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2010 Quality and Regulatory News

North America News

U.S. FDA Still Collecting Information on Pilot Program for Adverse Medical Products

December 20, 2010

Since February 2002, the Agency has been collecting information on a pilot program for reporting adverse medical products.

The Agency is still gathering information and has requested approval for an extension of the information gathering phase. They plan to will test its proposed system further before the current universal mandatory reporting system is changed.

Comments on the extension request should be submitted by January 6.

Draft Guidance Published on Codevelopment of Unmarked Investigational Drugs Used in Combination

December 16, 2010

The U.S. FDA has published a draft guidance on the codevelopment of two or more unmarketed investigational drugs for use in combination.

The guidance is intended to assist sponsors in the codevelopment of two or more novel (not previously marketed) drugs to be used in combination to treat a disease or condition. It provides recommendations and advice on how to address certain scientific and regulatory issues that will arise during codevelopment.

It is not intended to apply to fixed-dose combinations of already marketed drugs or to development of a single new investigational drug to be used in combination with an approved drug or drugs. It is also not intended to apply to vaccines, gene or cellular therapies, blood products or medical devices.

Comments should be submitted by February 14, 2011.

Agency Collects Information on Recordkeeping Requirements of Exports

December 15, 2010

The U.S. FDA has published a collection of information notice about recordkeeping requirements of exports.

The Agency is asking for comments on the notification and recordkeeping requirements for people exporting human drugs, biological products, devices, animal drugs, food and cosmetics that may not be marketed in the United States.

Comments should be submitted by February 4.

NIH Establishes New Center for Advancing Translational Sciences

December 14, 2010

The National Institute of Health (NIH) will establish a new center devoted to advancing translational sciences by October of next year.

The central role of the proposed National Center for Advancing Translational Sciences (NCATS) would be to establish a focused, integrated, and systematic approach for building new bridges to link basic discovery research with therapeutics development and clinical care.

The Center would be formed initially by integrating selected translational research programs now located within the National Human Genome Research Institute (NHGRI), the National Center for Research Resources (NCRR), and the NIH Director's Common Fund. Another component could be the new Cures Acceleration Network (CAN), which was authorized by the Affordable Care Act but has not yet received an appropriation.

Proposed Changes to EU GMP Guide Target Supply Chain Vulnerabilities

December 13, 2010

The EU is proposing revisions to Chapter 5, "Production," of the EU GMP Guide. Changes to Sections 25 and 26, if/when effective, reflect the legal obligation of manufacturing authorization holders to ensure that active substances are produced in accordance with GMP. Supply chain traceability for starting materials is also introduced. A new section, 31, is proposed in order to clarify and harmonize expectations of manufacturers regarding the testing of starting materials.

Further work on chapter 5 is ongoing, affecting section 19, pursuant to concept papers published by EMA in February 2005.

The deadline for comments is February 28.

U.S. FDA Requests Participation in Biosimilar User Fee Consultations

December 9, 2010

The U.S. FDA is requesting public stakeholders, including patient and consumer advocacy groups, health care professionals, and scientific and academic experts, to notify the Agency of their intent to participate in consultation meetings relating to the development of a user fee program for biosimilar and interchangeable biological product applications.

FDA is holding these consultation meetings to satisfy the requirement in the Patient Protection and Affordable Care Act that FDA consult with such public stakeholders regarding the development of recommendations to present to Congress with respect to the goals, and for the review process of biosimilar and interchangeable biological product applications for fiscal years (FYs) 2013 through 2017.

Submit your intent to participate by January 10.

Q&A Draft Guidance on Residual Solvents in Animal Drug Products Published

December 6, 2010

The U.S. FDA has published a question and answer draft guidance on Residual Solvents in Animal Drug Products.

The draft guidance addresses the United States Pharmacopeia General Chapter <467> Residual Solvents that applies to human and veterinary drugs and to compendial and non-compendial drug products. This document answers questions regarding CVM's implementation of USP <467> Residual Solvents.

Comments are due by February 1.

U.S. FDA to become 38th Member of PIC/S Jan. 1st

November 17, 2010

According to PIC/S, the U.S. FDA will be a member of PIC/S effective January 1, 2011. The Agency initially applied for membership in September 2005.

The Agency will become PIC/S' 38th participating authority.

Agency Extends Comment Period on PDUFA until Oct. 2011

November 12, 2010

FDA has extended the comment period for stakeholders to comment on the reauthorization of the Prescription Drug User Fee Act. To ensure that all interested person have sufficient opportunity to share their views, FDA is re-opening the comment period until October 31, 2011.

Postmarketing Requirements and Commitments Published

November 12, 2010

The summary of Postmarketing Requirements and Commitments has been published by the Agency. Fulfilling a requirement of the Food and Drug Administration Modernization Act requiring FDA to report annually on the status of these postmarketing commitments,  information in this report covers any postmarketing requirements (PMR)/postmarketing commitments (PMC) that were made, in writing, at the time of approval or after approval of an application or a supplement to an application, including postmarketing requirements required under FDAAA.

Information summarized in this report includes the following:

  1. The number of applicants with open (uncompleted) PMRs/PMCs
  2. The number of open PMRs/PMCs
  3. The status of open PMRs/PMCs
  4. The status of concluded PMRs/PMCs as determined by FDA
  5. The number of applications with open PMRs/PMCs for which applicants did not submit an annual report within 60 days of the marketing approval

Agency Seeks Comments on Qualification Process for Drug Development Tools

November 2, 2010

The U.S. FDA recently published a draft guidance, entitled, Qualification Process for Drug Development Tools.

The draft guidance describes the qualification process for drug development tools (DDTs) intended for potential use in multiple drug development programs. It provides a framework for interactions between CDER and DDT sponsors to qualify an identified DDT and creates a mechanism for formal review of data by CDER to qualify the DDT and ensure that the evaluation is comprehensive and reliable.

Comments should be submitted by January 24, 2011

Agency Collects Information on Medical Device Quality System Regs

October 29, 2010

The Agency has submitted a proposed information collection on the record keeping and reporting requirements established by the Medical Device Quality System Regulations.

The U.S. FDA estimates respondents will have a total annual recordkeeping burden of approximately 3,105,552 hours. This figure also consists of approximately 143,052 hours spent on a startup basis by 734 new firms.

U.S. FDA Seeking Comments on Information Requested in the "Absenteeism" Draft Guidance

October 27, 2010

The U.S. FDA is collecting comments on information requested in a draft guidance about ensuring that medically necessary drug products (MNP) are available when there are personnel shortages due to an emergency. FDA estimates that it will take about 35,000 hours to set up the initial plan and 32 hours to set up the notification to FDA of the Plan's activation and deactivation.

Entitled, Planning for the Effects of High Absenteeism to Ensure Availability of Medically Necessary Drug Products, the draft guidance recommends that an emergency plan should be developed for each individual manufacturing facility, as well as a broader plan that addresses multiple sites within the organization. The draft guidance discusses the issues that should be covered by the plan, such as:

  • Delegating who has the authority activate and deactivate the Plan and make decisions during the emergency
  • Prioritizing the manufacturer's drug products based on medical necessity
  • Identifying actions that should be taken prior to an anticipated period of high absenteeism
  • Ascertaining criteria for activating the plan
  • Performing quality risk assessments that would determine which manufacturing activities may be reduced to enable the company to meet a demand for MNPs
  • Returning to normal operations and conducting a post-execution assessment of the execution outcomes
  • Testing the Plan

In this proposed information collection, the Federal Register announcement includes FDA's responses to the comments submitted in response to the collection of information associated with the draft guidance that was been made available to the public in the original January 8, 2010 Federal Register announcement. FDA was informed then that there are business continuity plans already in place to address shortages of medically necessary products and that these plans take into account high absenteeism and other factors that could affect production. However, the Agency believes that a general business continuity plan is unlikely to take into account individual products or how execution of the plan would affect product quality.

Other comments suggested that the guidance's recommendations would be too burdensome and provide no value to ensure protection of the public health. FDA agrees with these comments and has revised the guidance to recommend that only the parts of the an absenteeism plan that could have an effect on product quality be reviewed and approved by the Quality Unit before implementation.

Some comments stated that testing an absenteeism plan and producing test batches would be impractical and expensive. FDA agreed with these comments and removed its recommendation to produce test batches of the drug product.

Draft Guidance Recommends How to Submit INDs for Early Clinical Trials

October 18, 2010

A draft guidance providing IND sponsors with recommendations on the submissions of IND's for early clinical trials with live biotherapeutic products is now available.

Comments on the draft guidance, entitled, Early Clinical Trials with Live Biotherapeutic Products: Chemistry, Manufacturing and Controls Information should be received by December 13, 2010.

Human Research Studies Conducted under IND Subject of Agency Draft Guidance

October 18, 2010

This draft guidance, which is intended to assist clinical investigators, sponsors and sponsor-investigators in determining whether planned human research studies must be conducted under an IND, is ready for comment.

Entitled, Investigational New Drug Applications (INDs) – Determining Whether Human Research Studies Can Be Conducted Without an IND, the guidance describes the basic criteria for when an IND is required, describes specific situations in which an IND is not required and discusses a range of issues that, in the U.S. FDA's experience, have been the source of confusion or misperception about the application of the IND requirements.

Comments on the associated proposed collection of information are due by December 13, 2010; comments on the draft guidance should be received by January 12, 2011.

Agency Looks for Participants to Develop Surveillance, Monitoring System

October 13, 2010

The U.S. FDA has announced an award for anyone who can develop a global surveillance and monitoring system for combating counterfeit/falsified medicines and risks and breaches in the supply chain.

The award would allow the winner to enter into a cooperative agreement with the World Health Organization (WHO), and the U.S. FDA anticipates providing one award of $960,500 (total costs including indirect costs) in fiscal year (FY) 2010 in support of this project.

This project represents a collaborative agreement between WHO and the Agency in building a global rapid alert surveillance/monitoring system(s) for combating counterfeit/falsified medicines and risks in the supply chain security that will assist in developing the global landscape and identifying areas of public health risk.

Agency's 2011-2015 Strategic Priorities Available for Comment

October 12, 2010

The U.S. FDA has published a draft version of its strategic priorities for the fiscal years of 2011 – 2015.The document outlines four key cross-cutting strategic priorities and four strategic program goals that will guide the Agency's efforts to achieve its public health mission, as well as to fulfill its role in supporting the larger mission and strategic goals of the Department of Health and Human Services.

The four cross cutting strategic priorities are:

  1. Advance regulatory science and innovation
  2. Strengthen the safety and integrity of the global supply chain
  3. Strengthen compliance and enforcement activities to support public health
  4. Expand efforts to meet the needs of special populations

The four strategic program goals are:

  1. Advance food safety and nutrition
  2. Promote public health by advancing the safety and effectiveness of medical products
  3. Establish an effective tobacco regulation, prevention and control program
  4. Manage for Organizational Excellence and Accountability

The strategic priorities draft document is available at Comments should be submitted by November 1, 2010.

Public Meeting to Focus on Challenges Associated with Implementing the BPCI Act

October 12, 2010

A public hearing to obtain input on specific issues and challenges associated with the implementation of the Biologics Price Competition and Innovation Act of 2009 ( BPCI Act) will be held on November 2 and 3.

The BPCI Act establishes an abbreviated approval pathway for biological products that are demonstrated to be "highly similar" (biosimilar) to or "interchangeable" with an FDA-licensed biological product. The purpose of the public hearing is to create a forum for interested stakeholders to provide input regarding the agency's implementation of the statute.

The public hearing will be held from 8:30 am – 4:30 pm at FDA's White Oak Campus. Individuals wishing to present at the public hearing must register on or before October 11. Electronic or written comments will be accepted after the public hearing until December 31.

U.S. FDA Prepares for Upcoming ICH Meeting with Public Meeting

September 24, 2010

The U.S. FDA is preparing for the International Conference on Harmonisation (ICH) Steering Committee and Expert Working Group Meetings Fukuoka, Japan by holding a public meeting on October 13 in Rockville, Md.

For more information about this public meeting, contact Jennifer Haggerty of the U.S. FDA at

The ICH Steering Committee and Expert Working Group meeting will take place in November.

Agency Releases Annex 11, 12

September 7, 2010

The U.S. FDA has released two guidances that recognize the interchangeability between the local regional pharmacopoeias. The two guidances are entitled: Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 11, Capillary Electrophoresis General Chapter and Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 12: Analytical Sieving General Chapter.

Agency Draft Guidance Recommends Residual Solvents Limits in New Animal Drugs

August 20, 2010

A U.S. FDA draft guidance entitled Residual Solvents in New Veterinary Medicinal Products, Active Substances and Excipients (Revision) VICH GL18(R) recommends acceptable amounts of residual solvents in new animal drugs for the safety of the target animal, as well as for the safety of human consumers in the case of those animal drugs intended for food producing animals.

The draft guidance updates a final guidance on the same topic and was prepared for veterinary use under the auspices of ICH.

Comments should be submitted by October 18.

Bill to Strengthen Manuf. Quality Standards, Enhance FDA Power

August 12, 2010

A bill has been introduced (S. 3690) that strengthens manufacturer quality standards, enhances FDA's ability to protect Americans through improved tracking of foreign manufacturing sites, and gives the FDA authority to recall potentially dangerous drugs.

TheDrug Safety and Accountability Act of 2010, sponsored by Senator Michael Bennet, D-Colorado,   would provide  FDA with additional recall power, as well as other enforcement options to respond appropriately to violations.  The bill would provide tools, such as:

•Granting FDA the authority to assess civil penalties for violations of the Food, Drug and Cosmetic Act and to subpoena documents and witnesses; •Facilitating exchange of information between the FDA and other regulatory agencies •Protecting industry whistleblowers that wish to bring information to the FDA

These tools would allow FDA to investigate threats to drug quality and safety.

U.S. FDA Guidance Helps Applicants Submit CMC Drug Substance Information in CTD Format

August 11, 2010

A Center for Veterinary Medicine guidance providing recommendations on the chemistry, manufacturing and controls (CMC) information for drug substances that should be submitted to support original new animal drug applications and abbreviated new animal drug applications is now available.

The Agency guidance, Drug Substance Chemistry, Manufacturing, and Controls Information is  structured to facilitate the preparation of applications submitted in Common Technical Document format

House Bill to Provide U.S. FDA with Recall Powers for Adulterated, Misbranded Drugs

August 2, 2010

A bill, HR 5740, introduced in the House of Representatives by Chairman Edolphus Towns (D-NY), amends the Food, Drug and Cosmetic act and gives the U.S. FDA the authority to demand a recall when there are signs that a drug has been adulterated, misbranded, or exposure to a drug may cause serious adverse health consequences or death.

Referred to the House Committee on Energy and Commerce, the bill also requires that anyone that the believes a drug is adulterated or misbranded or thinks that there is a reasonable probability that the use, consumption of or exposure to the drug will cause a threat of serious adverse health consequences or death should notify the FDA.

Four-Part MOU to Strengthen Collaborations among FDA, NIH, NTP and EPA

August 2, 2010

A four-part Memorandum of Understanding (MOU) has been signed by the U.S. FDA; the National Toxicology Program (NTP); the Environmental Protection Agency (EPA), Office of Research and Development; and the National Institutes of Health (NIH): National Institutes of Environmental Health Sciences, National Human Genome Research Institute and NIH Chemical Genomics Center.

This MOU will strengthen the existing collaborations that utilize the complementary expertise and capabilities of the parties in the research, development, validation and translation of new and innovative methods that characterize key steps in toxicity pathways.

The MOU became effective June 4, 2010.

Agency Draft Guidance on ICH Annex 14 Available for Comment

July 20, 2010

An Agency draft guidance on bacterial endotoxin testing is now available for comment. The draft guidance, entitled, Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 14: Bacterial Endotoxins Test General Chapter is available for comment until September 14.

Agency Draft Guidance on ICH Annex 13 Available for Comment

July 20, 2010

An Agency draft guidance on Bulk Density and Tapped Density of Powders is now available for comment. The draft guidance, entitled, Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 13: Bulk Density and Tapped Density of Powders General Chapter is available for comment until September 13.

Agency Guidance Helps Manufacturers Develop, Conduct IVD Studies

July 8, 2010

A guidance designed to assist manufacturers in developing and conducting studies forIn Vitro Diagnostic (IVD) devices, particularly for those exempt from most of the Investigational Device Exemption  regulations is now available.  The guidance, In Vitro Diagnostic Device Studies – Frequently Asked Questions explains data considerations that ultimately will affect the quality of the premarket submission.

Agency Collects Information on Medical Device Reg.'s  Requirements

July 8, 2010

The Agency is soliciting comments about recordkeeping requirements related to the medical devices CGMP quality system regulation via its collection of information requirement.  

Comments can be submitted on the collection of information until August 23.

Draft Guidance Recommends Changes to Information Included in Annual Reports to Agency

July 8, 2010

A draft guidance that provides recommendations to holders of NDAs and ANDAs regarding the types of changes that may be reported in annual reports is now available.

Entitled, CMC Postapproval Manufacturing Changes Reportable in Annual Reports, the draft guidance describes CMC postapproval manufacturing changes that the U.S. FDA has determined will likely present minimal potential to have adverse effects on product quality and may be reported by applicants in an annual report.

The draft guidance excludes PET drug products.

Comments are due to FDA by September 23, 2012.

Agency Data Standards Plan to Allow More Efficient Review  of Standardized data

June 17, 2010

A draft document, entitled, CDER Data Standards Plan Version 1.0, is now available for public comment. The U.S. FDA draft plan outlines the general approach proposed for the development of a comprehensive data standards program in CDER by identifying objectives of the program; processes that will be developed, and a set of recommended projects to begin in 2010.

The standards plan will ensure the development and successful use of data standards for all key data needed to make regulatory decisions, since currently the lack of standardized data does not allow CDER to efficiently and effectively perform  review processes of items such as data submissions. 

Comments are requested by September 15, 2010.

Agency's CDER, CBER Seeks Feedback on Product Labeling Indexing Process

June 15, 2010

The U.S. FDA's Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) are currently indexing certain categories of information in product labeling for use as terms to search repositories of approved prescription medical product structured product labeling. CDER and CBER have established a public docket to provide an opportunity for interested parties to share information, research and ideas on FDA's indexing process.

Previously, the Agency has identified the pharmacologic class as a top priority for indexing of product labeling information;  FDA is now announcing that medical product indications is another category of product labeling information that is a high priority.

Public Workshop on Drug Resistance, Development in Held in July

June 15, 2010

A public workshop, sponsored by the National Institute of Allergy and Infectious Diseases and the Infectious Diseases Society of America will be held on July 26-27 in Silver Spring.

The workshop will address scientific and potential research issues in antibacterial drug resistance, rapid diagnostic device development for bacterial diseases and antibacterial drug development.

New BE Study Procedures Articulated in FDA Guidance

The U.S. FDA has released a guidance entitled, Bioequivalence Recommendations for Specific Products, which describes a new process for making available recommendations on how to design product-specific bioequivalence (BE) studies to support abbreviated new drug applications (ANDAs). Under this process, applicants planning to carry out such studies are able to access BE study guidance on the FDA website. The Agency believes that the use of the internet will streamline the guidance process and will provide a meaningful opportunity for the public to consider and comment on product specific BE study recommendations.

Agency to Collect Comments on General Licensing Provisions for Biologic Applications

The US FDA filed a collection of information notice on general licensing provisions for biologics license applications related to post-marketing studies status reports has been filed.

Section 130(a) of the Food and Drug Administration Modernization Act amended the Federal Food, Drug, and Cosmetic Act by adding a new provision requiring reports of postmarketing studies for approved human drugs and licensed biological products. Section 506B of the act also provides FDA with additional authority to monitor the progress of postmarketing studies and requires the Agency to make information publicly available that pertains to the status of these studies.

Comments on this collection of information should be submitted by July 9.

Agency Seeks Feedback on Methods for Co-Developing Investigational Drugs used in Combination

The U.S. FDA wants public input on how two or more novel, investigational drugs used in combination to treat a single disease or condition can be clinically evaluated. The Agency is establishing a docket to collect public comment and wants to use the information received to publish guidance for industry.

Comments should be submitted by September 7, 2010.

FDA Emergency Call Center Information Amended

The Agency has published a final rule amending their regulations to reflect changes in the contact information for the FDA's Emergency Call Center.

The affected sections of the regulations are 21 CFR Parts 106 (Infant Formula Quality Control Procedures); 107 (Infant Formula); 312 (IND's); and 803 (Medical Device Reporting).

The new contact numbers are 866-300-4374 (phone) and 301-847-8544 (fax). The change is effective June 11, 2010.

Genzyme Signs Consent Decree and Limits Production of Hormone, Receives Marking Approval for Unrelated Drug Product

On May 24, the U.S. FDA announced that Genzyme signed a consent decree to correct manufacturing quality violations at its Allston, Mass., manufacturing facility and has agreed to pay to the U.S. government a $175 mil. disgorgement penalty equaling the profits from the sale of products that were made at the plant. Under the consent decree of permanent injunction, the plant agreed to adhere to a strict timetable to bring it in line with the regulatory requirements of the Agency.

The regulatory and legal case began with a late 2009 FDA inspection that uncovered a number of serious GMP problems.

In the decree, Genzyme agreed to submit to a remediation plan based on recommendations by an independent expert. FDA has the right to refuse the plan if deemed inadequate. In addition, the consent decree provides a deadline for Genzyme to transfer its operations for filling drug vials from its Allston facility to other manufacturing sites or else it will have to give up profits from the sales of drugs filled at Allston after that specific date.

FDA is working with Genzyme during the company's remediation to ensure availability of the company's medically necessary drugs since it is the sole supplier of several enzyme replacement drugs for injection that are used to treat rare genetic disorders.

In a corporate release, Genzyme announced a day after entering the consent decree that the Agency has granted it U.S. marketing approval for Lumizyme, which is used to treat patients with late onset Pompe.

Agency Proposed Rule Would Allow CBER, CDER Directors to Approve Exceptions/Alternations to Biologics Reg

The U.S. FDA would like to amend the biologics regulations to permit the Directors of CBER and CDER, as appropriate, to approve exceptions or alternatives to the regulation for constituent materials.

FDA is taking this action due to advances in recent biological products licensed under the Public Health Service Act and to provide greater "flexibility" for the manufacturers of biologics products, as it is deemed that some provisions of the Act that make the existing regulations are "too prescriptive and unnecessarily restrictive."

The rule provides manufacturers of licensed biological products with flexibility, as appropriate, to apply advances in science and technology as they become available without diminishing public health protections.

Comments on the proposed rule should be submitted by June 28.

The Federal Register announcement also contained an information collection provision on the proposed. Comments on the information collection requirements should be submitted by April 29, 2010.

Agency Public Meeting to Prepare the ICH Steering Committee and EWG for Tallinn Meeting

An Agency public meeting entitled "Preparation for ICH Steering Committee and Expert Working Group Meetings in Tallinn, Estonia" will be held May 5 from 2:30 to 4:30 p.m. The purpose of this meeting is to receive input from the public prior to the next Steering Committee and Expert Working Group meetings Tallinn, Estonia June 5–10, 2010. 

Three Q4B Agency Guidances Available

The U.S. FDA has announced the availability of three Q4B guidances: Annex 7, Dissolution Test General Chapter; Annex 9; Tablet Friability General Chapter;  and Annex 10, Polyacrylamide Gel Electrophoresis General Chapter. The guidances are intended to recognize the interchangeably between the local regional pharmacopoeias, so redundant testing can be avoided in favor of a common testing strategy in each regulatory region. 

U.S. FDA Guidance to Close Gaps in Supply Chain by  Identifying and Tracking Prescription Drugs

A recently released Agency guidance will help the Secretary of Health and Human Services develop standards, identify and validate effective technologies for the purpose of securing the drug supply chain against counterfeit, diverted, subpotent, substandard, adulterated, misbranded or expired drugs.

The guidance, Standards for Securing the Drug Supply Chain – Standardized Numerical Identification for Prescription Drug Packages, is intended to assist with the standards and systems for identification, authentication and tracking and tracing of prescription drugs.  The guidance identifies SNI for package-level identification only.

More guidances and regulations are anticipated that will implement the requirements of the U.S. FDA Amendments Act of 2007.

Agency Proposed Rule Would Allow CBER, CDER Directors to Approve Exceptions/Alternatives to Biologics Reg

The U.S. FDA would like to amend the biologics regulations to permit the Directors of CBER and CDER, as appropriate, to approve exceptions or alternatives to the regulation for constituent materials.  

FDA is taking this action due to advances in recent biological products licensed under the Public Health Service Act and  to provide greater "flexibility" for  the manufacturers of biologics products, as it is deemed that some provisions of the Act that make the existing regulations are "too prescriptive and unnecessarily restrictive."

The rule provides manufacturers of licensed biological products with flexibility, as appropriate, to apply advances in science and technology as they become available without diminishing public health protections.

Comments on the proposed rule should be submitted by June 28.

The Federal Register announcement also contained  an information collection provision on the proposed. Comments on the information collection requirements should be submitted by April 29, 2010.

ClassPCV 1 Found in Rotavirus Vaccine, Regulators Investigating

The rotavirus vaccine, Rotarix, that is used to guard against severe diarrhea and dehydration in infants, was found to contain components of PCV 1, a virus composed of a single strand of DNA not known to cause disease in animals or humans.

An independent U.S. academic research team discovered the virus in the vaccine when they applied a new technology for detecting viral genetic material to two lots of the Rotarix. When the researchers notified the manufacturer, GlaxoSmithKline, of their findings, the firm initiated extensive experiments to confirm the results and investigate further. The follow-up tests confirmed the presence of copies of DNA from PCV 1 in the two finished lots.

The U.S. FDA and GlaxoSmithKline are currently investigating how DNA from PCV 1 came to be present in the Rotarix. There is no evidence at this time that this finding poses a safety risk, though the FDA is temporarily suspending the use of the vaccine while gathering additional information about the situation.

The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) currently has determined that no action is necessary and the findings of the PCV 1 do not present a public health threat. However, they do acknowledge that the virus should not be present in the vaccine and that further information is needed from the manufacturer.

The CHMP Vaccine Working Party is holding meetings with the participation of the WHO and international counterparts from Canada and the United States. The next steps will be considered at the CHMP extraordinary meeting on March 25.

Agency Collection of Information Notice on Product Jurisdiction Available

The U.S. FDA is allowing the public to comment on a proposed FDA collection of information notice which is related to product jurisdiction and the determination of organizational components that are assigned primary jurisdiction for premarket review and regulation of products that are comprised of any combination of drug, device or biological product.

A second purpose of the regulation is to enhance the efficiency of Agency management and operations by providing procedures for classifying and determining which Agency component is designated to have primary jurisdiction for any product where such jurisdiction is unclear or in dispute.

Comments should be submitted by April 16.

U.S. FDA to Hold Public Meeting on Reauthorization of PDUFA

By September 2012 new legislation will be required to replace the expiring Prescription Drug User Fee Act (PDUFA) which enables the Agency to continue collecting user fees for the prescription drug program. Without new legislation, the U.S. FDA will no longer be able to collect user fees to fund the human drug review process.

A meeting will be held on April 12 for the public to present its views on the reauthorization of PDUFA.

FDA Seeks Suggestions for Improved Regulatory Transparency

The U.S. FDA is requesting comments on ways it can increase transparency between the Agency and the regulated industry. Specifically, FDA is looking for comments on how they can make improvements in training and education for regulated industry about the FDA regulatory process in general and/or about specific new requirements; the guidance development process; maintaining open channels of communication with industry routinely and during crises; providing useful and timely answers to industry questions about specific regulatory issues; and communicating with sponsors during review of applications.

Comments must be submitted by April 12, 2010.

Provide CDER Staff Exposure to Drug Development Processes – Invite Them to Your Plant

CDER's Regulatory Project Management Site Tours and Regulatory Interaction Program has been continued by the U.S. FDA. The goals of this program are to provide CDER staff first hand exposure to the industry's drug development processes and a venue for sharing information about project management procedures (but not drug-specific information) with industry representatives.

Interested pharmaceutical companies may submit proposed agendas to the FDA by May 10.

Guidance on Cell Substrates Replaces 2006 Draft Guidance and 1993 Points to Consider Document

The U.S. FDA has finalized a draft guidance from September 2006 on the characterization and qualification of cell substrates and other biological materials used in the production of viral vaccines for infectious disease indications.

The finalized guidance provides recommendations to manufacturers of viral vaccines for the characterization and qualification of cell substrates, viral seeds and other biological materials used for the production of viral vaccines for human use.  The Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications guidance replaces the information specific to viral vaccines for the prevention and treatment of infectious diseases that the Agency provided in the 1993 document entitled, Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals.

Guidance Recommends Information to be Included in Applications Pertaining to Parametric Release for Sterile Products

A newly released U.S. FDA guidance, Submission of Documentation in Applications for Parametric Release of Human and Veterinary Drug Products Terminally Sterilized by Moist Heat Processes, provides recommendations on information to include in applications in support of parametric release for sterile products terminally sterilized by moist heat.

Agency Collection of Information on Shipments of Non-sterile devices for Sterilization

The U.S. FDA is collecting information about the shipment of non-sterile medical devices for sterilization. Currently the Agency allows firms to manufacture and label these devices as sterile at one establishment and ship them in interstate commerce to another establishment for sterilization using an appropriate control mechanism. . This control mechanism requires the preparation of agreements and maintenance of certain associated records.

The collection of Information will provide for the Agency an estimate of the burden on the industry to comply with these requirements.

Comments are due by April 19, 2010.

Guidance to Assist Industry When Submitting Product Information

A guidance entitled, Contents of a Complete Submission for the Evaluation of Proprietary Names is now available. This guidance is intended to promote the prevention of medication errors. It will assist industry in the submission of complete product information; this will help the U.S. FDA evaluate the safety of proposed proprietary drug and biological product names by taking into account factors that can contribute to medication errors.

Collection of Information on Postmarket Surveillance Activities for Medical Devices

Through the Federal Register, the U.S. FDA has announced a collection of information relative to postmarket surveillance activities for medical devices.  The notice references the appropriate sections of the regulations and provides the Agency's estimate of the burden on the industry to comply with the reporting requirements.

If anyone desires to comment on the collection of information, comments are due by April 6, 2010.

Comments Needed For the Assessment of Abuse Potential of Drugs

The U.S. FDA has released a draft guidance entitled, Assessment of Abuse Potential of Drugs. It is intended to assist sponsors who are developing drug and other medical products with the potential for abuse that may need to be scheduled under the Controlled Substances Act.

Comments should be submitted by March 29, 2010 as FDA develops a final guidance on the subject.

Agency Guidance to Help with Mechanical Calibration of Dissolution Apparatus 1 and 2

The Use of Mechanical Calibration of Dissolution Apparatus 1 and 2 – Current Good Manufacturing Practice (CGMP) guidance has been released by the U.S. FDA.

The guidance recommends an alternative method for manufacturers to comply with FDA's CGMP regulations that require laboratory apparatuses  to be calibrated at suitable intervals in accordance with established written specifications. It is intended to aid drug manufacturers (including ancillary testing laboratories) in calibrating USP Dissolution Apparatus 1 (basket apparatus) and 2 (paddle apparatus) to help assure that critical parameters associated with the dissolution apparatus meet certain mechanical calibration tolerances.

Agency Draft Guidance Available on the Immunogenicity Testing of Therapeutic Proteins

A U.S. FDA draft guidance entitled, Assay Development for Immunogenicity Testing of Therapeutic Proteins, is now available. It provides recommendations to facilitate industry's development of immune assays for assessment of the immunogenicity of therapeutic proteins during clinical trials.

Comments should be submitted on the draft guidance before February 2, 2010.

Guidances Covering Annex 5, 8 published by the U.S. FDA

The U.S. FDA has published two guidances that are a part of the Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions. One guidance contains information about sterility testing (Annex 8) and the other conveys information about disintegration testing (Annex 5).

The guidances convey recognition of the three pharmacopoeial methods by the three ICH regulatory regions and provide specific information regarding the recognition. The guidances recognize the interchangeability between the local regional pharmacopoeias, thus avoiding redundant testing in favor of a common testing strategy in each regulatory region.

Agency Extends Comment Period for Postmarketing Safety Report Requirements

The U.S. FDA has extended the comment period for the Agency's proposed rule on postmarketing safety reporting requirements for combination products in response to requests for extensions.

Comments must now be submitted by January 29, 2010.

U.S. FDA Clinical Trail Workshop Registration Available

The U.S. FDA has announced a public workshop on Clinical Trial Requirements, Regulations, Compliance and Good Clinical Practices on March 3-4, 2010 at the Wyndham Orlando Resort in Orlando, Fla.

Registration should be made by February 26, 2010.

U.S. FDA Guidance on PET Drugs Published to Provide Clarity to Final Rule

A Final Rule, by the U.S. FDA, providing regulations on cGMP for Positron Emission Tomography (PET) drugs has been published. The regulations will apply to approved PET drugs. For investigational and research PET drugs, the requirements to follow CGMP may be met by complying with the GMP regulations and/or by producing PET drugs in accordance with the USP General Chapter on compounding PET radiopharmaceuticals. The regulations are effective December 12, 2011.

A guidance entitled, PET Drugs – Current Good Manufacturing Practice (CGMP) has also been published in the Federal Register to help producers of PET Drug products better understand FDA's thinking concerning compliance with the PET cGMP regulations.

U.S. FDA Wants Feedback on draft ICH Annex 11 and 12

The Federal Register has announced that comments are due by February 16 on draft ICH Q4b guidances: Annex 11 on Capillary Electropheresis and Annex 12 on Analytical Sieving.

Europe News

EMA Notes Need for Guidance on Storage Conditions for Drug Products during Transport

November 23, 2010

The European Medicines Agency has indentified the need for a guidance on regulatory expectations for ensuring that medicinal products and APIs are not damaged during transportation. A concept paper on its website calls for the oversight of cold chain and non-cold chain products in the different stages of manufacture, importation and distribution.

Its proposal will create a new GDP and GMP guidance and may lead to the need to revise guideline: CPMP/QWP/609/96/Rev2 – Guideline on Declaration of Storage Conditions: A: In the Product Information of Medicinal Products B: For Active Substances as well as any other relevant guidances.

Comments should be sent to by February 28, 2011.

EMA to Revise Chapter 6 of the EU GMP Guide on Quality Control

November 23, 2010

The European Medicines Agency will be revising the quality control chapter of the EU GMP Guide. A guidance about globalized transfer of analytical methods worldwide both within and between companies, within the same country as well as between countries has been identified as a necessity to mitigate out-of-specification results commonly found in test method validations at contract quality control laboratories.

The revision process for Chapter 6 will take into consideration:

  • The current guidance in Annexes 16, 19 and 20 ICH Q8, Q9, Q10 documents
  • Draft document ICH Q11
  • Ongoing revision of Chapters 4, 7 and Annex 11
  • The development of new technologies such as Near Infrared Spectroscopy in the context of raw material identification and PAT
  • The need to provide specific guidance for endotoxin and microbiological testing will also be considered.

Chapter 7 of EU GMP Guide Proposed for Updating

November 23, 2010

A revision to Chapter 7 of the EU GMP Guide has been proposed in order to provide updated guidance on outsourced GMP regulated activities beyond the current scope of contract manufacture and analysis operations.

The revised draft chapter calls for:

  • The control and review of any outsourced activities to be a part of the quality system and the responsibility of management. The contract giver is ultimately responsible for ensuring that processes to assure control are in place. These processes should incorporate quality risk management. 
  • All needed information, including that from assessments of the suitability of the subcontractor is available in the same way as between the original contract giver and contract acceptor. 
  • The contract to permit the contract giver to audit the contract acceptor or his subcontractors.

Comments are due on the draft of Chapter 7 on February 28, 2011.

EMA Posts Q&A about Post Approval Change Management Protocol

November 11, 2010

The European Medicines Agency has posted a questions and answers document on its website about post approval change management protocols that is expected to lead to faster and more predictable implementation of changes post-approval.

According to the document, in order to support the proposed change, the company should submit all relevant information that can demonstrate that it has acquired adequate knowledge to prepare and manage the impact of the change. But, it is strongly recommended that companies submit post approval change management protocols only for those changes that they are highly likely to implement and whose feasibility has already been investigated and is supported by relevant data.

The deadline for comments on the draft post approval changes ends on February 28, 2011.

PhRMA Comments at Public Hearing on BPCIA

November 5, 2010

PhRMA spoke at the U.S. FDA's public hearing on the implementation of the Biologics Price Competition and Innovation Act (BPCIA).

At the hearing, PhRMA requested the Agency to require:

  • High quality, well-designed comparative studies beginning with molecular evaluation and ending in safety and efficacy trials in patients
  • Post-marketing commitments to biosimilars using the same scientific rigor and criteria as for any new product
  • Any difference in structure of the product accompanied by data demonstrating differences in safety, purity or potency from a previous product to warrant a product receiving its own 12-year exclusivity period.

The Act authorizes the approval of biosimilars and interchangeable biologics in the United States.

Danish Medicines Agency to Extend Labeling and Packaging Updates

November 5, 2010

The deadline for implementation of updates to labeling and packaging should be extended to 12 months or take place in connection with the next production, instead of six months, according to the Danish Medicines Agency. This implementation of the Danish Government's "Easy Administration" program, which was enacted to reduce the bureaucracy in business, stresses that the labeling and package leaflet must be updated at the same time.

Measures required by the Danish Medicines Agency to initiate the extended deadline will be carried out during spring 2011.

ICH Q11 to Reach Step 2, ICH Q3D to be Drafted at ICH Fukuoka, Japan

October 29, 2010

The International Conference on Harmonisation quality guideline on drug substance development and manufacturing (Q11) is expected to reach Step 2 of the harmonization process at the upcoming meeting of the ICH Steering Committee, according to U.S. FDA Assistant Director for Policy Jon Clark. Clark spoke at a meeting hosted by the U.S. FDA and the Pharmaceutical Research and Manufactures of America (PhRMA) on Oct. 13 in advance of the ICH Steering Committee meeting next month in Fukuoka, Japan; FDA and PhRMA are represented on the committee.

Q11 is intended to extend the principles of ICH's Q8, Q9 and Q10 principles to active pharmaceutical ingredients. A key aspect of the document is the inclusion of guidance for both small and large molecule products. The expert working group has been pulling together the guideline for over two years.

Clark also announced that Q3D, which will provide clarification on the requirements for metals, will move forward at the Steering Committee Meeting next month. He said that there was a "race" to get some harmonized interpretation out on metals before the USP and Europe Medicines Agency update their heavy metal chapters and guidelines in 2013.

Clark said that the goal is for the Steering Committee to provide direction to the drafting expert working group regarding the metals to be addressed in the document and the daily exposure limits for Cadmium, Arsenic, Lead and Mercury. Harmonized limits for these metals will be beneficial to industry, helping firms avoid the uncertainty and duplication of work.

ICH Q3D follows on the steps of the ICH Q3A, Q3b and Q3C guidelines that classify impurities as organic, inorganic and residual solvents.

TGA Publishes Results of International API Inspection Pilot Program

October 22, 2010

The Therapeutic Goods Administration (TGA) of Australia has published an interim report on the results of the international API inspection pilot program.

After 18 months the results are in line with the expected deliverables. These included:

  • An increase in transparency and visibility of inspections performed by participating authorities
  • A decrease in "duplicate inspections"
  • An increase in the number of inspections of value
  • An overall increase in the number of API sites inspected

Inspectors participated from such authorities as the TGA, U.S. FDA and European Medicines Agency, as well as from a number of European Union Member States.

MHRA Requiring Inspectors to Assign Risk Rating to Sites

September 24, 2010

The MHRA is starting to require inspectors to use inspection outputs and a number of other factors to identify a risk rating for a site. This rating will determine future inspection frequency. The process is being introduced on a rolling basis, and it will be two to three years before all sites will have been formally assessed.

Risk ratings can change following inspection resulting in either increased or decreased risk. Inspection risk ratings will not be published by the MHRA and there will be no formal process of appeal against risk ratings and future inspection frequency. However, any rating that results in an increased inspection frequency from the previous standard will be peer reviewed before conclusion by a GMP Operations Manager or a GMP Expert Inspector.

The MHRA does have a formal complaints process if sites wish to log an issue, however any concerns regarding the inspection process should be raised with the inspector in the first instance.

Questions or comments on risk-based inspection should be addressed to your inspector in the first instance.

EMA and U.S. FDA Seeking Candidate Companies for Joint GMP Inspection Pilot Program

August 13, 2010

The European Medicines Agency (EMA) and the U.S. FDA are seeking potential candidate companies for a joint GMP inspection pilot program for manufacturers of medicinal products.

The overall objective is to see whether greater international collaboration can help to distribute inspection capacity by allowing more manufacturing sites to be monitored and reducing unnecessary duplication.

Companies that have submitted in parallel two equivalent marketing authorization applications for the same medicinal product to both the EMA and FDA can request to participate in the pilot program for joint pre-approval inspection should such an inspection be considered necessary by both agencies.

Companies can also participate in the pilot exercise by hosting a single join re-inspection (routine surveillance) where both the EMA and the US FDA have separately planned routine surveillance inspections (re-inspections) to take place within a similar time period at a manufacturing site of a medicinal product authorized in the United States and in the European Union

Companies that wish to participate should contact either and/or 

EMA Requests Comments on Advanced Therapy Medicinal Products Document

August 13, 2010

The European Medicines Agency has published a document containing procedural advice about the interactions between its Committee for Advanced Therapies (CAT) and notified bodies for medical devices. The document provides details of possible scenarios and timelines for the assessment of combined advanced therapy medicinal products by the CAT.

The deadline for comments is October 29.

MHRA Clarifies Guidance on Supply Chain Obligations

August 2, 2010

Clarifying a November 2009 guidance, entitled, Trading medicines for Human Use: Shortages and Supply Chain Obligations, the MHRA says that a registered pharmacy, which also holds a wholesale dealer's license, should ensure that its "retail" and "wholesale" transactions are clearly separated and fully documented.

This ensures that: * Medicinal products for wholesale supply are kept in the licensed distribution chain at all times, under a full quality system that is expected to be operated by licensed wholesale dealers and Good Distribution Practice controlled conditions before they are distributed for retail supply * The obligation in Article 81 of European Directive 2001/83/EC, for the maintenance of an appropriate and continued supply of medicinal products is being met by licensed distributors. This is because those in the supply chain can be clearer as to which medicines are going to meet the needs of patients in the UK.

The guidance requests that the various parties in the supply chain to bear in mind their obligations in respect of supply of medicines and to be aware of the consequences of exporting medicines for the supply of medicines to UK patients.

ICH Amends Daily Limits for Solvent Cumene

August 2, 2010

ICH has amended Q3C: Impurities: Residual Solvents, recommending that the permitted daily exposure of the solvent cumene should be revised. The expert working group deemed cumene as more toxic thus changing its designation to Class 2 instead of Class 3.

Comments should be submitted by September 20, 2010.

European Medicines Agency Organization Guide Published

August 2, 2010

The European Medicines Agency has published a guide to their various units, sectors and sections. The guide gives the names of the Heads of units, sectors and section heads, as well as a general description of what each unit does within the European Medicines Agency.

Second Public Consultation on EU GMP Annex 2, covering Biological Medicinal Substances and Products

April 29, 2010

Annex 2 of the GMP Guide entitled, Manufacture of Biological Medicinal Substances and Products has recently been published by the European Commission for a second public consultation. The original consultation closed in March of 2008 after an 6 month period which included a public meeting on the Annex, organized by PDA in Budapest, Hungary.

The Annex has been revised as a consequence of the restructuring of the GMP guide; the increased breadth of biological products now includes several new product types such as transgenic derived products and advanced therapy medicinal products (ATMPs). There will also be a public Stakeholders Meeting at the EMA offices in London on May 18, 2010, which will primarily focus on the ATMP (e.g., gene therapy, cell therapy, tissue engineering, etc) aspects of the revised Annex.)

Please send comments to The deadline for comments is July 15.

European Medicines Agency Draft Guideline on Real Time Release Testing Available for Comments

April 29, 2010

The European Medicines Agency's note for guidance on Parametric Release, now revised as a draft guideline on Real Time Release (RTR) Testing, has been published for public consultation.

The draft guidance is intended to outline the requirements for applications that propose RTR testing for active substances, intermediates and finished products. The guideline highlights the different requirements that have to be fulfilled in the application and the role of related inspections (pre-authorization and routine GMP inspections).

The guideline was renamed because it elaborates on the application of RTR testing to a number of areas of pharmaceutical development and manufacture, in addition to traditional sterilization processes associated with parametric release.

Consultation Paper Proposals to Boost MHRA Authority Against Counterfeiters

February 15, 2010

The MHRA has published for consultation  a proposal to better control the movement of medicines throughout the legitimate supply chain. Some of the provisions of the document provide for:

  • An applicant for a Wholesale Dealer's license demonstrate that he/she is a "fit and proper person" to undertake such a role, with minimum requirements to be set out in guidance
  • A disclosure is made by applicants of relevant criminal records
  • Enabling the MHRA to decline a Wholesale Dealer's license if an applicant discloses a relevant criminal conviction
  • Introduction of a "due diligence" obligation into the legislation, with a requirement to notify the MHRA of suspicious events

The consultation deadline for responses is March 12, 2010.

European Medicines Agency Requests Comment on Road Map Initiative

January 27, 2010

The European Medicines Agency has published a draft paper outlining its vision for the strategic development of the Agency for five years to 2015. Building on the previous strategy paper of 2010, this paper, called The European Medicines Agency Road Map to 2015: The Agency's Contribution to Science, Medicines, Health, chart's the future direction of the Agency through developments in medical science and pharmaceutical research.  It also looks at the evolution of the European and international regulatory environments.

European Medicines Agency Consults Toxicological/Pharmacological Experts Regarding Dedicated Facilities Policies

January 12, 2010

The European Medicines Agency is making progress in its effort to align its dedicated facilities policies with the ICH guidance, Q9, Quality Risk Management, according to a recent update.

The Agency is looking to clarify the dedicated facilities language in the existing GMP guide. Specifically, Chapters  3 (Sec. 6) and 5 (Sec. 18, 19) were singled out in a 2005 Concept Paper as lacking clarity with respect to when a medicinal product should be manufactured in  dedicated, self-contained facilities.

In looking at the different aspects of the issue, an Agency drafting group has received input from toxicologists and pharmacologists. The Agency recommends companies also consult with toxicologists whenever introducing a product into a shared facility for product types covered by GMP Annexes that do not contain language on dedicated facilities. Currently, only new draft Annex 2 (biologicals), which is due out for comment later this year, and Annex 4 (veterinary products) address this issue.

European Commission Regulation Expands Variation Application Procedure to Mutual Recognition and Centralized  Procedure

January 8, 2010

An application form for variations to a marketing authorization for medicinal products will now be used in the mutual recognition and the centralized procedure in accordance with Commission Regulation (EC) No. 1234/2008. This variations regulation aims to establish a simple, clearer and more flexible legal framework for variations to marketing authorization while ensuring a high level of protection of public and animal health.

Asia Pacific News

Australia's TGA Increases Transparency of Prescription Medicine Regulatory Process

November 19, 2010

Australia's Therapeutic Goods Administration (TGA) has increased the transparency of its prescription medicine regulatory process with a public assessment report (AusPAR).

Before a prescription medicine can be made available in Australia, the company legally responsible for supplying the product must lodge a submission with the TGA. The TGA will then evaluate the safety, quality and effectiveness of the product to determine if the benefits to people taking the medicine outweigh the risks. AusPAR provides information to companies about the evaluation of the prescription medicine and the considerations that led the TGA to approve or not approve an application.

TGA Publishes Results of International API Inspection Pilot Program

October 27, 2010

The Therapeutic Goods Administration (TGA) of Australia has published an interim report on the results of the international API inspection pilot program.

After 18 months the results are in line with the expected deliverables. These included:

  • An increase in transparency and visibility of inspections performed by participating authorities
  • A decrease in "duplicate inspections"
  • An increase in the number of inspections of value
  • An overall increase in the number of API sites inspected

Inspectors participated from such authorities as the TGA, U.S. FDA and European Medicines Agency, as well as from a number of European Union Member States.