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We are pleased to attend together with SE Pharma for the upcoming IPL Forum 2021- supply chain management conferences for the healthcare and food-tech industries!
The conference was held on 20.10.2021 at the Avenue Congress Center.
Gsap experts provide professional lectures:
The Annual Healthcare Industry Supply Chain Management Conference-IPL Forum 2021
9:20 – Implementing GDP in Israel – Regulatory Challenges and Key Insights from Audits:
We are happy to share our range of services that we are providing to the digital health community to accelerate and promote startups- from concept stage to product approval.
You can find us also in the digital edition of” digital health” magazine in the “HAARETZ” newspaper: (page 16 )
The Digital Health Revolution is happening all around us and it is both exciting and terrifying. As a member of the Medical Device community, we have a responsibility to our patients, our families, and our shareholders to follow the current best practices. To date, the standards and regulations have not been able to keep pace with the needs of the patients and the industry that satisfies these patient and user needs.
Topics in this newsletter:
Many regulatory agencies including the FDA are talking about forming committees that will codify the “current best practice”, often referred to as GxP or “Good [insert name] Practice”. In January 2020, the FDA released a discussion paper titled US FDA Artificial Intelligence and Machine Learning Discussion Paper, in this paper, the agency proposes a framework for Good Machine Learning Practices, and below is a visual representation of the GMLP workflow.
In addition, to address the critical question of when a continuously learning AI/ML SaMD may require a premarket submission for an algorithm change, this discussion paper proposes a framework for modifications to AI/ML-based SaMD.
To date, the FDA has cleared or approved several AI/ML-based SaMD however these have only included algorithms that are “locked”. The power of many of these AI/ML-based SaMD lies within the ability to continuously learn, where the adaptation or change to the algorithm is realized after the SaMD is distributed for use and has “learned” from real-world experience. Following the distribution, these types of continuously learning and adaptive AI/ML algorithms may provide a different output in comparison to the output initially cleared for a given set of inputs.
To adapt to this, the FDA is proposing a principle of a “predetermined change control plan.” The predetermined change control plan would include the types of anticipated modifications based on the retraining and model updating strategy, and the associated methodology – referred to as the Algorithm Change Protocol (ACP) – to be used to implement those changes in a controlled manner that manages risks to patients, see below for an outline of the main components of an ACP:
The result is a modification to the current guidance for software Deciding When to Submit a 510(k) for a Software Change to an Existing Device | FDA. See below for a proposal to the current guidance
Back in July 2020, the FDA released a Final Guidance Document looking at what happens when the same medical product has both functions covered by the FDA and functions not covered by the FDA. The uniquely unclear guidance titled Multiple Function Device Products: Policy and Considerations look at what happens when a single product with multiple functions have some that are “regulated” and require FDA review, clearance, or approval other functions that do not require FDA involvement (other regulations like FCC or CE standards for electronics, RoHS, WEEE, UL and other TLA’s may be required).
A “function” is a distinct purpose of the product, which could be the intended use or a subset of the intended use of the product. A product with an intended use is to store, transfer, and analyze data has three functions: (1) storage, (2) transfer, and (3) analysis.
While storage & transfer may not be considered requiring regulatory oversight, the addition of analysis and the type of analysis may require FDA involvement. To make things even more complicated, the FDA has issued guidance that indicates while not “fully ok” the FDA does not intend to focus its regulatory oversight on some devices that pose a low risk to patients for more on this ever-growing category see the FDA’s guidance “Policy for Device Software Functions and Mobile Medical Applications” and “General Wellness: Policy for Low-Risk Devices.”
Many CEO’s will attempt to push themselves into this “low-risk category”, as with most things, the agency has discretion, but with software being the leading cause of recalls in the US, the FDA will be waiting to investigate any complaints and will be looking to punish those that have not followed the guidelines to the agencies liking.
So how do we determine if the “non-FDA-regulated” or as the FDA likes to call it the “other function” impacts on the “regulated” feature?
Start with 2 questions, and answer them as if you were working for the FDA:
1) Is there an impact on the safety or effectiveness of the “regulated” feature as a result of the “other function?”
2) Could the impact result in increased risk or have an adverse effect on the performance of the device function-under-review.
I would very much like to say that from the FDA’s perspective the following is true:
However, there are always exceptions and those edge cases are why we sometimes need to speak with a member of the Gsap digital health team Regulatory Review Team to confirm.
Below are a number of relevant examples from the guidance for your consideration, while some may enlighten, others may confuse, but that is the art of regulatory science.
This Newsletter Prepared by:
Yaron Eshel, Q&R project manager
Medical device, Digital Health Discussion Team
How did Gsap experts accelerate Healthcare companies during the COVID-19 pandemic?
Interview with Our CEO Dr. Sigalit Ariely-Portnoy
The Nobel Prize for Chemistry was awarded this year for the invention of Genetic Scissors: a tool for rewriting the code of life.
Emmanuelle Charpentier and Jennifer A. Doudna have discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, the DNA of animals, plants and microorganisms can be changed/edited with extremely high precision.
This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true.
Since the discovery of CRISPR/Cas9, the research of this tool has led to a blooming landscape of pre-clinical and clinical studies in humans.
FDA considers any use of CRISPR/Cas9 gene editing in humans to be gene therapy, thus requiring extensive regulatory efforts in order to bring such products from early concept to clinical application.
Gene therapy products are regulated by the FDA’s Center for Biologics Evaluation and Research (CBER). Clinical studies of gene therapy in humans require the submission of an investigational new drug application (IND) prior to their initiation in the United States, and marketing of a gene therapy product requires submission and approval of a biologics license application (BLA).
At Gsap, our team of Advanced Therapies experts is excited to be at the frontier of this field, with a unique portfolio of process development, preclinical, clinical and regulatory services, assisting our clients to bring gene-therapy products from early POC to realization into clinical use.
If you develop a gene-editing product, do not hesitate to contact us!
This Newsletter Prepared by:
Diana Gershtein, M.Sc., M.B.A.
Cell Therapy Section Manager
Dr. Sigalit Arieli Portnoy, CEO and Founder of Gsap, talks in an exclusive interview about accelerating the development and approval processes of drugs and medical equipment for COVID, including from foreign companies, and reports On the enormous scope of action that accompanies a sense of mission.
What needs to be reviewed?
Where to Start?
What to do?
1. Classification – This will lead to updating the Declaration of Conformity.
2. GSPR – any gaps identified (validations or issues that have not been reviewed in the past) must be closed. *** See table below for an example of the GSPR vs. the Essential requirements
3. PMS (Post Marketing Surveillance), PMCF (Post Marketing Clinical Follow Up) – start the implementation of the plan as soon as possible and write a summary report of all data collected to date.
4. Risk Management – verify that hazards have been identified and that the clinical risks have been mitigated.
5. Any Biocompatibility testing that has not been done and cannot be rationalized should be performed.
6. Make sure your QMS adheres to the requirements of the MDR – the following requirements are unique to the MDR:
Example of the GSPR vs. the Essential requirements
|Wording GSPR (MDR)||Wording Essential Requirements (MDD)||Explanation of the Gap|
|That the residual risk associated with each hazard as well as the overall residual risk is judged acceptable. In selecting the most appropriate solutions, manufacturers shall, in the following order of priority: 4(a)Eliminate or reduce risks as far as possible through safe design and manufacture 4(b) Where appropriate, take adequate protection measures, including alarms if necessary, in relation to risks that cannot be eliminated 4(c) Provide information for safety (warnings/precautions/ contraindications) and, where appropriate, training to users.”||Information needed to use the device safely.” Within the framework of labeling||Management would need to be “information for safe use” with the quote and where this information is supplied and a usability study to support the information for safe use is valid.|
|“11. Infection and microbial contamination 11.2 Where necessary devices shall be designed to facilitate their safe cleaning, disinfection, and/or re-sterilization”||13. Information Supplied by the Manufacturer h) if the device is reusable, information on the appropriate processes to allow reuse, including cleaning, disinfection, packaging and, where appropriate, the method of sterilization of the device to be reserialized, and any restriction on the number of reuses.”||The MDR has defined a particular consideration for reusable devices, meaning a clearly stated requirement that must be validated. The MDD does not clearly state a validation requirement for reusable devices, only the requirement to supply the information to ensure safety.|
|“14.1 If the device is intended for use in combination with other devices or equipment the whole combination, including the connection system shall be safe and shall not impair the specified performance of the devices. Any restrictions on use applying to such combinations shall be indicated on the label and/or in the instructions for use. Connections which the user has to handle, such as fluid, gas transfer, electrical or mechanical coupling, shall be designed and constructed in such a way as to minimize all possible risks, such as misconnection.”||“9.1 If the device is intended for use in combination with other devices or equipment, the whole combination, including the connection system must be safe and must not impair the specified performance of the devices. Any restrictions on use must be indicated on the label or in the instruction for use.”||The MDR has added an additional requirement regarding connections that are user dependent for combination devices.|
|“15. Devices with a diagnostic or measuring function”||10. Devices with a measuring function”||The inclusion of diagnostic devices within the requirements of a measuring function is new to the MDR, emphasizing the need for validation of measuring functions in diagnostic devices.|
|“17.2 For devices that incorporate software or for software that are devices in themselves, the software shall be developed and manufactured in accordance with the state of the art taking into account the principles of development life cycle, risk management, including information security, verification and validation.”||“12.1a For devices which incorporate software or which are medical Software in themselves, the software must be validated according to state of the art taking into account the principles of development lifecycle, risk management, validation and verification.”||The MDR has set design and development requirements for software. This means that the D&D software process must be managed by means of documented inputs, outputs, risk assessments, verifications and validations|
Gsap will be happy to support you in getting ready for the MDR storm!
This Newsletter Prepared by:
Ossie Milanov, BA
Quality & Regulatory Project Manager
Learn how to implement EU GMP standards in medical cannabis. The EU GMP presents the requirements for facility, equipment, documentation, and process control for the production of herbal products.