Last updated: 20 December 2023
See updates at the end of the post.
Chatbots have finally come of age and are here to stay. On 21 March 2023, Google launched Bard.
The launch of ChatGPT late last year created a buzz across the globe that is unlikely to be diminished anytime soon. There will no doubt be other chatbots beyond OpenAI’s ChatGPT and Google’s Bard. Baidu’s Ernie will be one to look out for once it gets going. The expectation is that with each iteration, all of these chatbots should get better. It will become important to understand what each chatbot has to offer and when and how to use them to your advantage in all walks of life.
A brief and recent timeline of chatbots/search engine(s) incorporating chatbot technology
- 30 November 2022 OpenAI introduced the world to ChatGPT
- 6 February 2023 Google announced that it was working on a ChatGPT competitor called Bard
- 7 February 2023, Microsoft announced a new version of its search engine Bing (New Bing), which incorporates OpenAI’s ChatGPT technology
- 21 March 2023, Google launched Bard.
- On 11 July 2023, Anthropic launched a beta version of Claude (Claude 2).
- On 21 September 2023, Microsoft announced the launch of Microsoft Copilot, your everyday AI companion. On 15 November 2023, Microsoft confirmed that to simplify the user experience and make Copilot more accessible to everyone, Bing Chat and Bing Chat Enterprise will now simply become Microsoft Copilot.
- On 6 December 2023 Google announced the launch of its latest, most powerful AI model, Gemini, which has three sizes. Of these three, the Pro model can be accessed on Google’s Bard chatbot. Gemini. The upgrade was rolled out in the UK on 19 December 2023. The Bard upgrade has not yet been released in Europe as Google seeks clearance from regulators.
About Bard
You can find out more about Google’s Bard on its FAQ Page. In response to the question What’s Bard all about? it states:
We’ve long seen the potential to make information and computing much more accessible through conversational AI. Two years ago, we unveiled LaMDA (Language Model for Dialogue Applications), a conversational AI model capable of fluid, multi-turn dialogue, and last year, we launched the AI Test Kitchen, a new space where people could learn about, get hands-on experience with, and provide feedback on LaMDA.
Bard is an experiment based on this same technology that lets you collaborate with generative AI. As a creative and helpful collaborator, Bard can supercharge your imagination, boost your productivity, and help you bring your ideas to life—whether you want help planning the perfect birthday party and drafting the invitation, creating a pro & con list for a big decision, or understanding really complex topics simply.
Like me, I suspect that at least some of you may find the above technobabble irritating! I think that best way to learn more about Bard is to use it and see whether it meets your expectations.
On the web, you will find a plethora of articles just as you will find YouTube clips that will give you endless details about Bard.
How to access Bard
At the time of writing this post, Bard is only available to people over the age of 18 and you need a Google account to use it.
To access Bard, go to the Bard homepage and click on the “Join waitlist” button. Click the blue “Join waitlist” button to join the waitlist. You will have to sign in with a Google account. Having joined the waitlist, you will receive a “You’ve been added to the waitlist” message from bard-noreply@google.com. When it’s your turn to try Bard, you will receive another email titled “It’s your turn to try Bard.” You can read more about how to use Bard here or via a large number of other articles on the web or YouTube clips.
Update– At its annual developer conference, Google made the following announcements:
- The company said it was removing the waitlist for “Bard”, its experimental, conversational, chat service, which will be rolled out in English in 180 countries and territories.
- It also said the chatbot would soon be able to respond to prompts with images as well as text
- It is rolling out generative artificial intelligence (AI) to its core search engine. However, the system will only be available to a limited number of users and is still in “experimental” phase.
Using Bard
In a previous blog post I compared answers from ChatGPT and New Bing (Microsoft), to ten regulatory questions.
This time, I have compared multiple answers from Bard to each of five regulatory questions (Table 1 below) as well as comparing answers from Google Bard, Chat GPT and New Bing (Microsoft), to the same five regulatory questions.
As with ChatGPT and New Bing (Microsoft), the Bard Interface is easy to use.
On the correctness of answers from Bard
As always, caveat emptor applies when using Bard (just as it does when using any other chatbot). In response to the question “Does Bard give accurate and safe responses?”, it states the following:
Bard is experimental, and some of the responses may be inaccurate, so double-check information in Bard’s responses. With your feedback, Bard is getting better every day. Before Bard launched publicly, thousands of testers were involved to provide feedback to help Bard improve its quality, safety, and accuracy.
Accelerating people’s ideas with generative AI is truly exciting, but it’s still early days, and Bard is an experiment. While Bard has built-in safety controls and clear mechanisms for feedback in line with our AI Principles, be aware that it may display inaccurate information or offensive statements.
Multiple draft answers to each question from Bard
Interestingly, Bard doesn’t just give you one answer to a question. Instead it gives you three draft answers to each question. There is nothing on the Bard screen or in the FAQ to explain why this is the case, so I checked on the world wide web. According to an article form TechRadar:
This is known as ‘AI branching’ and we think it’s a helpful tool, particularly if you’re looking to use it for creative reasons like generating a covering letter. We’ve also already seen this kind of AI-generated drafting previewed for the likes of Gmail and Google Docs, where it’s a very natural fit.
On the other hand, it also gives you a lack of confidence in Bard’s first answer being the definitive one. And it sometimes feels like the main answer you’ve been given lacks something that’s been kept in reserve for its other drafts. It ultimately all comes down to how you’re looking to use Bard.
About Claude
This article from The Guardian and this one from The Verge provide the basic details about Claude. You can access Claude here.
The regulatory questions asked
I asked the following five questions to Google’s Bard, ChatGPT, New Bing (Microsoft) and Claude:
- Q1. Which marketing authorisation route is appropriate for the authorisation of a CAR-T cell product in the EU?
- Q2 Which authorisation route is appropriate for the authorisation of a biological product in the US and how long is the process likely to take?
- Q3. I wish to market a Class II medical device in the European Union. Please help me with a step by step guide on the authorisation process.
- Q4. I want to market a generic medicine in Brazil. What are the steps for the authorisation of a generic medicine in Brazil?
- Q5. What documentation do I need in order to seek approval for a substantial modification for a clinical trial authorised in the EU?
The answers received
The answers to the five regulatory questions are tabulated at the end of this post as follows:
- Table 1: Bard, a comparison of the multiple answers to each of five regulatory questions
- Table 2: A comparison of answers from Google Bard, Chat GPT, New Bing (Microsoft) and Claude, to five regulatory questions
Some thoughts/comments/questions about the answers
As always, I shall leave it to you the reader, to decide on the correctness/ incorrectness and or/completeness of the answers. Your decision making will no doubt be dependent on your knowledge of the regulatory subjects in question.
With reference to the multiple answers to each question from Bard, do you think that in each case, one answer (of three answers provided each time) is the best or would you prefer to use a combination of snippets from all three answers? Could it be that none of the answers to one or more questions is/are either correct or complete?
The devil as they say is always in the detail. What you ask and how you ask it is always very important as this will probably impact the answer that you get. This means that the choice of words used in a question is always going to be very important.
Just as I found out that ChatGPT and New Bing (Microsoft) do not give an identical answer to the same question when asked on multiple occasions (days or weeks apart), does the same apply to Bard? This is something that I shall endeavour to find out over the coming weeks and you may want to find out for yourself too.
When you compare the answers from Bard, ChatGPT and New Bing (Microsoft), do the answers from one of them stand out against the others every time or must the response to each question be considered on its own merit each time it is asked?
One very important question to ask is whether you would be able to rely solely on a response from Bard, ChatGPT or New Bing (Microsoft), to a regulation question about a topic that you are either unfamiliar with or not particularly knowledgeable about. My answer to this question is that I could only use a response from a chatbot (if at all) as a starting point for further research and verification.
Please share any thoughts, comments, or your own experiences of using these chatbots to answer regulatory questions, via the feedback form.
Table 1
Bard, a comparison of the multiple answers to each of five regulatory questions
| Question | Bard Draft 1 answer | Bard Draft 2 answer | Bard Draft 3 answer |
|---|---|---|---|
| Q1. Which marketing authorisation route is appropriate for the authorisation of a CAR-T cell product in the EU? | The appropriate marketing authorisation route for the authorisation of a CAR-T cell product in the EU is the centralised procedure. The centralised procedure is the only procedure that allows for the authorisation of ATMPs, which are a type of medicinal product that is derived from human cells, tissues, or genes. The centralised procedure is a two-stage process. The first stage involves the assessment of the scientific quality, safety, and efficacy of the product by the European Medicines Agency (EMA). The second stage involves the authorisation of the product by the European Commission (EC). The EMA’s assessment of the CAR-T cell product will include a review of the product’s clinical data, manufacturing process, and quality control measures. The EMA will also consider the product’s safety and efficacy in the treatment of patients with cancer. The EC’s authorisation of the CAR-T cell product will be based on the EMA’s assessment. The EC will also consider the product’s potential benefits and risks for patients with cancer. The centralised procedure is a complex and time-consuming process. However, it is the only way to ensure that ATMPs are authorised in the EU in a way that is consistent with the highest standards of quality, safety, and efficacy. | The centralised procedure is the most appropriate route for the authorisation of a CAR-T cell product in the EU. This is because CAR-T cell products are advanced therapy medicinal products (ATMPs), which are subject to a more rigorous regulatory process than conventional medicinal products. The centralised procedure is a single, unified process for the assessment of ATMPs by the European Medicines Agency (EMA), which allows for a more efficient and consistent assessment of these products. The decentralised procedure is another option for the authorisation of ATMPs in the EU, but this route is only available for products that are not considered to be of major interest to public health. CAR-T cell products are likely to be considered to be of major interest to public health, as they are breakthrough therapies that have the potential to save lives. The EMA has also established a number of other initiatives to facilitate the authorisation of CAR-T cell products, including the PRIME (Priority Review of Innovative Medicines) and RMAT (Regenerative Medicine Advanced Therapy) designations. These designations allow for a faster and more streamlined authorisation process for products that meet certain criteria. The EMA has also published a number of guidance documents on the authorisation of CAR-T cell products, which provide further information on the regulatory requirements for these products. | The marketing authorisation route for a CAR-T cell product in the EU is the Centralised Procedure. This is the only route available for advanced therapy medicinal products (ATMPs), which are defined as medicinal products comprised of cells, genes, or tissues. The Centralised Procedure is a two-step process. The first step is for the applicant to submit a marketing authorisation application (MAA) to the European Medicines Agency (EMA). The EMA then assesses the MAA and makes a recommendation to the European Commission (EC). The EC has the final decision on whether to grant marketing authorisation. The Centralised Procedure is a more complex and time-consuming route than the decentralised procedure, but it has a number of advantages. First, it allows for a more rigorous assessment of the safety, efficacy, and quality of ATMPs. Second, it provides for a more coordinated approach to the authorisation of ATMPs across the EU. Third, it allows for the development of common standards and guidelines for the manufacture and use of ATMPs. The Centralised Procedure is the only route available for the authorisation of CAR-T cell products in the EU. thumb_up |
| Q2 Which authorisation route is appropriate for the authorisation of a biological product in the US and how long is the process likely to take? | The biological product authorisation route in the US is the Biologics License Application (BLA). The BLA is a comprehensive application that provides detailed information about the product, including its manufacturing process, clinical trials, and safety and efficacy data. The BLA must be submitted to the Food and Drug Administration (FDA) for review and approval. The BLA process is a multi-step process that can take several months or even years to complete. The first step is for the FDA to review the application to ensure that it meets all of the requirements. The FDA will then conduct a scientific review of the product, which will include an assessment of its safety, efficacy, and quality. The FDA will also conduct inspections of the manufacturing facility to ensure that it meets all of the FDA’s Good Manufacturing Practice (GMP) standards. Once the FDA has completed its review, it will issue a decision on whether to approve the product. If the product is approved, the FDA will issue a license to the manufacturer that allows them to market the product in the US. The BLA process is a complex process that can take several months or even years to complete. However, the FDA is committed to ensuring that biological products are safe and effective before they are marketed in the US. | The appropriate authorisation route for the authorisation of a biological product in the US is the New Drug Application (NDA). The NDA is a comprehensive document that provides the FDA with all the information it needs to make a decision about whether to approve a new product. The NDA must include information about the product’s chemistry, manufacturing, and controls; preclinical testing; clinical trials; and post-marketing studies. The FDA has a goal of reviewing NDAs within 10 months, but the actual review time can vary depending on the complexity of the product and the amount of information submitted. The FDA may also require additional information or studies before it can approve a product. If the FDA approves an NDA, the product can be marketed in the US. The FDA also has the authority to approve a product for a specific use or patient population. For example, the FDA may approve a product for the treatment of a specific type of cancer or for use in a certain age group. | The appropriate authorization route for the authorization of a biological product in the US is the Biologics License Application (BLA). The BLA is a comprehensive application that must be submitted to the Food and Drug Administration (FDA) to demonstrate the safety, efficacy, and quality of a biological product. The BLA process is a complex and time-consuming one, and the length of time it takes to complete the process can vary depending on the complexity of the product and the quality of the application. The BLA process typically begins with the FDA’s review of the product’s preclinical data, which includes information about the product’s safety and efficacy in animal studies. The FDA then conducts a clinical trial of the product in humans to assess its safety and efficacy. The FDA’s review of the clinical data is the most critical part of the BLA process, and it can take several months or even years to complete. Once the FDA has reviewed the clinical data, it will issue a Complete Response Letter (CRL) to the applicant. The CRL will list any deficiencies in the application that need to be addressed before the product can be approved. The applicant will then have the opportunity to address the deficiencies in the application and resubmit it to the FDA. The FDA will review the resubmitted application and issue a final decision on the product’s approval. If the product is approved, the FDA will issue a biologics license, which allows the product to be marketed and sold in the US. The BLA process is a complex and time-consuming one, but it is the only way to obtain FDA approval for a biological product. The length of time it takes to complete the process can vary depending on the complexity of the product and the quality of the application. |
| Q3. I wish to market a Class II medical device in the European Union. Please help me with a step by step guide on the authorisation process. | Sure. Here is a step-by-step guide on the authorization process for a Class II medical device in the European Union: 1. Identify the regulatory requirements for your device. The first step is to identify the regulatory requirements that apply to your device. These requirements will vary depending on the type of device, its intended use, and the country in which you plan to market it. 2. Design and manufacture your device. Once you have identified the regulatory requirements, you can begin designing and manufacturing your device. It is important to ensure that your device meets all of the relevant requirements, including those for safety, efficacy, and quality. 3. Prepare the technical documentation. You will need to prepare a number of technical documents for your device, including a user manual, a technical description, and a risk management plan. These documents will need to be submitted to the authorities in the country where you plan to market your device. 4. Submit the application for approval. Once you have prepared the technical documentation, you can submit your application for approval to the authorities in the country where you plan to market your device. The application will be assessed by the authorities, and if it is approved, your device will be granted a CE mark. 5. Market your device. Once your device has been granted a CE mark, you can begin marketing it in the European Union. You will need to comply with the relevant marketing requirements, including those for labeling and advertising. The authorization process for a Class II medical device in the European Union can be a complex and time-consuming one. It is important to consult with a qualified professional to ensure that you understand the requirements and that you are able to comply with them. | Sure, here is a step-by-step guide on the authorisation process for a Class II medical device in the European Union: 1. Determine the classification of your device. Class II devices are medical devices that are intended for use in diagnosis or treatment of a disease or injury, and that do not require a surgical intervention. 2. Designate a person responsible for regulatory compliance. This person must be responsible for ensuring that the device meets all applicable requirements and for complying with all applicable regulations. 3. Implement a quality and risk management system. This system must be designed to ensure the quality and safety of the device. 4. Prepare technical documentation. This documentation must include information on the device’s design, manufacturing process, and clinical performance. 5. Implement supplier management system. This system must be designed to ensure the quality of the components and materials used in the device. 6. Submit a conformity assessment application to a notified body. A notified body is an organization that has been accredited by the European Commission to assess the conformity of medical devices to the Medical Devices Regulation. 7. Undergo a conformity assessment. This assessment will involve an audit of your quality and risk management system, as well as the review of your technical documentation. 8. Receive a certificate of conformity from the notified body. This certificate will confirm that your device meets the requirements of the Medical Devices Regulation. 9. Market your device in the European Union. You must display the CE marking on your device to indicate that it has been certified. The authorisation process for a Class II medical device in the European Union is a complex and time-consuming one. It is important to start the process early and to work with a qualified consultant to ensure that your device meets all applicable requirements. | Here are the steps on how to market a Class II medical device in the European Union: 1. Determine the classification of your device. Class II medical devices are devices that are intended for use in humans and are not intended to be implanted. They are subject to the Medical Devices Regulation (MDR) and must be CE marked. 2. Designate a Person Responsible for Regulatory Compliance (PRRC). The PRRC is a person who is responsible for ensuring that the device complies with the MDR and for managing the CE marking process. 3. Implement a Quality and Risk Management System (QMS). The QMS is a system that is used to ensure that the device is manufactured in a controlled environment and that any risks associated with the device are identified and controlled. 4. Prepare Technical Documentation. The Technical Documentation is a set of documents that describes the device, its intended use, and its design and manufacturing process. The Technical Documentation must be submitted to a Notified Body for review. 5. Implement Supplier Management System (SMS). The SMS is a system that is used to ensure that the suppliers of the device meet the requirements of the MDR. 6. Submit the Technical Documentation and SMS to a Notified Body. The Notified Body is a third-party organization that reviews the Technical Documentation and SMS to ensure that they comply with the MDR. 7. Obtain a CE Marking. The CE Marking is a symbol that indicates that the device complies with the MDR. The CE Marking must be placed on the device and its packaging. 8. Market the device in the European Union. Once the device has been CE marked, it can be marketed in the European Union. The MDR is a complex regulation, and there are a number of other steps that may be required, depending on the specific device. It is important to consult with a qualified professional to ensure that all of the necessary requirements are met. |
| Q4. I want to market a generic medicine in Brazil. What are the steps for the authorisation of a generic medicine in Brazil? | The steps for the authorization of a generic medicine in Brazil are as follows: 1. Submit an application to the Ministry of Health (SUS). The application must include information about the drug, its intended use, and its manufacturing process. 2. The SUS will review the application and decide whether to approve the drug. If the drug is approved, it will be listed on the National Formulary (Farmacopeia Nacional). 3. The drug can then be marketed in Brazil. The following are some additional requirements for the authorization of a generic medicine in Brazil: · The drug must be manufactured in accordance with Good Manufacturing Practices (GMP). · The drug must be tested for its safety, efficacy, and quality. · The drug must be labeled in accordance with the Brazilian Pharmacopeia. · The drug must be registered with the National Agency of Sanitary Surveillance (ANVISA). The approval process for a generic medicine in Brazil can take several months. | The steps for the authorization of a generic medicine in Brazil are as follows: 1. Submit an application to the National Health Surveillance Agency (ANVISA). The application must include information on the product’s composition, manufacturing process, stability, and quality control. 2. ANVISA will review the application and conduct an inspection of the manufacturing facility. If the application is approved, ANVISA will issue a license to market the product. 3. The product must be registered with the Brazilian Drug Regulatory Agency (ANVISA). The registration process includes providing information on the product’s name, dosage form, and indication. 4. The product must be marketed in accordance with the terms of the license and registration. This includes ensuring that the product is labeled appropriately and that it is only sold to licensed pharmacies. The authorization process for generic medicines in Brazil is a complex one, but it is necessary to ensure that the products are safe and effective. ANVISA is a responsible agency that ensures that the health of the Brazilian population is protected. | Here are the steps on how to market a generic medicine in Brazil: 1. Submit an application to the Ministry of Health. The application must include information on the generic medicine, its intended use, and its safety and efficacy. 2. The Ministry of Health will review the application and approve or reject it. If the application is approved, the generic medicine can be marketed in Brazil. 3. The generic medicine must be registered with the National Health Surveillance Agency (ANVISA). ANVISA is responsible for ensuring the safety and efficacy of medicines in Brazil. 4. The generic medicine must be manufactured in accordance with good manufacturing practices (GMP). GMP is a set of standards that must be met in order to ensure the quality of medicines. 5. The generic medicine must be labeled in accordance with the Brazilian Pharmacopoeia. The Brazilian Pharmacopoeia is a book that sets standards for the quality and purity of medicines. 6. The generic medicine must be marketed in accordance with the laws and regulations of Brazil. These laws and regulations include the Pharmaceutical Law and the Law of Generic Medicines. The process of obtaining authorization to market a generic medicine in Brazil is a complex one. It is important to consult with a qualified professional to ensure that all of the necessary requirements are met. |
| Q5. What documentation do I need in order to seek approval for a substantial modification for a clinical trial authorised in the EU? | To seek approval for a substantial modification for a clinical trial authorised in the EU, you will need to submit the following documentation: · A letter to the competent authorities explaining the nature of the modification and why it is necessary. · A statement from the sponsor or principal investigator of the trial explaining the impact of the modification on the trial. · A copy of the original clinical trial authorisation application. · A copy of the original clinical trial protocol. · Any supporting documentation, such as data from the trial or expert opinions. The competent authorities will review the documentation and decide whether to approve the modification. If the modification is approved, the sponsor or principal investigator of the trial will need to update the clinical trial protocol and the clinical trial authorisation application. · | To seek approval for a substantial modification for a clinical trial authorised in the EU, you will need to submit the following documentation: · A substantial modification notification form · A detailed description of the modification · A justification for the modification · Evidence that the modification will not affect the safety or efficacy of the trial · Evidence that the modification will not affect the quality of the data collected in the trial The substantial modification notification form will need to be completed and signed by the sponsor of the clinical trial. The form will need to include the following information: · The name of the sponsor · The name of the clinical trial · The number of the clinical trial · The description of the modification · The justification for the modification The detailed description of the modification will need to be provided in a separate document. The description should include the following information: · The nature of the modification · The reason for the modification · The impact of the modification on the clinical trial The justification for the modification will need to be provided in a separate document. The justification should explain why the modification is necessary and how it will improve the clinical trial. The evidence that the modification will not affect the safety or efficacy of the trial will need to be provided in a separate document. The evidence should include the following information: · The results of any studies that have been conducted to assess the safety of the modification · The results of any studies that have been conducted to assess the efficacy of the modification The evidence that the modification will not affect the quality of the data collected in the clinical trial will need to be provided in a separate document. The evidence should include the following information: · The results of any studies that have been conducted to assess the quality of the data collected in the clinical trial · The results of any studies that have been conducted to assess the impact of the modification on the data collected in the clinical trial The documentation should be submitted to the competent authority in the EU member state where the clinical trial is taking place. | To seek approval for a substantial modification for a clinical trial authorized in the EU, you will need to submit the following documentation: · A letter to the competent authority in the member state where the clinical trial is taking place, explaining the nature of the modification and why it is necessary. · A copy of the clinical trial protocol, as amended. · A copy of the informed consent form, as amended. · A copy of the risk management plan, as amended. · A copy of the quality assurance plan, as amended. · A copy of the financial plan, as amended. · Any other relevant documentation, such as correspondence with the competent authority or the results of any additional studies. The competent authority will review the documentation and decide whether to approve the modification. If the modification is approved, it will be implemented and the clinical trial will continue. If the modification is rejected, the clinical trial will be stopped. |
With no particular reasoning in mind, Draft Answer 1 to all five questions from Bard has been used in the following table.
Table 2
A comparison of answers from Google Bard, Chat GPT, New Bing (Microsoft) and Claude, to five regulatory questions
| Questions | Bard Draft 1 answer | ChatGPT answer | New Bing (Microsoft) answer | Claude (by Anthropic) answer |
|---|---|---|---|---|
| 1) Which marketing authorisation route is appropriate for the authorisation of a CAR-T cell product in the EU? | The appropriate marketing authorisation route for the authorisation of a CAR-T cell product in the EU is the centralised procedure. The centralised procedure is the only procedure that allows for the authorisation of ATMPs, which are a type of medicinal product that is derived from human cells, tissues, or genes. The centralised procedure is a two-stage process. The first stage involves the assessment of the scientific quality, safety, and efficacy of the product by the European Medicines Agency (EMA). The second stage involves the authorisation of the product by the European Commission (EC). The EMA’s assessment of the CAR-T cell product will include a review of the product’s clinical data, manufacturing process, and quality control measures. The EMA will also consider the product’s safety and efficacy in the treatment of patients with cancer. The EC’s authorisation of the CAR-T cell product will be based on the EMA’s assessment. The EC will also consider the product’s potential benefits and risks for patients with cancer. The centralised procedure is a complex and time-consuming process. However, it is the only way to ensure that ATMPs are authorised in the EU in a way that is consistent with the highest standards of quality, safety, and efficacy. | The appropriate marketing authorization route for a CAR-T cell product in the EU would depend on various factors, such as the specific characteristics of the product, its intended use, and the regulatory requirements applicable to the product. In general, the most common routes for marketing authorization in the EU are the centralized procedure, the decentralized procedure, and the national procedure. The centralized procedure is typically used for innovative products and involves the submission of a single application to the European Medicines Agency (EMA), which is evaluated by the Committee for Medicinal Products for Human Use (CHMP) and results in a single marketing authorization that is valid throughout the EU. The decentralized procedure involves submitting applications to multiple national regulatory authorities, with one authority acting as the reference member state (RMS) and coordinating the evaluation process. The result is a series of national marketing authorizations that are valid only in the member states where they have been granted. The national procedure involves submitting an application to the national regulatory authority of each individual member state where the product will be marketed. For CAR-T cell products, the centralized procedure may be the most appropriate route, given the complex nature of these products and the need for a harmonized approach to their assessment and authorization across the EU. However, the final decision on the most appropriate route for a specific CAR-T cell product would depend on the specific characteristics of the product and the regulatory requirements applicable to it. | The European Medicines Agency (EMA) has recommended the first two marketing authorisations for chimeric antigen receptors (CAR) T-cells medicines in the European Union (EU). Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) are advanced therapies for blood cancer1. The EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended granting marketing authorisations for the first two chimeric antigen receptors (CAR) T-cell therapies in the European Union on June 28, 20182. Learn more: 1. ema.europa.eu 2. esmo.org 3.pharmatimes.com 4. ema.europa.eu 5. gilead.com | There are a few potential marketing authorisation routes for CAR-T cell products in the EU: -Centralised procedure: This is the standard route for advanced therapy medicinal products (ATMPs) like CAR-T cells. The marketing authorisation application is submitted to the European Medicines Agency (EMA) and if approved, leads to a marketing authorisation that is valid in all EU member states. -National procedure: This involves submitting applications to individual EU member states. However, this route is generally not used for innovative medicinal products like CAR-T cells. -Conditional marketing authorisation: This can be considered for CAR-T cells that address an unmet medical need, based on less comprehensive clinical data than normally required. The marketing authorisation is subject to certain obligations to provide further confirmatory data. -Accelerated assessment: This can be requested for innovative medicinal products of major public health interest. It provides an accelerated EMA evaluation timeline. So in summary, the centralised procedure is typically the most appropriate route for obtaining EU-wide marketing authorisation for a novel CAR-T cell therapy. The conditional marketing authorisation route may also be considered if the relevant criteria are met. The accelerated assessment can be used in conjunction with the centralised procedure to expedite the review. |
| Q2. Which authorisation route is appropriate for the authorisation of a biological product in the US and how long is the process likely to take? | The appropriate authorization route for a biological product in the US is typically the Biologics License Application (BLA) route. This route is used for the approval of biological products that are intended to treat, prevent, or diagnose diseases. The BLA route involves a comprehensive review process by the US Food and Drug Administration (FDA), which includes preclinical and clinical data, as well as manufacturing and control information. The FDA evaluates the safety, efficacy, and quality of the product before making a decision on its approval. The length of the BLA review process can vary, depending on the complexity of the product and the amount and quality of data submitted by the manufacturer. The FDA aims to complete its review of a BLA within 10 months of receiving the application, although the actual review time can be longer or shorter than this depending on the circumstances. In addition to the BLA route, there are other authorization pathways for biological products in the US, such as the Emergency Use Authorization (EUA) for products intended to address urgent public health needs, and the Biological Product Deviation Reporting (BPDR) pathway for products that deviate from established manufacturing standards. It is worth noting that the BLA route can be a lengthy and expensive process, and may require several rounds of review and additional data submission. It is therefore important for manufacturers to engage with the FDA early in the development process and to carefully plan and manage their regulatory strategy to maximize the chances of success. | The Biologics License Application (BLA) is a request for permission to introduce, or deliver for introduction, a biologic product into interstate commerce in the US1. The BLA is regulated under 21 CFR 600 – 6802. The process of getting a BLA approved can take up to 10 months3. However, it can take longer if there are any issues with the application3. Learn more: 1. fda.gov 2. bing.com 3. fda.gov 4. gov.uk 5. gov.uk | For a biological product like a CAR-T cell therapy, the appropriate regulatory pathway for authorization in the US is via a Biologics License Application (BLA) submitted to the FDA. The BLA process and timeline typically includes: -Preclinical testing and IND submission – Takes 2-3 years to complete preclinical studies and submit an Investigational New Drug (IND) application to start clinical trials. -Clinical trials – Phase 1, 2 and 3 clinical trials are conducted over 5-7 years to demonstrate safety and efficacy. These trials and data are included in the BLA. -BLA submission and review – The BLA is submitted to the FDA for review. The FDA reviews the data and conducts facility inspections over a 10-month standard review period. -Approval – If the FDA deems the product safe, pure and potent, it will approve the BLA and issue a license to market the product in the US. So the entire BLA process from preclinical through approval typically takes 8-12 years for a standard review biological product. The FDA does offer expedited programs like Fast Track, Breakthrough Therapy, Priority Review and Accelerated Approval that can shorten the clinical development and review timeline to 5-7 years total for qualifying products that address an unmet need. | |
| Q3. I wish to market a Class II medical device in the European Union. Please help me with a step by step guide on the authorisation process. | Sure. Here is a step-by-step guide on the authorization process for a Class II medical device in the European Union: 1. Identify the regulatory requirements for your device. The first step is to identify the regulatory requirements that apply to your device. These requirements will vary depending on the type of device, its intended use, and the country in which you plan to market it. 2. Design and manufacture your device. Once you have identified the regulatory requirements, you can begin designing and manufacturing your device. It is important to ensure that your device meets all of the relevant requirements, including those for safety, efficacy, and quality. 3. Prepare the technical documentation. You will need to prepare a number of technical documents for your device, including a user manual, a technical description, and a risk management plan. These documents will need to be submitted to the authorities in the country where you plan to market your device. 4. Submit the application for approval. Once you have prepared the technical documentation, you can submit your application for approval to the authorities in the country where you plan to market your device. The application will be assessed by the authorities, and if it is approved, your device will be granted a CE mark. 5. Market your device. Once your device has been granted a CE mark, you can begin marketing it in the European Union. You will need to comply with the relevant marketing requirements, including those for labeling and advertising. The authorization process for a Class II medical device in the European Union can be a complex and time-consuming one. It is important to consult with a qualified professional to ensure that you understand the requirements and that you are able to comply with them. | Sure, here is a step-by-step guide to the authorization process for marketing a Class II medical device in the European Union (EU): Step 1: Determine the classification of your medical device The first step in the authorization process is to determine the classification of your medical device. Medical devices are classified into four classes (I, IIa, IIb, III) based on their level of risk to patients. Class II devices are those that have a moderate level of risk and are subject to a conformity assessment procedure that involves a notified body. Step 2: Choose a Notified Body Once you have determined the classification of your device, you need to choose a notified body. Notified bodies are independent organizations that are designated by EU member states to assess the conformity of medical devices to the relevant EU legislation. You must choose a notified body that has been designated to assess your type of medical device. Step 3: Prepare a Technical File You need to prepare a technical file that includes all the information required to demonstrate the conformity of your medical device to the relevant EU legislation. The technical file should include information on the design, manufacture, and performance of the device, as well as any clinical data that support its safety and performance. Step 4: Perform a Conformity Assessment Your notified body will perform a conformity assessment on your medical device based on the technical file you have submitted. The assessment will include a review of your technical file, as well as an audit of your quality management system (QMS) if applicable. Step 5: Issue a Declaration of Conformity If your medical device meets the requirements of the relevant EU legislation, your notified body will issue a Declaration of Conformity (DoC). The DoC is a formal statement that confirms that your device complies with the essential requirements of the legislation and can be placed on the market in the EU. Step 6: Affix the CE Mark Once you have received a DoC, you can affix the CE mark to your medical device. The CE mark is a symbol that indicates that your device meets the requirements of the relevant EU legislation and can be placed on the market in the EU. Step 7: Register the Device You need to register your medical device with the national authorities in the EU member state where you intend to place it on the market. The registration requirements vary between member states. Step 8: Maintain Compliance You must maintain compliance with the relevant EU legislation throughout the lifecycle of your medical device. This includes ongoing monitoring and reporting of any adverse events, as well as updating your technical file and quality management system as required. I hope this step-by-step guide helps you in the authorization process for marketing your Class II medical device in the European Union. However, please note that this is only a general guide, and specific requirements and procedures may vary depending on your specific device and the relevant EU legislation. It is always recommended to seek advice from a regulatory expert to ensure that you are following the correct procedures and requirements. | The process of authorising a Class II medical device in the European Union (EU) involves several steps. Here is a brief step-by-step guide12345: Determine if your product is a medical device. Identify relevant legal regulations. Define the regulatory requirements. Comply with the regulatory requirements. Obtain CE marking for your product. The CE marking is a certification mark that indicates conformity with health, safety, and environmental protection standards for products sold within the European Economic Area (EEA). It is mandatory for products covered by one or more of the European product directives2. Learn more: 1. johner-institute.com 2. emergobyul.com 3. advisera.com 4. joharidigital.com 5.health.ec.europa.eu | Here is a step-by-step guide for obtaining marketing authorization for a Class II medical device in the European Union: 1. Identify the proper classification of your device according to the EU Medical Device Regulation (MDR) rules. As a Class II device, it has a moderate risk profile. 2. Prepare your technical documentation including device description, design information, performance testing results, risk analysis, clinical evaluation, and labeling. Your documentation must meet the Essential Requirements in the MDR for safety and performance. 3. Identify a Notified Body to assess your conformity with the requirements. They will audit your Quality System and review your technical documentation. 4. The Notified Body will issue a CE Certificate if you meet the requirements, allowing you to affix the CE mark to your device. This certifies your conformance with the MDR. 5. Register your device in the EUDAMED database. This must include information about the device, certificate, manufacturer, authorized representative if applicable, etc. 6. Prepare a Declaration of Conformity stating that your device meets the MDR requirements. This must be kept on file and provided to authorities upon request. 7. Affix the CE marking to your device to signify it is approved for sale in the EU market. The CE mark must be visible on the device, packaging and instructions for use. 8. Comply with post-market surveillance requirements. This includes reporting serious incidents or recalls and periodically updating your technical documentation. Let me know if you need any clarification on the specific requirements for the technical documentation, clinical evaluation, labeling or other aspects of the process. The key steps are obtaining Notified Body certification and registering in EUDAMED before placing your Class II device on the EU market. |
| Q4. I want to market a generic medicine in Brazil. What are the steps for the authorisation of a generic medicine in Brazil? | The steps for the authorization of a generic medicine in Brazil are as follows: 1. Submit an application to the Ministry of Health (SUS). The application must include information about the drug, its intended use, and its manufacturing process. 2. The SUS will review the application and decide whether to approve the drug. If the drug is approved, it will be listed on the National Formulary (Farmacopeia Nacional). 3. The drug can then be marketed in Brazil. The following are some additional requirements for the authorization of a generic medicine in Brazil: · The drug must be manufactured in accordance with Good Manufacturing Practices (GMP). · The drug must be tested for its safety, efficacy, and quality. · The drug must be labeled in accordance with the Brazilian Pharmacopeia. · The drug must be registered with the National Agency of Sanitary Surveillance (ANVISA). The approval process for a generic medicine in Brazil can take several months. | Sure, here are the general steps for the authorization of a generic medicine in Brazil: Step 1: Submission of an application The first step is to submit an application to the Brazilian Health Regulatory Agency (ANVISA) for the registration of the generic medicine. The application must contain all the necessary documents, such as the product dossier, clinical study reports, and labeling information. Step 2: ANVISA review ANVISA will review the application to ensure that the generic medicine meets the safety, efficacy, and quality requirements of Brazilian regulations. The review process includes an evaluation of the documentation provided by the applicant and may also include site inspections. Step 3: Bioequivalence study For generic medicines, bioequivalence studies are required to demonstrate that the generic product has the same pharmacological and therapeutic properties as the reference product. The bioequivalence study should be conducted in compliance with ANVISA’s guidelines and must be included in the product dossier submitted for review. Step 4: Approval of the registration If the application and bioequivalence study meet ANVISA’s requirements, the agency will issue an approval for the registration of the generic medicine. The approval will be published in the Brazilian Official Gazette. Step 5: Production and sale of the generic medicine Once the registration is approved, the applicant can produce and sell the generic medicine in Brazil. The applicant must comply with ANVISA’s regulations for manufacturing, labeling, and marketing of the product. It is worth noting that the registration process for generic medicines in Brazil can take several months, and the timeline may vary depending on the complexity of the product and the quality of the application. It is important to ensure that the application and bioequivalence study are prepared in compliance with ANVISA’s guidelines to avoid delays or rejection of the application. | According to 1, there are different steps for drug registration in Brazil. The first step is the preparation and submission of registration dossier to ANVISA. The second step is ANVISA GMP inspection of manufacturing sites. The third step is local testing. The fourth step is ANVISA review timelines. The approval times for drug products are 15 to 18 months and 24 months for fixed-dose combinations on average 2. Variations take six to 14 months. A conditional approval pathway was established through regulation. “It may be granted if ANVISA does not initiate the review within the timelines established by law, after the submission” 2. Learn more: 1.globalregulatorypartners.com 2. redica.com 3.informaconnect.com | Here are the main steps for obtaining marketing authorization for a generic medicine in Brazil: 1. Perform pharmaceutical equivalence and bioequivalence studies – These compare your generic version to the reference branded product to demonstrate pharmaceutical equivalence and bioequivalence according to ANVISA’s guidelines. 2. Submit documentation to ANVISA (National Health Surveillance Agency) – This includes study data, proposed labeling, GMP certifications for the manufacturing sites, and a Risk Management Plan. 3. ANVISA performs technical analysis – They evaluate the quality, safety and efficacy of your generic medicine based on the submitted documentation. 4. Satisfactory inspection – ANVISA will inspect the manufacturing sites to confirm GMP compliance. 5. Approval and registration – If approved, ANVISA will grant a product registration that allows your generic medicine to be marketed in Brazil. 6. Monitor and report – You must continually monitor your product’s safety and efficacy, and report any issues arising post-approval to ANVISA. The approval process usually takes about 1 year if all documentation and technical requirements are met. Accelerated 90-day approval is possible for certain priority generic medicines. Let me know if you need any details on the specific documentation requirements. The key steps are demonstrating pharmaceutical equivalence and bioequivalence compared to the reference product in Brazil. |
| Q5. What documentation do I need in order to seek approval for a substantial modification for a clinical trial authorised in the EU? | To seek approval for a substantial modification for a clinical trial authorised in the EU, you will need to submit the following documentation: · A letter to the competent authorities explaining the nature of the modification and why it is necessary. · A statement from the sponsor or principal investigator of the trial explaining the impact of the modification on the trial. · A copy of the original clinical trial authorisation application. · A copy of the original clinical trial protocol. · Any supporting documentation, such as data from the trial or expert opinions. The competent authorities will review the documentation and decide whether to approve the modification. If the modification is approved, the sponsor or principal investigator of the trial will need to update the clinical trial protocol and the clinical trial authorisation application. | In order to seek approval for a substantial modification for a clinical trial authorised in the EU, you will need to submit the following documentation to the relevant regulatory authorities: 1. Cover letter: This should include a summary of the proposed modifications, the reason for the modification, and any other relevant details. 2. Protocol amendments: Any proposed changes to the clinical trial protocol should be clearly outlined and explained in detail. This includes modifications to the study design, objectives, endpoints, eligibility criteria, or statistical analysis plan. 3. Investigator’s brochure: If there are any changes to the Investigator’s brochure as a result of the modification, these should be provided. 4. Informed consent forms: Any changes to the informed consent forms should be included and explained. 5. Safety reporting: Any changes to the safety reporting procedures or adverse event reporting requirements should be clearly outlined. 6. Statistical analysis plan: If the modification will affect the statistical analysis plan, the changes should be described. 7. Clinical study report: If the modification will affect the clinical study report, the changes should be described. 8. Other relevant documentation: Depending on the nature of the modification, additional documentation may be required. It is important to note that the exact documentation requirements may vary depending on the specific regulatory authorities involved and the nature of the modifications being proposed. Therefore, it is advisable to consult with regulatory authorities and/or seek the advice of a regulatory expert to ensure that all necessary documentation is provided. | According to a source, substantial modifications to clinical trials will be required to undergo a similar (although shorter) authorisation process to the original application via the EU portal. If you need to update your details for an ongoing trial in the EU/EEA then the substantial amendment must be submitted to the EU/EEA competent authorities using your usual method. However, there is no need to submit an amendment to MHRA if: · The amendment is not substantial · The amendment is substantial but does not affect the safety of subjects or data integrity · The amendment is substantial and affects safety or data integrity but has already been approved by a competent authority of another Member State Learn more: 1. mesm.com 2. gov.uk 3. ppd.com 4. ema.europa.eu | Here are the key documents required to seek approval for a substantial modification to an already authorized clinical trial in the EU: -Modification request cover letter – This should provide an overview and justification for the proposed changes. -Revised clinical trial application form – An updated application form should be submitted highlighting all proposed modifications in track changes. -Supporting information for changes – This includes revised protocol, updated investigator’s brochure, amended informed consent forms, new safety information, etc. -Competent authority notifications – Copies of any notifications submitted to other EU Member States due to safety measures or urgent actions. -Updated EU trial database information – Revised details to update the clinical trial information in the EudraCT database. -Assessment of foreseeable risks and benefits – An evaluation of any impact of the changes on the risk-benefit assessment of the clinical trial. -Substantial modification submission form – The official submission form declaring that this is a request for a substantial modification to the trial. The changes can only be implemented after approval by the national competent authority and ethics committee. The revised documents should clearly highlight all changes to allow the authorities to conduct the review appropriately. Let me know if you need any clarification on the EU substantial modification submission requirements. |
Updates
| Date | Update(s) |
|---|---|
| 20 Dec 2023 | in the section A brief and recent timeline of chatbots/search engine(s) incorporating chatbot technology, added link confirming roll out of Google Gemini in the UK. |
| 6 Dec 2023 | under the heading A brief and recent timeline of chatbots/search engine(s) incorporating chatbot technology, two more bullet points added to provide information on the launch of Microsoft COpilot and Google Gemini. |
| 13 July 2023 | Information added on a new chatbot called Claude, launched on 11 July 2023 under the following headings: -A brief and recent timeline of chatbots/search engine(s) incorporating chatbot technology -The answers received – Table 2: A comparison of answers from Google Bard, ChatGPT, New Bing (Microsoft) and CLaude 2, to five regulatory questions A new heading About Claude 2 was also added, with relevant information. |
| 11 May 2023 | Section entitled How to access Bard updated with information from announcements at Google’s annual developer conference. |