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In early August, the U.S. FDA released the draft guidance, CMC Postapproval Manufacturing Changes for Specified Biological Products To Be Documented in Annual Reports. This draft guidance provides recommendations to holders of biologics license applications for specified products regarding the types of minor changes that need to be documented in an annual report. In particular, the document outlines CMC controls for post-approval changes the Agency considers to have minimal adverse impact on product. Under current regulations, such minor changes must be documented in an annual report.

Comments are due Oct. 10.

EMA continues to make preparations ahead of the departure of the United Kingdom from the European Union. In light of these preparations, the Agency has temporarily suspended some of its activities, including the e-submission project, the development of a transparency roadmap, and their participation in the benchmarking of EU regulatory agencies.

Additionally, the Agency’s headquarters will eventually locate from its present site in London. As of August 1, the EMA has received 19 offers from member states to host its new headquarters. A final decision will be made on Nov. 20.

The East African Community (EAC), a regional intergovernmental organization of six partner states in East Africa (Burundi, Kenya, Rwanda, South Sudan, Uganda and Tanzania), is exploring if the EMA can serve as model for developing a similar regulatory framework in the East Africa region. Representatives from medical regulatory agencies within these states visited EMA in May to explore potential opportunities for harmonization within the region.

Recently, the U.S. FDA led a collaboration effort with participating Asia Pacific Economic Cooperation (APEC) regions to create a Supply Chain Security Toolkit for Medical Products. This toolkit contains training materials to educate regulators and industries in the Asia-Pacific region on best practices for ensuring the security of medical products in the supply chain. Training materials cover GMP, GDP, track and trace systems, surveillance/monitoring, etc. To further establish best practices in the global supply chain, APEC plans to also develop Training Centers of Excellence for Regulatory Science which will be responsible for furthering training on the toolkit.

In early June, the China FDA released its annual drug inspection report for 2016. The Agency conducted 431 total inspections, including GMP inspections. The report shows another year of growth in the number of inspections of overseas manufacturers ordered by CFDA; however, the Agency only performed a fraction of these planned visits.

According to a June press release from the German Federal Institute for Drugs and Medical Devices, a batch of hepatitis C drug, Harvoni®, has entered the German drug supply chain. A patient notified authorities of a difference in the color of the product. Gilead Sciences, the manufacturer, recalled the batch; analysis showed that the product had been repackaging and relabeled.

Counterfeit Harvoni® batches have also been discovered in Israel, Japan and Switzerland over the past 18 months. The Federal Institute for Drugs and Medical Devices is working with EMA and other regulatory agencies to determine if other European markets have been affected.

The U.S. FDA has extended the commenting period relating to supply chain elements of the Drug Supply Chain Security Act (DSCSA). The Agency is requesting comments on product identifiers for product tracing, supply chain technical capabilities, and identification of system attributes needed under the DSCSA.

Comments now close April 30, 2018.

MHRA released its annual report covering inspection findings of facilities producing drug product for the UK market in May. This report covers 324 inspections in 2016, of which 34% were of overseas facilities. Top deficiencies noted in the report included issues with quality systems, sterility assurance concerns, production problems, complaints/recalls, and more. MHRA releases this data publicly so companies can use it as part of continuous improvement.

On May 2, EMA released a Q&A document in response to the United Kingdom’s withdrawal from the European Union. This document covers procedures for marketing authorization holders currently established in the United Kingdom, orphan designation procedures, role of Qualified Persons, etc. EMA expects to update this document in the future.

In addition, a recent meeting of EMA’s Management Board covered how the Agency will handle the UK’s plans to exit the European Union. The Agency is working on the assumption that the UK will be considered a third country outside the EU and European Economic area as of March 30, 2019, and will continue to participate in all formal meetings and retain its speaking and voting rights.

PIC/S expressed concerns about the European Commission’s proposed advanced therapy medicinal products (ATMP) GMP guidelines in a letter dated Feb. 24. In particular, PIC/S is concerned the proposed guidelines will lead to a nonharmonized approach to ATMP GMPs in addition to lowering standards for ATMP GMPs.

In March, EMA released a concept paper outlining plans to revise the Agency’s guidance covering the quality of water used for pharmaceutical purposes. The revision takes into account the recent decision by the European Pharmacopoeia to accept non-distillation water technologies to produce water for injections (WFI).

Comments are due June 6.

In early March, both the US FDA and EMA announced that the European Union and United States have agreed to recognize each region’s GMP inspections of pharmaceutical manufacturing facilities. This agreement follows three years of work between both agencies on the Mutual Reliance Initiative. Mutual recognition of inspections is expected to result in avoidance of duplicate inspections, reduced inspection costs, and allows regulators to better allocate resources to other regions that present greater risks.

The European Union is expected to have completed its assessment of FDA by Nov. 1, with FDA having completed its own assessment of eight EU member states.

In late February, the China FDA published its five-year plan (2016–2020) on food and drug safety. The Agency intends to use the plan to set stricter standards for medical equipment and drug quality by enhancing supervision. The plan finalizes the quality consistency evaluation for 289 generic drugs, revises 3050 national drug standards and 500 medical equipment standards, and requires 100% rate of updates for periodic drug safety reports.

The US FDA has established the Oncology Center of Excellence (OCE) and appointed Richard Pazdur, MD, as its director. The OCE is part of the FDA’s larger effort to better address the needs of cancer patients through a coordinated clinical review of drugs, biologics, and devices across the Agency’s three medical product centers.

ICH Q3C (R6), Impurities: Guideline for Residual Solvents, has entered the implementation period. The most recent update revises the Permissible Daily Exposure for Methyl isobutyl ketone (MIBK) and adds Triethylamine (TEA) as a new solvent.

The China Food and Drug Administration has committed to adopting a “double random” approach to inspections to improve oversight. This approach involves random selection of both the inspector and the organization or process being inspected.

(Link in Chinese)

Japan’s Pharmaceutical and Medical Devices Agency (PMDA) announced in December plans to join the U.S. FDA and EMA to improve the GMP inspection process for sites producing APIs through a collaborative effort. Under this agreement, PMDA will be able to share information related to GMP inspections. This information would include inspection plans and results. This is part of PMDA’s International Strategy.

EMA will launch a biosimilar-focused pilot project this month. The Agency plans to use this pilot to provide biosimilar developers with recommendations as to what studies they should be conducting based on data from the innovator product. This program is open to all companies looking for scientific advice on developing a biosimilar product.

The FDA recently announced that the Agency hopes to sign an agreement with the European Union soon on the Mutual Reliance Initiative (MRI). At this time, the two entities are completing assessments of drug manufacturing inspectorates for two to four EU countries. The Agency launched this initiative with the EU in 2014 to create an expanded inspectorate that enables FDA investigators and trusted EU partners to work together to avoid duplicate inspections by relying on each region’s inspection information. This would allow the United States and European Union to devote more resources to regions where drug manufacturing has greatly increased, such as China and India.

Effective Dec. 29, certain data on FDAregulated products imported into the United States must be submitted through the Agency’s Automated Commercial Environment (ACE) system. This more streamlined import process is expected to result in efficient use of Agency resources and more effective enforcement of FDA regulations. ACE replaces the older Automated Commercial System. The new system offers a single window for importers, eliminating the need to submit information more than once.

The FDA released a guidance for industry on Nov. 22 describing how contract manufacturing organizations can use quality agreements to delineate their manufacturing activities to ensure compliance with current GMPs. According to this document, companies outsourcing pharmaceutical operations are responsible for the quality of the final product, not the outsourcing firm.

Comments on the guidance are due at any time.

In early January, the FDA released its final guidance on cGMPs for combination products. The finalized guidance addresses concerns industry had expressed regarding FDA communications related to combination products. In addition, the guidance discusses the role of the lead center and other Agency divisions responsible for cGMP issues for these types of products.

On Dec. 13, President Barack Obama signed the 21^st Century Cures Act into law. This Act creates a new pathway for regenerative medicines, requires less use of data in bringing drugs and devices to market, and encourages adoption of continuous manufacturing through FDA-provided grants.

The Act also provides additional funding for research on cancer and opioid addiction.

On Nov. 23, the U.S. FDA released its revised guidance on quality metrics. This version includes comprehensive definitions for metrics categories as well as reporting tiers for various types of organizations. In addition, the document establishes an initial period where reporting of metrics will be voluntary.

Comments are due March 27.

PIC/S has released a draft data integrity guidance. This draft guidance is being made available to facilitate the effective implementation of data integrity elements into the routine planning and practice of GMP/GDP inspections. The guidance also provides support for risk-based data integrity inspections.

India’s Central Drug Standards Control Organization (CDSCO) recently announced plans to recruit more than 500 new drug inspectors in 2017 as part of a five-year plan to ensure the quality of drug product manufacturing within India and drug product manufactured for export. In addition, CDSCO hopes to train the recruiters effectively to ensure uniform GMP inspections.

CDSCO recently finished recruiting 147 drug inspectors as part of a push to enhance cGMP inspections of manufacturing units.

The British regulatory authority MHRA released a guidance in August outlining when certain health apps can be considered medical devices. The guidance features an interactive step-by-step PDF to help developers determine if their product constitutes a medical device. In addition, the guidance offers recommendations for navigating the regulatory pathways for approval. The guidance was developed due to the proliferation of health-related apps available on the marketplace and to clear up confusion.

EMA has provided a set of draft questions and answers on the production of water for injections by nondistillation methods, i.e., reverse osmosis, to provide preliminary guidance until the ongoing revision of Annex 1 of the GMP guide is complete.

Industry comments on the document are due Nov. 4.

The FDA plans to change its internal procedures for responding to sponsors on preliminary product classification assessments from the Office of Combination Products (OCP). This new process, the Pre-Request for Designation (Pre-RFD) process, will require sponsors to provide a detailed product description. Once OCP receives this information, the Office will make an assessment regarding product classification and Center assignment. The Agency’s goal is to respond to sponsors 60 days following receipt of all the necessary information. A draft guidance on this process is forthcoming.

This summer, Health Canada announced it is on track to meet requirements for reporting drug shortages via a third-party reporting site by its spring 2017 deadline. After the new reporting site is launched, it will replace the current drug shortages website. Before the new site is up, however, Health Canada expects companies to continue posting information about drug shortages and product discontinuances on the drugshortages.ca website.

In August, the U.S. FDA proposed amending its Good Laboratory Practice (GLP) regulations to require a complete quality system approach for nonclinical laboratory studies. This approach is called a GLP Quality System and features safety and toxicity studies used to support product submissions to FDA. The Agency also seeks to revise the definition of a “testing facility” in light of current practices, such as multisite studies. This proposed revision is intended to build quality into nonclinical laboratory studies and help ensure data integrity.

Comments are due Nov. 22.

Beginning Sept. 1, EMA will reduce the number of divisions dealing with human medicines from four to three, create a new function to strengthen collaboration between the Agency and national competent authorities, and streamline the division responsible for administration and corporate management. These changes are expected to result in leaner operations and better administrative support. This reorganization builds on the Agency’s 2013–2014 reorganization.

On July 7, the U.S. FDA issued two draft guidances regarding compounded drug products that are “essentially a copy” of approved and commercially available drug products. Comments on both draft guidances are due Oct. 11.

U.S. FDA Commissioner Robert Califf, MD, selected Richard Pazdur, MD, to become acting director of the new Oncology Center of Excellence. This Center will be a place where regulatory scientists and reviewers with oncology clinical expertise in drugs, biologics and devices will collaborate and support an integrated approach to the advancement of cancer treatment.

Over the summer, members of the U.S. FDA met with several European Union regulatory counterparts and stakeholders in Brussels to discuss ways to strengthen their shared commitment to product safety and public health. Discussions covered global supply chain issues, globalization of drug development, and the Mutual Reliance Initiative (MRI). Toward the conclusion of the trip, FDA officials reviewed EMA’s mutual reliance plans. Both agencies expressed hope to continue regulatory alignment.

In a blog post over the summer, the U.S. FDA announced its plans for minimizing the impact of the Zika virus by partnering with other U.S. government agencies, the private sector and the international regulatory community, including the WHO and ANVISA (the Brazilian Health Regulatory Agency) on vaccines and treatments. As of July, 120 FDA staff members are working in response to the outbreak.

To advance its mission of becoming a global platform for harmonization for better health, ICH has welcomed two new members and 14 observers who represent regulatory authorities, regional health initiatives and pharmaceutical industry groups at its June meeting. These include:

• Association of Southeast Asian Nations (ASEAN)
• Biotechnology Innovation Organisation (BIO)
• Central Drugs Standard Control Organization (CDSCO, India)
• Council for International Organizations of Medical Sciences (CIOMS)
• Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS, Mexico)
• East African Community (EAC)
• European Directorate for the Quality of Medicines & HealthCare (EDQM)
• Health Sciences Authority (HSA, Singapore)
• International Pharmaceutical Excipient Council (IPEC)
• Ministry of Food and Drug Safety (MFDS, South Korea)
• Roszdravnadzor (Russia)
• Food and Drug Administration (TFDA, Chinese Taipei)
• Therapeutic Goods Administration (TGA, Australia)
• United States Pharmacopeia (USP)
• International Generics and Biosimilars Association (IGBA)
• World Self-Medication Industry (WSMI)

The World Health Organization has released Technical Report Series No. 996, which provides guidance on good data and record management practices based on feedback collected at an October 2014 meeting.

[Editor's Note: Check out PDA's data integrity resource page for more information on this important topic!]

The U.S. FDA draft guidance, Elemental Impurities in Drug Products, provides recommendations regarding the control of elemental impurities of human drug products marketed in the U.S. in order to remain consistent with the implementation of ICH Q3D. The draft guidance will also assist manufacturers of compendial drug products in responding to the issuance of the USP requirement for the control of elemental impurities.

Comments on the this guidance are due Aug. 30.

In Q2, CDER launched its new electronic CDER Export Certification and Tracking System. The system allows users to request a CDER Certificate of a Pharmaceutical Product (CPP) online as an alternative to a paper submission. The new software provides many features; including reducing the amount of time it takes to process a certificate, a step-by-step guide to applying for a CPP, real-time validation of data submitted and email notifications regarding the status of a CPP request.

The U.S. FDA continues to develop EvGen, its national system for evidence generation. In practice, EvGen would be an umbrella for all activities that help inform all stakeholders about making treatment decisions. The platform is built on the concepts of interoperability and connectivity—essential prerequisites for the creation of a successful national system for evidence generation.

The U.S. FDA draft guidance, Technical Considerations for Additive Manufactured Devices, outlines the Agency’s initial thinking on technical considerations specific to medical devices using additive manufacturing (AM), the broad category of manufacturing encompassing 3-dimensional (3D) printing. The draft guidance outlines technical considerations associated with AM processes and recommendations for testing and characterization for devices that include at least one AM fabrication step. This draft guidance is a “leap-frog guidance,” intended to serve as a mechanism by which the Agency can share initial thoughts regarding emerging technologies that are likely to be of public health importance early in product development.

Comments on this document should be submitted by Aug. 8.

The European Medicines Agency’s (EMA) 2015 annual report, published May 17, 2016, focuses on the Agency’s core tasks, including evaluation of medicines, support of research and development of new and innovative treatments and the monitoring of benefits and risks of medicines in practice. The Annual Report also highlights some of the main projects, initiatives and achievements from 2015 that have had a significant impact on EMA and its operations.

In April, the Subcommittee for Advanced Manufacturing of the National Science and Technology Council, a Cabinet-level council in the U.S. executive branch, published a report that captured technology areas in advanced manufacturing that are current priorities for the U.S federal government and are strong candidates for focused Federal investment and public-private collaboration. Emerging technology areas include advanced materials manufacturing, engineering biology to advance biomanufacturing, biomanufacturing for regenerative medicine, advanced bioproducts manufacturing and continuous manufacturing of pharmaceuticals.

The U.S. FDA is working on strengthening its protection of pharmaceutical data submitted in regulatory filings during the approval process of new drugs. According to the Agency’s 2015-2018 Information Technology Strategic Plan, the U.S. FDA will implement independent verification and validation for high‐risk systems, move to a next‐generation network security architecture and improve the agency's patch management plan.

EMA's guideline on process validation for the manufacture of biotechnology-derived active substances and data to be provided in the regulatory submission will go into effect Nov. 1, 2016.

The U.S. FDA’s Case for Quality initiative encourages open engagement between all members of the device ecosystem to enhance the quality of medical devices. This program is one of the Center for Devices and Radiological Health’s 2016-2017 strategic priorities.

An INTERPOL sting operation, which targeted the illegal online sale of medicines and medical devices, resulted in 393 global arrests and the seizure of more than 12.2 million fake and illicit medicines valued at more than $53 million.

At its June meeting, the European Medicines Agency (EMA) Management Board adopted EMA’s multiannual work program to 2020 and its framework for stakeholder relations management. In addition, the Board approved an updated schedule for the implementation of the new EudraVigilance system.

To assist industry in preparing premarket applications, humanitarian device exceptions, investigational device applications and premarket notifications, the U.S. FDA has released its Use of International Standard ISO 10993-1, ‘Biological evaluation of medical devices—Part 1: Evaluation and testing within a risk management process' guidance.

Comments may be submitted at any time.

The U.S. FDA recently released its Quality Metrics Technical Conformance Guide, Version 1.0, which serves as the technical reference for the draft FDA guidance, Request for Quality Metrics. The guide provides recommendations about submission of information that will support the FDA’s calculation of quality metrics.

CBER recently published its Annual Summary for 2015. This summary contains an overview of the reports CBER received during the fiscal year, including detailed information regarding the number and types of deviation reports.

The U.S. FDA continues to respond to concerns about pharmaceutical compounding with the release of three additional guidances on April 15. These guidances cover prescription requirements, regulation of compounding in state-licensed hospital or health system pharmacies and facility definitions.

Comments on all three are due by July 18.

CDER launched its new electronic CDER Export Certification and Tracking System. The system allows users to request a CDER Certificate of a Pharmaceutical Product (CPP) online as an alternative to a paper submission. The new software provides many features; including reducing the amount of time it takes to process a certificate, a step-by-step guide to applying for a CPP, real-time validation of data submitted and email notifications regarding the status of a CPP request.

The U.S. FDA has released the draft guidance, Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products. This draft guidance provides recommendations regarding development and validation of immune assays for assessment of the immunogenicity of therapeutic protein products during clinical trials.

Comments are due June 24.

EMA released concept paper on April 28 outlining how to assess the potential environmental risks of medicinal products. The paper includes considerations for risk mitigation strategies for reducing the impact of drug products on the environment.

Comments are due Oct. 31.

The U.S. FDA recently released a draft guidance outlining technical considerations for device manufacturers using 3D printing.

Comments are due Aug. 8.

The U.S. FDA proposes to amend standards for biologics that pertain to preparations and limits to potency due to the availability of new technology and testing capabilities.

Comments on this proposed rule are due July 18.

The U.S. FDA recently established the Agency’s first Combination Products Policy Council. This Council will serve as communications hub for discussing, resolving and implementing product and policy issues related to combination products. In addition, the Council will play an integral role in the development of internal and external communications such as draft guidances, publications and blog posts regarding policy decisions.

The European Union and China Working Group on Pharmaceuticals recently met to discuss drug evaluation and approval procedure reform, anticounterfeiting legislation and management of online pharmacies. This comes as part of the Consultation and Cooperation Mechanism agreement signed in 2013, which states the China Food and Drug Administration and the European Commission will meet more regularly for constructive dialogue on pharmaceutical laws and regulations.

On Apr. 5, the U.S. FDA approved a second biosimilar product, Inflectra (infliximab-dyyb), which is administered by intravenous infusion to treat Crohn’s disease, ulcerative colitis and moderate to severe rheumatoid arthritis. Inflectra is biosimilar to Janssen Biotech, Inc.’s Remicade (infliximab).

EMA has released a draft guideline on the sterilization of medicinal products, active substances, excipients and primary containers. This draft guideline describes expected documentation for sterile products in the quality dossier for a marketing authorization application or a variation application for a medicinal product.

Comments are due Oct. 13.

The U.S. FDA recently released a long-awaited draft guidance on data integrity and compliance with cGMPs. This document clarifies the role of data integrity in cGMPs.

Comments are due June 14.

Staff from the FDA’s China Office recently met with provincial FDA regulators, industry and academia in China’s Yangtze River Delta region to discuss strengthening partnerships, sharing information and building the foundation for future cooperative engagement.

The U.S. FDA is building the foundations of a national medical device evaluation system to generate better evidence more efficiently for medical device evaluation and regulatory decision making. The collaborative national evaluation system, one of CDHR’s 2016–2017 strategic priorities, will link and synthesize data from different sources across the medical device landscape and improve the quality of real-world evidence that healthcare providers and patients can use to make better informed treatment decisions.

On April 8, for the first time, the U.S. FDA approved a manufacturer’s change from batch to continuous manufacturing. This was for Janssen Product’s HIV-1 medication, Prezista. The company relied on a recently released FDA draft guidance to support the change.

On Mar. 17, Christa Wirthumer-Hoche was elected as chair of the European Medicines Agency’s Management Board for a three-year term. The Management Board sets the Agency’s budget, approves the annual work program and is responsible for ensuring that the Agency works effectively and cooperates successfully with partner organizations across the EU and beyond.

In order to improve the overall efficiency, consistency and predictability of combination product review, the U.S. FDA is developing a lean management process mapping approach, which includes an analysis of current processes to highlight existing sources of delay or redundancy, and creation of a “future state” map that identifies a streamlined process that addresses the previously identified delays and redundancies.

EMA recently launched PRIME—PRIority MEdicines—its new scheme to strengthen support for the development of medicines that target an unmet medical need. PRIME is based on enhanced interaction and early dialogue with developers of promising medicines to optimize development plans and speed up evaluations so that these medicines can reach patients earlier.

The European Pharmacopoeia has revised its monograph on water for injection (WFI) to accept WFI that undergoes a purification process equivalent to distillation, such as reverse osmosis. This revision becomes effective April 2017.

The FDA has issued a draft guidance that lists which devices medical device manufacturers must have human factors data included in their premarket submissions. The Agency believes that inclusion of this data will help it evaluate the potential for use errors in these devices.

Comments are due May 3.

Dec. 1, 2015, the China Food and Drug Administration (CFDA) announced that the 2015 edition of the Chinese Pharmacopoeia (ChP) has gone into effect. The new edition will drive the overall improvement of drug quality and play a significant role in ensuring drug safety and effectiveness for the public by requiring any drug product and drug ingredient intended for marketing in China to comply with ChP 2015 requirements or use ingredients that comply with ChP 2015 requirements.

CDRH has released its list of guidance documents for 2016. The documents listed fall under three categories: "A-list" documents the Center fully intends to publish, "B-list" documents to be published as resources permit, and final guidance documents issued in 2006, 1996, 1986 and 1976 subject to retrospective review.

Jessica Zeller is the new ombudsman in the U.S. FDA’s Office of Regulatory Affairs. Her responsibility is to resolve, when possible, problems between the Agency and external partners.

CBER has released the list of guidance documents the Center plans to publish in 2016. Documents of particular interest include early clinical trials with live biotherapeutic products and recommendations for screening donors for Zika in cell, tissue and gene therapy products.

On Feb. 24, the U.S. Senate confirmed Robert Califf, MD, as commissioner of the U.S. FDA. He is currently Vice Chancellor of Clinical and Translational Research at Duke University. His background is in cardiology.

Califf replaces Margaret Hamburg, who stepped down last year. Stephen Ostroff has been serving as interim commissioner.

EMA has set up a task force to look into the recent Zika outbreak. As part of the Agency's efforts to combat the outbreak, EMA wants input from drug developers working on products that may prove promising in stopping the spread of the disease.

On Feb. 3, the U.S. FDA released the draft guidance, Enforcement Policy on National Health Related Item Code and National Drug Code Numbers Assigned to Devices. This guidance will outline FDA’s plan to not enforce the prohibition against providing National Health Related Item Code (NHRIC) or National Drug Code (NDC) numbers on device labels and device packages, with respect to certain finished devices manufactured and labeled prior to Sept. 24, 2018 before Sept. 21, 2021.FDA realizes developers need additional time to ensure that unique device identifiers (UDIs) do not include NHRIC or NDC numbers and does not wish to disrupt the supply chain.

Comments due April 4.

New EU regulations now require new safety features to prevent counterfeiting: a unique barcode and an anti-tampering device for drug products.

The U.S. FDA recently issued a guidance on applying human factors and usability engineering to medical device due to concerns that user interfaces are designed to minimize or eliminate the risk of errors.

WHO released a revised set of guidelines for GMPs for biologics in the last quarter of 2015. This set of guidelines accounts for changes since initial recommendations made in 1992.

Effective Jan. 1, the Pharmacy and Poisons Board of Hong Kong SAR (PPBHK) and Croatia’s the Agency for Medicinal Products and Medical Devices (HALMED) joined PIC/S.

The U.S. FDA continues to take steps toward encouraging modernization of pharmaceutical manufacturing, including establishment of the Emerging Technology Team and a recent draft guidance.

Australia’s Therapeutic Goods Administration (TGA) has joined ICH as its latest observer, allowing TGA representatives to attend ICH Assembly meetings and participate in ICH activities.

EMA has published its workplan for 2016 for the GMP/GDP Inspectors Working Group. Topics to be discussed during meetings of the working group throughout 2016 include Mutual Recognition Agreements (MRAs), the Joint Audit Programme, data integrity, GMPs for active biological substances, and more.

Medical devices are becoming ever more interconnected with not just other devices but other forms of technology as well. For this reason, on Jan. 26, the U.S. FDA released the draft guidance, Design Considerations and Pre-market Submission Recommendations for Interoperable Medical Devices. This document outlines the Agency's "specific considerations related to the ability of electronic medical devices to safely and effectively exchange and use exchanged information," and includes considerations that should be included in the development and design processes for these interconnected devices.

Comments are due March 28.

CDER has released its list of planned guidances for 2016. These include guidances concerning statistical approaches to support a demonstration of biosimilarity, combination products that utilize software, CMC post-approval change documentation and more.

Recently, the U.S. FDA's Center for Devices and Radiological Health (CDRH) released its 2016-2017 strategic priorities. These priorities fall under one of the three following critical areas: establishing a national evaluation system for medical device, partnering with patients and promoting a culture of quality and organizational excellence.

U.S. FDA recently released a draft guidance regarding cybersecurity of medical devices. A growing number of medical devices, such as "smart" devices,  are networked and incorporate software that could be vulnerable to cybersecurity threats. 

Comments are due April 21.

In 2015, EMA recommended 93 medicines for approval, including 39 new active substances.

Recently, the U.S. FDA's Center for Devices and Radiological Health (CDRH) released its 2016-2017 strategic priorities. These priorities fall under one of the three following critical areas: establishing a a national evaluation system for medical device, partnering with patients and promoting a culture of quality and organizational excellence.

In December, the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) published a Q&A document summarizing the most common questions asked by stakeholders regarding EMA’s Qualified Person (QP) declaration template and associated guidance document. The Q&A document addresses the QP's role in evaluating the final active substance manufacturer versus factoring in the sites for all raw materials within the supply chain as well as the role of audits from national regulatory bodies.

The U.S. FDA approved 45 novel therapies in 2015—placing overall U.S. drug approvals to their highest level since 1996. More than one-third of these were identified as “first-in-class,” meaning drugs utilizing a new and unique form of action to treat a medical condition.

At the China-U.S. Joint Commission on Commerce and Trade in Guangzhou, China in late November, both countries agreed to enhance cooperation on efforts to prevent the selling of counterfeit drugs online.

The U.S. and China also made efforts to work together on drug and medical device registration approval and greater regulation of clinical trials.

On Dec. 18, EMA announced that its Management Board and Heads of Medicines Agencies have adopted a network strategy for the next four years. This strategy outlines common challenges and opportunities across the EMA network that pertain to regulating public health, setting out a roadmap for addressing these priorities by 2020. It also builds on EMA’s roadmap to 2015 and the HMA strategy for 2011–2015, and will result in multiannual implementation plans for EMA and related bodies.

In late December, the U.S. FDA’s CDER office released its 2016 priorities. These include renegotiating parts of PDUFA and GDUFA, a continuing focus on drug compounding and furthering implementation of Track and Trace.

CDER Director Janet Woodcock also outlined the Center’s 2015 accomplishments. During the past year, CDER stabilized the new Office of Generic Drugs, completed the standup of the Office of Pharmaceutical Quality, established multiple guidances pertaining to pharmacy compounding and responded to congressional queries related to the 21st Century Cures Act.

The U.S. FDA launched its precisionFDA platform in mid-December. This Web- and cloud-based portal allows scientists spanning industry, academia and government to collaborate on the science behind next-generation sequencing (NGS) of DNA. The Agency launched this portal as part of the Precision Medicine Initiative, which began in early 2015 and focuses on fostering the development and expansion of personalized medicines.

On Dec. 23, the U.S. FDA released a draft guidance about a new program for companies interesting in submitting CMC information on emerging manufacturing technologies. This information would be submitted as part of an IND, NDA, ANDA or BLA.

Comments are due Feb. 22.

CBER has released its fiscal year report for 2015. Among the highlights:

• Licensing of the first vaccine in the United States for prevention of meningitis disease caused by Neisseria meningitidis serogroup B
• Extensive involvement in the containing the Ebola virus outbreak and working with industry groups on strategies for a vaccine
• More than 70% of CBER's 2015 program alignment objectives were implemented on time

In addition, CBER Director Karen Midthun, MD, has retired from her position and the FDA is actively seeking a replacement for her role.

At its October meeting in Indonesia, PIC/S elected Paul Hargreaves of the UK's Medicines & Healthcare Products Regulatory Agency (MHRA) as Chairman for 2016–2017. New office holders were also elected for seven PIC/S subcommittees

USP Chapter <1231> Water for Pharmaceutical Purposes is now under revision. Changes include organizing the chapter into nine specific sections, removal of language redundant to referenced wording in monographs and the addition of a detailed table of contents which will be hyperlinked in future online USP versions.

Those interested in commenting on the revision can register with the Pharmacopeial Forum for free.

The European Commission has received a proposal from the French government for the use of a pictogram label for medicinal products that would indicate that the product or its excipients was sourced in the European Union.The proposed pictogram would be a rectangle divided into four sections corresponding to four categories: active ingredients, excipients, production and packaging. For any category produced in the European Union, the word “Europe” would appear in white letters on a blue background. For those manufactured outside the European Union, a black cross would appear.

This comes in response to concerns about GMP quality for products manufactured outside the European Union.

The proposed pictogram is currently up for review by the Commission.

The United States Pharmacopeial Convention (USP) submitted comments on the U.S. FDA’s Nonproprietary Naming of Biological Products draft guidance, which proposes that all biologic products bear a nonproprietary name designated by the Agency. The USP comments were made in support of a uniform and scientifically based approach to naming that does not create unintended risks for patients and practitioners.

The U.S. FDA continues to look at Cost of Quality for device manufacturing. The Cost of Quality consists of a focus on quality, stakeholder engagement and data transparency. At this time, the Agency continues to explore development of tools to assess and quantify quality in device manufacturing.

The U.S. FDA recently released its finalized guidance on formal meetings between the Agency and sponsors of biosimilar products that provides recommendations to industry on formal meetings between the Agency and sponsors concerning the development and review of biosimilar products regulated by CDER and CBER.

This finalizes the April 1, 2013 draft guidance.

The U.S. FDA has released a mobile version of its Approved Drug Products with Therapeutic Equivalence Evaluations (commonly referred to as the "Orange Book") as a PDF document and an app for both Apple and Android products. The app can be purchased through the Apple and Google app stores.

Guatemala’s official medicines control laboratory has retained its ISO 17025 accreditation, certifying its expanded ability to operate and reliably test the quality of its medicines to world-class standards.

The revised U.S. FDA Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic (FD&C) Act Guidance describes some of the possible enforcement actions FDA can bring against individuals or firms that compound drugs in violation of the FD&C Act.

This document was released in October.

On Oct. 5, the United Kingdom’s Medicines and Healthcare products regulatory agency, MHRA, recently signed a Memorandum of Understanding with India’s Central Drug Standard Control Organization (CDSCO) as part of an agreement to increase collaboration between the two countries on public safety.

This is the first Memorandum of Understanding signed with CDSCO. Both agencies hope this agreement facilitates expanded exchange of information and opportunities for collaboration.

Guido Rasi officially assumed his duties as Executive Director of EMA this week. He was appointed on Oct. 13 for this five-year role. In December, he will outline his plans for the next five years.

The U.S. FDA recently awarded a $4.9 million grant to support research and development of continuous manufacturing techniques for the pharmaceutical industry at the Engineering Research Center for Structured Organic Particulate Systems, a research consortium led by Rutgers University School of Engineering.

This grant will be administered by NIH over a three-year period and will increase research and development efforts at the Engineering Research Center for Structured Organic Particulate Systems (C-SOPS) over the next 3 years.

In late September, USP released its proposed revision to General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. This revised chapter has been under review since 2010.Changes include collapsing the microbial risk categories of low, medium and high-risk into two categories (Category 1 and 2).

Comments are due Jan. 31.

In October, the European Commission released the revision to Annex 16: Certification by a Qualified Person and Batch Release. This revision takes into account the globalization of supply chains and new quality control strategy. In addition, it takes into account the ICH Q8-Q10 documents.

The revised Annex 16 comes into effect April 15, 2016.

In late October, ICH held its first Assembly and Management Committee meetings. These meetings are part of an overall reform of the organization that seeks to expand ICH into a worldwide initiative that goes beyond current ICH members. In addition, ICH seeks to include a wider selection of representatives from global industry sectors impacted by ICH harmonization.

The China FDA recently released four guidelines promoting GMPs for medical devices. These guidelines strengthen regulatory oversight of medical device manufacturing in the country and cover onsite inspections of sterile medical devices, implantable devices and in vitro diagnosis reagents.

The European Medicines Agency released a reflection paper on a proposal to enhance early dialogue to facilitate accelerated assessment of priority medicines. This is in response to a recognized need to foster development of medicines that address unmet medical needs. Earlier efforts to address this need have included the Adaptive Pathways pilot and revisions to the guidance on accelerated assessment.

Comments are due by Dec. 23.

FDA recently released a draft guidance on the ICH revision to its technical requirements for registering pharmaceuticals for human use, also known as M4E(R2). This revision standardizes how benefit-risk information is included in regulatory submissions. FDA hopes the revision facilitates greater communication between regulators and the industry.

Comments are due Dec. 1.

Earlier this week, the European Commission released  Annex 16: Certification by a Qualified Person and Batch Release. Annex 16 was revised on account of the greater globalization of pharmaceutical supply chains and the Falsified Medicines Directive. In addition, this revision also looks at implementation of ICH Q8, Q9, and Q10.

This revision becomes effective April 15, 2016.

The revised PIC/S GMP Guide became effective Oct. 1. This revision incorporates the EU’s Annex 15 revision covering qualification and validation. 

EMA has nominated Guido Rasi as the Executive Director of the Agency at an Oct. 1 session of EMA’s Management Board. He is expected to appointed following a statement to the European Parliament on Oct. 13.

Andreas Pott, Deputy Executive Director, will continue to head EMA’s operations until Rasi officially assumes responsibilities as Executive Director.

In mid-September, New Zealand announced plans to introduce a new bill in 2016 that would align the country’s medical device and drug product regulations with global standards. In addition, the new regulation would cover cell and tissue therapies, which are currently not regulated in the country. Regulators hope the new regulation will be flexible enough to ensure effective oversight while also being efficient in light of technological advances in therapeutic products.

This development follows the end of efforts to create a joint regulatory body between New Zealand and Australia.

The European Commission released the comprehensive draft paper, Annex 17: Real Time Release Testing. This paper revises the 2002 version and incorporates the application of real-time release testing to any stage of the manufacturing process. Since 2002, the adoption of ICH Q8–Q11 has led to changes in the manufacturing environment, requiring an updated version of the document.

Comments are due Dec. 11.

ICH finalized its Q3D guideline that covers elemental impurities in January. Global regulators identified elemental impurities as an area in need of international harmonization and consensus. This guideline limits metal impurities in drug products and ingredients.

In September, FDA released its final guidance on ICH Q3D. The guidance establishes permitted daily exposures (PDE) for 24 elements according to toxicity data. In addition, the guidance allows for a risk-based approach to assessing the possibility that elemental impurities with allowed PDE will be present in a drug product.

Effective Oct. 15, FDA now has the authority to destroy any drug valued at $2,500 or less if it has been refused entry into the United States per provisions of the Food and Drug Administration Safety and Innovation Act (FDASIA). This final rule gives the owner of the drug in question the opportunity to receive written notice about the Agency’s intent to destroy the drug and to provide testimony to FDA prior to destruction.

FDA hopes this serves as a disincentive for importing adulterated, misbranded or unapproved drugs into the country.

On Sept. 24, the U.S. FDA released an interim report that contains preliminary data regarding workload and the full costs associated with reviewing biosimilar applications. According to this data, the labor costs associated with biosimilar reviews at the Agency stood at over $742 million in 2014 compared to $680 million in 2013—a 9% increase.

Comments are due Oct. 26.

The White House announced on Sept. 15 the nomination of Dr. Robert Califf for the post of Commissioner of the U.S. FDA. Since January, he has been serving as the Deputy Commissioner for Medical Products and Tobacco at the Agency. Prior to joining FDA, he served as Vice Chancellor of Duke University's School of Medicine and was also a professor of cardiology and medicine at the same school.

He will replace Dr. Margaret Hamburg, who stepped down in March. Dr. Stephen Ostroff has been serving as Acting Commissioner following her departure.

In late August, the European Commission released three documents for public consultation on GMPs for investigational medical products (IMPs). One document is a consultation paper that outlines the Commission’s views on GMPs for IMPs and the second document covers detailed guidelines in this area. And the third details implementation of the proposed GMPs.

Comments are due Nov. 24.

The ICH Expert Working Group behind the Q3C Guideline recently revised the Permitted Daily Exposure (PDE) for Methyl isobutyl ketone (MIBK). This was listed in Q3C as a Class 3 solvent. Based on new data suggesting MIBK causes carcinogenic health problems in rodents, the Expert Working Group recommends upgrading MIBK to a Class 2 solvent.

Comments are due Dec. 31.

The U.S. FDA has released a guidance regarding naming of biologics and biosimilars. Under the Public Health Service Act, biologics must bear a nonproprietary name with an FDA-designated suffice. The Agency believes that shared nonproprietary names are not appropriate for all biologics. To ensure clear identification of biologics for the purposes of pharmacovigilance and to differentiate biologics that are not interchangeable, the Agency proposes that the suffix for biologics comprises four lowercase letters based on the nonproprietary name of the product.

As far as interchangeable products, i.e., biosimilars, the Agency is still considering whether the suffix should be unique or share the same suffix as the reference product.

Comments are due Oct. 27.

The U.S. FDA’s new search tool enables those using the FDA website to search the Agency’s growing list of over 3,000 guidance documents quickly and efficiently. This search feature covers the entire FDA space—devices, drugs, biologics, etc. And the information is available in one centralized location for easy searching. Content is also tagged with metadata as well based on identified search terms.

The search tool can be accessed at www.fda.gov/RegulatoryInformation/Guidances/.

On July 27, the U.S. FDA released an updated version of the Analytical Procedures and Methods Validation for Drugs and Biologics guidance. This guidance replaces the draft guidance of the same name published in Feb. 2014 and explains how to submit analytical procedures and methods validation data to support the documentation of the identity, strength, quality, purity and potency of drug substances and drug products.

In late July, the U.S. FDA released the draft guidance, Request for Quality Metrics. This document outlines a set of measurements the Agency will use to evaluate the quality of facilities and manufacturing processes. These measurements are: lot acceptance rate, product quality complaint rate, invalidated out-of-specification (OOS) rate and annual product review (APR) or product quality review (PQR) on time rate. Manufacturers will need to submit data to FDA covering the number of attempted lots, lots pending disposition for more than 30 days, lots released, OOS results, etc.

Comments are due Sept. 25.

Following completion of Step 2b of the ICH process, the Addendum for ICH M7 Guideline Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk is now available for comment. This addendum complements the current harmonized M7 guideline and summarizes known mutagenic impurities regularly found during synthesis.

The deadline for comments is January 31, 2016.

The European Commission in early July added Israel and Brazil to its list of countries with API manufacturing standards equivalent to those of the European Union. This means that API manufacturers in Israel and Brazil will not need written confirmation from European regulators that their GMPs are equal to European GMPs.

Currently, the United States, Switzerland, Japan and Australia are already on the list. Other countries seeking to be added to the list include New Zealand, South Korea, Taiwan, India and China.

The U.S. FDA, the EMA and the European Commission plan to mutually align with regard to inspections of drug manufacturing sites in addition to stressing the importance of data integrity. Representatives from these three agencies met to discuss cooperative activities for the next two years at a recent meeting at the FDA headquarters in Silver Spring, Md.

This meeting was part of a regular series of bilateral meetings between senior European and U.S. regulators. Other topics of interest at the meeting covered included cluster reviews for bilateral pharmacovigilance, biosimilars, pediatric and veterinary medicines.

On July 10, the U.S. House of Representatives approved the 21^st Century Cures Act. The proposed law now heads to the Senate for a vote

In mid-July, EMA released its guideline covering manufacturing of finished dosage forms. This guideline details information that must be included in CTD Module 3 of the marketing authorization application. In addition, the guideline looks at current practices as they relate to global supply chains and manufacturing and takes the ICH Q8 guideline on pharmaceutical development into account.

Comments are due Jan. 9, 2016.

The Q&A for ICH Q7 has now entered the implementation state. Since the establishment of Q7 in 2000, uncertainties have arisen with regard to interpretation of sections concerning GMP of APIs. The new Q&A document seeks to harmonize regulatory expectations in this area.

Malaysia’s Medical Device Authority (MDA) has extended the deadline for temporary fast-track device registrations to June 30, 2016.

On June 25, U.S. FDA released its final guidance on requirements and regulations pertaining to allowable excess volume in injectable vials. This guidance also reinforces the importance of appropriate fill volumes and labeled vial fill sizes for injectable drug and biological products.

This guidance replaces the 2014 draft guidance on the topic.

Recent proposed amendments to Canada’s Food and Drugs Regulations would require manufacturers to provide notice to Health Canada six months in advance of a possible shortage or discontinuation of a drug product. This legislation follows an increase in shortages of medication within Canada over the past few years. In 2011, Canadian manufacturers created a voluntary, Web-based reporting system (www.drugshortages.ca).

Comments on the amendments are due Sept. 2.

WHO has published its final guidelines on nonsterile process validation in an appendix to its Technical Report Series 992. It outlines WHO’s support for linking process validation to Quality Risk Management and QbD principles.

WHO recently published 16 supplements to its 2011 guidance, Model guidance for the storage and transport of time- and temperature–sensitive pharmaceutical products. These supplements offer principal requirements for safe storage and distribution of pharmaceutical products. Topics covered include storage facility design, temperature monitoring, temperature-controlled transport, shipping container qualification, management of refrigerant gases, among others.

At the end of May, EMA released concept paper offering new guidelines for importers of medicinal products in the EU for public comment. This paper was developed in response to the growing numbers of drug products manufactured outside of the EU. The drug supply chain has increased in complexity; most GMP noncompliance statements loaded into the EudraGMDP database concern thirty party manufacturers.

Comments are due August 29.

On June 1, the FDA released the draft guidance, Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products. This document outlines the Agency’s current thinking on what CMC information needs to be reported to the FDA in the event it is changed. In addition, the document provides recommendations for managing CMC changes over a product’s lifecycle.

Comments are due July 31.

On May 11, the European Commission has the responses from public stakeholders on the Annex 15: Qualification and Validation revision.

The U.S. FDA recently announced plans to withdraw 47 guidance documents published prior Dec. 31, 2013 that remain unfinalized.

In late April, the U.S. FDA released finalized three guidance documents concerning biosimilars. One document specifies how sponsors should approach developing evidence demonstrating biosimilarity to the reference product. Another addresses quality considerations as well as CMC information used for a biosimilar application. And the third is a Q&A document looking at implementation of the Biologics Price Competition and Innovation Act of 2009.

On April 30, a draft bill of the 21st Century Cures legislation was presented at a hearing in the U.S. House of Representatives. This proposed legislation seeks to streamline the drug approval process. Earlier proposals had sought a more aggressive accelerated approval process for drugs; the current draft document has been scaled-down.

The European Pharmacopoeia posted a proposed draft of a revision to its Water for Injections (WFI) monograph on April 1. This revision takes into account nondistillation methods for producing injection-quality water, namely reverse osmosis combined with deionization and ultrafiltration.

Comments on the proposed revision are due June 30.

Former U.S. FDA Commissioner Margaret Hamburg, MD, is now foreign secretary for the Institute of Medicine, an arm of the National Academy of Sciences. She will advise the Institute on international health matters as well as liaise with foreign medicine and health academies. Her term began April 6 and lasts until June 30, 2019.

Previously, she served as FDA Commissioner from 2009 to March 2015.

Annex 15, “Qualification and Validation,” of the EU GMP Guide has been updated. The new version will harmonize with the principles of ICH Q8–Q10 as well as the EMA guidance on process validation. These updates include the following: retrospective validation no longer considered acceptable, new points on data integrity, “ongoing process verification” now must be based on equivalent documentation, and more.

The updated version of Annex 15 becomes effective Oct. 1.

The European Commission announced on March 21, an updated and more detailed version of its Guidelines on Risk Assessment of Excipients. Under these new guidelines, manufacturing authorization holders are required to implement risk assessments of their entire supply chains from raw material sources to packaging.

The steps taken for maintaining quality of an excipient must be extensively documented with a track-and-trace system fully in place. A quality control expert is now required to assess the excipients and release batches.

These guidelines become effective March 21, 2016.

On March 21, the European Commission announced changes to its Guidelines on GDP for APIs, aimed at API importers and distributors. These changes include: requirements for API distributors to implement a quality system featuring a designated person with risk management responsibility at each point in the distribution chain, a traceable supply chain, suitable cold chain conditions, documented and investigated deviations to established procedures, effective CAPAs in place, one-year record retention policies, and examinations of all API deliveries for damage.

The new guidelines become effective Sept. 21.

EMA released a consultation paper March 31 outlining a draft network strategy for European Medicines Agencies Network. EMA along with various health authority leaders developed this strategy to focus on expanding collaboration across the European Union on health matters. The strategy’s four themes are: human health, animal health, optimization of the network’s operations, and the global regulatory environment.

Comments from stakeholders are due June 30.

Comments due June 30 on EMA’s concept paper on the need to revise requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials.

WHO released a report on substandard and counterfeit medicinal product March 20 that features recommendations for health authorities to detect and respond to the issues of substandard and counterfeit products, including greater inspections focusing on quality monitoring, laboratory testing throughout the supply chain, implementation of track-and-trace systems, and a system of regional alerts.

WHO developed this report during an October 2014 Member State Meeting. The next such meeting will be held in the fall of 2015.

A bill was recently introduced in Congress that, if passed, would require the U.S. FDA to review drug products approved by EU authorities within 90 days. This bill, the Speeding Access to Already Approved Pharmaceuticals Act, seeks to address the lag between approval of a drug product in Europe and in the United States. Currently, the shortest time between approval is six months.

ICH seeks input concerning its ICH Q11 Q&A document for potential issues that should be included.

The EMA’s Management Board has elected Christa Wirthumer-Hoche as its Vice-Chair. She replaces Walter Schwerdtfeger.

Wirthumer-Hoche is currently Head of the Austrian Medicines and Medical Devices Agency.

Australia’s TGA recently released a guidance on batch release containing two parts. The first offers guidance on general requirements and the other provides examples of how these general requirements can be met. This latter part is currently being developed.

USP announced that the chapters pertaining to elemental impurities, <232> Elemental Impurities—Limits and <2232> Elemental Contaminants in Dietary Supplements, will be applicable Jan. 1, 2018 in order to align <232> with implementation of ICH Q3D.

Angela Thomas is now the vice chair of MHRA’s Commission on Human Medicines. She replaces Ian Weller.

The U.S. FDA approved the first U.S. biosimilar, filgrastim-sndz (ZARXIO Injection, Sandoz Inc.). This is a biosimilar for Neupogen, a treatment for lack of white blood cells due to certain cancers.

The U.S. FDA has established a public docket to receive comments on matters concerning pharmacy compounding regulations. This docket is intended for general comments and not directed at a specific document or issue.

In late February, Health Canada announced plans to ramp up announced and unannounced inspections of manufacturing facilities due to increasing API concerns and data integrity issues.

The Agency has also posted an online Inspection Tracker for drug manufacturing facilities that provides a snapshot of the health and safety issues the Agency is tracking on a regular basis.

Following recommendations from the WHO, the U.S. FDA in early March recommended that the influenza vaccine for the 2015-2016 season include the following strains:  A/California/7/2009, A/Switzerland/9715293/2013, and B/Phuket/3073/2013. This follows a particularly deadly 2014-2015 flu season where the vaccine proved to be only 23% effective.

The U.S. FDA released a report with the Brookings Institution in late February outlining recommended steps to develop a National Medical Device Postmarket Surveillance System. This report offers a strategy for developing a nationwide system that harnesses data, analysis and stakeholder participation to optimize surveillance in an effort to achieve optimal patient care.

This report has its origins in CDRH’s 2012 initiative to strengthen the U.S. surveillance system for devices. This initiative also includes efforts to implement unique device identifiers for devices.

In February, the U.S. FDA released five draft documents concerning drug compounding and repackaging in an effort to ensure relevant entities comply with key public health regulations. These documents follow the enactment of the Drug Quality and Security Act (DQSA) in November 2013. Products compounded in outsourced facilities under certain conditions may be exempt from provision of the Food, Drug, and Cosmetic Act.  

One document details the regulatory impact of registering as an outsourcer. Another document explains how FDA will respond to repackaging violations by entities falling under the DQSA. A third document describes conditions under which the Agency will not take action for certain regulatory violations that occur due outsourcing facilities mixing, diluting and repackaging biologics. A fourth explains adverse reporting steps for recognized outsourcing facilities. And a fifth, a draft Memorandum of Understanding, outlines a state’s responsibilities when signing the MOU to investigate complaints regarding compounded drug product.

Comments on all of these documents, except the MOU are due May 20. MOU comments are due June 19.

The U.S. FDA released a request for information concerning the recordkeeping of cGMP requirements for finished pharmaceuticals.

Comments are due March 27.

This week U.S. FDA Commissioner Margaret Hamburg, MD, announced plans to step down from her position at the end of March. Acting Chief Scientist Stephen Ostroff, MD, has agreed to serve as Acting Commissioner when Hamburg leaves.

EMA’s concept paper covering the revision of Annex 1’s GMP guidelines for manufacturing sterile product has been released for comment. This follows agreement on the document in January between EMA’s GMP/GDP Inspectors Working Group and PIC/S.

Comments are due March 31.

Chapters 3 and 5 of the GMP Guide covering premises and equipment and production respectively have been updated to account for improvements to the guidance on cross-contamination and references to toxicological assessment.

These updates become effective March 1 in an effort to align with the EMA guideline Setting Health Based Exposure limits for Use in Risk Identification in the Manufacture of Different Medicinal Products in Shared Facilities.

On Jan. 15, WHO released a draft document covering Good Pharmacopoeial Practices. This document seeks to ensure harmonization of global pharmacopeial practices.  

Comments are due March 10.

On Feb. 3, the U.S. Congress’ Committee on Energy and Congress will hold a hearing to explore public health responses to seasonal influenza. The hearing will look at modernization of current standards for selecting strains of influenza virus for vaccines as well as improving the production process for flu vaccines.

India’s Central Drugs Standard Control Organization (CDSCO) laid out plans to formalize presubmission meetings in a Jan. 28 notice. Presubmission meetings allow companies and regulators an opportunity to review potential submissions and ensure they conform to regulatory requirements. By formalizing these meetings, CDSCO is aligning itself with practices of other global regulators.

Recently released draft legislation from the U.S. Congress’ House Energy and Commerce Committee includes provisions focusing on expediting U.S. FDA regulatory review of new and existing drug and device products. This legislation, the 21^st Century Cures Initiative, seeks to improve the efficiency of the development process for innovative medical products.

The Chinese Food and Drug Administration recently issued the country’s first GSP regulations for all Class 1, 2, and 3 medical device distributors. Third-party logistics providers also fall under these new regulations, which establish minimum standards for procurement, storage, transportation and postsale services and require distributors to implement quality management systems for all aspects of the delivery process.

These new GSPs became effective Dec. 12.

China’s Food and Drug Administration recently revised its GMPs for medical devices, updating the regulations to require manufacturers to setup quality management systems adhering to the GMPs.

These revised GMPs become effective March 1.

On Jan. 27, the U.S. FDA released a draft guidance on cGMPs for combination products that further clarifies the final rule on these types of products. The guidance looks at general considerations for cGMP requirements for combination products, addressing the purpose and content of specific cGMP provisions within the final rule. Additionally, the guidance includes hypothetical scenarios clarifying how to comply with specific cGMP requirements.

Comments are due March 30.

On Jan. 23, Britain’s MHRA released a guidance outlining the authority’s expectations for data integrity within the industry. The document also lists MHRA’s definitions for data integrity-related terms.

The guidance is intended complement existing EU GMP regulations.

As part of the International Generic Drug Regulators Pilot (IGDRP), EMA will share its assessments of generic medicine applications with collaborating regulatory authorities outside the European Union as part of an effort to facilitate efficient access to affordable generics across the globe.

Global manufacturers interested in marketing medical devices in Australia, Brazil, Canada and the United States have been invited to participate in the Medical Device Single Audit Program, a pilot program sponsored by the U.S. FDA and regulatory agencies in Australia, Brazil, Canada, and Japan.

In December the ICH Q3D Guideline on Elemental Impurities reached Step 4 of the ICH process. Now the guidance has entered the implementation period, or Step 5. The ICH Q3D Guideline provides global policy for limiting metal impurities in drug products and ingredients.

The U.S. FDA officially launched its new Office of Pharmaceutical Quality on January 12. The new office creates a streamlined drug quality program responsible for drug application review, postapproval improvements, and inspections and surveillance of manufacturing facilities.

In late December, the U.S. FDA started publishing joint Q&A documents with EMA outlining conclusions of the agencies’ first parallel assessment of QbD elements of a marketing authorization application. Both FDA and EMA found the assessment useful, reaching agreement on many QbD aspects. Experts from the Japanese Pharmaceuticals Medical Devices Agency also participated as observers for this assessment.

EMA approved Holoclar in December for use in the European Union. This is the first advanced therapy medicinal product (ATMP) using stem cells that has been approved in Europe. Holoclar treats limbal stem cell deficiency, a rare eye condition that can cause blindness.

On Dec. 18, the U.S. FDA released the final version of the guidance Providing Regulatory Submissions in Electronic Format—Standardized Study Data. This guidance covers how the Agency will implement electronic submission requirements for standardized study data contained in NDAs, BLAs, INDs and ANDAs.

Comments may be submitted at any time on this document.

Along with the final guidance for electronic submissions of standardized study data, on Dec. 18, the U.S. FDA released the final version of the guidance Providing Regulatory Submissions in Electronic Format—Submissions Under Section 745A(a) of the Federal Food, Drug, and Cosmetic Act, which describes how the Agency will implement electronic submission requirements under the Food and Drug Administration Safety and Innovation Act (FDASIA).

Comments may be submitted at any time on this document.

In Q4, the ICH Steering Committee along with its Expert Working Groups met in Lisbon. Among the topics under discussion were GMP-related Quality Updates. These included agreeing upon the final set of Q7 Q&As on APIs, convening the new Expert Working Group on Technical and Regulatory Considerations for Pharmaceutical Lifecycle Management (Q12), and approving a concept paper and business plan for developing Q11 Q&As to clarify selection of starting materials and information that needs to be provided for marketing authorization applications.

In November, the European Commission published a new regulation covering GMPs for APIs. This regulation outlines principles and guidelines for active substance GMPs. This includes exported active substances.

The regulation became effective Dec. 15.

EMA recently published the final version of its Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities. This document takes a risk-based approach to the management of contaminants in shared facilities.

The guideline comes into effect June 1.

On Dec. 5, the U.S. FDA released a “roadmap,” a report commissioned from the Brookings Institution, for how provider systems, patients, payers, supply chain personnel, and many others, can adopt and utilize unique device identifiers. The Agency hopes these recommendations ensure that the UDI system not only runs efficiently but serves as a tool for unlocking important data to help patients.

The U.S. FDA is concerned that equipment addenda published in 1998 and 1999 on scale-up post-approval changes (SUPAC), may not reflect current practices and possibly limit manufacturers from continually evaluating and updating practices. For this reason, on Dec. 2 the Agency released the guidance SUPAC: Manufacturing Equipment Addendum.

Comments on the guidance may be submitted at any time.

The Australian and New Zealand governments confirmed in late November that both governments will cease efforts to establish the joint therapeutic products regulatory body, or Australia New Zealand Therapeutic Products Agency (ANZTPA), following an assessment of the costs and benefits for both countries.

Australia’s Therapeutic Goods Administration (TGA) and New Zealand’s Medicines and Medical Devices Safety Authority (Medsafe), however, plan to continue exploring other harmonization activities between both regulatory authorities, including the development of a new agreement on information sharing as well as a formalized mutual recognition of GMP audits.

Representatives from the U.S. FDA met with a cross-agency team comprised of members from EMA, the European Commission and GMP experts from various EU member states in London Nov. 14 and 17 to discuss progress on mutual reliance between FDA and the European Union on GMP inspections.

Although there has been an ongoing initiative around GMP inspections and mutual recognition for many years, due to increased momentum, this meeting is supposed to be the first face-to-face meeting of both teams.

The ICH Steering Committee recently endorsed the final concept paper Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management. This new document offers guidance on building a framework to facilitate efficient management of postapproval CMC changes.

ICH Q12 is a continuation of the Q8–Q11 guidelines and seeks to promote innovation, continual improvement while also strengthening QA and reliable supplies of the product.

ICH plans adoption of a Step 2 document in 2016.

The U.S. FDA has updated its Manual of Policies and Procedures to require reviewers to use a Question-based Review (QbR) for NDAs submitted using a QbR format. In addition, reviewers may choose to follow a QbR review template for NDAs not submitted in a QbR format.

Previously, QbR had been used solely for ANDAs. This format grew out of the FDA’s Pharmaceutical cGMP’s for the 21^st Century Initiative.

Britain’s MHRA recently published its inspection trend data from January 2013 to December 2013 in a revised format. The report also includes information about long-term trends in the “top 10 deficiencies” categories.

Representatives from PDA were also involved in the revision of this report; see page 43 of the November/December 2014 PDA Letter.

At the PIC/S Committee meeting in Paris Oct. 20–21, the Committee established the PIC/S Inspectors Academy (PIA). This Academy—a PIC/S initiative—will feature a Web-based educational center with a focus on harmonizing and standardizing GMP training at the international level using an accredited qualification system.

PIA should be in operation by the third quarter of 2015.

EMA has released the third module of a new overarching guideline on influenza vaccines. This guideline proposes establishment of a revised regulatory framework to facilitate more efficient assessment of new flu vaccines. It applies only to vaccines which have received ample regulatory experience as well as some new forms.

Comments are due January 30.

EMA has adopted a new guideline on biosimilars. This guideline allows for the possibility for companies to use a comparator authorized outline the European Economic area during clinical investigation. This is expected to facilitate global development of biosimilars as well as avoid repetition in clinical trials.

The guideline becomes effective April 30.

On Oct. 22, the U.S. FDA released a guidance, Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection, per Section 707 of the Food and Drug Administration Safety and Innovation Act (FDASIA). This guidance defines the types of actions or inactions that the Agency considers as constituting delaying, denying, or limiting inspection, or refusing to permit an inspection. This draft follows up on the July 2013 draft guidance of the same name; this guidance clarifies FDA expectations regarding the types of circumstances that make a drug adulterated under the Food, Drug and Cosmetics Act.

PDA commented on the July 2013 guidance.

WHO is expected to present its Proposal For Revision Of The 3 Supplementary Guidelines On 4 Good Manufacturing Practices: Validation, 5 Appendix 7: Non-Sterile Process Validation at the WHO Expert Committee on Specifications for Pharmaceutical Preparations meeting in October. These guidelines reflect the draft revision of the EU’s Annex 15 and allow for different approaches to process validation.

The U.S. FDA has announced the launch date of the Office of Pharmaceutical Quality. OPQ is scheduled to launch January 1, 2015 with Janet Woodcock, MD, as the first acting director, supported by Lawrence Yu as Deputy Director.

The U.S. FDA recently announced changes in the organizational structure of the Office of Regulatory Affairs. To ensure better collaboration with Centers as well as efficiency, each Center will have a single senior executive within ORA responsible for each commodity program. ORA will also work with other Centers such as CBER and CDRH on new initiatives in the area of inspections and training.

On Oct 2, EMA’s Management Board adopted a new policy to publish clinical reports contained in all applications for centralized marketing authorizations. The Agency hopes this new policy will better allow the general public to understand its decisionmaking as well as avoid duplication of clinical trials, foster innovation and encourage development of new products. Information that may be considered commercially confidential will be redacted.

The policy will be effective January 1, 2015 and will apply to all authorizations submitted after that date.

On Oct. 3, the U.S. FDA published its 2015 regulatory science priorities pertaining to generic drugs in accordance with GDUFA. These priorities were prepared based on comments received at the May 16 public meeting and through public dockets. These priorities include: postmarket evaluation of generic drugs, equivalence of complex products, equivalence of locally acting products, therapeutic equivalence evaluation and standards, and and computational and analytical tools.

Under the Prescription Drug User Fee Act Reauthorization of 2012, the U.S. FDA is mandated to advance the development of use of biomarkers, which are key in the development of “targeted therapies,” also known as “personalized medicines.” As part of this plan, the Agency partnered with the Brookings Institution’s Engelberg Center for Health Care Reform to host a public workshop Sept. 5 on biomarker development.

During the workshop, the following were topics of discussion: need for clear standards for the evidence supporting biomarker use, infrastructure and policies promoting development of tests to identify patients for clinical trials, new models for clinical trials that accelerate biomarker development, and methods for assessing treatment effects in small populations.

The information gathered in this workshop will be used to guide the Agency’s decisionmaking with regard to biomarkers.

As part of the Presidential Memorandum on Regulatory Compliance, issued January 2011, the U.S. FDA has released a new online dashboard that allows the public access information on the Agency’s compliance, inspection and recall activities. Providing data from FY 2008 to FY 2013, the dashboard includes information on inspections, warning letters, seizures and injunctions, and statistics specific to recalls. This data will be updated semiannually.

Hosted in a cloud environment, the data can be downloaded, manipulated through the selection of filters, rearranged to format datasets and columns, drilled down and exported.

The 2011 Memorandum requires federal agencies to make compliance information publicly available using an easily accessible, downloadable and searchable online format.

Sept. 10–11, the European Directorate for the Quality of Medicines & Healthcare (EDQM) held its second symposium on strategies to combat counterfeit and other illegal medicinal products. The symposium consisted of representatives from forensic and customs laboratories, national food and drug regulatory agencies, enforcement groups and the European Commission. According to participants, undeclared APIs and other active substances in products offered for sale remain a pressing issue within Europe. These products are often purchased from the legal market as well as acquired from uncontrolled sources.

On Sept. 10 the EMA released a document featuring frequently asked questions from companies regarding the Agency’s adaptive licensing pilot project. The document also clarifies terms of engagement and possible outputs for applicants.

In early September, the U.S. FDA released a guidance finalizing the October 2013 draft guidance, ANDA Submissions—Refuse-to-Receive Standards. This guidance highlights deficiencies in ANDA submission that could cause the Agency to refuse to receive the submission, meaning the ANDA is not considered sufficiently complete by FDA to permit a more substantive review.

Comments on the guidance can be submitted at any time.

On Sept. 17, the U.S. FDA released the draft guidance, ANDA Submissions—Refuse to Receive for Lack of Proper Justification of Impurity Limits. This draft guidance is aimed at applicants submitting abbreviated new drug applications (ANDAs) for approval of drug products with new strengtSh, and highlights specific deficiencies of information that may lead the Agency to refused to receive an ANDA.

These deficiencies are failing to justify proposed limits for specified identified impurities in drug substances and drug products that are above qualification thresholds, failing to justify proposed limits for specified unidentified impurities that are above identification thresholds, and proposing limits for unspecified impurities (e.g., any unknown impurity) above identification thresholds.

Comments are due Nov. 17.

The European Commission has published the final version of the Chapters 3, 5, and 8 of the EU GMP Guide. Chapter 3 covers premises and equipment, Chapter 5 covers production, and Chapter 8 covers complaints, quality defects and product recalls.

These chapters will be effective March 1, 2015.

Effective Sept. 1, the European Commission has published a revised version of Part II of the EU GMP Guide – Basic Requirements for Active Substances used as Starting Materials. This revision is due to changes in various Annexes of the Guide.
 

In late August, the U.S. FDA announced the release of the draft guidance, Controlled Correspondence Related to Generic Drug Development. This document outlines the process for generic drug manufacturers to submit correspondence when the Agency requests information on generic drug development as well as the FDA’s process for communications related to this correspondence. This part of the Generic Drug User Fee Amendments (GDUFA) of 2012 requiring the Agency to meet certain obligations as part of an effort to speed the delivery of safe and effective generic drugs to the public.

Comments are due Oct. 27.

The European Union is currently leading the International Generic Drug Regulators Pilot (IGDRP) to share, upon request from generic pharma companies, the assessment reports generated as part of the decentralized procedure with collaborating regulatory authorities outside the European Union. The initial phase of the project will involve collaborating with Australia, Canada, Taiwan and Switzerland.

The European Union hopes to use this pilot to expand information-sharing so that medicines can be authorized in different countries at approximately the same time.

Australia’s Therapeutic Goods Administration (TGA) recently adopted a number of EU/ICH guidelines, including EMA’s guideline on real-time release testing and ICH Q4B annexes on microbiological analysis of nonsterile products.

These guidelines became effective Aug. 1.

The final draft of the ICH M7 Guideline on Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk is being recommended for adoption by EU, Japanese and U.S. regulatory authorities.

In late May, the Taiwan Food and Drug Administration signed a confidentiality agreement with the European Directorate for the Quality of Medicines and Healthcare (EDQM), the authority behind the European Pharmacopoeia.

In late June, the African Medicines Regulatory Harmonization Project announced that ten institutions and institution partnerships were designated as Regional Centres of Regulatory Excellence (RCOREs). These centers will participate in the development of a regulatory workforce across Africa through hands-on training within companies or regulatory authorities.

On July 11, the U.S. FDA released a draft guidance that explains how GDUFA performance metrics goals will be applied to ANDAs and prior approval supplements.

Comments due Sept. 9.

On July 11, the U.S. FDA released a draft guidance intended to assist ANDA applicants preparing to submit Prior Approval Supplements (PASs) and PAS amendments. In addition, the draft describes the Agency’s performance metrics goals for PASs and clarifies how FDA will handle a PAS for an ANDA subject to GDUFA performance metric goals.

Comments due Sept. 9.

The U.S. FDA provided an update on July 17 regarding the Medical Device Technology Innovation Partnership. This partnership grew out of a CDRH innovation initiative in 2011 to reduce the cost device development and expedite the regulatory evaluation of devices. To help, the Partnership worked with several universities to develop a curriculum to provide students and industry with information about the regulatory framework for developing devices for the market. This curriculum, referred to as the National Medical Device Curriculum consisting of case studies, is now available.

Following the two-year anniversary of the signing of the Food and Drug Administration Safety and Innovation Act (FDASIA), the U.S. FDA highlighted its efforts to meet Title VII requirements. Title VII of the law addresses the safety and integrity of drug products and drug product ingredients in the supply chain. The Agency’s efforts to meet Title VII include a proposed and final rule extending its administrative detention authority to include drugs, a draft guidance on actions the FDA considers constitutes delaying, denying or limiting an inspection, a public meeting held July 12, 2013 on Title VII, a draft guidance on the unique facility identifier system, an annual report outlining the number of registered domestic and international establishments, and a proposed rule on administrative destruction of drugs refused importation into the United States.

The U.S. FDA posted highlights of deliverables required under the Food and Drug Administration Safety and Innovation Act (FDASIA) on its blog following the second anniversary of the law’s passing. These highlights include efforts to address drug shortages, promoting innovation, strengthening user fee programs and enhancing patient engagement.

U.S. FDA has announced an opening for public comment concerning a proposed extension of data gathering for cooperative manufacturing arrangements for biologics.

Comments are due Sept. 5.

USP’s Expert Microbiology Committee recently published the draft USP 1223, Validation of Alternative Microbiological Methods for comment.

Comments are due Sept. 30. The draft is available at the Pharmacopeial Forum. This site requires registration but is free to join.

The U.S. FDA released its strategic plan for 2014-2018 on July 1. Highlights include expanding data sharing and bioinformatics capabilities along with overall increased investment in IT.

Comments are due July 31.

The Agency is seeking input from stakeholders on an interim guidance concerning cGMPs for facilities registering with FDA as compounding outsourcing facilities under the Drug Quality and Security Act. Specifically, FDA intends to focus on how such facilities can meet 21 CFR Parts 210 and 211. In addition, the Agency seeks comments on alternative approaches that would enable an outsourcing facility to have confidence in the quality of incoming components from sources used by multiple outsourcing facilities without each individual outsourcing facility having to conduct periodic laboratory testing to confirm the information in the third-party supplier's certificate of analysis, and alternative approaches minimizing the need for outsourcing facilities to establish an in-house laboratory while providing confidence about the accuracy of testing performed by a third party used by more than one outsourcing facility.

Comments are due Oct. 31.

There is a U.S. FDA guidance available announcing the Agency’s plans to enforce provisions of the Food, Drug, and Cosmetic (FD&C) Act for regulation of compounding facilities. The Act was recently amended by the Drug Quality and Security Act. Specifically, the guidance addresses provision 503A which covers compounded drug products.

The Active Pharmaceutical Ingredients Committee (APIC), part of the European Chemical Industry Council, recently released two documents. One, “How to document,” offers instruction on implementing EU draft guidelines from February 2013 on GDPs for APIs and the WHO guideline on GTDP for starting materials. The other publication provides information on how companies can formulate cleaning validation programs.

The U.S. FDA remains committed to reducing the impact of shortages of critical drugs, including encouraging more suppliers, expediting review of new drug applications for products in short supply, and greater communication on impending shortages.

U.S. FDA guidance on Global Unique Device Identification (GUDID) finalizes all section of the document, Global Unique Device Identification (GUDID): Draft Guidance for Industry, including sections on how device labelers interface with the GUDID, establishment of GUDID accounts and initial submissions.

The EMA has released a guidance on how advanced therapies should be classified, particularly which products can be classified as ATMPs and which cannot. Comments are due Oct. 31.

Britian’s MHRA has published meeting minutes for the GMP/GDP Consultative Committee meeting that occurred April 11 in London. Discussion topics included GDP deficiency data, the Compliance Management Project, the new process licensing portal, self-inspection and data integrity, and more.

In May, EDQM accepted Australia’s Therapeutic Goods Administration (TGA) as an assessor in EDQM’s procedure for the Certification of Suitability to the monographs of the European Pharmacopoeia, also known as CEPs. Assessors with TGA will participate in the scientific assessment of applications submitted to obtain a CEP. This process involves assessing whether or not monographs control for chemical purity, microbiological quality and, if relevant, risk of transmissible spongiform encephalopathy (TSE) transmission.    

ANVISA, the Brazilian regulatory authority has proposed easing registration requirements for Class I and Class II medical devices. One of these proposals involves changing the format of Technical Dossiers to match those in other countries.

The public consultation period on these proposals ends July 25.

(Link goes to the ANVISA Portuguese-language page on the proposals.)

On June 17, the U.S. FDA released two draft guidances concerning social media communications from companies concerning their drug and medical device products. The first guidance offers the Agency’s recommendations for communicating risk and benefit information for products using character space-limited online platforms such as Twitter. The second guidance offers recommendations for how companies can respond to and correct online third parties communicating inaccurate or misleading information about a product.

Comments for both guidances are due September 16.

Comments due Aug. 11 on the U.S. FDA draft guidance, ANDA Submissions—Content and Format of Abbreviated New Drug Applications. As part of an effort to increase the number of original ANDAs the Agency can receive while also shortening the review cycles, the FDA seeks to improve the quality of original ANDA.

To quickly provide industry with information critical to successful use of the Global Unique Device Identification Database (GUDID), the U.S. FDA is issuing the GUDID Guidance in two phases.The first phase includes updates to sections on establishing and using a GUDID account, the unique device identifier, Global Medical Device Nomenclature (GMDN), and electronic records/electronic signatures. Also included in this phase are GUDID attributes mapped to a fictitious medical device label and a glossary.

To access an overview of the GUDID database, visit http://www.fda.gov/medicaldevices/deviceregulationandguidance/uniquedeviceidentification/globaludidatabasegudid/default.htm.

In late February, the EMA published its revised process validation guideline. This revision emphasizes continuous process verification and incorporates modern GMP aspects into the guideline, including integration of ICH Q8–Q10, process analytical technology (PAT), QbD, real-time release testing, inclusion of the Annexes and harmonization with the U.S. FDA’s process validation guidance. This revised guideline will then come into effect in August.

In late February, the U.S. FDA officially initiated its two-year Secure Supply Chain Pilot Program. The Agency selected 13 companies to participate in this program; these  companies will be allowed to receive expedited entry for importation of up to five selected drug products into the United States. The Agency will use this program to evaluate resource savings efforts that focus less on low-risk drugs coming into the country, and instead emphasize surveillance on importations of high-risk drug products.

In early October, the U.S. Congress released a proposed bill, the Drug Quality and Security Act, which includes language tightening U.S. FDA oversight of compounding pharmacies. The bill creates a class of compounders, called “outsourcing facilities,” that would be regulated by the Agency. This classification will be voluntary; if enacted, hospitals and clinics would have the option of choosing to use either the FDA-regulated pharmacy or one that is not.

The bill also creates a “track and trace” system for following the movement of prescription drugs across the supply chain. This system would require bar codes on packages of drugs shipped.

As part of a short-term action to address drug shortages in the European Union, EMA launched a public catalog of drug shortages on its website. The Agency announced that any drug that’s in shortage in more than one member state would be listed. The catalog would be similar to the U.S. FDA’s list of drug shortages on its website. The EMA catalog is part of the Agency’s 13-point plan to address drug shortages.

In January, the U.S. FDA released a draft guidance, Submissions for Postapproval Modifications to a Combination Product Approved Under a BLA, NDA, or PMA, intended to provide underlying elements for determining which marketing submission should be required for postapproval changes to a combination product approved under one marketing application, such as a biologics license application (BLA), a new drug application (NDA) or a device premarket approval application (PMA). Comments are due by April 22.

Comments should be submitted by April 22.

On April 18, EMA announced that the Agency had updated the EudraGMP database to include GDP information in addition to GMP information. The new database will now be called EudraGMDP and will be gradually updated by various E.U. regulatory bodies to include information on wholesale distribution authorizations, GMP certificates, statements of GMP non-compliance, and registrations of active substance manufacturers, importers and distributors.

This database is one of the deliverables of the Falsified Medicines Directive and is intended to make supervision of drug manufacturing and distribution stronger due to greater availability of the information for all parties involved in the supply chain.

In April, the European Commission published Version 4.1 of its Q&A document concerning importation of active substances into the European Union. Version 4.1 includes two new questions—2A and 10A. Question 2A deals with applicability of the rules to blood plasma while Question 10A deals with applicability of the rules for starting materials undergoing additional purification or chemical synthesis.

Version 4.1 also removes Question 11B, which dealt with atypical active substances, as further discussion on the topic is warranted.

The EMA has announced the retirement of Patrick Le Courtois, Head of Human Medicines Development and Evaluation. Le Courtois first joined EMA in 1997 and had been part of EMA’s senior management team since 2001. He had been in his current position since 2009.

The U.S. FDA has adopted International Conference on Harmonization (ICH) guidelines concerning requirements for ANDA stability testing. The ICH guidelines adopted cover stability testing of new drug substances, photostability testing new drug substances, stability testing for new dosage forms, bracketing and matrixing designs for stability testing of new drug substances, and evaluation of drug safety data.

In June, the U.S. FDA announced the Agency had developed a Web-based addendum to Form 3486 that provides additional information when a BPD report has been reviewed and evaluated by the Agency as a possible recall. The additional information requested includes information that is not contained in Form 3486, such as distribution patterns, methods of consignee notification, consignees of products for further manufacturing, additional product information, updated product dispositions and industry recall contacts.

Comments are due Aug. 12.

Effective June 1, the Australian Therapeutic Goods Administration (TGA) has adopted four EU/ICH guidelines. These include EMA’s guidelines on plasma-derived products, active substance master file procedures, and bioanalytical method validation in addition to the ICH Q3 (R5) guideline on residual solvents.

The adoption of these guidelines followed consultations between TGA and members of industry.

The consolidation of the China Food and Drug Administration, formerly the State Food and Drug Administration, has been finalized.

New pharma-related duties of the CFDA will include pharmacopoeia codification, drug manufacturing certification, GMP certification, drug supply certification and GSP certification. Local FDAs will handle reregistration of drugs, changing approval of class III medical device registrations and contract manufacturing applications.

Comments can be submitted at any time for the recent guidance released by the U.S. FDA on Q4B evaluation and ICH harmonization. The Agency worked with ICH on the development of this guidance which contains results of ICH’s Q4B evaluation of bulk density text from U.S., European and Japanese pharmacopoeias. This guidance recognizes interchangeability between these local pharmacopoeias in an effort to avoid redundant testing.

The United States Pharmacopeia announced the launch of its Center for Pharmaceutical Advancement and Training (CePAT) in May. CePAT is located in Accra, Ghana and will play a key role in tackling the issue of drug counterfeiting in sub-Saharan Africa. Counterfeit medications are a significant issue in this region, as shown by 90% of drug samples tested by USP in Sub- Saharan Africa failed API or sterility.

This new center is also part of a larger effort within USP promoting access to good quality medications across the globe.

EMA announced in early May initial details regarding the Agency’s planned reorganization. These changes are focused on increasing the efficiency of the organization’s committees. Additionally, EMA expanded access to its centralized databases to partners and stakeholders, making the Agency an informational hub.

Changes start to go into effect at the beginning of August 2013. The full reorganization is expected to take approximately 18 months.

On May 2, EMA released the Agency’s draft guidance on biosimilars. This draft establishes principles for establishing whether or not a product can be classified as a biosimilar. Additionally, the document lists principles that must be applied to biosimilars as well as outlining the choice of reference product.

Comments should be submitted by Oct. 31.

On April 17, the U.S. FDA released a guidance concerning implementation of controls for prevention of cross-contamination of pharmaceuticals and APIs with non-penicillin beta-lactams. At this time, CGMPs only require separation measures for penicillin products. Due to potential cross-contamination health risks, FDA would like to expand the framework to include separation measures for all classes of beta-lactam drugs.

Comments can be submitted at any time for this proposed guidance.

The CBER division of the U.S. FDA is inviting IND sponsors to participate in the Center’s eSubmitter Program, which is an automated, computer-based program, as part of a pilot of the system. eSubmitter includes a template geared specifically for IND applications pertaining to antivenom drugs. This pilot is supposed to provide industry and regulatory staff an opportunity to review the new system and ascertain if it facilitates IND submissions.

Companies interested in participating must submit a request by July 8; only nine sponsors will be selected for the pilot program.

The U.S. FDA’s Office of Combination Products released its draft guidance, Glass Syringes for Delivering Drug and Biological Products: Technical Information to Supplement International Organization for Standardization (ISO) Standard 11040-4, April 3. This draft guidance offers information for sponsors seeking to conform to ISO Standard 11040-4 for glass syringe product submissions. The Agency has stated that demonstrating ISO conformity does not necessarily ensure that the glass syringe can be joined properly to connecting devices. This guidance identifies additional information that needs to be included in exemptions and applications. Companies involved in developing or marketing injection devices or components are urged to become familiar with the guidance. Comments are due July 2.

In early April, the U.S. FDA released a draft guidance for industry concerning scale-up and post-approval changes, titled, SUPAC: Manufacturing Equipment Addendum. The Agency has revised the draft manufacturing equipment addenda by removing equipment examples and clarifying referenced processes. This draft supersedes addenda released in 1998 and 1999.

Comments on the draft guidance are due by July 1.

Beginning April 1, the EMA will conduct single assessments of periodic safety update reports (PSURs) of active substances used in both centrally and nationally authorized medicine products. Until recently, EMA had only assessed PSURs for centrally-authorized products. This new assessment will require the Agency to analyze all reports for medicines containing certain active substances, including for medicines authorized in more than one member state.

A draft five-year plan is now available showing the U.S. FDA's approach to implementing a framework for benefit-risk assessment in the drug review process under PDUFA.

Comments should be submitted by May 7.

Submit your comments at any time on the U.S. FDA's recent guidance concerning financial disclosures for clinical investigators.This guidance will help clinical investigators, industry, and U.S. FDA staff in interpreting and complying with regulations on financial disclosure information required by clinical investigators, including the Agency’s FAQs regarding financial disclosure by clinical investigators. Ultimately, this guidance finalizes the draft guidance on the same topic dated May 2011 and replaces the guidance entitled, Guidance for Industry: Financial Disclosure by Clinical Investigators, dated March 2001.

The EMA has announced that adjusted fees for applications will come into effect April 1. The European Commission plans to adjust fees due to the Agency according to the 2012 inflation rate and expects fees to increase by 2.6%, although the exact figure is not yet known. Information on the revised fees will be published by EMA at the end of March.

Applications received by March 31 will be charged the current fee while applications received after this date will be charged the adjusted fee.

A U.S. FDA draft guidance concerning the establishment of criteria for individuals performing premarket reviews of medical devices is now available.

Comments should be submitted by April 16.

Under the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA), the U.S. FDA is required to draft a strategic plan to tackle the issue of drug shortages. The Agency's Drug Shortages Task Force, therefore, seeks public comments on the development of the strategic plan. The strategic plan will focus on both drug and biological product shortages.

Comments should be submitted by March 14.

On February 11, the U.S. FDA released a draft guidance for industry addressing immunogenicity assessments for therapeutic protein products. This guidance is intended to assist drug manufacturers in developing risk-based approaches in both the preclinical and clinical phases of the development of therapeutic protein products that evaluate and mitigate immune responses that could adversely affect safety and efficacy.

Adverse events caused by immune responses have caused sponsors to terminate development of therapeutic protein products. The Agency hopes the guidance will spur the development of risk mitigation strategies.

Comments should be submitted by April 12.

The U.S. FDA proposes to collect information from interviews with manufacturers submitting new molecular entity new drug applications (NMEs) and original biologics license applications (BLAs). This proposal is part of the Agency's performance commitments under PDUFA.

Comments should be submitted by April 22.

In early February, the European Commission published two GMP-related guidelines: Guidelines On The Formalised Risk Assessment For Ascertaining The Appropriate Good Manufacturing Practice For Excipients Of Medicinal Products For Human Use and Guidelines On The Principles Of Good Distribution Practices For Active Substances For Medicinal Products For Human Use. The first guideline requires companies to use quality risk management principles within ICH Q9 to assess and clarify risks presented by excipients while the second requires distributors of active substances to develop and maintain a quality system that lays out responsibilities, processes, and risk management procedures.

Comments on both draft guidelines are due April 30.

The U.S. FDA has published a draft guidance on photosafety testing with the goal of harmonizing international assessments. In November 2012, the ICH Steering Committee released a draft guidance, S10 Photosafety Evaluation of Pharmaceuticals, for public comment. This guidance provides recommendations on when photosafety testing is needed in the evaluation of pharmaceuticals. The FDA guidance seeks to harmonize U.S. thinking on photosafety with the ICH guidance.

Comments should be submitted by March 21.

A U.S. FDA guidance is available concerning criteria for small businesses to receive Medical Device User Fee and Modernization Act (MDUFMA) fee waivers. In an effort to avoid harming small businesses, MDUFMA provides for reduced or waived fees for applicants who qualify as a "small business." There are two levels of fees: a standard fee and a reduced small business fee. A business qualifies for a small business if reported gross receipts or sales are of no more than $100 million on the company's federal income tax return for the most recent tax year.

Comments should be submitted by March 4.

The EMA recently released a draft guideline on setting exposure limits to use as risk identification for drug manufacturing in shared facilities, approved by the Safety Working Party in December. This draft guidance seeks to set scientifically-based threshold values for individual active substances applied as risk identification. The manufacturing of different pharmaceutical products in shared facilities provides the potential for cross-contamination due to active substance residues remaining on production equipment or other contact surfaces after cleaning. Active substances need to be restricted to a certain level considered safe. The development of a threshold value (a level of permitted daily exposure, or PDE) is key to this risk identification process.

The U.S. FDA published the Agency's final rule on CGMP requirements for combination products in January. This rule is supposed to clarify which CGMP requirements apply for drugs, devices and biological products united to create combination products. It also lays out a streamlined regulatory framework for companies to demonstrate CGMP compliance for "single-entity" and "copackaged" combination products.

The Agency began addressing CGMP requirements for combination products in 2004 with a draft guidance before issuing a proposed rule in 2009. This final rule will be effective July 22.

Earlier this year, the Chinese Ministry of Health released Good Supply Practice for Pharmaceutical Products, a decree adopted in late 2012, and expected to go into effect June 1. The act seeks to ensure the quality of drugs during distribution by focusing on organizational quality in addition to quality systems and quality control.

The information collection associated with the program will consist of elaborating on components of the decree, the China FDA (originally SFDA) recently released three guidelines for comment. One guideline concerns computerized systems and another deals with sampling operation of materials and finished products involved in the drug product manufacturing. The other focuses on GMP confirmation and validation.

In late January, EMA published a guidance for pharmaceutical companies detailing how to prepare and review summaries of product characteristics (SmPCs), consisting of presentations listing the information required in each section of the SmPC along with background information. Prepared by EMA's SmPC Advisory Group, the guidance also outlines the European Commission's guideline on SmPCs. The information within SmPCs is a core feature of marketing authorizations for all medicine products in the European Union and is also the basis for preparing package leaflets.

The U.S. FDA has released a proposal concerning electronic reporting of adverse events. Currently, the Agency has approval to receive three types of adverse event reports electronically using rational questionnaires. The Agency seeks comments on extending approval for the three existing questionnaires as well as comments on a fourth rational questionnaire that has been proposed.

Comments should be submitted by Feb. 15.

The European Commission has submitted a draft template to be used for the written confirmation of active substances for human medicinal products exported to the European Union. The document introduces E.U.-wide rules concerning the importation of active substances, allowing importation only if the substances are accompanied by written confirmation from the authority of the exporting third country proving that the manufacturing plant where the substance is made adheres to GMP standards equivalent to those in the European Union.

The U.S. FDA has posted a draft guidance concerning regulatory guidelines for the electronic submissions of applications for drug products, including NDAs, ANDAs, BLAs, and INDs. The guidance outlines requirements for electronic submissions in an FDA-approved format. At this time, the Agency can process and review submissions using eCTD specifications.

Comments on the draft guidance are due March 4.

Earlier this year, the Indian Pharmacopoeia Commission (IPC) released a compliance guide with a number of topics, ranging from good laboratory practices to stability testing as well as water quality regulations. This guide is the first of its kind for IPC and was written with both manufacturers and regulators in mind. IPC hopes the manual will ensure that manufacturers are better able to comply with regulatory and testing requirements.

Superseding the U.S. FDA's May 2003 guidance on premarket approval filing, there is a new guidance available on the acceptance and filing review criteria for premarket approval applications (PMAs). Due to recent changes in the law, including the reauthorized Medical 88 Device User Fee Amendments of 2012 (MDUFA III), acceptance review has taken on a larger role in encouraging quality PMA applications and allowing FDA to allocate resources more adequately on completed applications. The new guidance includes a modified PMA filing checklist.

On Jan. 2, the U.S. FDA posted the guidance, Refuse to Accept Policy for 510(k)s. This guidance specifies the criteria and procedures the Agency will use to determine when a 510(k) submission is administratively complete. After the draft of the guidance was posted in Aug. 2012, the Agency received comments concerning checklist questions related to performance data as well as comments on checklists identified as "analysis" or "discussion" as criteria for acceptance and relevant prior submissions. The Agency has addressed these comments in the guidance.

Effective Jan. 1, the U.S. FDA announced that the final guidance concerning the eCopy Program for medical device submissions is available. The eCopy Program is a new electronic review program for medical device submissions intended to expedite the efficiency of the review process. The new guidance contains standards for electronic submissions and identifies submission types that require an eCopy in order for the submission to be processed.