China’s New Pharmaceutical Excipient Regulation Stresses Responsibility for Quality Assurance, Supply Chain Management (Part One)

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This is the first of a two-part analysis on China’s new Pharmaceutical Excipient Measures. Part Two is available here.

On February 1, 2013, China’s “Measures to Strengthen the Supervision of Pharmaceutical Excipients” (Notice No. 212, 2012) (“Pharmaceutical Excipient Measures” or the “Measure”) came into force.  This Measure was issued by the State Food and Drug Administration (SFDA) in the wake of a recent drug contamination incident that began with the March 2012 discovery of 77 million medicinal gel capsules made from industrial gel containing chromium, a carcinogenic heavy metal.  The ensuing investigations led to the official announcement in May that 254 pharmaceutical suppliers, constituting 12.7% of capsule makers, were producing tainted products.  Ultimately, the authorities ordered 42 capsule makers to stop production, closed 84 production lines, revoked the licenses of seven companies, and referred 13 company officials for criminal prosecution..

The SFDA issued the Pharmaceutical Excipient Measures in August 2012, imposing new obligations on both pharmaceutical preparation producers (i.e., finished drug makers [“drug makers”] as distinguished from producers of active pharmaceutical ingredients) and excipient manufacturers.  The Measures place the responsibility for the quality of excipients directly on drug makers by requiring that they:  (1) audit suppliers both at the start of the business relationship and periodically throughout its duration, in accordance with the 2011 revision of pharmaceutical good manufacturing practice (GMP); (2) test batches of excipients according to relevant quality specifications; and (3) check the control records of each supplier.  Central to the drug maker/excipient producer relationship is the use of quality agreements: legally binding agreements negotiated by the parties to define mutual responsibilities for quality activities and how quality issues will be resolved, so as to ensure that the excipients produced under the agreement will be safe and are suitable for the drug maker’s intended use.

Likewise, excipient producers are responsible for taking measures to ensure the quality of their products, including:  implementing and adhering to excipient good manufacturing practices (e-GMP), as issued by the SFDA in 2006; auditing their own raw material suppliers; conducting testing on each batch of excipient produced; and notifying their customers of changes that may affect product quality.

In addition, the Pharmaceutical Excipient Measures set out an enhanced regulatory regime; namely, for drug makers, registration of their products will now include information identifying the types of pharmaceutical excipients used, suppliers, quality standards, and results of supplier audit.  Further, a supplemental application must be filed in connection with changes in excipient use and must include analytical data on the excipient as well as an audit of its supplier.

For excipients that are new to the (Chinese) market or considered high risk, prior registration and approval are required and their manufacturers must obtain a Drug Production License.  Excipient registration requirements include submission of certain requested documents and on-site inspection, in accordance with e-GMP, by provincial-level FDA (PFDA).  As for all other excipients, records of the product and its manufacturer must be established and maintained with the PFDA.  Again, appropriate documents must be provided, although on-site inspections and random testing will be conducted only as necessary.  Imported excipients will be regulated under this bifurcated scheme as well.  In addition, the SFDA will set up a national database to monitor the production and application of all pharmaceutical excipients, plus a credit reporting system for excipient producers.

For more on the Pharmaceutical Excipient Measures, read Part Two of our analysis.

EU Commission Releases Roadmap on Substances of Very High Concern

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EU REACH Substances of Very High Concern:

Last week, the EU Commission released its Roadmap on Substances of Very High Concern (SVHC). The Roadmap outlines a process for identifying and assessing potential SVHCs within the following categories: substances that are carcinogenic, mutagenic or toxic for reproduction (CMRs); substances that are persistent, bioaccumulative or toxic for the environment (PBTs); substances that are very persistent and very bioaccumulative (vPvBs); and substances of equivalent concern, such as endocrine disruptors. The Roadmap estimates that the process will evaluate up to 440 substances, a far lower number than the 1,900 substances originally anticipated, with an initial goal of completing 80 assessments by the end of 2014.

The Roadmap follows the Commission’s commitment to compile a comprehensive REACH candidate list of SVHCs and is designed to help meet the Commission’s plan to include all currently known SVHCs on the candidate list by 2020.

The SVHC Roadmap proposes first screening substances with REACH registration dossiers by applying a minimum quantity threshold and generally exempting substances registered only for intermediate uses. The second step entails conducting a “Risk Management Options” (RMO) analysis. Under this approach, the best regulatory option to manage a particular risk is chosen after considering actions available within REACH (like imposing authorization, restriction or substance evaluation requirements) or under other legislative schemes, such as RoHS. For example, the Roadmap suggests that substances with demonstrated risk should be restricted under REACH.

The roadmap is downloadable as a PDF from the EU website.

Upcoming Public Hearing on California's Draft Green Chemistry Regulations

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California Green Chemistry Regulations:

California EPA and DTSC have announced a public meeting on the draft regulations.  The meeting will occur on Thursday, February 28, 2013 at 9:00 a.m.

See announcement embedded below.

CALIFORNIA ENVIRONMENTAL POLICY COUNCIL

NOTICE OF PUBLIC MEETING

Department of Toxic Substances Control’s

Safer Consumer Products Proposed Regulations

Need for a Multimedia Evaluation

The Secretary of the California Environmental Protection Agency (Cal/EPA) will convene a public meeting of the California Environmental Policy Council (CEPC) to consider the need for a multimedia evaluation of the Safer Consumer Products regulations proposed by the Department of Toxic Substances Control (DTSC). The public meeting will commence as follows:

Thursday, February 28, 2013 at 9:00 a.m.

2ndFloor – Sierra Hearing Room

Joe Serna, Jr. Cal/EPA Building

1001 “I” Street, Second Floor

Sacramento, California

At the public meeting, the CEPC will consider the DTSC staff report on the Need for a Multimedia Evaluation of the Safer Consumer Products Regulations. Based on the report and public comments, the CEPC will determine whether or not DTSC’s proposed regulations will have a significant adverse impact on public health or the environment.  The public comments made in this public meeting should be primarily focused on the recommendation contained in the DTSC report.

Persons interested in commenting on the DTSC Safer Consumer Products regulations must do so by sending their comments directly to DTSC as part of the rulemaking process,  by email to gcregs@dtsc.ca.gov, fax (916) 323-5542, or by mail to:

Department of Toxic Substances Control

Regulations Section

PO Box 806

Sacramento, CA 95812-0806

For further details or for a copy of the report, please visit Cal/EPA’s website at: http://www.calepa.ca.gov/Cepc/

 

 

The European Commission Reviews REACH.

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The European Commission published its long-anticipated REACH Review on February 5, concluding that chemical use in Europe was much safer since REACH entered into force in 2007. The Review declined to propose any major changes to the regulatory scheme.

The Commission published a 13-page report and 148-page Staff Working Document which covers topics including the law’s operation, scope, and application; achieving REACH objectives like human health and market competitiveness; and enforcement.

The Review focused on ways to reduce the costs of REACH compliance for small and medium-sized enterprises (SMEs). The Commission anticipates further action to help SMEs comply with the law, including revising the REACH Fee Regulation and publishing guidance on transparency, non-discrimination and cost-sharing in preparing registration dossiers.

Other areas of improvement highlighted by the Commission include encouraging registrants to improve the quality of registration dossiers and enhancing the coordination of REACH enforcement in EU member states, especially with regard to “substances of very high concern” (SVHCs).

The Review concluded that there was insufficient information available to propose changes to registration requirements for substances produced in small quantities (1 to 10 tons) or for polymers. The Commission will continue to study these issues and, if appropriate, will release a new proposal by January 1, 2015.

The Review also did not propose any changes to the EU’s regulation of nanomaterials. The Commission will make an “impact assessment of relevant regulatory options” on the issue and may develop a draft implementing act by the end of the year.

The EU Executive is expected to organize a conference on REACH Review in the coming months.

The full report and Staff Working Document are available on the European Commission’s website.

Virginia Assembly Opposes Agenda 21

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Sustainability:

Yes, from the state that brought us Thomas Jefferson and so many other leaders, we now get the following.  Leaders or not?  You decide.

______________________________________________________________________________________________________________

HOUSE JOINT RESOLUTION NO. 654

Offered January 9, 2013

Prefiled January 8, 2013

Recognizing the need to oppose United Nations Agenda 21.

———-

Patrons– Lingamfelter, Cole, Hodges, Landes and Peace

———-

Referred to Committee on Rules

———-

WHEREAS, United Nations Agenda 21, a comprehensive nonbinding, voluntarily implemented action plan concerning sustainable development, environmentalism, social engineering, and globalism, was first presented at the United Nations Conference on Environment and Development in Rio de Janeiro, Brazil in 1992; and

WHEREAS, United Nations Agenda 21 is being covertly introduced in states and local communities across the nation by the International Council for Local Environmental Initiatives through local sustainable development policies such as Smart Growth, Wildlands Project, Resilient Cities, Regional Visioning Projects, and other “green” or “alternative” projects; and

WHEREAS, United Nations Agenda 21, a radical plan of purported “sustainable development,” envisions the American way of life of private property ownership, single-family homes, and individual freedoms as destructive to the environment; and

WHEREAS, in addition, social justice is described by United Nations Agenda 21 as the right and opportunity of all people to benefit equally from the resources afforded by society and the environment that would be accomplished by the redistribution of wealth; and

WHEREAS, United Nations Agenda 21, referring to the 21st century, is an action agenda of the United Nations, other multilateral organizations, and individual governments around the world that can be executed at local, national, and global levels; United Nations Agenda 21 has been affirmed and modified at subsequent United Nations conferences and various countries have become signatories, including the United States; and

WHEREAS, because United Nations Agenda 21 is not a treaty, the United States Senate has been unable to hold a formal debate or vote to ratify it, and the executive branch has not acted on it in any way; nevertheless, there is support in Congress for United Nations Agenda 21 and over 528 United States cities have become members of the International Council for Local Environmental Initiatives, an international sustainability organization that helps to implement the Agenda 21 and Local Agenda 21 concepts across the world; and

WHEREAS, according to the United Nations Agenda 21 policy, national sovereignty is deemed a social injustice and opposition to the policy has increased over the last 10 years in the United States at the local, state, and federal levels, and several state and local governments have passed legislation rejecting United Nations Agenda 21 as “erosive of American sovereignty”; now, therefore, be it

RESOLVED by the House of Delegates, the Senate concurring, That the General Assembly recognize the need to oppose United Nations Agenda 21 due to its radical plan of purported “sustainable development,” and that the General Assembly recognize the policy’s infringement on the American way of life and individual freedoms and ability to erode American sovereignty.

RESOLVED FURTHER, That the Clerk of the House of Delegates transmit a copy of this resolution to the United States Secretary of State, the Secretary-General of the United Nations, and the members of the Virginia Congressional Delegation in order that they may be apprised of the sense of the General Assembly of Virginia in this matter during their deliberations.

DTSC Requests Public Comment on Another Draft of the Green Chemistry Regulations

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California Green Chemistry Regulations:

The saga of California’s nascent Green Chemistry program continues. Last week, the Department of Toxic Substances Control (DTSC) released the revised text (PDF) of its proposed Safer Consumer Product Regulations. The comment period for the revisions started on January 29 and closes on February 28, 2013.

Notably, the revised rules significantly pare down the list of potential Chemicals of Concern (COCs), which are now referred to as “Candidate Chemicals,” from over 3,000 to approximately 1,200. The Candidate Chemicals  are drawn from lists of substances which exhibit one or more hazard trait. The revisions also clarify that the list of Priority Products to be regulated will be developed and updated through the Administrative Procedure Act rulemaking process.

In addition, DTSC modified the applicability of upfront exemptions for certain products, providing an exemption for products already regulated by other laws that provide comparable health and environmental protections. However, products which are manufactured, stored, or transported through California solely for use outside of the state, or used in California solely for the manufacture of non-consumer products will no longer be exempted, although these factors will be considered in the product prioritization process.

Requirements for the certification and accreditation of assessors involved in developing Alternatives Analyses (AA) have been relaxed in favor of a public review and comment process for AA reports, a choice that seems likely to increase the administrative burden and place confidential business information at greater risk. The scope of evaluating economic impacts for AA reports has also been limited to “a monetized comparison of public health and environmental costs, and costs to governmental agencies and nonprofit organizations that manage waste, oversee environmental cleanup and restoration efforts, and/or are charged with protecting natural resources, water quality, and wildlife.”

Finally, DTSC’s ability to make regulatory responses has been further refined and clarified. For example, the revised proposal requires DTSC to provide notice (with accompanying public comment period) of its proposed regulatory response determination no later than 90 days after it issues a notice of compliance or disapproval for a submitted AA report. The revised proposal also limits the agency’s ability to impose certain regulatory responses on manufacturers only, and not on retailers or importers.

More details on the revised proposed regulations, including how to submit comments and a comprehensive summary of changes from the agency’s last proposal, are available on the DTSC’s website.

EPA Announces FIFRA/TSCA Settlements with Finland-Based Kemira Group

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TSCA/FIFRA Enforcement:

EPA continues to steadily increase its enforcement of U.S. chemical control laws.  Last Thursday, the EPA announced settlements with two subsidiaries of the Finland-based Kemira Group to resolve alleged violations of Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and Toxic Substance Control Act (TSCA). Kemira Chemicals agreed to pay a civil penalty of over $300,000 to settle claims that the company sold and distributed unregistered and misbranded pesticides, and violated pesticide production reporting requirements. Kemira Chemicals also agreed to correct the alleged violations.

In addition, Kemira Water Solutions agreed to pay a civil penalty of over $500,000 regarding violations of TSCA’s Inventory Update Reporting (IUR) rule during the 2006 reporting period. Under the IUR rule, manufacturers and importers of substances included on the TSCA Chemical Substances Inventory must report the production volume and location of each facility processing such chemicals; this information is used to develop risk-screening and assessment. EPA discovered Kemira Water Solutions’ reporting violations following a January 2012 inspection and the company has since submitted the required information.

Global Mercury Reduction Treaty Finalized

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UN/Mercury:

Last week in Geneva, Switzerland, over 140 countries finalized the first global mercury reduction treaty, the Minamata Convention on Mercury. The treaty follows four years of negotiations among national environment ministers.

The Convention is named in honor of Minamata, the Japanese city which suffered severe public health effects from mercury pollution over 50 years ago, and where the diplomatic ceremony and official signing of the treaty will take place in October.

The Minamata Convention commits countries to reducing mercury in two main ways: (1) by phasing out its use in products and (2) by requiring new coal-fired power plants to employ the best available technology to cut mercury emissions. By 2020, manufacturing and trading in “mercury-added” products – like batteries (except ‘button cell’ batteries used in implantable medical devices); switches and relays; certain types of light bulbs; and soaps and cosmetics – will be banned. Other provisions of the treaty include phasing out primary mercury mining and restricting trade on mercury from decommissioning chlor-alkali plants.

Critics such as environmental NGOs have already found fault with the Convention’s lenient approach to existing coal plants and artisanal small-scale gold mining, the two largest global sources of mercury emissions. Under the Convention, countries where artisanal small-scale gold mining is practiced have within three years of the treaty entering into force to implement action plans to reduce mercury use in mining, but the treaty does not provide for an enforcement mechanism. Likewise, decisions on triggering thresholds for existing mercury-emitting facilities have been deferred until the first meeting of the treaty after it comes into force. Negotiators also agreed to funding mechanisms to assist developing countries implement the Convention and support capacity-building and technical assistance.

China’s Ministry of Environmental Protection (MEP) Releases Regular Reporting Requirements for Four New Substances

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China:

On January 4, 2013, China’s Ministry of Environmental Protection (MEP) released regular reporting requirements for four new substances under its chemical registration regime. Two of the newly certified compounds are classified as hazardous and the other two as dangerous.  Under China’s new chemical registration regime, the “Provisions on the Environmental Administration of New Chemical Substances (MEP Decree No. 7),” companies with certificates must file annual reports to the Chemical Registration Center (CRC) of the MEP.  The reports detail activities that occurred with the registered chemicals.

This announcement marks the sixth set of chemicals to be certified under China’s registration program for new chemical substances. More details on the affected chemicals, as well as reporting deadlines and contact information with the Chemical Registration Center of the MEP, are available in the MEP’s original notice (in Chinese).

International Negotiations on Mercury Treaty

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UN/Mercury:

International negotiators in Geneva for the fifth and final Intergovernmental Negotiation Committee (“INC 5”) hope to complete a mercury reduction treaty by the end of this week, although officials warn that difficult issues remain to be resolved. Delegates from over 130 countries are expected to establish the first international legal instrument with enforceable limits on mercury emissions.

The negotiators must still determine issues including: the selection of products and processes containing mercury to be phased out; the deadline for such phase-outs; whether to adopt a complete ban on primary mercury mining; and programs for financial assistance, technology transfer, and capacity-building.

A draft text of the treaty provides for regulation of the supply and trade in mercury, as well as its use in products and processes. The draft also addresses how to: reduce mercury emissions from power plants and metal production facilities; safely store and treat waste containing mercury; and identify and evaluate contaminated sites.

A joint proposal submitted by the EU, Japan, and Jamaica would phase out mercury in products like fluorescent lamps, pesticides, and cosmetics by 2018, with a later phase-out of 2020 for batteries and measuring devices. The joint proposal also calls for phasing out mercury in the production of chlor-alkali, polyurethane, and acetaldehyde by 2018 to 2025.

Negotiators are still considering a ban on the export and sale of mercury from countries with primary mercury mining. Delegates have already reached a compromise on the use of mercury in artisanal and small-scale gold mining (“ASGM”), which recently surpassed coal burning as the major source of global mercury emissions. Under the deal, countries could continue to import mercury for ASGM if they develop national action plans to reduce mercury emissions. In addition, the draft treaty permits the continued use of mercury in producing vinyl chloride monomer (“VCM”), an intermediary chemical used in manufacturing PVC plastic.

In the run-up to the conference, UNEP released two reports warning of the growing environmental and health risks of mercury exposure. The reports present estimates and trends of mercury contamination; for example, in the past century, mercury levels have doubled in the top 100 meters of the world’s oceans. UNEP argues that a global reduction treaty would reduce health problems linked to mercury, including neurological and behavioral disorders.