outsourcing facilities have recalled large numbers of products due to concerns about sterility assurance.  We include one example of this type of facility in the collection presented below.  Failure to complete adequate cleaning validation for multi-product equipment is often another source of potential cross contamination even when products do not include high potency compounds or sensitizing agents.

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These 3 companies got slammed by the FDA. (1)

The Story of 3 Consent Decrees

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

A consent decree agreement is an agreement filed in the US courts formalizing a voluntary agreement between two parties.  Here we will address consent decree agreements between FDA and several pharmaceutical companies based on repeated failures to adequately address CGMP deficiencies.  It is not an action taken on the basis of a single form 483, or a single warning letter.  Generally, a series of events play out over time when critical inspection observations are not addressed and are identified in subsequent inspections.  Frequently one or more warning letters are involved.  Consent decree agreements often include fines, with the option for additional financial penalties if conditions to which the firm agrees are not met.  Often these firms are required to use a 3rd party consultants to perform lot release.  Firms operating under a consent decree agreement have largely lost their independence in GMP activities.  Unlike Corporate Integrity Agreement which have a defined duration, firms must petition to have the consent decree agreement condition rescinded.

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Haven’t visited us for a while? Get up to speed in 4 minutes

If you haven’t been to in a while, then you’ve come to the right place. If any part of your job involves preparing your company for FDA GMP inspections, let me take you on a quick tour of some tools and resources that you might find useful!

Take 4 minutes and check out these 4 things:

  1. DECREASE YOUR RISK WITH DATA: Companies like P&G, Altria, AbbVie, Novartis, Astellas, and many others now count on accessing a new data analytics tool called Enforcement Analytics. Imagine being able to “google” FDA inspections and inspectors. Here’s a short video.
  2. INSPECT YOUR INSPECTOR: FDA inspector coming on Tuesday? Or worse yet, she’s in your conference room right now?  You can get her inspector profile, which includes her most frequently cited CFR code, most frequent co-inspectors, enforcement metrics, and inspection history. In just the last few weeks, customers from 3 continents have purchased these in preparation for an upcoming (or current) inspection.
  3. READ FRESH INSIGHTS: The blog you’re on now is a treasure trove of resources and insights from me (Tony Chen, CEO of FDAzilla) and Barbara Unger, GMP Quality Expert, who has been in your shoes. Why not start here – our 14 most popular posts of all time. If you feel that getting needed info is like finding a needle in a haystack (or drinking from a firehose!), let us do the work for you. Get our comprehensive, succinct weekly synthesis of the latest GMP regulations, guidelines, enforcement actions, and developments here.
  4. GET 483s (AND NOW EIRs): The FDAzilla store houses 7,000 483s, with hundreds added every month. We’ve also just added 2,000 EIRs and 150 483 response letters. If you’re a heavy 483 user, you should also consider our 483 service.

Learn more about how FDAzilla can help you achieve your quality and inspection preparation goals: get 483sInspector ProfilesEnforcement Analytics, and GMP Regulatory Intelligence. Contact Ben if you ever have questions at

Huge Cost of a GMP Failure

What Does Getting an 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