E-DRUG: WHO Drug Information - recommendations from 17th ICDRA
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[Thank you Andy for extracting all this important material for us. BS]
Dear E-druggers
The most recent WHO Drug Information [posted yestereday] (Volume 30, No. 4, 2017; accessible at
http://www.who.int/medicines/publications/druginformation/issues/DrugInformation2016_Vol30-4/en/
includes the full set of recommendations from the 17th International Conference of Drug Regulatory Authorities, held in Cape Town in late 2016.
The recommendations are presented per ICDRA session, and not as a consolidated or prioritised set.
There is an attempt to draw out some key elements: "Several common cross-cutting themes emerged from the discussions. These can be further grouped and consolidated and include e.g. improving coordination, reliance, worksharing and use of regional networks; promoting greater transparency, awareness and communication; enabling preparedness to facilitate crisis management; development of international standards; and provision of technical assistance to support implementation."
Further, it is stated that "WHO intends to develop a further more concise iteration of these recommendations in the form of a work plan, integrating any feedback received and ensuring greater alignment and consistency across the various work streams. This work plan will be prepared later in 2017, and the outcomes of the deliverables will be presented to the 18th ICDRA in September 2018.
WHO will also conduct a general survey seeking feedback on the 17th ICDRA to help inform the structure and content of the next ICDRA. More information on this survey will be published in the next issue of WHO Drug Information. Please send your feedback on the 17th ICDRA recommendations to: druginfo@who.int."
It is useful to compare these recommendations with those offered by the Lancet Commission on Essential Medicines Policies with regard to medicines quality and safety (accessible at http://www.thelancet.com/commissions/essential-medicines or in PDF at http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31907-9/fulltext):
The Commission's full recommendations were:
1. Global efforts must be made to promote the harmonisation of quality assurance eff orts through the use of an international standard regulatory dossier that covers both format and content. The implementation of e-CTD globally should be promoted to facilitate rapid exchanges of product assessments and site inspection reports among agencies. More intensive international collaboration and electronic exchange of information could simplify processes, prevent unnecessary duplication of eff ort in dossier assessments and site inspections, facilitate innovation, and shorten approval times.
2. WHO should evolve the WHO/UN Prequalification Programme to maintain a moving focus on new essential medicines. This evolution should move attention from mature products towards priority essential medicines that pose special challenges to regulators, such as human insulin and other biosimilars, and newly developed essential medicines. Its standards and public assessment reports should form the basis for regulatory convergence and mutual recognition, leading to rapid regulatory approval. A sustainable financial base must be created to maintain its full independence from donors and manufacturers.
3. Payers and procurement agencies must adopt good procurement practices that incorporate effective and transparent quality assurance. Quality assurance mechanisms must exist at all points in the supply chain. Appropriate quality assurance systems require investment. Sharing test results and findings of inspections can avoid duplication and increase efficiency.
4. Governments must redirect the activities of national regulatory agencies towards those that add value and reduce duplication of effort, and engage with a system for independent and public assessment of the performance of NMRAs. Activities aiming to address efficiency and effectiveness should cover all the basic components of a national medicines regulatory authority, with special focus on international harmonisation, prevention of duplicative efforts, maintenance of a single or central NMRA within a country, inspections and enforcement of regulations, assessments of new essential medicines for neglected diseases in their jurisdiction, regulation of medicine promotion, transparent reporting on the prevalence of substandard medicines in the market, pharmacovigilance, collaborating with domestic manufacturers in promoting GMP, and abstention from patent linkage and extended periods of data exclusivity.
5. Regulatory agencies must encourage the involvement of other stakeholders and the general public in promoting the quality and safety of essential medicines. This action can be achieved through, for example, the involvement of stakeholder representatives before regulatory decisions, the use of product quality verification testing at the point of sale, involving unique barcodes, portable low-cost quality-control equipment, or other technical devices linked via smartphones and the internet.
6 WHO and national governments must establish concrete targets and a public accountability mechanism for assessing the performance of national regulatory authorities. The goals should encompass all the basic components of a national regulatory authority, as listed in appendix 3.3, recommendations 4 and 5, and panel 12.
The ICDRA recommendations are as follows:
THEME: Regulatory systems strengthening
Plenary 3: Strengthening of regulatory systems: Follow-up on WHA Resolution 67.20 Recommendations to WHO
-1. Implement a unified policy and harmonized global benchmarking tool, applicable for all medical products; streamline processes where possible to increase efficiency of benchmarking and capacity building
-2. Incorporate an innovative and more coordinated approach to regulatory systems strengthening such as coalition of interested partners and centres of excellence
-3. Promote the concept of reliance, where appropriate, and collaborative decision-making at regional level
-4. Increase transparency in the outcome of benchmarking activities, thereby facilitating reliance.
-5. Consider moving away from using the term "Stringent national regulatory authority".
Recommendations to Member States
-1. Work towards attaining at least minimal capacity (functionality) of "regulatory systems", which includes the concept of reliance and collaborative decision-making.
-2. Encourage best use of existing networks for capacity building - e.g., the African Vaccines Regulatory Forum (AVAREF), the Developing Country Vaccine Regulators' Network (DCVRN), the Pan American Network for Drug Regulatory Harmonization (PANDRH) - to foster collaboration in regulatory activities, including work-sharing.
-3. Invest in human resources with the goal of achieving more systemic and predictable outputs from assessors and promote documentation of training and maintaining competency records.
Plenary 5: Good regulatory practices
Recommendations to WHO
-1. Develop a training curriculum for promotion and implementation of the WHO Good regulatory practices (GRP) guideline for all layers of regulatory bodies (supranational, national and subnational levels)
-2. Incorporate the use of information technology (websites, mobile applications, etc.) and emphasize staff competency and training as enablers for promoting and implementing GRP Recommendations to Member States
--1. Concerned bodies including parliamentarians, policy makers and regulators (supranational, national and subnational levels) to be informed/ educated on aspects of good regulatory practices
--2. National/subnational levels of regulatory authorities to harmonize legal frameworks and implementation of GRP, requiring both sufficient and competent human resources.
Plenary 7: Global scenery of regulatory convergence initiatives: linking opportunities Recommendations to WHO
-1. Encourage communication and information/ work-sharing across existing initiatives in order to optimize their outputs.
-2. Explore opportunities to identify technical platforms that would facilitate interactions and acquisition of existing knowledge.
-3. Leverage all opportunities for collaboration and de-duplication of work.
-4. Start working on indicators of medicinal products' regulation systems in order to capture progress made in the area of access to medicines.
Recommendations to Member States
-1. Prioritize initiatives regarding different areas of regulations that will result in facilitating access to medicines for patients.
-2. Focus on appropriate resourcing models in order to build a regulatory system that is fit for purpose.
-3. Look for opportunities to obtain technical support and capacity building across existing initiatives and networks.
-4. Take into full consideration the existing technical standards, while respecting national realities and contexts.
Workshop B: Model regulatory framework for medical devices: how to take steps for successful implementation Recommendations to WHO
-1. Create a technical working group on medical devices.
-2. Collaborate with partners - International Medical Device Regulators Forum (IMDRF), Pan African Harmonization Working Party (PAHWP), Asian Harmonization Working Party (AHWP) - in strengthening medical device regulatory functions as well as in capacity building for regulators on medical devices.
Recommendations to Member States
-1. Between 2016-2018, ten Member States implement the basic level of regulatory control as set in the WHO Global Model Regulatory Framework in their national regulatory system.
- 2. Strengthen regulation capacity of regulators on medical devices, both in countries that do have regulation in place as well as countries that start regulating.
Ideas from the pre-ICDRA workshop Regulating medical devices: the involvement of stakeholders Implementing regulation is more effective and efficient if regulators and stakeholders interact in a timely and interactive manner. Patients would want a plan with clear steps to have safe and accessible medical devices.
Workshop C: Harmonization and work-sharing in pharmacovigilance Recommendations
-1. Take stock of work-sharing solutions from established cooperation initiatives (like EU) or bilateral agreements (like ARFA and ANVISA/Infarmed) and strengthen and maintain a pharmacovigilance system based on clear and transparent rules, engagement of all stakeholders and coordinated by an established platform such as WHO.
-2. Promote and take advantage of emerging opportunities and harmonization frameworks (such as the African Medicines Regulatory Harmonization African Medicines Regulatory Harmonization, AMRH) including common standards, definitions, instruments and channels of communication.
-3. Pharmacovigilance systems should be able to act locally, addressing appropriately any emerging safety concerns.
-4. Avoid duplication, in particular share information and existing assessments on signals and safety issues in a timely manner.
-5. Consider integrating vigilance systems across different types of products including medical devices and cosmetics.
-6. Maintain and further improve centralized system of signal detection, providing a tailored service to Member States on their specific requests.
-7. Strengthen collaboration with existing centralized systems/databases (e.g. Eudravigilance and WHO's global Individual Case Safety Reports database, Vigibase), in order to avoid duplication.
-8. Support an integrated pharmacovigilance strategy that engages key stakeholders in an open, transparent and collaborative way to strengthen systems, avoids duplication of efforts and promotes effective use of the limited resources.
THEME: Public health emergencies
Plenary 4: Regulatory preparedness for public health emergencies Recommendations to WHO
-1. Consider the formation of a special WHO led task force on medicine regulation that can be deployed during a public health crisis to provide advice to countries on issues that may arise.
-2. Ensure that regulatory support is a priority area of activity as the R&D Blueprint for emerging infectious diseases is implemented.
-3. Consult on the needs for further development of the Emergency Use Approval and Listing mechanisms established through the Prequalification programme.
-4. Develop guidance, and appropriate forums for dialogue, for developed and developing country regulators, on regulatory pathways, platform technologies and novel clinical trial designs for products against emerging infectious disease pathogens, ensuring that the guidance includes more vulnerable populations such as pregnant women and children.
-5. Report back at the 18th ICDRA on progress made on regulatory preparedness for public health emergencies and the integration of this activity into NRA systems strengthening.
Recommendations to Member States
-1. Preparedness for public health emergencies is key, so all NRAs should ensure they proactively participate in national preparedness planning processes.
-2. Regulators should help drive product development for public health emergencies, not only for diagnostics, vaccines and therapeutics but also for relevant infection control products.
-3. Crisis communications are particularly challenging and NRAs need to proactively develop a general communication plan that would include crises, and to develop their capacity, overall, to communicate more effectively
-4. Public health emergencies require rapid, extensive regulatory collaboration and cooperation so development and maintenance of appropriate platforms for this purpose is a high priority
- 5. Timely sample and data-sharing remain barriers to product evaluation, so regulators should help drive change through advocacy for the national benefits of sample and data-sharing.
-6. Member States should improve their pharmacovigilance systems to ensure that safety of investigational products is effectively monitored during public health emergencies.
Workshop I: Regulatory responses to shortages of supplies Recommendations to Member States
-1. Regulators should encourage and enable the authorization of alternative active pharmaceutical ingredient (API) sources, manufacturing processes and sites for all medicines identified as vulnerable or critical.
-2. Governments/regulators should consider shortage reporting systems which feed to national, to regional and to global systems.
-3. Governments/regulators should consider the process for special access (including donations) to meet the particular needs of patients.
Workshop J: Regulatory role in addressing anti-microbial resistance Recommendations to WHO
-1. Continue to support countries on monitoring antimicrobial consumption and use in human and animals. Increase the systems of gathering data on antimicrobial resistance in the health care setting.
-2. Continue supporting countries in strengthening their regulatory systems to ensure that the quality of antibiotics / antimicrobials can be assured.
Recommendations to Member States
-1. Regulators should consider ways that will facilitate the development of new antibiotics such as harmonized technical standards, scientific advice, accelerated pathways and incentivized research.
-2. Member States/regulators should promote the rational use and prescribing of medicines. Actions can include: prohibiting the dispensing of medicines without a prescription, information campaigns, requirements for proper diagnostics, considering the indications for which medicines are indicated.
THEME: Biologicals Workshop A: Similar biotherapeutic products
Recommendations to WHO
-1. Expand support to Member States in implementing guiding principles for regulatory evaluation of biotherapeutics, including biosimilars, for example to Russian-speaking countries and low- and middle-income countries.
-2. Foster collaboration and use of existing regulatory networks to promote information and work-sharing among regulators and provide technical support to enable regulatory evaluation on the basis of up-to-date scientific principles and evidence.
-3. Further development, and communication about use, of public standards should be prioritized to help assure quality of biotherapeutics including biosimilars.
-4. Provide technical assistance and guidance for regulatory oversight of biosimilars developed through technology transfer.
-5. Develop mechanisms to assist countries in linking regulation with guidance on the appropriate use of similar biotherapeutic products.
Recommendations to Member States
-1. Given the number of available guidelines for biosimilars (e.g, WHO, EMA, national guidance), the focus should be on the implementation of the existing guidelines.
-2. Collaboration is the key for overcoming lack of expertise and experience in many NRAs. For that purpose, better use of existing resources through the networks (e.g. AVAREF and Zazibona in the African region and other relevant networks in other regions) is the way forward.
-3. Training as part of long term strategy for building capacity should be accelerated and all relevant training opportunities should be used. For example, the European Network Training Center will soon become available to non-EU regulators.
-4. Regulators should provide relevant and useful information to enable health care providers to prescribe and patients to use biosimilars with confidence.
Workshop D: Blood products - old and new challenges
Recommendations to Member States
-1. Member States are encouraged to implement regulation of blood and blood components for transfusion as essential medicines covering all steps "from vein to vein and back" based on current WHO Guidelines including "Good Preparation Practices (GPP)" analogous to pharmaceutical good manufacturing practices and to assure availability and quality of plasma suitable for use in fractionation.
-2. Member States are encouraged to implement regulation of reagents and devices essential to the preparation of blood and blood components (e.g. anticoagulant solutions, donor screening assays, compatibility tests, etc.).
-3. Member States are encouraged to model new blood regulations on those already established in other countries and to seek any necessary assistance from such countries and from WHO.
-4. Member States are encouraged to regulate snake antivenoms as biological products and to assess the quality, effectiveness and specificity of these products in the context of the country`s specific needs, making use of tools available from WHO including the revised WHO Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins and the updated WHO database on snake species and antivenoms.
Recommendations to WHO
-1. WHO, at the request of Member States, should continue to provide assistance for assessments of national blood regulatory systems.
-2. WHO, at the request of Member States, should offer specific training for inspectors and assessors in the regulation of blood and blood components and related reagents and devices, including a focus on strengthening of regional networks.
-3. WHO should regularly update the global data base on snake species and antivenoms.
-4. WHO, at the request of Member States, should assist in the development of regional reference standards for venoms.
-5. WHO should take steps towards eventual inclusion of snake antivenoms in its prequalification programme. The current assessment programme should be continued, with consideration of expansion of support for NRA inspections, critical laboratory testing and promotion of quality-assured manufacturing.
Workshop G: Vaccine regulation
Recommendations to WHO
-1. Assist Member States to build capacity at the regional level (e.g., regional blocks and networks) for regulation of vaccine
-2. Assist Member States that will transition from vaccine procurement through GAVI to self-procurement of vaccines to prepare adequately and in a timely way for the change.
-3. Assist Member States to build pharmacovigilance capacity for vaccine
-4. Consider removal of the innocuity test as a requirement for lot release from WHO vaccine guidelines but encourage maintenance of some capacity to perform this test, if needed.
-5. Establish a global network of national vaccine control laboratories involved in testing of WHO-prequalified vaccines
Recommendations to Member States
-1. Consider using regional level approaches (e.g., regional blocks and networks) for regulation of vaccines
-2. For efficient lot release testing of vaccines, consider a risk-based approach or networking (reliance) approach
-3. Utilize opportunities through WHO, and links with international regulatory platforms (e.g., PAHO, ASEAN, AVAREF and DCVRN), to build capacity for vaccine regulation.
THEME: Substandard and falsified medical products
Formerly known as substandard, spurious, falsely labelled, falsified and counterfeit (SSFFC) medical products
Plenary 6: SSFFC medical products and supply chain integrity
Recommendations to WHO
-1. WHO is urged to continue regulatory strengthening, with particular emphasis on training in relation to all aspects of the prevention, detection and response to substandard and falsified medical products.
-2. WHO is urged to publish data on the scope, scale and harm caused by substandard and falsified medical products.
-3. WHO is urged to examine all available and emerging technologies to assist in the tracking, tracing and authentication of medical products, and where necessary screening, testing and reporting of substandard and falsified medical products.
Recommendations to Member States
-1. Heads of regulatory agencies are encouraged to raise awareness amongst policy and decision makers, relevant stakeholders and most importantly civil society of the threat posed by substandard and falsified medical products.
-2. Member States and regulatory authorities are encouraged to set and implement national/regional strategies to prevent, detect and respond to substandard and falsified medical products, embedded within core regulatory functions.
-3. Member States are requested to nominate regulatory technical experts to participate in the WHO Member State Mechanism, and specifically national regulatory focal points to engage with the WHO Global surveillance and monitoring system for substandard and falsified medical products.
Workshop F: Effective communications - SSFFC
Recommendations to WHO
-1. WHO is encouraged to provide best practice communications guidance to Member States, including templates and models for communication, education and awareness campaigns.
-2. WHO is encouraged to provide guidance on communication strategies specifically in relation to reacting to substandard and falsified medical products discovered in the supply chain.
-3. WHO is encouraged to provide a central communications hub with access available to communications experts in Member States which will house all the advice, knowledge and experience gained from the communications programme developed by WHO.
Recommendations to Member States
-1. Member States are encouraged to play an active role in the Communications Working Group of the WHO Member State Mechanism to ensure the proposals developed reflect the needs of all countries.
-2. Member States are encouraged to share examples of communication campaigns implemented in their countries to the Member State Mechanism, to improve the knowledge base of communications activities globally, and to enable this experience and learning to be shared with other Member States.
-3. Member States are encouraged to deliver national communication and awareness campaigns, offering accurate information, sound advice and reassurance to relevant stakeholders specifically civil society and the young.
THEME: Special topics
Workshop E: Regulatory challenges of medical products for maternal and child health
Recommendations to Member States
For maternal immunization Maternal immunization is a field of growing importance to reduce neonatal, infant and maternal mortality, and new vaccines are in development for Group B Streptococcus (GBS) and respiratory syncytial virus (RSV).
-1. Implementation of recently developed WHO guidelines on influenza vaccine labelling was recognized as an important step towards wider immunization of pregnant women, and women during the lactation period, with inactivated influenza vaccines.
-2. Collection and review of safety data from post-marketing surveillance and post-licensure studies of existing vaccines would contribute to better understanding of the safety in the field.
-3. For new vaccines to be used for maternal immunization, randomized, controlled designs with pre-specified clinical and immunological outcomes are the gold standard, with consideration in the trial design of correlates of protection.
-4. All national regulatory authorities should review their current language in package inserts/labelling to accurately reflect data while avoiding misleading statements.
For paediatric medicines
--1. Member States are still facing challenges to get optimal formulations for children, and there is a need to incentivize research and licensure of paediatric formulations.
--2. It is good to see an increase of the number of ongoing studies and registration, but problems still exist in treating children in countries. Every effort should be made to define regulatory requirements for involvement of children in clinical trials.
--3. Member States should consider putting in place post-marketing surveillance and pharmacovigilance when new paediatric formulations are introduced.
Recommendations to WHO
-1. WHO guidelines on quality, safety and efficacy of RSV vaccines: standardization and coordination in reaching consensus on that matter is critical.
-2. Guidelines for paediatric medicines used in emergency situations (such as the Ebola outbreak) should be developed.
-3. There is a need for a clear definition of a child and an adolescent, and consideration of what this means for clinical trials and licensure (particularly important for medicines used in oncology).
-4. Registry practices need to be standardized. Good practices for registries need to be developed by WHO.
-5. Regulation of paediatric medicines should be a permanent theme for ICDRA.
Workshop H: Safety of herbal medicines
Recommendations to Member States
-1. Member States are encouraged to adopt and subsequently monitor the implementation of existing WHO guidelines pertaining to herbal medicines, according to national circumstances, to define/determine the scope of the effective regulation and safety monitoring of herbal medicines.
-2. Member States are encouraged to identify and develop tools to implement appropriate communication strategies aimed at consumers, health care providers, manufacturers and distributors of herbal medicines, in order to facilitate them to make informed decision/choice in their use and clinical application.
-3. Member State are encouraged to share good practices in setting key objectives, and/or action taken to overcome safety concerns of herbal medicines, among Member States.
Recommendations to WHO
-1. WHO should further coordinate and support Member States in order to strengthen and facilitate collaboration and communication among national regulatory authorities in the area of herbal medicines, especially in sharing information on safety of herbal medicines and on public awareness campaigns relating to herbal medicines, through relevant mechanisms, such as the International Regulatory Cooperation for Herbal Medicines.
-2. In order to strengthen the national capacity at the regulatory authorities in conducting comprehensive effective regulation of herbal medicines, WHO should:
--a) identify and coordinate with possible partners to provide tailored capacity-building opportunities to the concerned regulatory authorities;
--b) support exchange among Member States of technical expertise and technical resources that are required in the assessment of herbal medicines for inclusion in the national registration; and
--c) further support Member States in developing methodologies in setting required national standards and reference sources (such as
pharmacopoeia) taking into account particulars of herbal medicines, in order to enhance mutual reliance basis for convergence of standards among Member States.
One of the key overlaps between the Lancet Commission and ICDRA recommendations is that dealing with the issue of transparency, not just in relation to decision-making, but also in relation to measures of regulatory performance. Both are critical enablers of greater work-sharing and reliance in order to reduce duplication of effort, improve efficiency and build capacity.
Driving this agenda will require concerted effort at the national level first, to identify barriers to transparency in current legislation and practice. Such efforts can also be supported by effective advocacy from civil society, access campaigns and groups such as E-druggers.
Regards
Andy
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Andy Gray BPharm MSc(Pharm) FPS FFIP
Senior Lecturer
Division of Pharmacology
Discipline of Pharmaceutical Sciences
School of Health Sciences
Consultant Pharmacist (Research Associate) Centre for the AIDS Programme of Research in South Africa (CAPRISA) University of KwaZulu-Natal PBag 7 Congella 4013 South Africa
Visiting Fellow, Faculty of Pharmacy, Rhodes University, Grahamstown
email: graya1@ukzn.ac.za or andy@gray.za.net