"The Gold Sheet" :: Elsevier Business Intelligence

DoJ and GMPs: A Prosecutor’s Take on Enforcing Product Quality

Thu, 25 Apr 2013 00:00:00 -0400

The wave of marketing promotions undertaken by the Department of Justice over the past decade may be abating, but prosecutors are looking at manufacturing violations as fertile new territory for cases. One prosecutor shares her thoughts on how companies can protect themselves.

Are GMP Violations The “Next Hot Thing” In False Claims Act Litigation?

b.sandburg@elsevier.com — Thu, 25 Apr 2013 00:00:00 -0400

Former prosecutors say there are cases pending under seal, but it is uncertain whether the government will intervene. They note the difficulty in proving the allegations and say FDA’s regulatory regime may be a better route for handling GMP issues.

Industry Concerned About Excipient Registration and Data Protection Under FDASIA

j.eglovitch@elsevier.com — Thu, 25 Apr 2013 00:00:00 -0400

FDA faces a heavy workload in implementing the supply chain provisions of FDASIA, yet developing a unique facility identifier (UFI) for foreign and domestic establishments will be a priority, as many aspects of the law hinge on having this identifier, said an agency official. In the meantime, there are questions concerning the workability of FDASIA’s excipient registration provision and whether confidential information will be protected when FDA exchanges information with foreign governments during inspections.

EU and U.S. Developing New Approaches to Prevent Drug Shortages

j.eglovitch@elsevier.com — Thu, 25 Apr 2013 00:00:00 -0400

A UK MHRA official said there is a “regulatory dilemma” between meeting GMP enforcement obligations and preventing drug shortages. New changes in the EU GMP Guide aim to take a more proactive approach to drug shortages by requiring early notification by manufacturers, while in the U.S. a new drug shortage prevention program called the Accelerated Recovery Initiative (ARI) is finally getting off the ground.

Compounding: How Does FDA Expand Oversight Without Legislation?

d.gingery@elsevier.com — Thu, 25 Apr 2013 00:00:00 -0400

After House Republicans indicate legislation expanding agency’s oversight of compounding is unlikely, FDA could consider other regulatory options, like changing internal policies or hoping a court clarifies its regulatory authority.

FDA Finds More Action Required in Less Developed Nations – and Denver

b.cox@elsevier.com — Thu, 25 Apr 2013 00:00:00 -0400

FDA inspection data shows a clear trend over the past four years: Investigators are somewhat more likely to find GMP issues at manufacturing facilities in less developed nations and less developed regions. However, the data shows more pronounced variation among FDA districts in the U.S., with some finding far greater needs for corrective action than others.

In Brief

Thu, 28 Mar 2013 00:00:00 -0400

WHO GMP revisions proposed; ICH M7 guide drafted; four CEPs withdrawn; 28th China plant added to FDA’s import alert list.

FDA Drug GMP Warning Letters from FY 2012

Thu, 28 Mar 2013 00:00:00 -0400

The 40 drug GMP warning letters FDA issued in fiscal year 2012 are listed here by type of manufacturing facility, along with a summary of the issues raised.

Manufacturers Provide SEC GMP Enforcement Updates

b.cox@elsevier.com — Thu, 28 Mar 2013 00:00:00 -0400

Recent portrayals of drug GMP enforcement activity in reports to stockholders ran the gamut from acknowledging the likelihood of adverse financial impacts to suggesting that remediation in response to 483s must be going well because there hasn’t been a warning letter.

FDA Calls for Greater Compliance With FAR Reporting Requirements

b.cox@elsevier.com — Thu, 28 Mar 2013 00:00:00 -0400

FDA examines field alert report data for early warnings of emerging quality issues, but finds only questions as many companies submit few if any FARs to the agency. Meanwhile, some manufacturers are finding benefits from reporting and dealing with drug defects and errors, improving corporate culture and in one case saving nearly $1 billion.

After Issuing 40 Drug GMP Warning Letters in FY 2012, FDA Aims to Improve Drug Quality This Year

j.eglovitch@elsevier.com — Thu, 28 Mar 2013 00:00:00 -0400

FDA Commissioner Margaret Hamburg said that improving drug product quality will be one of the agency’s highest priorities this year and advised industry to do the same as the agency spearheads a number of new initiatives in this area. Yet is FDA taking a similarly aggressive approach to enforcement, given that the number of drug GMP warning letter declined 23%?

Regulators Closer to Harmonizing QbD Review Approaches Under Pilot

j.eglovitch@elsevier.com — Thu, 28 Feb 2013 00:00:00 -0500

Regulators in the U.S. and Europe are a little closer to harmonizing their reviews of new drug applications containing QbD elements under a joint review program. Areas of agreement include what is meant by QTPP and criticality, while areas of disagreement include NIR methods and design space development.

Drug Shortages Give Ben Venue Relief In FDA Consent Decree

b.sandburg@elsevier.com — Thu, 28 Feb 2013 00:00:00 -0500

The consent decree permits the company to continue to manufacture more than 100 drugs, 20 of which are on FDA’s current drug shortage list. Ben Venue must prove compliance with good manufacturing practice requirements before it can manufacture its other drugs.

Pharmaceutical lndustry Proposes Ideas for Number of Batches, Monitoring Production

j.eglovitch@elsevier.com — Thu, 28 Feb 2013 00:00:00 -0500

The pharmaceutical industry is advancing ideas for estimating the number of batches to run during process validation as well as how to establish robust monitoring and testing programs for products on the market. Industry has been hammering out these details in the absence of many specifics in the FDA’s 2011 process validation guidance on these areas.

Friend or Foe? The Role of Regulatory Relief in Drug Shortages

b.cox@elsevier.com — Thu, 28 Feb 2013 00:00:00 -0500

FDA’s Janet Woodcock argues that strong enforcement prevents drug shortages, dismissing allegations that crackdown under Hamburg triggered shortage crisis. There is more agreement, however, on the role of other factors such as group purchasing organizations, or GPOs, in the crisis.

Generic Industry Has Made Progress Implementing QbD

j.eglovitch@elsevier.com — Thu, 28 Feb 2013 00:00:00 -0500

The generic drug industry has progressed swiftly with QbD, reports an FDA OGD official. The share of ANDAs containing QbD elements has tripled from 25% in June 2012 to 83% in January 2013 – while brands struggled to reach 14% QbD last year with their NDA filings.

FDA Quality Metrics Could Lead Market to Pay for Quality, Prevent Shortages, Woodcock Says

b.cox@elsevier.com — Thu, 28 Feb 2013 00:00:00 -0500

FDA aims to establish quality metrics that GPOs could use to choose the most robust, highest quality drug manufacturers, CDER Director Janet Woodcock says. Move could strengthen position of quality units as firms shift to compete on quality instead of price.

FDA, Industry Group Seek Input on How to Prevent Drug Shortages

b.cox@elsevier.com — Thu, 28 Feb 2013 00:00:00 -0500

FDA requests comment on quality metrics, BARDA and other ideas for resolving and preventing drug shortages, while ISPE conducts industry survey on root causes and strategies for addressing the shortages.

GDUFA: How Much Does FDA Know About U.S. Generic Market After Facility Self-Identification?

d.gingery@elsevier.com — Fri, 25 Jan 2013 00:00:00 -0500

FDA continues to analyze facility data following generic drug facility fee announcement; some fees were higher than anticipated after fewer manufacturing plants registered than expected. But industry believes the count is accurate and illustrates the influence of foreign manufacturers.

Five Years Later, Legacy Biologics Still Face ‘Next Heparin’ Risks

b.cox@elsevier.com — Fri, 25 Jan 2013 00:00:00 -0500

Several factors continue to slow efforts to modernize legacy biologics’ compendial monographs against fake ingredients like the ones someone put in heparin in 2008. Hyaluronate, the ‘poster child’ for monograph modernization; New NDAs for pancreatin create new modernization challenges; Heparin maker vertically integrates to prevent adulteration.

Industry Urges EU to Align Draft Validation Guidance with ICH and FDA

j.eglovitch@elsevier.com — Fri, 25 Jan 2013 00:00:00 -0500

European pharmaceutical manufacturers say that the European Union’s draft process validation guidance should be better aligned with the International Conference on Harmonization and FDA lifecycle approaches to process validation and that major changes are needed before it is a workable guideline. EMA issues two concept papers to revise Annex 15 and Annex 17 to reflect lifecycle approaches.

EU Revising Four GMP Chapters on Production Controls

j.eglovitch@elsevier.com — Fri, 25 Jan 2013 00:00:00 -0500

The European Commission on Jan. 17 announced four proposed revisions of GMP chapters on preventing contamination in facilities, transferring test methods, and investigating complaints and quality defects. Comments are due in July.

Incorrect Use of Process Validation Tools Led to FDA Warning Letters

b.cox@elsevier.com — Fri, 25 Jan 2013 00:00:00 -0500

Manufacturers have been learning the hard way not to use fancy statistical tools for process validation without really understanding them. Inappropriate sampling plans, Cpk analyses, defect/complaint rate analyses and other such failures recently triggered FDA warning letters.

FDA’s Combo Product GMP Reg Speeds Ahead Unchanged

d.gingery@elsevier.com — Fri, 25 Jan 2013 00:00:00 -0500

Agency decides to keep the proposed rule, issued in 2009, “largely identical” and denies requests to delay implementation a year.

Bioequivalence Testing Is First Step In China’s Pharma Industry Upgrade – RDPAC

b.yang@elsevier.com — Thu, 20 Dec 2012 12:00:00 -0500

Time is tight for China to complete an ambitious generic bioequivalence testing schedule, and the stakes couldn’t be higher for the industry, a top executive of the leading trade association in China says.

FDA Developing Initiatives to Improve Quality of Drug Master Files

j.eglovitch@elsevier.com — Thu, 20 Dec 2012 12:00:00 -0500

The quality of DMFs is expected to improve thanks to a soon to be released question- based review system for DMF holders as well a recently issued draft guidance calling for new procedures for reviewing master files called “completeness assessments,” said a pharmaceutical industry official who was a former team leader in FDA’s Office of Generic Drugs.

GDUFA Self-Identification Woes Can’t Deflate Industry, FDA Enthusiasm

d.gingery@elsevier.com — Thu, 20 Dec 2012 12:00:00 -0500

As the grace period nears its close, industry officials say they expected problems getting generic drug manufacturing facilities to self-identify under the new user fee requirement; meanwhile, FDA expects to hire nearly three times the staff in the Office of Generic Drugs to meet GDUFA commitments.

Worldwide Regulatory Inaction on FMD May Result in Drug Shortages

j.eglovitch@elsevier.com — Thu, 20 Dec 2012 12:00:00 -0500

There could be the potential of drug shortages in the EU unless more countries certify that drug substances made within their borders are equivalent to EU GMP standards, say pharmaceutical industry and EU health authorities. Many regulators are sitting on the sidelines and have taken no action to comply with FMD’s import provisions for active substances, which goes into effect in July.

FDA Signals Progress In War On Adulterated Supplements

d.schiff@elsevier.com — Thu, 20 Dec 2012 12:00:00 -0500

CDER data show class I recalls of supplements spiked with undeclared drug ingredients fell dramatically the past two years after peaking in fiscal 2010.

Slogging Toward Quality by Design

b.cox@elsevier.com — Thu, 20 Dec 2012 12:00:00 -0500

Ten years into FDA’s quality initiative, CDER Director Janet Woodcock acknowledges continued resistance to investing in QbD as a way of preventing quality problems in commercial manufacturing. Yet others in FDA and industry see adoption of the science- and risk-based approach spreading, even though manufacturers are often reluctant to disclose how much money it’s saving them.

Global Harmonization of CMC Review Explored

b.cox@elsevier.com — Thu, 20 Dec 2012 00:00:00 -0500

Quality by design (QbD) and certificates of pharmaceutical product (CPPs) suggested as concepts the world’s regulatory authorities could use to harmonize CMC requirements so new medicines could reach their markets more quickly. Meanwhile, in the world’s regulatory affairs trenches, industry is engaged in a complex, difficult, country by country, region by region lobbying effort.

Generic Drug Bioequivalence Testing Details Emerge In China

b.yang@elsevier.com — Thu, 29 Nov 2012 12:00:00 -0500

Bioequivalence testing is sure to have a profound effect on pricing, bidding and reimbursement, Chinese pharmaceutical industry players say. Now draft guidelines shed light on SFDA’s thinking on the issue.

FDA Contracts in Brief

Thu, 29 Nov 2012 12:00:00 -0500

As fiscal year 2012 drew to a close, FDA awarded contracts to assess pharmaceutical quality systems, compare antiepileptics, audit recalls and provide training on leadership, fraud detection and conducting inspections.

Early Notification Helping to Resolve Drug Shortages

Thu, 29 Nov 2012 12:00:00 -0500

Despite a growing number of shortages, FDA has helped to prevent many more through its early notification program. An agency official predicted that shortages will be fewer this year thanks to combined FDA and industry efforts and intervention strategies.

NECC Crisis Festered in Ambiguity That Reigns Over Compounding

b.cox@elsevier.com — Thu, 29 Nov 2012 12:00:00 -0500

As FDA, Congress and the courts stumbled, compounding pharmacies such as NECC took advantage of a gray area of the law. Legislators will get another try; one proposed subjecting such pharmacies to cGMP requirements.

A Lesson on Outsourcing: The NECC Fungal Meningitis Outbreak

b.cox@elsevier.com — Thu, 29 Nov 2012 12:00:00 -0500

The multistate outbreak of fungal meningitis due to sterility failures at a Massachusetts compounder provides a lesson on outsourcing. Health systems let NECC make their high-risk sterile preparations and left oversight to agencies with uncertain authority.

What FDA Saw at Compounder Behind Fungal Meningitis Outbreak

b.cox@elsevier.com — Thu, 29 Nov 2012 12:00:00 -0500

There was greenish-black and white filamentous matter in vials that had been recalled. The question confronting FDA investigators at NECC: How could it have gotten there?

Pharmaceutical Companies Starting to Adopt Track-and-Trace Systems

j.eglovitch@elsevier.com — Thu, 29 Nov 2012 12:00:00 -0500

The pharmaceutical industry is starting to implement new track-and-trace systems to monitor the movement of their drugs through the supply chain to comply with a California pedigree law that goes into effect in 2015. There are low expectations that a federally mandated track-and-trace program will be implemented by then.

Lack of Microbiological Controls Had Grave Consequences for Compounders

j.eglovitch@elsevier.com — Thu, 29 Nov 2012 12:00:00 -0500

The current public health crisis stemming from microbiological contamination of sterile injectables at drug compounding pharmacies demonstrate the importance of having robust aseptic sterile processing programs, said an FDA official. Some problems at drug manufacturers were also highlighted showing inadequate microbiological controls.

Contamination is Major Problem Seen in GMP Warning Letters

j.eglovitch@elsevier.com — Thu, 25 Oct 2012 00:00:00 -0400

FDA’s aggressive enforcement against pharmaceutical manufacturers for GMP violations continued in the first half of the year through its use of warning letters. Inadequate contamination controls was a common deficiency found in eight of the 18 drug GMP warning letters, failure to investigate out-of-specification results continues to be the most frequent GMP deficiency in warning letters, and cites of stability problems are increasing.

ICH Q11 Valued for Bringing Clarity on Starting Materials, Risk Ranking

j.eglovitch@elsevier.com — Thu, 25 Oct 2012 00:00:00 -0400

ICH Q11 outlines a set of principles for choosing starting materials, illustrates how a risk assessment can be used to evaluate process changes, and demonstrates how prior knowledge can be used to develop new drug substances, according to members of the working group that wrote the guideline. They also discussed what the guideline does and does not do.

FDA Approving More ANDAs That Use Novel Bioequivalence Methods

j.eglovitch@elsevier.com — Thu, 25 Oct 2012 00:00:00 -0400

OGD officials report on the progress being made in approving generic drugs using more novel and science-based bioequivalence methods than in the past. Officials impart tips on how to submit review-ready bioequivalence applications.

Drug Makers Look to Strengthen Supplier Relationships

b.cox@elsevier.com — Thu, 25 Oct 2012 00:00:00 -0400

Pharmaceutical companies are exploring how to strengthen their global supply chains by deepening their relationships with CMOs and ingredient suppliers. Industry and regulatory participants at last month’s Xavier University Global Outsourcing Conference described some of the conflicts and how they could manage suppliers better and achieve seamless partnerships.

Generics Firms Raise Concerns About FDA’s Stability Testing Guidance

j.eglovitch@elsevier.com — Thu, 25 Oct 2012 00:00:00 -0400

The generic drug industry needs to place more drug batches on stability for a longer time to meet the new, stricter stability testing requirements scheduled to take effect Jan. 1, 2014. However, industry says there are still some outstanding issues that need to be resolved before these new requirements go into effect, such as the size of pilot batches subject to testing.

In Brief

Thu, 25 Oct 2012 00:00:00 -0400

More FDASIA reorganizations at FDA; Key QbD elements expected in ANDA supplements.

China Looks To Step Up Overseas GMP Inspections With New Draft Guidance

j.dai@elsevier.com — Thu, 27 Sep 2012 00:00:00 -0400

China’s SFDA releases draft guidance on overseas GMP inspections, which requires foreign pharmaceutical companies to submit additional documentation, including sales, import and production reports spanning three years.

Fercy Warning Letter Confirms OTC Monograph Fears

b.cox@elsevier.com — Thu, 27 Sep 2012 00:00:00 -0400

Drug maker in China found to exploit gap in U.S. regulatory system, exporting OTC monograph drugs without key quality controls or registration until FDA inspection led to import suspension.

FDA Reorg Elevates Generic Review Activities

cole.werble@previsionpolicy.com — Thu, 27 Sep 2012 00:00:00 -0400

In the two months since the enactment of the Generic Drug User Fee Act, FDA has announced a major recruitment from the brand sector to head its generic drug activities (Gregory Geba), approved one controversial transdermal generic (Watson’s lidocaine topical patch), and elevated the generic review activities to “Super Office” status.

Pharmaceutical Industry Has Not Made Business Case for Quality

j.eglovitch@elsevier.com — Thu, 27 Sep 2012 00:00:00 -0400

The pharmaceutical industry has not made the business case for quality, according to a recent PDA survey. A majority of pharmaceutical manufacturers did not calculate the cost of poor quality, yet many have adopted Six Sigma and similar programs for improving quality.

Europe in Brief

Thu, 27 Sep 2012 00:00:00 -0400

More objections to EU GMP requirements for active substances; clarification of import requirements under FMD; new GMP guides incorporate ICH Q10.