Silencing Pharma’s cGMP high priesthood

We all know that cGMPs are essential to safety. But has the industry gone too far with them?  Has pharma, in effect, created a high priesthood of cGMP that stymies creativity, and even common sense?

In his latest editorial, PharmaManufacturing’s resident Andy Rooney, NIR guru Emil Ciurczak, looks back on some experiences and asks whether pharma’s cGMP orthodoxy isn’t turning out “good little soldiers” —scientists who follow procedures but can’t think for themselves. (And who invent procedures when they’re not needed).  

Do you encounter the cGMP priesthood on a regular basis where you work? How do you deal with them, or have you drunk the KoolAid, too?

Please write in and let us know.

-AMS

Looking for FDA anecdotes

We’re working on a project for FDA’s anniversary that will look at past slogans, campaigns and programs within the Agency (in an effort to contrast them with current programs such as 21st Century GMPs, The Critical Path, etc.). 

We often hear that the industry has been jaded, and reluctant to see these new projects as the ”sea change” that they are because of past FDA “flavors of the month.”

Just what were some of those “flavors of the month” dating back from the 70’s, 80’s and 90’s?  Please write in, anonymously if you wish, with any examples that come to mind. Thank you!

-AMS

Merck goes green with first major roof-based solar energy system

Merck has apparently installed one of the largest solar-energy systems in New Jersey  at its research and manufacturing facility in Linden/Rahway.  The 500-kW facility features 1500 solar panels on two roof tops.  Are other pharma companies doing this?  Let us know!

-AMS

Is the Senate paving the way for drug reimportation from Canada?

As part of a Homeland Security spending bill, the U.S. senate recently approved a loophole in FDA regulations that could allow reimportation of prescription drugs from Canada.

-AMS

Will FDA keep Biopharma out of Phase Zero clinical trials?

A recent RPM report by Windhover suggests that FDA may be restricting “Phase Zero” clinical trials, or early small-dose drug tests, to small molecules. This is believed to have been driven by the TeGenero clinical trial disaster last March in the U.K.

-AMS

Fuzzy Logic and Biopharma - What are the Japanese doing right re: control and IT validation?

Fuzzy logic and other advanced control concepts have yet to find a home in most U.S. pharmaceutical operations.  Why is that?  Of course, it’s due to the way that validation is approached today, as process engineering expert Pankaj Mohan made clear in a recent interview for PharmaManufacturing.com.

The idea that one unchanging “output” number must be used to establish a basis for validation is hard to change. FDA may be embracing the concepts of PAT and advanced automation, but clear guidance on the validation and acceptance of “soft sensors” and other adaptive control technologies could help encourage more companies to explore their use.

Interestingly enough, Japanese and Indian biopharma manufacturers lead the way in applying fuzzy logic to their operations, as Pennsylvania-based biopharma process control consultant Christian Julien has pointed out, and will make clear in an exhaustive analysis for a supplement due to be published soon by one of our competitors.  “If biopharma wants to break through the 10g/L barrier, it will need just these types of control systems,” says Julien, who has analyzed over 5,000 relevant abstracts written by specialists around the world in the course of his research.

He also cites a November article in Pharmaceutical Engineering that suggests Japan’s clear lead in this area.

Perhaps U.S. regulators could carefully study the wording of Japan’s regulations, and consider it as a model?  How is it that Japan’s agencies, known for their obsession with quality,  still manage to regulate in a way that doesn’t discourage Japanese manufacturers from applying advanced automation or innovative process control?

Look for more on this topic in our magazine and web site.

-AMS

When Will Pharma Address Operator Error and Alarm Management? Recent Merck Spill Begs the Question

Recently it was reported that Merck operators at a vaccine pilot plant in West Point, Pennsylvania released 25 gallons of untreated potassium thiocyanate directly into the local sewer system in Wissahickon Creek.  The spill killed hundreds of fish, triggered an EPA fine and launched an investigation.

But it also leads to much broader questions:

• When will the pharmaceutical industry, as a whole, analyze operator error and its root causes, in depth?
• When will drug companies implement the Poka Yoke, or error-proofing systems, routinely found in most aerospace and automotive plants? When will they truly embrace the Toyota Production System concept of Jidoka?
•   A recent Pharmaceutical Manufacturing survey showed that very few drug manufacturing plants even have a formal “alarm management” system in place right now. And, given the level of automation in place at some facilities, alarm management is a critical part of eliminating operator error.

 The chemical process industries have already conducted major investigations into operator error and its sources, following major petrochemical plant explosions. Not that this has stopped human error of course ( a recent incident at Nova underscores this point), but other industries at least appear to be giving the issue the attention it deserves.

Is pharma behind in studying operator error because such error manifests itself so quietly at drug plants— in rejected batches of product, recalls, or heavy FDA or EPA fines for noncompliance?

Should it take plant explosions to focus more attention on this subject?

Interestingly enough, within Merck’s MPS team in Arecibo, Puerto Rico, IPT leader Luis Garcia is studying Jidoka closely to determine how it might be applied to operations.  Stay tuned to our magazine and web site for more on his work, and what your peers are doing in this area, in the future.

-AMS

Survival tips for road warriors: get the best seat and cut through the Expendia/Travelocity/Priceline/Cheaptickets clutter

Attention, tall people everywhere. Having just endured a five-hour leg cramp —that is, flight in coach, I discovered a web site called Seatguru.com , which allows you to compare seat roominess and quality on all carriers, domestic and international, and for first class as well as coach seats.  Do a bit of due diligence before booking that next trip. It will pay off.

And for those of you with Expedia/Travelocity/HotTickets/CheapTickets/Priceline.com-itis, there’s an alternative: a neat, uncluttered site called Kayak.com that allows you to select flights easily and without all the distractions— it’s definitely worth a look.

Happy (and safe) travels.

-AMS

Malvern buys Spectral Dimensions

Malvern Instruments Ltd. (Malvern, Worcs, UK), a specialist in particle and flow characterization systems, has bought Spectral Dimensions, Inc. (Olney, Maryland) a privately held company producing near infrared (NIR) chemical imaging instrumentation and software.  Chemical imaging development and applications teams will continue to operate from the former Spectral Dimensions facility in Maryland. Financial terms were not disclosed.

Sanofi receives FDA Warning Letter for flu vaccine cGMP violations

FDA just sent a warning letter for cGMP violations relevant to flu vaccine manufacturing, this time to Sanofi-Aventis.

Pasted below, the full text of the letter sent to company SVP of vaccines, David Williams, on July 1st. 

This letter provides more insights into the challenges of ensuring compliance in flu vaccine manufacturing.  Problems included failure to segregate equipment, processing areas and materials adequately to prevent cross-contamination,  insufficient equipment maintenance, adherence to written procedures and validation of the methods used to ensure sterility.

Can isolators and fully automated equipment prevent more cGMP problems at vaccine manufacturing facilities? Stay tuned to Pharmaceutical Manufacturing and PharmaManufacturing.com for coverage of “hands off” aseptic manufacturing technology such as the mobile isolators now being used at the University of Kentucky. (For best practices from Japan, see the article recently published by Jim Akers and colleagues from Handai Biken and Shibuya Koygo.)

-AMS

“…The Food and Drug Administration (FDA) conducted an inspection of Sanofi Pasteur, Inc. (Sanofi), Discovery Drive, Swiftwater, Pennsylvania, between April 18 and April 28, 2006.  During the inspection, FDA investigators documented significant deviations from current good manufacturing practices (CGMP) in the manufacture of licensed biological products and Fluzone® monovalent concentrate batches.  These deviations from CGMP include the applicable requirements of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), Section 351(a) of the Public Health Service Act (PHS Act), and Title 21, Code of Federal Regulations, (21 CFR) Parts 210, 211, and 600-680.

At the close of the inspection, FDA issued a Form FDA 483, Inspectional Observations, that described a number of significant objectionable conditions relating to your facility’s compliance with CGMP.  Significant deviations observed during the inspection include, but are not limited to, the following:

Failure to keep equipment and supplies used in work on or otherwise exposed to any potentially pathogenic agent separated from equipment and supplies used in the manufacture of products to the extent necessary to prevent cross-contamination [21 CFR 600.11(e)(5)].  Hallway 135 in building 37 (Fluzone® production floor), which connects directly to the sterile gowning suite used for sterile processing and to the equipment airlock for passing equipment in and out of the sterile filtration room, does not provide for adequate segregation of early production materials from materials used in sterile processing.  During sterile filtration of influenza concentrate lot U08182, this common hallway was utilized to transport already-sterilized equipment into the equipment airlock as well as to transport soiled equipment and carts containing inoculated eggs, for personnel traffic, and to transfer reagents between rooms.