By: Helen Kargaryani, Global Head of Quality at NDA Group.
In this whitepaper, Helen provides tips and good practices for remote audits as an alternative method to conducting traditional on-site audit.
The COVID19 pandemic is presenting unprecedented challenges to healthcare, the pharmaceutical industry’s supply chain and the ways in which companies operate “business as usual”. Quality and compliance activities have been particularly affected, areas that are crucial to ensure the long-term safety and efficacy of treatments.
Quality audits and inspections are essential aspects of the checks and balances in a pharmaceutical Quality Management System (QMS). With new guidance’s, constrained travel and limited access to buildings, suppliers, records and people, manufacturer, regulatory and quality personnel must now explore methods and techniques to evaluate quality and compliance in light of these restrictions. To meet these challenges, regulatory agencies and companies alike are adapting to the situation, relying heavily on remote mechanisms to continue delivering lifesaving medicines and products globally.
In this whitepaper, we will provide tips and good practices for remote audits as an alternative method to conducting traditional on-site audit. This paper will also cover circumstances in which remote audits may be necessary and preferable to an on-site audit. Furthermore, we will discuss potential challenges and benefits when auditing remotely and how to adapt your processes and systems to prepare your company for remote audits.
In this white paper, NDA’s Laurie Smaldone discusses the potential impact of COVID-19 on on-going clinical trials.
The virus SARS-CoV-2 and the resulting COVID-19 disease have created devastating impacts around the globe on lives and livelihood, including major disruption of ongoing research and development activities for innovative therapies. From many perspectives the spread of SARS-CoV-2 has impacted and will continue to impact ongoing global registrational programs for a variety of disorders especially those not directly addressing the treatment or prevention of the SARS-CoV-2.
This disruption impacts all facets of the drug development process, from the Sponsor company, to the supply chain of investigational treatments to the productivity of study sites. The FDA has issued guidance to address the challenges that may arise from a range of disruptions that could impact the validity and integrity of clinical programs.
The FDA has noted that the spread of the virus may lead to GCP violations and protocol deviations, including impact on trial endpoints and safety collection. FDA’s Center for Drug Evaluation and Research Director Janet Woodcock stated that “trials may be able to shift to tele-outcome assessments”, but others “may be damaged and may have to halt and not start up again until we can interact more freely”.
FDA’s recent guidance, “Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic” addresses the potential impacts to ongoing trials. The guidance provides stakeholders in the drug development and approval process with critical considerations for ongoing trials.
Potential COVID-19 impacts
Trials may be impacted in a variety of ways. Some sites have had to close down or have witnessed significant recruitment delays due to the inability of patient travel, illness, or redeployment of study personnel to address COVID-19 patients or trials. These limitations can greatly impact study continuity and procedures to maintain study integrity. In making decisions on trial continuity, Sponsors will need to do a robust assessment of trial conduct that may impact patient safety, GCP, drug storage and administration, and protocol procedures .
By: Steffen Thirstrup, Director, NDA Advisory Board & Eva Lilienberg, Principal Consultant
A timely market introduction is a critical component of any drug development strategy – not only from a commercial stand point, where an early introduction can mean beating competition to market or simply significantly increased revenue, but also to patients awaiting better or alternative treatment options.
The debate around how regulators can facilitate this process on both sides of the Atlantic has resulted in new pathways for new medicines of major public interest. The FDA have the Breakthrough/RMAT pathways, and in the EU, EMA has put the PRIME process in place.
In this white paper, Steffen and Eva discuss the different tools available to European regulators and the experiences so far with the PRIME pathway.
NDA Group supports life science companies all over the world with the aim to streamline the global development and commercialization process in order to accelerate patient access to important medical therapies.
Whatever regulatory hurdle you’re facing, we can help you optimize every regulatory interaction and shape the dialogue about your product to create a more direct path to approval.
To learn more about our services and how we can help click here
By: Lisa Peluso, Director, Coaching and Client Engagement, NDA Group/PharmApprove
In this white paper, PharmApprove’s Lisa Peluso, discusses how excellent communications are the backbone of streamlined, efficient programs achieving approval and market access.
The ever-changing complexities of the regulatory world demand excellence in communicating science, data, development program goals and intentions, as well as how foreseen risks are being managed.
These complexities also mean that drug development companies must engage candidly with regulators and lead the scientific conversation with clarity and flexibility, yet be poised to negotiate their position.
While we work with global companies to strategize and execute successful engagements with regulators at critical junctures such as Oral Explanations and FDA Advisory Committee meetings, excellent communications are the backbone of streamlined, efficient programs achieving approval and market access.
A number of potential pitfalls await companies with even the most solid science and robust datasets
To avoid costly delays along the path to regulatory approval and commercialization, companies need to:
1. Communicate internally
To ensure alignment of clinical goals and regulatory approvability with the reality of a product’s potential market value and accessibility the company needs efficient internal communication. The danger lies in a narrow focus on just regulatory considerations: A product may be effective but if there is no place in the market or doubtful economic defense of pricing, the company is wasting time and money. Development plans must be based on all considerations, requiring careful coordination and collaboration across all divisions.
2. Communicate with regulators
Unfortunately, too many companies engage with regulators much too late, or not at all, or lack the candor and skill needed to usher a product smoothly through the approval process. Excellent communication means asking the right questions, clarifying any questions from the regulators and responding in a collaborative and transparent manner. Remember that specific expertise in your company’s product is rare, hence it’s critical to clearly shape the story of not just the data but also the program, goals and risk management commitments.
3. Communicate globally
Just as internal divisions must be aligned, regional requirements vary in Europe and across the globe. Companies risk costly mistakes and a need to “redo” when they don’t share knowledge freely internally.
This is particularly important for US/EU programs. Learnings from multiple regulatory authorities or groups of payers must be transferred so there is no duplication of effort – or waste of time – on the other side of the pond. Constructive interactions speed efficiency.
4. Engage physicians, patients and advocacy groups
Get the community involved early, including doctors and potential study sites as well as patients and advocacy groups. Communicating with these stakeholders also demands delivering the messages behind the data in a concise and compelling manner to a wide variety of physicians, KOLs and other influencers.
With such deep knowledge of one’s product, it’s a daunting challenge to distill the information, refine the message and keep it brief and clear for the audience.
5. Negotiate with payers
Companies put enormous effort into developing slide decks, internal FAQs and value proposition documents. This plethora of planning and information is to no avail if the company does a poor job of interacting with payers. In addition to understanding the audience around the table and their goals, the company must respond deftly to questions, defend the data, and communicate persuasively. Every interaction is an opportunity and certainly, when it’s time to negotiate pricing, excellence in communications is critical.
How we can help?
NDA Group supports life science companies all over the world with the single aim to streamline the global development and commercialization process in order to accelerate patient access to important medical therapies.
Whatever regulatory hurdle you’re facing — a Type B meeting, a document submission, or a SAG hearing — our industry-leading professionals will help you strategize and execute successful engagements with any global authority. We’ll help you optimize every regulatory interaction and shape the dialogue about your product to create a more direct path to approval.
In the US, our Principals and Communications Strategists are particularly experienced at preparing for FDA Advisory Committee meetings, in addition to pre-IND, end of phase 2, pre-NDA/BLA, PMA, and mid- and late-cycle review meetings. In Europe, we assist with Scientific Advice Group meetings, Oral Explanations, PRAC meetings and preparation for intense pricing negotiations. We offer our clients an unparalleled breadth of global experience and expertise to drive efficient product development and health authority interactions across the US and Europe.
By: Dr Mira Pavlovic-Ganascia & Claes Buxfeldt, NDA Group
In this white paper NDA’s Dr Mira Pavlovic-Ganascia and Claes Buxfeldt provide insight into the reasons to seek scientific advice and elaborate on what the expected outcomes of constructively engaging with regulators and HTA bodies could be.
In Europe there are many routes to gain scientific advice directly from official authorities. National regulatory advice is a routine practice of most regulatory agencies, as well as of the European Medicines Agency (EMA).
Scientific advice in the HTA arena is more recent. In this context, national HTA advice is provided against the backdrop of country or region-specific policies and legal requirements. Early dialogue involving multiple HTA bodies is also rather recent, provisioned in the context of the European Network of Health Technology Assessment (EUnetHTA) Joint Action 2 as well as specific actions financed by the European Commission (SEED)(ref) and involving both EMA and EUnetHTA. Indeed, in recent years, EMA and EUnetHTA have led several combined regulatory-HTA pilots to get experience both on the process and the content of such an exercise (1,2,3).
Since the creation of our NDA Joint Advice service offering in 2011, the NDA Advisory Board has also conducted numerous such projects for clients, focusing on ensuring a thorough understanding of the varying regulatory and HTA requirements and bridging the relative efficacy – relative effectiveness gap.
The means to gain scientific advice are many and diverse, but so are the reasons companies strive to get it.
Why seek scientific advice?
The combined scientific advice/early dialogue processes allow a company to engage relatively early in discussions with regulators and HTA bodies. The label on the tin indicates that the main interest of such an engagement would be to gain scientific input into the development program of a product to be able to steer it away from regulator, HTA and payer pitfalls and towards rapid patient access.
The scientific input usually covers the proposed study design(s), comparators, endpoints, target study population and inclusion criteria’s, study length and other key aspects important both for regulatory and HTA bodies. More in general, this early discussion will allow a company to check if the evidence to be generated for EMA is relevant for HTA submissions.
Asking for a combined regulatory and HTA advice is even more important in cases where treatment guidelines are weak or inexistent and/or there is no relevant HTA decision available in the field of interest.
Reality, however, is even more diverse than this and the reasons and rationales for companies to go for scientific advice therefore vary greatly.
1. Stake holder engagement
Engaging early with regulators and HTA bodies can be a crucial motivation for engaging in the scientific advice process, as it provides a unique opportunity to introduce these two key stake holders to the science and circumstances behind the company’s product. This can benefit the process in two ways:
In any future engagements the regulators and HTA bodies will know the product/technology and targeted patient population better. This will potentially enhance future interactions and remove communication hurdles.
By engaging with the right individuals in the right agencies, interest in the product can be sparked which can lead to constructive and positive input along the product’s development path. Building rapport with assessors are again an important vehicle to friction less communication.
2. Demonstrating progress
Engaging with external experts in a structured manner is also an excellent way to demonstrate to boards and stake holders that the product is progressing through the development process. Constructive feedback from regulators and HTA bodies can help steer the product development but can also be a value driver for the company.
If this is a main driver for expert engagement or seeking scientific advice, other reasons should also be carefully considered to optimize the value of the interaction. Seeking endorsement for the sake of it is rarely the optimal use of the time spent by external experts or regulatory agencies and HTA bodies.
Many multi-product pipeline companies have highly controlled processes for how to progress products through the development process. This may well include the consideration and execution of a formal scientific advice procedure.
As this reason is not a value driver in itself, the reasons that the company put this requirement in place in the first instance should be carefully considered when running through the motions. Teams following a check list risk missing the underlying strategic reasons for why the process is necessary and may therefore not consider alternatives or options that might fit better or add more value.
4. Internal alignment
Although not its primary purpose, internal alignment is an incredibly valuable potential outcome of any scientific advice/early dialogue process. Teams working towards a clear goal along a clear timeline tend to glue together and more easily visualize the ultimate outcome. At NDA Group we’ve seen many occasions where the formal process has created strong composite teams. These teams are primed to progress the product through development with a determination and shared purpose that would not have been possible without the structure and clear goal that the scientific advice process offers.
Achieving internal alignment should therefore always be considered a potential beneficial outcome and should be planned for accordingly.
Don’t miss the opportunity to hear to Dr Mira Pavlovic-Ganascia and Claes Buxfeldt speak about HTA and Europe at our complimentary seminar: Optimizing Value – Regulatory and Market Access Considerations in Stockholm on the 21st May.
In this white paper NDA’s CEO, Johan Strömquist, discusses four ways that Health Technology Assessments will change under the new proposed European regulation.
Over many years the European Network for Health Technology Assessment (EUnetHTA) has been working to HTA bodies into the same room to harmonise and develop thinking around the assessment of medicines from a societal point of view. The approaches to HTA assessment across Europe vary significantly across member states causing confusion, challenges and increased costs for drug development so the work of this voluntary network has been greatly appreciated by industry, payers and politicians alike.
However, the network’s voluntary nature and a lack of a formalized framework for the continuation of the activities have caused issues to progress and harmonization throughout its existence. To stabilise the situation and institutionalise the continued efforts, the European Commission (EC) has therefore presented a new HTA regulation back in January 2018 that will be up for decision in the European Parliament in spring 2019.
The regulation does not put any restrictions on how health economic decisions should made or how pricing of products should be carried out
Should this new regulation be endorsed as it is it will have important impact on drug developing companies and the way that drugs will and should be developed if drug developers want to optimise their path to market.
The regulation addresses four things that every biotech CEO and industry leader should be aware of.
1. Joint Clinical Assessments
Years of experience and significant respect for the subsidiarity principle enshrined in the Maastricht Treaty has enabled a pragmatic approach in the draft regulation. The regulation does not put any restrictions on how health economic decisions should made or how pricing of products should be carried out. Instead it focuses on the area of commonality that has been agreed and pushed with EUnetHTA (with varying support from different member states). This area is clinical assessment or the assessment of relative effectiveness of the product.
Should the regulation pass as it is this means that all novel products (defined as any medicinal product passing through the centralised procedure or any medical device or IVD that receives an opinion under the new Medical Device Regulation) will be assessed under a new centralised clinical assessment scheme. This would in theory replace national clinical assessments and could straighten a product’s road to market.
Once a product has been assessed for its clinical benefits, national authorities would still have to assess its value in the local market but one crucial step in this process would have been eliminated and the outcome would be harmonised across the EU.
At NDA we will be ready to support clients managing this process when / if the regulation kicks in. Through our extensive experience in the market access area and by support of collaboration partners we are ideally placed to work with companies pulling their HTA dossier together.
2. Joint Scientific Consultations
The practice of scientific consultations has become increasingly well-established yet is a relatively under-utilised mechanism for companies to improve their understanding of the different stake holder requirements. One reason why this is the case is because the process is time consuming. Another is because the procedure is under resourced and to a great extent based on voluntary contributions from the member agencies.
Under the new regulation all scientific consultations would be managed centrally, including the parallel consultations with the EMA.
This is most likely going to have relatively little impact on the use and performance of consultations to begin with, but by establishing a long-term platform for these activities there will be greater room to expand resources, improve the process and harmonise the contributions from the member states.
NDA’s Joint Advice services addresses several of the weaknesses of parallel consultations. By relying on the experts that built the European regulatory systems we deliver high quality, high speed advice. This is used by many companies as a proxy for formal consultation when time is tight, or as a way to prepare for the formal process to maximise the value that can be attained from engaging early with HTA bodies.
3. Identification of emerging health technology
Horizon scanning as it’s popularly called is a resource intensive activity when it is performed at the member state level. Consolidation of this to a central European function will allow more efficient use of resources, but it will also result in an overall higher quality of the output and material that will be used for training and intelligence at the member state level.
In the long run biotechs and pharma companies can expect their HTA counterparts to be more up to speed with emerging health technologies and that the playing field will become gradually more level across countries thanks to this.
4. Voluntary Cooperation
A clause that is easy to dismiss in the new regulation is where it speaks of voluntary cooperation. However, this means that the current cooperation, which has been moving slowly but has left important marks in the way assessments are carried out, has a formal home. This is important as it gives legitimacy and encourages the continuation of EUnetHTA’s activities in a new and more official format.
Expect this to lead to increased cooperation between HTA bodies in Europe and an increased exchange of scientific and methodological ideas across the member states.
NDA continually monitors the regulatory development to cover any relevant regulatory changes. As many changes are not publicised through regulation, but are a matter of practice in the agencies, our exposure to on-going procedures and 25% of our staff having experience working at a regulatory body are essential in staying on top of the change. Over the last five years NDA has been involved in more than 40% of the new medicinal products approved in the EU.
Will it lead to harmonisation?
There are still big differences in the legal traditions, pricing and reimbursement systems and the socio-economic circumstances across the member states of the EU. We will not see these things change overnight, hence it will take substantial time for these collaborative efforts to bear fruits across the range of the spectrum. Since health care systems and financing is a country matter, appraisals of value and decisions if a new medicine should be granted access is still a country matter. This includes all decisions around pricing as well.
We have however already seen how collaboration, exchange of ideas and development of joint therapeutic area specific methodologies are spreading. This does lead to harmonisation in a few crucial areas around clinical assessment and this is not just progress, but also important for drug developers across the world, as it has the potential to make HTA more transparent and therefore predictable.
The new HTA regulation builds on these important steps to increase the transparency and predictability even further. Despite the challenges that remain, this is progress.
As a partner NDA is ideally placed to support drug development companies navigate through the changes that this new regulation entails. By tracking and reflecting the current thinking and practices of the agencies and by providing tailor made, actionable advice and the help to operationalise this we are looking forward to seeing how this new regulation can help increase predictability and improve the speed with which important therapies reach patients in need, all across the EU.
On Thursday 4th October, at the prestigious Royal Society of Medicine in London, the Chartered Institute of Ergonomics & Human Factors (CIEHF), launched their much-awaited White Paper setting out CIEHF’s vision for the integration of Human Factors in Health & Social Care.
The launch event was a great opportunity for individuals working in Health and Social Care, both clinical and non-clinical, to understand how human factors expertise can help and benefit patients, staff and their organisations.
Dr Brian Edwards, Principal Consultant, Pharmacovigilance & Drug Safety, NDA Group gave a talk, outlining the multi-faceted work of CIEHF’s unique Pharmaceutical Sector Group and its growing influence in a number of important areas such as manufacturing, technology and device design.
Key numbers drop, but Advisory Committees hold steady in complex year for drug approvals.
Earlier this year NDA released its 2016 annual report on drug approvals in both the EU and the US. One striking finding: US approvals (NMEs) plummeted from 45 (2015) to 19 — a drop of almost 60 percent.
That dramatic number wasn’t the only thing that caught our attention though. When we drilled down into all the applications, we spotted some important trends that you can read about in this article written by Christine Chirdo – Service Area Lead: High Stakes Meetings.
You will also learn how we can support you with key activities to make your high-stakes meetings a success. Prepare to Win.
Christine Chirdo – Service Area Lead: High Stakes Meetings, NDA Group/PharmApprove
Partnership with Payers: Communicating and Negotiating with Impact.
Your product is barreling toward approval and you are on the cusp of bringing it to market and to the patients that need it most. Your company has put enormous effort into developing your value proposition documents, slide decks, internal FAQs and objection handler booklets.
This plethora of planning and information is disseminated to your Market Access and Medical Affairs teams across the globe.
Read the full article written by Lisa Peluso, Director Coaching and Client Engagement, to learn more about why excellence in communications is critical when it’s time to defend the value and negotiate pricing. Prepare to win.
Lisa Peluso – Director Coaching and Client Engagement, NDA Group/PharmApprove
Small and Medium Sized Companies in North America Lead Novel Drug Innovation
Small and medium sized companies and academia are important drivers of innovation in drug development. To investigate the profile of the organisations originating and developing novel drugs approved in the EU and US during 2013-2016 we have compiled all medicinal products containing novel substances (e.g. NAS, NME and Biologics) from the EMA and FDA websites.
For each novel drug we mapped the approval pathway, rare disease (orphan) status and post-approval licensee. The innovator(s and the development organisation(s) were mapped in accordance with the ADIS insights database. Each originator and developer was categorised as a large pharmaceutical company, a small or medium sized pharmaceutical company (SME) or an academic and/or public body.
We also mapped and analysed the geographical origin (e.g. Europe, North America or Rest of the World) of the SME or the academic and/or public body. Altogether, 178 novel drugs received approval from the EMA and/or the FDA during 2013-2016.
To read the White Paper written by Dr Terese Johansson, Regulatory Affairs Consultant NDA Group click here.
Dr Terese Johansson, Regulatory Affairs Consultant NDA Group
Selecting product candidates with the highest probability of success and applying rigorous risk-based management in development maximises the value of biopharmaceutical products and increases speed to the clinic and registration.
Due to the high costs for product development, few small and medium sized pharmaceutical companies will take their product to the market on their own. Therefore, the goal is often to develop the product to a stage where partnering becomes feasible. However, the aim should be to add as much value as possible to the product during early development, as this will maximize the likelihood of a successful deal with a corporate partner and provide alternative exit opportunities for the company.
Read the full article written by Niamh Kinsella, Principal Consultant, VP Early Stage Development, Paul Chamberlain Biopharmaceutical and Immunogenicity Expert and Josefin-Beate Holz, Clinical Strategy Expert, to learn how you can maximise the value of your product by having an early development strategy.
The ever-changing complexities of the regulatory world demand excellence in communicating science, data, development program goals and intentions, as well as how foreseen risks are being managed. These complexities also mean that drug development companies must engage candidly with regulators and lead the scientific conversation with clarity and flexibility, yet be poised to negotiate their position.
While we work with global companies to strategize and execute successful engagements with regulators at critical junctures such as Oral Explanations and FDA Advisory Committee meetings, excellent communications are the backbone of streamlined, efficient programs achieving approval and market access.
A number of potential pitfalls await companies with even the most solid science and robust datasets.
Read the full article written by Lisa Peluso, Director, Coaching and Client Engagement, to learn how you can avoid costly delays along the path to regulatory approval and commercialization.
By Lisa Peluso – Director, Coaching and Client Engagement,
The company had no paediatric expertise and limited understanding of the requirements of the EU Paediatric Regulation. They required help in understanding the requirements of the Regulation and its implications on development of their compound. They needed support in to developing a strategy for the paediatric investigation plan (PIP) and so approached NDA because of our extensive paediatric and regulatory expertise in this area.
The company approached NDA as it had no expertise or experience of paediatric requirements in Europe. Before the company could submit the MAA, it was necessary for a PIP (Paediatric Investigation Plan) to be approved.
The client is developing a pipeline of biosimilar monoclonal antibodies for approval in Japan, EU and US. While the regulatory pathway is well-defined in the EU, the pathway to approval of biosimilar products is at a much earlier stage in US and Japan. Although some requirements appear to be aligned across most phases of development, there are still are still major differences in the regulatory requirements from the different regions.