FiercePharmaManufacturing

Executive suite not spared in J&J reorg tied to quality concerns

Eric Palmer — Thu, 02 Feb 2012 09:07:11 -0500

Management at the factory level feel the heat under any FDA consent decree, but a shake-up at Johnson & Johnson ($JNJ) this week showed that the pressure can extend into the executive suite.

Two J&J group chairmen and long-term executives left this week, presumably because of ongoing difficulties in the company's consumer health business, The Wall Street Journal reports. The departures come less than a year after manufacturing problems sparked a revamp that gave them new authority in consumer health.

Patrick Mutchler, who was put in charge of overseeing the McNeil Consumer Healthcare unit in April, is retiring after 35 years at the company. The company also confirmed that Pericles Stamatiades, a 28-year J&J veteran, is also leaving. He was named strategist for consumer businesses in the same April reorganization. Mutchler's duties will be taken over by Roberto Marques, who heads J&J's consumer businesses in North America. Stamatiades' responsibilities are being parsed out among other management.

A string of recalls of J&J products began in late 2009 affecting products including Tylenol, Benadryl, Motrin and Zyrtec, prompting FDA intervention and congressional hearings. McNeil Consumer Healthcare immediately closed its Fort Washington, PA, plant after an April 2010 recall of more than 136 million children's and infants' products.

McNeil entered into a consent decree with the FDA in March covering plants in Lancaster, PA, and Las Piedras, Puerto Rico, in addition to the Fort Washington facility, which is undergoing a $100 million renovation.

Johnson & Johnson moved some of the affected products to other plants but problems have persisted. Just in August the company yanked another 2.5 million units of Tylenol.

U.S. sales at McNeil fell to $1.4 billion last year, from a peak of $3.1 billion in 2008, WSJ notes, citing Fargo Securities.

Suggesting, however, that the quality control issues CEO William Weldon wants addressed extend beyond McNeil, Johnson & Johnson said day-to-day operations at McNeil Consumer Healthcare will continue to be led by the executive named in April to oversee the unit.

In a statement sent to FiercePharmaManufacturing, the company said: "The U.S. OTC business will continue to be operated as a separate, integrated business in order to maintain its focus on quality and compliance, and on the successful reintroduction of OTC medicines in the U.S. market. The business will continue to be led by U.S. OTC President Denice Torres."

- here's the WSJ story

Pfizer suspects 30 packs of contraceptives mispackaged; pulls 1 million just in case

Eric Palmer — Thu, 02 Feb 2012 06:53:35 -0500

Workers at a Pfizer ($PFE) plant in upstate New York that makes birth control pills are learning that if you mispackage pills, it can create unwanted problems.

Pfizer announced Wednesday that it is recalling 1 million packets, 14 batches of Lo/Ovral-28 pills and 14 batches of its generic counterparts, norgestrel and ethinyl estradiol tablets. The pills were manufactured and packaged by Pfizer but, Bloomberg says, marketed by Akrimax Rx Products under the Akrimax Pharmaceuticals brand.

Some packets were found with too many active tablets, while others had too few and so the active and inert pills were out of order. Pfizer was notified after an alert customer noticed she had a pink pill where a white one belonged, indicating the active and inert portions of the pack were out of order.

Pfizer told the media there were three ways that on rare occasions the problem could have materialized:

The design of the packaging line could allow for incorrect placement of the pills;

A mechanical system for detecting defective packs could miss one in "very, very infrequent" times; or

Plant workers could also miss problem packs.

Pfizer said it has since fixed the problems. The company said it believes that only 30 packs were mispackaged, but it withdrew an additional 999,970 just to be safe.

- here's the WSJ story
- read Bloomberg's take
- here's the Pfizer statement

Related Article:
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Roche plant spared from sale runs into GMP issues

Eric Palmer — Wed, 01 Feb 2012 21:39:02 -0500

A South Carolina plant Roche ($RHHBY) had on the auction block last year has developed manufacturing issues that have interrupted production of its weight control drug Xenical.

Health officials in the U.S. and Europe have been notified, and the Swiss company is bringing in an expert to help it get a handle on "Good Manufacturing Practice (GMP) deficiencies discovered during an internal audit," the company said in a statement emailed to FiercePharmaManufacturing. No specifics were given.

The Florence, SC, plant manufactures intermediates and active pharmaceutical ingredients (API) used in Tamiflu, Xeloda, Xenical and Valcyte as well as the PEG reagent for Pegasys. The company said "based on the current benefit/risk assessment and high medical need for patients," it continues to release Xeloda, Pegasys, Valcyte, Tamiflu and previously released Xenical material. No recalls have been requested by authorities.

The plant, built in 1992, was one of 6 U.S. facilities targeted in late 2010 when the company announced it would close facilities and layoff 4,800 employees to save $2.4 billion by 2012. That is about half the $5.7 billion it bid last week for gene sequencer Illumina ($ILMN). In its earnings announcement Wednesday, the company reported net income last year rose to 9.5 billion Swiss francs ($10.3 billion) from 8.9 billion francs a year earlier. It said its cost-cutting had saved the company 1.8 billion francs last year and will lead to 2.4 billion francs in savings this year.

Cuts elsewhere apparently were enough to save the Florence plant, at least in the short term. Roche announced in July it would keep the plant open for now.

- get the Bloomberg earnings story

Related Stories:
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Medical devicemakers double down on FDA

Eric Palmer — Wed, 01 Feb 2012 17:30:11 -0500

Medical device manufacturers are doubling down on the FDA, agreeing to pay $595 million in fees over 5 years in exchange for promises of more and faster approvals and better communication from the agency. That is about twice what was paid under the program that expires Sept. 30. The FDA said it will hire about 200 people to speed up the process, and an independent consultant to recommend process improvements. Release | Story

Pakistan drug manufacturers make plea for oversight

Eric Palmer — Wed, 01 Feb 2012 16:07:09 -0500

In many countries, asking for more regulation of the pharmaceutical industry would seem like asking for trouble. But not in Pakistan, where a drug manufacturing scandal involving the deaths of more than 130 patients and the sickening of hundreds more has led the industry to ask the government for oversight.

Pharma Bureau, an association of multinational pharmaceutical companies, sent a statement to the government saying an independent Drug Regularity Authority is needed to rebuild public trust and prevent episodes like the one playing out in Lahore. In that case, patients died after being treated at the Punjab Institute of Cardiology, which reportedly gave them drugs received as a donation.

Following a meeting of the Khyber Pakhtunkhwa chapter of the Pakistan Pharmaceutical Manufacturing Association, Riaz Arshad, the former chairman of the PPMA, told a Pakistani newspaper the pharmaceutical industry was the country's most-deregulated sector because there is no authority overseeing its operations.

"A mechanism to regulate drug manufacturing, registration, licensing, pricing, import and export and quality control of drugs is need of the hour, but the matter has remained in limbo," Arshad told The News International.

He said the industry is producing about 90% of the drugs used in Pakistan.

Gulf News said samples of drugs tested in Paris and London were reportedly contaminated with a very high quantity of an anti-malarial chemical. The plant where the drugs were believed to have been manufactured has been sealed.

- read The News International story
- check out the Gulf News story
- here's more

Amylin's OH plant prepped for Bydureon's U.S. debut

Eric Palmer — Wed, 01 Feb 2012 13:16:01 -0500

In anticipation of the U.S. approval of Bydureon, San Diego's Amylin Pharmaceuticals ($AMLN) was already amping up production of the diabetes drug at its West Chester Township, OH, plant where the med was being manufactured for the European market.

The company has been making some parts of the drug and holding it for final packaging, a spokeswoman told the Middleton Journal.
The drug is now being rolled out for delivery to pharmacies this month.

The FDA gave approval of the first once-weekly version of Amylin's diabetes shot last week. It was the third try for the company and its Dublin-based partner Alkermes ($ALKS). The drug uses Alkermes' polymer microsphere technology, manufactured in Wilmington, Ohio, to make it last longer. Alkermes has said it will receive 8% of the drug's net sales and its financial release Thursday it reported it earned $300,000 in the third quarter from sales in the EU.

There are significant expectations for Bydureon, which is intended to replace standard twice-a-day injections, both because of its dosage and the so-called Type 2 diabetes epidemic in the U.S. Most of the estimated 28.5 million people in the country with diabetes have Type 2. The disease costs the nation an estimated $174 billion a year in medical expenses and lost productivity. A federal report in 2010 estimated the disease costing $83 billion annually in hospital fees--23% of total hospital spending.

Deutsche Bank analyst Robyn Karnauskas in New York told Bloomberg Bydureon's U.S. revenue may surpass $1 billion in 2015.

But it is not all upside for the drug. In a head-to-head study with Victoza earlier this year, the rival Novo Nordisk ($NVO) drug had a superior result. Now analysts will be studying whether Amylin's pricing strategy--it intends to charge $323 for a month's supply versus $421 for the high-dose version of Victoza--will help make up the difference.

The Ohio plant, with about 300 employees, started operations in 2009, but approval of Bydureon proved elusive. Amylin's second attempt was thwarted in October 2010, when U.S. regulators expressed concern about irregular heartbeats in patients with impaired kidney functions. It received approval in Europe last June.

- here's the Middleton Journal story
- read the Bloomberg story

Special Report: Bydureon - 15 top blockbuster contenders

Novartis says Nebraska plant to reopen midyear

Eric Palmer — Tue, 31 Jan 2012 08:46:19 -0500

The Novartis ($NVS) Nebraska plant closed in December because a host of over-the-counter products contained stray pieces from other drugs is expected to reopen this summer.

Twice in recent days officials with the Swiss company said manufacturing problems that led to a January recall of Excedrin and other products were being addressed and that the Lincoln plant should reopen midyear.

CEO Joseph Jimenez included sales from the plant in his guidance for 2012 during a conference call with investors, reported In-Pharmatechnologist.com.

"We have people in the site right now working on remediation," he said. "We wanted to put an assumption into our guidance that we felt that we could deliver upon. So I'm fairly confident that we can do this."

Then in a statement emailed to FiercePharmaManufacturing today relating to reports that the company had released, temporary worker's spokeswoman Julie Mascow said: "Novartis Consumer Health is actively working toward a plan to resume manufacturing operations at the site and expects to start shipments midyear."

"We do not expect the temporary suspension in production to impact employees. However, we've had to release some of the temporary workers. Approximately 40 temporary workers are currently being retained to work in manufacturing and packaging," she continued.

Novartis set aside $120 million to address the issues. The shutdown not only cost Novartis time, sales and reputation, it has affected Endo Pharmaceuticals ($ENDP), which had the Opana ER painkiller and other analgesics produced there.

Pharmalot reported today that a new FDA inspection report, which includes inspections from Dec. 14 through Jan. 20, suggested that problems are ongoing. The report also pointed out that Novartis only recently got around to notifying veterinarians that the same potential problems could affect a drug used to treat dogs for separation anxiety.

A Novartis spokesman wrote FiercePharmaManufacturing to say that while there was only a rare chance of a problem, it notified vets out of an abundance of caution.

- get the the In-Pharmatechnologist story
- here's the WOWT.com report
- read the Pharmalot story
- here's the inspection report (.pdf)

Related Article:
FDA: Novartis plant shows patterns of problems

Teva's Cephalon recalls leukemia drug over fragments in vial

Eric Palmer — Mon, 30 Jan 2012 19:18:15 -0500

Teva Pharmaceutical Industries' ($TEVA) Cephalon has recalled one lot of leukemia drug Treanda after glass fragments were found in one of the vials.

FDA-approved labeling for Treanda states that the product, lot TB30111, is manufactured by Teva's Dutch subsidiary, Pharmachemie BV, the Israeli online news service Globes reported. Israel-based Teva acquired Pennsylvania-based Cephalon in October for $6.8 billion.

Wholesalers, distributors, hospitals and providers have been notified. Cephalon has not received reports of an adverse event and a Teva spokeswoman said the company does not believe that much of the lot remains in stock.

The recall was only one of several factors that weighed on the stock price of the world's largest maker of generic pharmaceuticals, Bloomberg Business News reported. Teva shares declined 2.7 percent Jan. 29, the biggest slump since Dec. 29, to the equivalent of $44.84, at the 4:30 p.m. close in Tel Aviv. The U.S.-traded shares closed at $44.91 on Jan. 27. The Tel Aviv shares are up 9.5 percent this year, compared with a 3.2 percent gain for the benchmark TA-25 Index.

Other factors affected the decline in stock as well. Last week, a U.S. federal court ruling cleared the way for competitor Watson Pharmaceuticals ($WPI) to sell a generic version of Sanofi's blood thinner Lovenox, a drug for which Teva also is seeking to market a copy.

Also depressing investor enthusiasm, according to analysts, was a Medicaid rule issued Jan. 27 that will raise the rebates drugmakers pay each time their products are dispensed to Medicaid patients in the U.S. Rebates will rise to 13 percent from 11 percent for generic-drug manufacturers.

- read Globes' story
- here's the FDA recall
- get the Bloomberg story

Pfizer workers at manufacturing hub sue over whiplashed retirement plans

Eric Palmer — Mon, 30 Jan 2012 19:05:11 -0500

Pfizer ($PFE) employees at the company's manufacturing hub in Puerto Rico are not happy with what company shenanigans did to Pfizer's stock price and to their retirement plans.

They allege in a class action lawsuit that the company's controversy over the safety of painkillers Celebrex and Bextra took a toll on their retirement funds, and that the company did not sufficiently manage the funds. Bextra was taken off the market.

Pharmalot reports that the employees claim that the stock also was hurt by sales and marketing practices that eventually resulted in Pfizer paying a $1.2 billion fine and a felony plea to settle an investigation into what the U.S. Department of Justice called fraudulent marketing of several drugs.

The lawsuit says the retirement plans were vulnerable to Pfizer's practice of matching employee contributions with shares. It was filed on behalf of employees who held more than 30% of their assets in Pfizer securities or common stock funds.

A Pfizer spokesman pointed out to The Associated Press that a New York court had rejected similar claims in 2009. But a lawyer for the Pfizer employees claims that tax and retirement plan laws in Puerto Rico make this suit different.

- read the AP story
- here's the Pharmalot article

Medicines Company, APP settlement includes manufacturing agreement

Eric Palmer — Mon, 30 Jan 2012 17:11:41 -0500

A fill/finish manufacturing agreement is part of the settlement between The Medicines Co. ($MDCO) and APP Pharmaceuticals ($APPX) over generic versions of The Medicines Co.'s lead product, Angiomax. In an SEC filing, The Medicines Co. said it would pay $30 million to license some APP drugs. It also said The Medicines Co. will buy from APP "a specified minimum percentage of its requirements for Angiomax finished product for sale in the U.S. at a fixed price per vial supplied and reimburse APP for specified development costs and capital expenditures made by APP." The fill/finish agreement is slated to end May 1, 2019--the date upon which APP has been granted a license to launch a generic version of the anticoagulant--but may be extended for two years at the option of The Medicines Co. The generic could be launched earlier under certain specific circumstances and could include an authorized generic version that would be supplied by The Medicines Co. Story

Company whistleblower program part of Ranbaxy consent decree

Eric Palmer — Mon, 30 Jan 2012 16:52:48 -0500

Ranbaxy Laboratories has been given a blueprint for removing regulatory constraints it incurred when it was discovered that some of its plants had severe manufacturing and data integrity issues. Now it must prove it can follow it.

The company has said it is pleased with the progress being made, but read the 55-page consent decree with the Justice Department, disclosed last week, and you see just how many hoops the Indian company must jump through. These include a requirement that it establish a whistleblower-like disclosure program for employees.

A big part of the decree--as pointed out by FiercePharma on Friday--is that the Indian company is giving up the first-to-file (FTF) exclusivity rights on three undisclosed generics. It has 8 pending applications, some obviously worth more than others, so the potential impact is yet unknown.

But as Ravi Ananthanarayanan points out in an article on livemint.com, for another four FTF drugs it has to comply with data submission and audit requirements by certain dates or lose exclusivity for those as well.

A review of the consent degree to which the blog Pharmalot links shows just how high the hoops are being held. It essentially requires the company to hire experts in data integrity and manufacturing who will watch over its shoulder, make recommendations, and, if they don't like the responses they get, take the issues up with the FDA.

Among other things, Ranbaxy must hire a completely independent and outside auditor to be a data integrity expert to work with the company and the FDA on internal audits. The data expert's purview can extend to auditing third-party suppliers and if any resist, the expert promptly notifies the FDA.

Ranbaxy has about four months to establish an Office of Data Reliability, staffed by the chief data reliability officer who shall report directly to the managing director of Ranbaxy and will have broad powers to make recommendations about applications and how employees are performing. Any recommendations made to the director must be reported to the FDA as well. Tight limits are put on all applications from Ranbaxy until this office is running.

The decree puts severe limits on a closed plant in Gloversville, N.Y., if it is reopened, along with plants in India. For its plants in Paonta Sahib and Dewas in India, it must hire an independent current good manufacturing practices expert who can report to the FDA independently if there are any disagreements with Ranbaxy over recommended improvements.

And in case anything slips by these controls, Ranbaxy must establish, and publicize, an anonymous disclosure program so employees can report to the data reliability office any "suspected violations."

As the livemint.com article points out, the fact that regulators approved Ranbaxy to sell generic Lipitor in the U.S. may be a sign of faith. Still, all of these stipulations take time and money. And violate the decree, or submit false data again, and the company faces tens of millions of dollars in fines.

- see the decree (.pdf)
- read the article on livemint.com
- here's the Pharmalot story

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Gutted J&J consumer healthcare plant another year from reopening

Eric Palmer — Mon, 30 Jan 2012 16:14:51 -0500

Johnson & Johnson ($JNJ) will continue to ramp up its supply of over-the-counter drugs this year but it will be another year before its key manufacturing facility in Fort Washington, PA, will reopen.

Chairman and CEO William Weldon, in a conference call with investors last week, said its McNeil Consumer Healthcare company expects to open the "state-of-the-art" plant in 2013.

The facility was immediately closed after the April 30, 2010, recall of more than 136 million children's and infants' products in the largest recall of children's medication in history, according to an article on Montgomerynews.com. It was one in a string of recalls tied to the facility. Just last August the company yanked another 2.5 million units of Tylenol.

McNeil entered into a consent decree with the FDA in March 2011 covering plants in Lancaster, PA, and Las Piedras, Puerto Rico, in addition to the Fort Washington facility. In April 2011, Weldon said the plant was being gutted and the company would invest more than $100 million for its renovation.

In his call, Weldon said supply issues and remediation expenses had nicked 2011 operating sales 0.7%. In the three years prior to the closing, the plant generated average annual revenues of $650 million.

He told investors in the call that all commitments to date under the consent decree had been met and that Tylenol Severe Cold caplets and certain children's and infants' Tylenol products, have been reintroduced to the market.

The McNeil product recalls brought to light shortcomings of the company's plant recovery and supply chain process. Weldon said in the calls that Johnson & Johnson was making good strides in revamping its manufacturing and quality processes "with our goal of significantly reducing the number of suppliers and external manufacturers while improving quality."

"Our efforts in this area are already paying off with better inspection records despite an increase in regulatory activity," he said.

- listen to the conference call
- here's the Montgomerynews.com story

Lonza board boots CEO Borgas

George Miller — Thu, 26 Jan 2012 10:49:41 -0500

Pressure from Asian low-cost chemical and drug ingredient suppliers, combined with high Swiss energy costs impacting manufacturing operations, have yielded poor financial performance at Lonza and the ouster of CEO Stefan Borgas. "Our decision to replace Borgas was made during the past 48 hours and is backed by the board and management," said board chairman and acting-CEO Rolf Soiron. Story

Ranbaxy, FDA enter consent decree over GMP, data breaches

George Miller — Thu, 26 Jan 2012 09:36:53 -0500

Plans for the $500 million that Daiichi Sankyo set aside to get problem child Ranbaxy out of regulatory jail became clearer Wednesday with the filing of a consent decree. The Indian-based drugmaker and the FDA have agreed to terms that will allow the manufacturer to end several years of market restrictions imposed by the regulator for manufacturing and data-reporting violations.

The court action stems from issues stretching back to 2008. Prominent among them was the company's inadequate separation of penicillin and non-penicillin drug production and inadequate attempts to prevent the contamination of sterile drugs, according to Bloomberg. Alleged falsification of data in manufacturing and other records was another driver, said IBN.

The consent decree was described as "unprecedented" in its international scope, said the Justice Department in the IBN report. The agreement was signed in December and filed Wednesday in a Maryland court.

The decree's terms prevent Ranbaxy from manufacturing drugs for the U.S. market at facilities in Paonta Sahib, Batamandi and Dewas, India, until drugs can be manufactured at such facilities in compliance with U.S. manufacturing quality standards. The facilities were previously tagged for GMP violations that led to an FDA import alert.

As reported last month, Daiichi earmarked $500 million to resolve Ranbaxy liabilities, causing the Japanese giant to cut pay for executives and directors.

- here's the FDA release
- see the Bloomberg report
- here's more from IBN Live

Warnings analysis spotlights analytics weakness

George Miller — Thu, 26 Jan 2012 08:11:15 -0500

Analytics issues appear in the majority of FDA warning letter citations for manufacturing, including unvalidated methods and inadequate procedures for responding to out-of-spec test results. The European Compliance Academy reported the findings after reviewing warning letters issued to 14 makers of drug ingredients.

The academy noted 2011 saw a nearly three times rise in the number of warning letters issued to such manufacturers. Companies in the U.S. and China led in terms of warnings with four each. India garnered three while China, Spain and the U.K. each earned one apiece.

The academy's analysis showed that manufacturer location had no bearing on the prevalence of analytics shortcomings. Another finding: They were prominent in 2010 warnings, as well.

Among specific issues the academy found were misinterpretation of analytical data, inadequate documentation, and failure to investigate out-of-spec findings.

Failure to conduct stability tests, missing analytical raw data, and lack of SOPs are among common citations.

- here's the report

Special Report: Fierce's 2011 warning letters report
Special Report: Frightening Phrases: Warning letter language to watch
Special Report: The Top 12 GMP Violations