"The Gold Sheet" :: Pharmaceutical and Biotechnology Quality Control

Inspectorates Share QRM Tools to Protect Quality from Downsizing

b.cox@elsevier.com — Fri, 25 May 2012 00:00:00 -0400

Quality risk management is touted as the key to preventing, or if needed, preparing for the brain drain that can affect drug quality when a plant loses key personnel due to staff cuts. PIC/S encourages drug makers to try the QRM tools its members use when inspecting plants.

With July 2013 Deadline Looming, Debate Continues Over How to Require GMPs for APIs in Europe

b.cox@elsevier.com — Fri, 25 May 2012 00:00:00 -0400

As Europe prepares to subject API imports to GMP controls, industry urges a different approach. Questions linger over how to keep Anti-Falsification Directive from drying up Europe’s API supplies.

China Expands GSP To Clarify Drug Distribution Roles

j.dai@elsevier.com — Fri, 25 May 2012 00:00:00 -0400

China’s Ministry of Health recently released a good supply practices (GSP) draft that would expand the rule from 88 articles to 201 articles; public comments close May 27.

USP Still Has a Long Way to Go in Updating Excipient Monographs

j.eglovitch@elsevier.com — Fri, 25 May 2012 00:00:00 -0400

U.S. Pharmacopeia officials say they have only modernized about 10% of the excipient monographs deemed a high priority in need of modernization by FDA and have received “minimal” input from industry in updating outdated monographs.

ICH Q11 Accord Brings QbD to APIs, Defines API Starting Materials

j.eglovitch@elsevier.com — Fri, 25 May 2012 00:00:00 -0400

After five years, working group members of the International Conference on Harmonization have adopted its Q11 guideline on drug substance development and manufacture, which advances QbD principles for drug substance development, especially for biotechnology products, endorses the use of prior knowledge, and establishes a harmonized definition for starting materials. Even though not everyone is happy with this definition, ICH members say that a harmonized definition is better than a non-harmonized one.

China Drug Safety Remains Front and Center In Chromium Capsule Scandal

b.yang@elsevier.com — Fri, 25 May 2012 00:00:00 -0400

China’s latest product safety scandal could have far-reaching implications, potentially even disrupting China's tendering system for essential medicines.

High Utilization Seen as GMP Issue Behind Cancer Drug Shortages

b.cox@elsevier.com — Fri, 25 May 2012 00:00:00 -0400

A lack of manufacturing capacity blamed for sterile injectable oncology drug shortages can be viewed as a GMP compliance issue, FDA official says, pointing to Section 211 process validation requirements. HHS analysis links the shortages to excessive utilization rates at generics firms.

Drug Shortages Proposal From Sen. Hatch Offers 7-Year Economic Incentives

c.dombrowski@elsevier.com — Fri, 25 May 2012 00:00:00 -0400

The Utah Republican’s draft bill would encourage industry to increase its capacity to manufacture sterile injectable drug products by providing higher reimbursement rates and exclusivity incentives. House Republicans continue to pursue economic options, but time and jurisdictional factors could work against such measures to address shortages.

FDA Drug GMP Warning Letters Increase 6%, Focus on Supply Chain and Sterility Assurance in FY 2011

j.eglovitch@elsevier.com — Thu, 26 Apr 2012 00:00:00 -0400

The number of drug GMP warning letters issued by FDA continued to climb in fiscal year 2011, with supply chain and sterility assurance issues dominating the agency’s attention. FDA is requesting a budget increase in FY 2013 to expand its inspectional presence abroad to better meet global supply chain threats, and agency officials are saying that failure to monitor contract manufacturers is a major problem shown in recent warning letters, but that failure to investigate out-of-specification results is still the No. 1 finding.

FDA Studies In Brief

Thu, 26 Apr 2012 00:00:00 -0400

FDA studies why patients can’t switch among bioequivalent antiepileptics, how potentially biosimilar protamine sulfates vary, which firms pose the greatest drug import/export risks, how to evaluate quality management systems and how to get more results oriented.

Legislation in Brief

Thu, 26 Apr 2012 00:00:00 -0400

The Senate user fee bill may get industry’s version of track-and-trace or FDA’s or neither, but certainly would free FDA from inspecting facilities every two years. Meanwhile, Congress keeps generating ideas for combating drug shortages.

FDA Drug GMP Warning Letters from FY 2011

Thu, 26 Apr 2012 00:00:00 -0400

This listing of all 52 drug cGMP warning letters FDA sent in fiscal year 2011 groups them by dosage form, and describes the issues each one addressed.

As ICH Q3D Metal Impurity Limits Near, Industry Worries What New Tests May Find

b.cox@elsevier.com — Thu, 26 Apr 2012 00:00:00 -0400

With ICH planning to propose Q3D metal impurity limits in June and USP requiring new metals test methods soon thereafter, pharmaceutical companies are wondering whether any of their ingredients might fail the tests, perhaps requiring them to reformulate products or suspend production. Early indications from FDA and industry testing are largely reassuring, while highlighting some areas for further inquiry.

Contamination Issues Drove Drug Recalls to Record Levels in 2011

b.cox@elsevier.com — Wed, 28 Mar 2012 00:00:00 -0400

How contamination, sterility assurance, OOS and other issues caused drug recalls to spike again last year. What happened at Aidapak, H&P, Ben Venue, Hospira, Teva and other manufacturers to set a new record.

“The Gold Sheet” Publishes Database of 2011 Drug Recalls

b.cox@elsevier.com — Wed, 28 Mar 2012 00:00:00 -0400

A first from “The Gold Sheet” – a database of drug recalls that can be searched by company, type of problem, type of product, country of origin and other factors. Open and download a copy here.

Recalls of Overweight Tablets Reflects Knowledge Gap in Industry on Tablet Making; Solutions Offered

j.eglovitch@elsevier.com — Wed, 28 Mar 2012 00:00:00 -0400

The high number of drug product recalls over the past few years for overweight tablets can be attributed to a poor understanding in the pharmaceutical industry on how tablets are made.

Better Trained Operators on Production Floor Can Improve Bottom Line

j.eglovitch@elsevier.com — Wed, 28 Mar 2012 00:00:00 -0400

Having better trained operators on the pharmaceutical production floor can help improve a company’s bottom line and would allow a better handling of fixed costs. It would also help drug product recalls.

Market Conditions and Cost Pressures are Prompting Redesign of Manufacturing Facilities

j.eglovitch@elsevier.com — Wed, 28 Mar 2012 00:00:00 -0400

The pharmaceutical and biotech manufacturing facilities of the future will be smaller and simpler than existing facilities, have more closed processes, combine clinical and commercial operations under one roof, and use more disposable equipment. Cost pressures and market conditions are behind some of these anticipated changes, some of which are occurring right now.

Drug Product Recalls In 2011: Categorized By Problem Area

Wed, 28 Mar 2012 00:00:00 -0400

This table lists every drug recall of 2011, along with a description of the drug product, the manufacturer, the recaller, the recall class and the reason for the recall.

FDA Sending More Drug GMP Warning Letters to Foreign Sites

j.eglovitch@elsevier.com — Tue, 28 Feb 2012 00:00:00 -0500

FDA warning letters are up at foreign sites and down at domestic sites as agency ramps up presence abroad. Inadequate OOS investigations and faulty testing of drug components were top violations; contamination was a common issue; firms cited included Novartis, Mylan, Smithkline Beecham, Lonza and Noven.

Biosimilars Trigger Analytical Frenzy as Innovators Look to Update Methods

b.cox@elsevier.com — Tue, 28 Feb 2012 00:00:00 -0500

As biosimilar developers ‘fingerprint’ molecules with state-of-the-art assays in hopes of winning reduced clinical trials or more, innovators are updating their analytical methods, hoping to alert FDA before their competitors about any issues the old methods may have missed. As the ‘totality of the evidence’ on their molecules increases exponentially, concerns are raised about the proliferation of non-critical specifications.

Pharma Raises Concerns About Draft EU GDP Guideline

j.eglovitch@elsevier.com — Tue, 28 Feb 2012 00:00:00 -0500

The European Commission needs to fine tune its good distribution practices (GDP) guideline, the pharmaceutical industry said in comments on a proposed draft revision. Key issues include segregating EU and non-EU product, transportation vs. storage conditions, applicability to investigational products and time limits for transportation hubs.

News in Brief

Tue, 28 Feb 2012 00:00:00 -0500

FDA hits heparin supply chain; Ranbaxy consents to data integrity oversight; multinationals find solutions to China’s vaccine compendial crisis; EU seeks comment on safety measures, API imports.

Mutual Reliance Blossoming Among FDA, EMA, Other Inspectorates

b.cox@elsevier.com — Thu, 26 Jan 2012 00:00:00 -0500

FDA, EMA and other agencies are increasingly relying on each others' inspection results in an effort to spread their inspectional resources throughout the furthest corners of the globe. Inspection coordination remains somewhat ad hoc, with EMA keeping a spreadsheet for some and PIC/S enabling others.

Pharmaceutical Industry Adopting QbD for Analytical Testing

j.eglovitch@elsevier.com — Thu, 26 Jan 2012 00:00:00 -0500

Both the pharmaceutical industry and regulators are exploring new QbD approaches for analytical method development. FDA regulators have approved analytical QbD submissions and say that regulatory relief will be granted to those firms that use this approach, while the EU has been less accepting.

Implementing Minor Changes is Hard to Do Under Variations Regulation

j.eglovitch@elsevier.com — Thu, 26 Jan 2012 00:00:00 -0500

European generic drug makers say that it is difficult to implement Type IA changes under the variations regulation because of all the paperwork involved in submitting these changes to competent authorities. A 26 percent fee hike in filing variations is also making it more costly and difficult for manufacturers to justify making changes.

ICH Impurity Thresholds are Unrealistic for Antibiotics

j.eglovitch@elsevier.com — Thu, 26 Jan 2012 00:00:00 -0500

EMA's proposal to apply the same ICH impurity limits to antibiotics produced by fermentation and semi-synthetic methods as new drug substances is considered unrealistic, and could result in market withdrawals of these products.

USP To Bring Global Perspective To Track And Trace Discussion

c.dombrowski@elsevier.com — Thu, 26 Jan 2012 00:00:00 -0500

The U.S. Pharmacopeial Convention released a framework Jan. 4 for instituting supply chain security measures and plans a May workshop with speakers from other countries to discuss their programs for tracking drug components and products through distribution channels.

Results from Last Month's "The Gold Sheet" Poll

Thu, 26 Jan 2012 00:00:00 -0500

Last month, we asked you how strong are your quality cultures, based on a five-point scale that Novartis uses. Now the results are.

19th Annual Euro-Biotech Partnering Summit

Thu, 26 Jan 2012 00:00:00 -0500

Publisher’s Spotlight: Join us in Paris, France from May 30-June 1, 2012 for the 19th Annual Euro-Biotech Partnering Summit. This year’s theme is Changing the Business Model: Drawing on Global Examples of Innovation to Find New Products and Maximize Efficiency.

9th Annual Pharmaceutical Strategic Outlook (PSO) Conference, April 11-13, 2012

Thu, 26 Jan 2012 00:00:00 -0500

Join us at PSO 2012 where we will delve into the top issues affecting the pharma industry. Experience a dynamic three days of networking and discussion - with a personal and interactive setting, in-depth on-stage interviews, thought-provoking panels, one-on-one partnering meetings and innovative company presentations by carefully selected biotech companies.

How Pharma is Working to Change Cultures With Q10 Quality Systems

b.cox@elsevier.com — Wed, 21 Dec 2011 00:00:00 -0500

Even the most highly regarded drug manufacturers can become complacent, allow their attention to wander, and the next thing they know, FDA is telling them their quality has spiraled out of control. They pay the price with FDA, they replace their management teams, they invest in new equipment, facilities and systems – and they vow never to let quality stray again.

API Firms Advised to Gear Up for Inspections Under GDUFA and FMD

j.eglovitch@elsevier.com — Wed, 21 Dec 2011 00:00:00 -0500

Legislation mandating stricter rules on sourcing and inspecting active pharmaceutical ingredients will soon be implemented in the European Union and similar legislation will be introduced in the U.S. as part of the Generic Drug User Fee Act. Under the EU's Falsified Medicines Directive, which is the EU's answer to fighting drug counterfeiting, pharmaceutical manufacturers will have to ensure that the APIs they source from countries outside the EU have been inspected by regulators to EU GMP standards.

Industry, Regulators Divided Over Q11 Definition of API Starting Materials

j.eglovitch@elsevier.com — Wed, 21 Dec 2011 00:00:00 -0500

While the International Conference on Harmonization Q11 guidance on drug substance development is advancing smoothly to the next step in the area of manufacturing process development, other areas such as the selection of starting materials continue to confound both regulators and industry alike. One of the upcoming changes would allow manufacturers of biotech products to make changes within an approved design space if they tell regulators how these changes will be managed post-approval.

Opportunities to Statistically Mine PAT Data for Release Testing Explored

j.eglovitch@elsevier.com — Tue, 22 Nov 2011 00:00:00 -0500

Manufacturers, compendial authorities and FDA officials recently explored ways the pharmaceutical industry could use sophisticated statistical methods to unlock the regulatory compliance potential of vast amounts of process analytical data it is generating. Discussions at a recent Product Quality Research Institute workshop focused mainly on batch release testing for content uniformity.

China's Inspectorate Begins Enforcing New Drug GMPs Overseas

b.cox@elsevier.com — Tue, 22 Nov 2011 00:00:00 -0500

China's State FDA this month will begin inspecting manufacturing facilities in the West for compliance with the GMP regulation it revised in January. The GMP rewrite and the overseas inspections are part of a concerted effort to raise the quality of China's domestic pharmaceutical industry to global standards.

FDA Sets Aside Industry 'Wish List' of Further CMC Change Reporting Downgrades

b.cox@elsevier.com — Tue, 22 Nov 2011 00:00:00 -0500

When FDA issues the final version of its guidance on annually reportable chemistry, manufacturing and controls changes, don't look for it to add any more CMC changes from industry's "wish list." Instead the final guidance, expected sometime next year, will mainly add some clarification to the June 2010 draft, FDA's Jon Clark told the American Association of Pharmaceutical Scientists annual meeting in Washington. Clark is associate director for program policy in the Office of Pharmaceutical Science in FDA's center for drugs.

FDA Presses for More Equivalent Generics

j.eglovitch@elsevier.com — Tue, 22 Nov 2011 00:00:00 -0500

FDA’s Office of Generic Drugs will soon be issuing a guidance to help generic drug manufacturers develop products that are as close as possible to the reference-listed drug in terms of size, taste and smell. OGD’s Vilayat Sayeed made this announcement Oct. 4 at the Generic Pharmaceutical Association’s fall technical conference.

Generics Joining the 12-Month Stability Data Club, But 'When?' Is Big Question

c.dombrowski@elsevier.com — Tue, 22 Nov 2011 00:00:00 -0500

Generic drug sponsors will need to submit six-month and 12-month stability data for their ANDAs under draft guidance being developed by the Office of Generic Drugs. Currently, only three-month data is required, so drug makers will need to revise their development, production and testing schedules accordingly. "You just start nine months earlier. … Eventually that will be the norm," Glen Smith, director of OGD's Division of Chemistry II, advised participants at the Generic Pharmaceutical Association's fall technical meeting.

Revised Stability Testing Requirements For Generic Drugs

Tue, 22 Nov 2011 00:00:00 -0500

FDA is developing draft guidance that would require generic drug sponsors to provide 12 months of stability testing with their ANDAs, the same as the International Conference on Harmonization’s Q1A standard, which the Office of New Drugs already has adopted for NDAs. While the draft guidance will be proposed shortly, the Office of Generic Drugs is still working on an implementation strategy for the new requirements.

Use QbD to Get Through Rough Patch, FDA Tells Transdermal Makers

Sat, 01 Oct 2011 00:01:00 -0400

FDA officials say that there are “scientific gaps” in how transdermal patches are developed, manufactured and regulated, and urged manufacturers to adopt quality- by-design methods to help bridge these gaps and to better ensure product quality and safety.

FDA Intends to Strengthen Recall Effectiveness Checks

b.cox@elsevier.com — Sat, 01 Oct 2011 00:00:50 -0400

FDA is preparing to monitor recall effectiveness more closely as a result of pressure from Congress, the news media and the White House.

FDA Attributes 40 Percent of Last Year’s Drug Shortages to Injectables GMPs

j.eglovitch@elsevier.com — Sat, 01 Oct 2011 00:00:40 -0400

Sterile injectables accounted for most of the drug shortages reported in 2010 and in most cases the injectables shortages were the result of GMP problems, according to Ilisa Bernstein, acting director of the Office of Compliance in FDA’s center for drugs.

Supply Chain GMP Rewrite, Guidance Documents in Works at FDA

b.cox@elsevier.com — Sat, 01 Oct 2011 00:00:30 -0400

FDA is continuing to draft a regulation for strengthening supply chain controls that he had announced in June 2010, Brian Hasselbalch of the agency’s center for drugs told a Parenteral Drug Association conference last month.

Perrigo Applies Crime Scene Investigation Model to Improve Quality Control

d.schiff@elsevier.com — Sat, 01 Oct 2011 00:00:20 -0400

Perrigo quality control managers emphasize immediate investigations of low-risk incidents and forward-looking remediation in the firm’s new corrective and preventive actions strategy.

FDA Grants and Contracts in Brief

Sat, 01 Oct 2011 00:00:10 -0400

NIPTE gets work under $35 million grant

Shortcuts Pursued in Effort to Close Compendial Gaps

b.cox@elsevier.com — Thu, 01 Sep 2011 00:00:20 -0400

Officials with FDA, the U.S. Pharmacopeia and the pharmaceutical industry are looking for a quicker way to remedy a situation underscored by the 2008 heparin crisis: the need to update hundreds, perhaps thousands of the compendial standards that the U.S.

FDA Warning Letters Hit Inadequate Investigations and QC Failings

j.eglovitch@elsevier.com — Thu, 01 Sep 2011 00:00:15 -0400

In recent warning letters, FDA continued to hammer manufacturers for inadequate investigation of out-of-specification results and lax oversight of manufacturing operations by quality control units.

Latin American Regulators Aligning API Registration Requirements with CTD

j.eglovitch@elsevier.com — Thu, 01 Sep 2011 00:00:10 -0400

Regulators in Latin America are requiring more information on drug substance manufacture and are incorporating the International Conference on Harmonization’s Common Technical Document in their registration requirements as the basis for this information.

In Brief

Thu, 01 Sep 2011 00:00:08 -0400

Correction