Novartis Slow To Correct Quality Problems


FDA issued (and released) Form 483 reports to three separate Novartis production facilities in 2011, including the Lincoln, Nebraska manufacturing plant. The Lincoln facility produces Excedrin, Bufferin, NoDoz and Gas-X Prevention – recalled last weekend due to potential product mix-ups –  in addition to manufacturing certain prescription drugs on behalf of Endo Pharmaceuticals.

The 483 report is issued at the close of a FDA inspection ONLY when inspectors have observed significant deviations from FDA regulations and/or Current Good Manufacturing Practices. Satisfactory inspections do not result in Form 483 reports.

The other two Novartis plants that received Form 483 reports in 2011 were the Sandoz manufacturing plant in Broomfield, Colorado (report issued 5/6/2011) and the Sandoz plant in Wilson, North Carolina (report issued 6/22/2011). Sandoz is a member of the Novartis family of companies.

All three FDA reports reveal significant lapses in attention to Quality Control and product safety. For example:

From the Sandoz Inc. (Wilson, NC) report

“Your Quality system is deficient and lacks an overall oversight of drug products manufactured at your site to ensure they have validated processes before release for commercial distribution.”

“Your firm released finished drug products for commercial distribution without a validated process.”

“Examination and testing of samples is not done to assure: that in-process materials conform to specifications.”

“Laboratory records do not include complete data derived from all tests, examinations and assay necessary to assure compliance with established specifications and standards.”

“There is a failure to supply potable water under continuous positive pressure.”

“There is no qualification performed for the … disinfection unit … installed in the water purification system. Your firm has never validated this unit after installed to ensure that it is effectively killing potential microorganisms.”

From the Sandoz, Incorporated (Broomfield, CO) report:

“Investigations of an unexplained discrepancy did not extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy.”

“The purified water in the laboratory failed specification for microbiology testing on 02/07/2011 … on 02/14/2011 … on 02/22/20 11 … and on 03/07/201 … The laboratory investigation stated that “the assignable cause is biological contamination due to stagnation of water in a non-circulating branch of the water system.” “Laboratory water is not a product ingredient and does not affect product quality.” Each time the problem was fixed with flushing of the system and retesting. Investigations were not performed on any impact the purified water might have had on the laboratory tests performed between the previous check and the one that was out of specification.”

“The quality control unit lacks authority to fully investigate errors that have occurred.” 

“Equipment was observed not clean and in sanitary condition.”

“An NDA-Field Alert Report was not submitted within three working days of receipt of information concerning significant chemical, physical, or other change or deterioration in a distributed drug product. Specifically, on 12/29/2010, your firm received a complaint from a pharmacist who reported finding a Methazolamide 50 mg tablet (batch number 191103) that appeared to look “twice as large as the others.” Your investigation found the tablet weighed {REDACTED} heavier than the targeted tablet weight of {REDACTED}. This exceeded your upper specification limit of {REDACTED} grams. The FDA Denver District was not notified of this out of specification.” 

“Not all adverse drug experiences that are both serious and unexpected have been reported to FDA within 15 calendar days of initial receipt of the information.”

And from the Novartis Consumer Health, Inc. (Lincoln, NE) report:

“Your Quality Unit has failed in the responsibility and authority to monitor Quality Systems designed to assure the quality of drug products manufactured and packaged at your firm. This failure is evidenced in the Observations below (2-13), as well as continued NDA Field Alerts and recalls for similar problems over the last several years.”

How long has this been going on? While FDA has not released the results of prior inspections at these three facilities, we can deduce the time frame from information contained in the reports resulting from the 2011 inspections.

Sandoz (Broomfield, CO): FDA inspectors noted four “repeat observations” from prior inspections; notably,

  1. Control procedures are not established which validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product (repeat observation from the 5/28/2010 FDA inspection),
  2. Investigations of an unexplained discrepancy did not extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy (repeat observation from the 5/28/2012 FDA inspection),
  3. Not all adverse drug experiences that are both serious and unexpected have been reported to FDA within 15 calendar days of initial receipt of the information (repeat observation from the 10/08/2008 FDA inspection), and
  4. Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to facility operations for its cleaning and maintenance (repeat observation from the 5/28/2010 FDA inspection).

Novartis Consumer Health (Lincoln, NE): FDA inspectors noted one repeat observation:

Investigations of an unexplained discrepancy did not extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy (repeat observation from the 4/5-16/10 FDA inspection).

Although the Novartis report contained “only” one repeat observation, the details contained in the report make it very clear that the problems at the Lincoln facility are long-standing. For example:

You have failed to adequately investigate 166 complaint instances of foreign tablets in your drug products since 2009.

You have failed to identify the root cause of customer complaints for solid dosage form foreign tablets of products manufactured at your firm since at least 2009.

This cavalier attitude towards quality control, customer complaints, and reporting requirements on the part of a major pharmaceutical corporation is unconscionable. And the delays in implementing corrections and improvements are inexcusable.

We wouldn’t hesitate to condemn this behavior by a manufacturing company that was based in China, India or some other “emerging” nation. Why should a North American plant get away with ignoring standard Good Manufacturing Practices?

Novartis – it’s time to clean up your act!

3 thoughts on “Novartis Slow To Correct Quality Problems

  1. From Indymedia portal:
    https://london.indymedia.org/articles/12078
    http://piemonte.indymedia.org/article/14735

    Here’$ how $andoz-Novarti$ foraging profe$$or$ and doctor$.
    Hundreds of thousands of euros, a river of money to bribe doctors to entice them to prescribe branded drugs SANDOZ (Novartis). So much for honoring the oath of Hippocrates.
    But not only so much money in cash, also leisure travel in London, Monaco, Kyoto and New York (pseudo scientific meetings), restaurant meals, and then again jewelery, leather bags, book publishing and editorial projects, notebook computers , blue jeans and promises of employment in Sandoz for friends and relatives. But there are also doctors more imaginative who have received sponsorship for cultural and scientific events, not there have been, and then a sales representative of Sandoz have filed a false certificate of participation and presence. During the conference, then these geniuses of doctors are absented from their hospital to go and enjoy some ‘well-deserved rest (both charged Sandoz). The greed that leads to overdoing it.
    All this to hospitals, doctors and professors complacent, who were willing to fill the patients with expensive medicines of the pharmaceutical giant Novartis. In particular two, quite expensive: the Omnitrope (Somatropin) and Binocrit. The first is a growth hormone and the second is a drug that increases red blood cell production ( well known in the world of doping as drugs of type anabolic and steroids). Reveal all this crappy things a database (which the leaders of Sandoz also had the foresight to keep prominently on the company server) and an embarrassing dossier of the pharmaceutical company (which very rocambolescamente came into our hands) and some “Letters of disciplinary complaint “that the leaders of the pharmaceutical company Sandoz, in these days, have sended to pharmaceutical employees and informants that were involved in the investigation, following investigations by the Prosecutor of the Republic of Busto Arsizio and” NAS “, Nucleus of the Anti -sophistication of the Carabinieri (coordinated by the Public Prosecutor of Rimini). The charges are quite heavy: conspiracy, corruption, incitement to corruption, distribution and administration of drugs that can to cause harm to public health, extortion, fraud against the national sanitary service, falsification of documents, comparaggio (bribery).
    Many the famous and renowned hospitals that were involved are from north to south of the Italian Country:
    Azienda Ospedaliera Universitaria “S. Luigi Gonzaga” di Orbassano (TO), Struttura Complessa di Diabetologia del Dipartimento Medico dell’Azienda Ospedaliera Universitaria ‘Maggiore della Carità’ di Novara, Modulo di Endocrinologia del Reparto di Medicina Generale dell’Ospedale “Versilia’ di Camaiore, Reparto di Endocrinologia del “Policlinico San Matteo” di Pavia, Onlus “Il bambino e il suo pediatra” di Galliate (NO), Struttura Semplice di Auxoendocrinologia dell’Azienda Ospedaliera “Spedali Civili’ di Brescia, Reparto di Malattie Endocrine Istituto Pediatrico “Giannina Gaslini” di Genova, Centro per la Prevenzione ed il Trattamento dell’Obesità in Età Evolutiva dell’Istituto Pediatrico “Giannina Gaslini” (GE), Struttura Semplice di Endocrinologia presso l’Ospedale Infantile “Regina Margherita” di Torino, Servizio di Endocrinologia Pediatrica dell’Ospedale Regionale per le Microcitemie Azienda USL, 8 di Cagliari, Reparto di Endocrinologia e Malattie del Metabolismo del “Policlinico Universitario Gemelli” di Roma, Reparto di Endocrinologia dell’Ospedale “Bambin Gesù” di Roma, Reparto di Endocrinologia dell’Ospedale “S. Anna e S. Sebastiano” di Caserta, Reparto di Pediatria dell’Ospedale “SS. Annunziata” di Chieti, Reparto di Endocrinologia e Diabete dell’Ospedale Pediatrico “Giovanni XXIII” di Bari, U.O. di Endocrinologia presso gli Ospedali Riuniti `Villa Sofia – Cervello” di Palermo, Divisione di Auxologia dell’Azienda Ospedaliera “Santobono” di Napoli, “Policlinico G. Martino” di Messina, Ospedale “Papardo” di Messina, Struttura Complessa di Nefrologia e Dialisi degli Ospedali Riuniti di Foggia, Ospedale “G. Mazzini” di Teramo, Ospedale di “Santa Maria della Misericordia” di Perugia, Casa di Cura privata “Ars Medica” di Roma, Casa di Cura “Guarnieri” di Roma, Reparto di Nefrologia e Dialisi dell’Ospedale di Anzio, Struttura Semplice Reparto di Endocrinologia e Malattie del Metabolismo presso il Policlinico Universitario “Agostino Gemelli” Roma, Casa di Cura Privata Accreditata “Nuova Clinica Annunziatella” di Roma, Reparto di Nefrologia – Dialisi dell’Ospedale “GB Grassi” di Ostia, Unità Cure Palliativo e Assistenza Domiciliare dell’Ospedale “S. Eugenio” di Roma, Reparto di Nefrologia e Dialisi dell’Ospedale “S. Eugenio” di Roma, Reparto di Endocrinologia Pediatrica del Policlinico “Umberto I’ di Roma, Reparto di Medicina, Nefrologia e Dialisi del Policlinico ‘Tor Vergata’ di Roma, Reparto di Nefrologia e Dialisi dell’Ospedale “C. Barnabeo” di Ortona, Reparto di Endocrinologia dell’Azienda Ospedaliera di Padova, Reparto di Endocrinologia dell’Ospedale “S. Anna e S. Sebastiano” di Caserta, Reparto di Pediatria dell’Ospedale ‘SS. Annunziata’ di Chieti, Reparto di Endocrinologia e Diabete dell’Ospedale Pediatrico “Giovanni XXIII’ di Bari,Francesco Saverio Indovina, U.O. di Endocrinologia presso gli Ospedali Riuniti “Villa Sofia – Cervello” di Palermo, Divisione di Auxologia dell’Azienda Ospedaliera “Santobono” di Napoli, Policlinico “G. Martino” di Messina, Ospedale ‘Papardo” di Messina, Struttura Complessa di Diabetologia del Dipartimento Medico dell’Azienda Ospedaliera Universitaria “Maggiore della Carità” di Novara, Modulo di Endocrinologia del Reparto di Medicina Generale dell’Ospedale ‘Versilia’ di Camaiore, Dipartimento di Endocrinologia e Malattie Metaboliche dell’Università di Genova, Servizio di Auxo-Endocrinologia Pediatrica dell’ Ospedale Pediatrico ‘Meyer’ di Firenze, Centro Dialisi della Casa di Cura privata ‘Nuova Casa di Cura’ di Decimomannu, Reparto di Nefrologia e Dialisi presso l’Ospedale “S. Carlo Borromeo” di Milano, Reparto di Nefrologia e Dialisi dell’Azienda Ospedaliera “S. Paolo” di Milano, Struttura Complessa di Nefrologia e Dialisi dell’ Azienda Ospedaliera ‘Carlo Poma’ di Mantova, Reparto di Pediatria dell’Ospedale “Stabilimento di S. Chiara” di Pisa, Reparto di Endocrinologia dell’Ospedale Infantile ‘Regina Margherita – S. Anna’ di Torino, Sezione Regionale della Federazione Nazionale Sindrome di Prader Willi di Torino.
    But it is all too easy to find scapegoats in the employees and absolve the entire ruling class. Certain decisions, as experience teaches (see case of the ENI corruption in Nigeria) are made at the level of the Board of directors and not certain to level of Group employees. Therefore it is unthinkable that certain determinations are taken to complete without the knowledge of the top management. So the question is, but company executives knew? Obviously yes. They knew, have approved, and foraggiavano. On the other hand is the ropponiano theorem, it is impossible to move a lot of money without the top of society are aware of. All this illegal and corruptions activities are clearly finalized at encouraging the sale of products of Sandoz to raise cashGiven this impressive round of money (the company’s money and not of the individual employees is good to specify this) the vertices of Sandoz could not not know. This comes as no surprise that much, we know very well that all the drug companies make these shady deals (as also demonstrated a news reports on Rai 3 Report and a dossier of the program of the Hyenas “ricettopoli”).
    Think about this the next time a doctor will prescribe to you a drug (especially if of one particular manufacturer). Di seguito la trascrizione del dossier Sandoz:
    Here is the transcript of the Sandoz dossier – in Italian – (see document attached and reproduced here pdf):

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  2. I haven’t found anything that works as well as Excedrin extra strength for my headaches as well. Looking forward to hearing when these products will be available again.

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  3. When will excedrin migrane be available again??? I really wish you could come up with a decision. They helped my migranes better than anything.. I dont take narcotics and they are easier to get than an OTC medication.. I just dont get it…. Please respond back.. Thank you

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