Frequently asked questions and answers
The combination of these two different worlds, that of traditional medicine and that of technology and digital health, will enable better quality, customized and more efficient patient care, with improved accessibility and costs.
HIPAA is the acronym for the US Health Insurance Portability and Accountability Act.of 1996. HIPAA defines the requirements for protecting sensitive data and patient information. This law applies to medical and digital healthcare companies dealing with patients’ medical and/or health information. Such companies have a duty to protect medical/health information, and to take physical, technological and network security measures, as well as monitor the data, to ensure that this information is not leaked and is maintained in its entirety and with high reliability.
Any body, company or other entity that provides treatment, information, data or personal information, whether directly or as part of working with such an entity, as a subcontractor or as a business partner, is also required to work in compliance with HIPAA requirements.
GDPR is the acronym for the EU General Data Protection Regulation which came into force in 2018. It deals with confidentiality of information and privacy.
The GDPR contains mandatory provisions to be applied by entities which, as part of their activities, collect personal information and/or process information from the internet.
HIPAA was created to protect sensitive data with two main purposes – to provide continuous health insurance coverage for workers who lose or change jobs, and to reduce the burden and health care costs provided to the insured, through standardization of how electronic means are used, medical information transmission and transmission of administrative and financial transactions, while improving the availability and accessibility of nursing and health insurance services to patients.
The privacy rules and confidentiality of medical information contained in HIPAA apply to any health information being held or transferred that allows for the individual identification of a person. Health information can be stored in any form, including digitally.
The digital health field is an innovative technological field that connects the high-tech world to the healthcare world.
Digital health is also called digital technology, e-Health or health-tech.
The digital health sector uses information, communication and technology (ICT) for the benefit of public health.
CE marking is a European system based on compliance of medical devices to regulatory requirements for maintenance of health, safety, effectiveness and performance, quality and the environment.
The CE mark on a medical device allows the medical device to be sold on the European market and in other markets that have adopted compliance to the EU requirements. In most cases, a CE mark application will be submitted by the legal manufacturer of the medical device.
ISO 13485 is an international standard relevant to quality management systems for medical devices. The latest version was published in 2016 and reconfirmed in 2020.
This standard specifies the requirements for quality management systems for medical device manufacturers to provide safe products for use and in accordance with the regulatory requirements of international bodies. It includes requirements for documentation, personnel qualification, risk management, change control and validation, among others, to ensure that medical devices are safe and effective, and that quality and compliance are maintained according to the applicable regulatory requirements.
The standard is suitable for medical equipment organizations regardless of their size or specific type of medical device or equipment.
To the article ISO 13485 in the medical industry
A harmonized, global definition of “medical device” (MD) does not yet exist.
US law and regulations define a medical device as “instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent…intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or Intended to affect the structure or any function of the body…and which does not achieve its primary intended purposes through chemical action …and which is not dependent upon being metabolized for the achievement of its primary intended purposes…”
EU law and regulations define a medical device as any “instrument, apparatus, appliance, software, material or other article… for the purpose of diagnosis, prevention, monitoring, treatment or alleviation of disease,…injury or handicap, investigation, replacement or modification of the anatomy or of a physiological process, control of conception, and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means…”
The different heath authorities have rules for determining the risk class of a medical device, based on its potential for harm if misused, design complexity, and use characteristics. Risk classifications generally range from Class I through Class III or IV, where Class I is the lowest level of risk. Risk classification has an impact on the regulatory pathway to be followed for product registration applications and may also influence the quantity and quality of documentation required to support the applications in each target market.
Lab-grown meat is made from stem cells, taken from farm animals such as live cows, which are transferred for propagation and then grown into muscle and tissue strips.
Clean meat is meat-free; that is, “meat” created from vegetable protein substitutes such as pea or bean protein.
On August 5, 2013, the first hamburger-sized, lab-grown food patty was eaten in a laboratory in London.
Scientists from the Netherlands used stem cells taken from a cow to subsequently grow them into muscle strips that were eaten as the first lab-grown hamburger.
The first lab-grown hamburger, created in 2013, then cost $325,000 per unit. In 2015, the unit cost plummeted to $11. As more companies enter this field, coupled with the use of advanced industrial technologies, the price will decrease and is expected to eventually be significantly less than that of a “regular” burger produced from animal meat.
Food products are consumed by humans and therefore non-quality or substandard food products can endanger human life.
With a quality system, the number of quality and safety defects, and risks from food products, will decrease accordingly.
Creating 150 grams of beef requires 660 liters of water, most of which is consumed by the cattle. To produce a vegetable-substitute “meatball” the same weight as a beef-based meatball, only 58 liters of water is required.
The more the food industry embraces technology, machinery and software, and adheres to standards of proper manufacturing conditions, the more efficient, profitable and high quality it will become, will enable companies to be competitive vis-à-vis the traditional food industry, and will boost consumer confidence.
Food tech is a combination of the words “food” and “technology”. Food tech companies combine the production of food products with the use of advanced technologies. Integrating advanced technology into the field of food production enables promotion, streamlining and supply of healthier food products, and reduction of the impact on the environment.
Data integrity is a cornerstone of the quality management system in pharma and medical device companies.
It is a company’s ability to make absolutely certain that the data used by the company are complete, consistent, reliable and accurate throughout their life cycle.
The Department of Pharmacy at the Ministry of Health is the body responsible for prescribing drugs, importing drugs, pharmacist control, providing pharmacological information, approval and supervision of human clinical trials, research on the effects of drugs on humans, herbal medicine approval, homeopathic products and cosmetics. Medicines used in Israel must be registered in the Medicines Register. A drug will only be prescribed after its safety, efficacy and quality have been demonstrated.
Due to the health danger of taking counterfeit medicines, be aware of the following warning signs:
- The drug is not listed in the Ministry of Health-approved drug repository
- The drug or product packaging lacks Hebrew and English consumer leaflets
- Essential details are missing from the packaging, such as manufacturer name, validity, batch number
- Product packaging has spelling errors
- Tamper evidence mechanism does not exist or is torn
- The drug/preparation was not purchased at a licensed pharmacy but via the internet, in a neighborhood grocery store or from an unauthorized person
- There are suspicious signs on the product packaging, such as foreign language captions in Chinese, Thai, Indian or other languages
Registration of medicines is carried out in the register of medicinal products in the Department of Pharmacy of the Ministry of Health. According to the Pharmacy Regulations, a drug will only be registered in the Register of Medicines after its safety, efficacy and quality have been proven.
An active ingredient is a chemical that is usually a small molecule produced in chemical synthesis processes, while a biological drug is based on components and processes derived from animal or fermentation and/or tumor microorganisms/cells.
1. Molecular weight: Biological drugs, such as peptides and proteins, are huge molecules compared to chemical drug molecule sizes.
2. 3D Structure: Proteins, unlike chemical drugs, have a 3D structure that affects their function.
3. Manufacturing process: The production process of a chemical drug is synthesized for specific molecules in a known process. The biological drug production process, on the other hand, is much more complex and may result in high variability of the final product.
The drug development process is a lengthy process, and one of the longest, most expensive and significant stages is the clinical phase, whose purpose is to show that the drug is safe to use and effective. The first phase of clinical studies (Phase 1) is the first human study, and comes after laboratory and animal studies (preclinical). The second phase (Phase 2) is the phase in which the drug’s effectiveness in humans begins to be tested. Phase 3 is the last step before submitting the product for regulatory approval. Phase 3 is the most valuable and significant stage because testings is being done on a larger population and in multiple locations. Phase 4 (post-market) studies deal with collection of clinical data after marketing the drug, in order to complete and process information about the drug’s safety and efficacy.
In accordance with the Pharmacy Regulations (proper production conditions), each batch and shipment of medical product imported into Israel, prior to release and marketing in Israel, must obtain authorization from a responsible pharmacist or Qualified Person (QP). The role of QP pharmacist is to ensure the quality of the preparations and to ensure that they are manufactured in proper production conditions according to current good manufacturing practice (GMP), shipped and stored in accordance with proper and current good storage practice (GSP) and under conditions of current good distribution practice (GDP).
Pharmaceutical crime is defined as the complex of offenses related to drugs, raw materials to produce drugs, and cosmetics. The introduction of counterfeit pharmaceutical or cosmetic products into the distribution and marketing system endangers public health, and many efforts are being made to minimize such phenomena.
Counterfeit medicines are medicines and medicinal products supplied by manufacturers which are unregistered and unapproved by the Ministry of Health.
Good manufacturing conditions, or good maufacturing practice (GMP), in the pharma industry are designed to ensure that the pharmaceutical products are manufactured in accordance with the requirements of the factory quality system. Implementation of GMP will minimize risks associated with production processes. GMP covers all aspects of production, ranging from vendor or suppler certification, raw material acceptance and storage, cleanliness and production facility infrastructure and support systems, production equipment, employee conduct and training, and cleaning and validation processes.
In Israel, Ministry of Health audit and enforcement procedures are carried out to evaluate and enforce GMP requirements.
In the US, GMP requirements are described and enforced for drugs and medicines under 21 CFR parts 210 and 211, and for medical devices under 21 CRF 800.
In Europe, GMP requirements for drugs and medicinal products are described and enforced as part of Directive 2003/94/EC, and for medical devices under the Medical Device Directives and the 2017 Medical Device Regulations.
A risk management plan (RMP) is an important tool used to detect, characterize, assess and minimize risks associated with the use of a medical device.
A risk management program includes three main steps:
- Characterization of the medical device safety profile, which includes both known safety information and what is still unknown about the product.
- Planning pharmacovigilance activities designed to characterize known risks, identify new risks and expand knowledge of the product safety profile.
- Planning and implementing a risk mitigation plan, as well as assessing the effectiveness of these activities.
A pharmaceutical quality system is designed to ensure the safety and quality of the product and minimize risk to the consumer’s health. There are many ways in which regulatory requirements and the responsibility of the organization can most effectively be implemented, including the use of audit documents, training and certifications, validation investigations, corrective and preventative actions (CAPA), and more.
Validation is well-documented proof with a high level of confidence that a system, equipment, software, test method, drug manufacturing, sterilization or cleaning process will be consistently and robustly delivered, providing a result that meets the requirements of predefined specifications in approved validation protocols.
The purpose of the validation process is to ensure that a pharmaceutical product meets all quality, efficacy and safety requirements that have been set for the final product, during all stages of production and in different batches of the same product, while adhering to a controlled and documented process.
Validation processes includes a validation plan (VP), risk assessment, system design or design qualification (DQ), installation qualification (IQ), operational qualification (OQ), system performance qualification (PQ), production process qualification (PPQ), and validation of cleaning processes, software and control systems and repeat/periodic validation.
A sterile product is a product free of live microorganisms and will usually undergo terminal sterilization in its final packaging (heat sterilization, steam, gamma radiation, ethylene oxide, etc.).
An aseptic product is a product that cannot be terminally sterilized for various reasons, such as product stability, heat sensitivity or radiation sensitivity.
As a result, such a product should undergo preparation, filling, and sometimes packaging, under conditions that will maintain its sterility.
Rule 29c is part of the State of Israel Pharmacy Regulations (Preparations) 1986, and is a specific, individual permit to import a drug that is not registered in the State of Israel for the purpose of using it as part of medical treatment or, alternatively, for permission to use a registered drug in a previously unregistered form.
The Pharmacists Ordinance, 1981, defines “drugstore” as “a business conducted by a responsible pharmacist approved by the Director in this matter and used for the storage, wholesale sale or wholesale distribution of drugs or raw materials for the manufacture of drugs”.
Good manufacturing practice (GMP) requirements in the medical industry are designed to ensure that medical devices and medical equipment (abbreviated as “AMAR” in Hebrew) are manufactured in accordance with quality system management principles, and include all aspects of production, including starting and raw materials, production facilities, employee training qualification and cleaning procedures.
In Israel, the Ministry of Health perform audits and conducts enforcement procedures.
In the US, GMP requirements for drugs and finished pharmaceuticals are enforced under 21 CFR parts 210-211, and quality system requirements for medical devices are covered by 21 CFR 800, also known as the Quality System Regulations (QSR).
In the EU, GMP requirements for drugs and medicinal products are enforced as part of Directive 93/42/EEC, and quality system requirement for medical devices are described in the Medical Device Directives and the 2017 Medical Device Regulations.
A medical device/accessory may be marketed only after having been approved as a medical device and registered in the Medical Devices Department of the Ministry of Health in accordance with the conditions of registration.
The purpose of medical device registration is to ensure the safety and effectiveness of medical devices and their accessories that are used in the health systems in the State of Israel. Medical device/accessory certification is for finished products only.
Importation of medical equipment into Israel through customs requires Ministry of Health approval via a free import order. There are two types of certification issued by the Ministry of Health Medical Device and Medical Equipment Division: The first type is periodic import clearance, which is divided into two groups: medical equipment registered in the medical device register, and unregistered products. The second type is a one-time import permit to bring medical supplies into Israel. This approval does not allow the importer to bring additional shipments of this product to Israel, nor does it mean that the products approved for import are registered in the medical equipment register.
The Medical Device and Medical Equipment Division of the Israel Ministry of Health may issue a “free sale permit” or “certificate of free sale” (CFS or FSC) to exporters, which facilitates approval by overseas health authorities of medical products and equipment that are registered and authorized for marketing and sale in Israel.
Fake or counterfeit medical equipment is equipment that has not been approved by the Ministry of Health and is branded by its manufacturer as original equipment that is recognized in the market, but actually is not produced by the original manufacturer.
The development of medical equipment can be done in two ways: The first is the fast track route, which refers to the process of developing medical equipment that is already on the market, i.e., upgrading existing medical equipment. The second way is to develop new medical equipment from beginning to end. As with the development of any new product, even within the framework of medical device development, the process begins with the development of a prototype. Subsequently, various experiments and tests are performed to check the safety of the various devices and to obtain preliminary approval from the Ministry of Health to proceed. After this step, clinical research should be performed to evaluate the safety and efficacy of the medical devices in a representative group of patients. Upon completion of the clinical study and analysis of its results, applications may be made to obtain required regulatory approvals and, upon approval, the device marketing process may begin.
A quality system in the medical field is designed to ensure the safety, efficacy and quality of a consumer medical product and has the aim of protecting public and patient health. Quality managers in development and/or at manufacturing companies must have the appropriate education and experience, while being familiar with specific, relevant standards and regulations.
To the article Quality Assurance Systems and CAPA
Validation is documented proof which provides a high degree of assurance that a system, process, equipment, manufacturing process, and/or medical device software will be properly installed, operated and processed, is robust, consistent, and delivers a result that meets the predefined qualifications and quality requirements. The purpose of validation is to ensure that the medical equipment meets all quality, efficacy and safety requirements defined for the final product, both in worst-case situations and during all stages of production, while adhering to a controlled and documented process.
HACCP is the acronym for Hazard Analysis Critical Control Point.
HACCP is a systematic, preventative approach to help ensure food safety and prevent risks to food products and dietary supplements. The HACCP system includes documentation and control mechanisms designed to identify and determine potential hazards in the production of food products and industrial food/nutritional supplements. Although HACCP is very important, it covers only part of food GMP requirements, and is currently considered inadequate on its own.
HACCP is based on a program created by NASA, Pillsbury and the US Army Laboratories in the 1960s to deal with safety and control of risks involved in manufacturing food products and industrial supplements, particularly for safe food to be used in space expeditions.
Good manufacturing practice (GMP) in the food and dietary/nutritional supplements industry is designed to ensure that food products and dietary/nutritional supplements are manufactured in accordance with quality system principles. Proper implementation of GMP will minimize risks involved in the production process and allow the manufacturer to identify, neutralize and prevent them prior to final product testing. GMP covers all aspects of production, supplier certification, raw material acceptance, production facilities and production operations, employee training, cleaning procedures and validation.
In the Israeli food industry, procedures are audited and enforced by the Ministry of Health monitoring unit.
In the US, GMP is enforced under 21 CFR part 101, and in Europe as part of Directive 2002/46/EC.
Israeli manufacturers of food and/or dietary supplements that meet the threshold conditions below:
- Holders of valid certificates attesting to the ISO 9001 quality system standard issued by Control Institutes recognized by the Ministry of Health.
- Owners of a valid business license provided by the local authority.
- Holders of a valid manufacturer’s license issued by the provincial health bureau within which the plant is located.
- There is a list of food products manufactured at the factory.
- The plant employs a food engineer/technologist at the plant.
- There is a good and valid health report.
- Application: The applicant must complete a permit application form for marking food products with the appropriate GMP conditions symbol, provide the required documents and submit them to the unit for adequate production conditions in the National Food Service.
- Examination of the application: Upon receipt of the application, and assuming that the documents are valid, the application will be referred for the Health Bureau’s opinion. The decision to audit or inspect the factory is at the discretion of the district engineer.
- Document completion: If, after reviewing the documents, there are any missing documents, a document completion request will be sent to the factory. Once the documents have been submitted completed, the process will continue.
- Issue permit: For food establishments and nutritional supplements that meet the requirements, a permit will be issued to mark the food products with the GMP symbol.
Nutritional supplements are products that are consumed in addition to regular foods. They are designed to supplement dietary needs and provide the body with nutrients that may be essential for its function, and which are either nonexistent or low in food, for example, vitamins, minerals, fatty acids, and amino acids.
Food additives, in contrast, are ingredients added to industrial foods for purposes of production, processing, preparation, handling, packaging, transport or storage of food, including improving its appearance, smell, texture, flavor or color. Examples of food additives include food colors, stabilizers and preservatives.
The National Food Service is the body of the Ministry of Health that deals with the registration of food and nutritional supplements. It has the authority to carefully review the safety and quality of each product. Only after meeting the conditions and guidelines for applying for registration and importing nutritional supplements, while implementing the high standards of the Ministry of Health, will approval for marketing of the nutritional/food supplement in Israel be granted.
Performing a Scientific and Systematic Risk Survey includes listing manufacturing processes in which potential hazards exist while describing the corrective and preventive actions for these risks.
- Perform hazard analysis.
- Find and identify the critical control points (CCP).
- Set boundaries (establish critical limits) for the critical control points, and determine the range beyond which the product will be considered unsafe.
- Determine and create monitoring measures for the control points and define them in work procedures and production instructions based on the limits defined at the identified critical control points.
- Decide on corrective actions to be taken if deviations from the critical limits occur.
- Verify and record (document) all actions, taken at all stages, of the process and controls.
- Write, approve and provide guidance on procedures to verify that the various systems and processes are working as required and are effective.
The National Food Service of the Ministry of Health monitors food and should ensure it has no biological or chemical contamination.
The Ministry of Agriculture veterinary services set standards and monitor all animal breeding conditions in the animal food industry.
A quality system in the food and dietary/nutritional supplements industry should ensure the quality of the food or dietary supplement to protect the health of the consumer. Quality and safety of food products and dietary supplements are important, and therefore it is the responsibility of quality managers to inform and involve the senior management of the company in any situation where a safe and high quality product which meets all release specifications cannot be reached.
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Validation is documented, proven evidence which provides a high level of assurance that the production process of food products and/or nutritional supplements will consistently produce products that meet predefined qualifications and quality features. The purpose of the validation process is to ensure that the food products and/or nutritional supplements meet all the quality, efficacy and safety requirements set for the final product, during all stages of production and in different batches of the same product, while adhering to a controlled and documented process.
Cosmetic products that do not contain color additives, or other materials that require approval for use, do not require FDA approval prior to marketing.
In contrast, cosmetic products that belong to the over-the-counter (OTC) category require listing of the drug product(s) and drug substance(s)/active ingredient(s) that are added to the cosmetic products. Cosmetic manufacturers and packaging companies (outside the US) who want to export their products to the US are committed to registering their foreign establishments, factories and manufacturing facilities.
Since the 1980s, the field of medical cosmetics has developed. Medical cosmetics can cure damage such as skin aging, sagging and scars, and many other aesthetic problems. Medical cosmetics, also known as paramedical cosmetics, combine medical and pharmaceutical substances (such as hyaluronic acid and sunscreens) in quantities that exceed the concentrations permitted in conventional cosmetics.
The process for authorization to market, import and manufacture cosmetics in Israel is designed to protect public health and constitutes a regulatory barrier to marketing of non-quality products and/or unsafe use. You must first apply for a general cosmetic license from the provincial (regional) pharmacy according to the location of the cosmetics warehouse. Only after obtaining that license can “Licensing Procedure and Registration of Cosmetics” forms and documents be submitted, according to the type of cosmetic. A license is granted for a period of five years.
Over-the-counter (OTC) medicines may be purchased without a prescription. In recent years, the selection of drugs that come under the category of OTC is growing. Manufacturers of cosmetics belonging to the OTC category are required to register the drug product(s) or drug substance(s)/active ingredient(s) that are added to the cosmetic products.
Organic cosmetic products contain mainly plant ingredients, are not tested on animals, and are packaged in glass containers and recycled cardboard.
They do not contain any harmful ingredients such as preservatives or petroleum products, and do not contain animal-derived ingredients.
Natural cosmetics are based on ingredients which include vegetable oils, essential oils, clay, herbs, vitamins, minerals, and natural waxes and butters of various kinds. The raw materials on which natural cosmetics, such as ointments, masks and more, are based must be prepared and used in ways that can maximize their benefits.
Cosmetic validation is documented evidence which provides a high degree of assurance that equipment, systems, process, testing methods, manufacturing processes, cleaning methods and software for cosmetics will consistently produce a result that meets predefined specifications and quality metrics. The purpose of validation is to ensure that the cosmetic products meet all the quality, efficacy and safety requirements that have been set for the final product, during all stages of production, and in different batches of the same product, while adhering to a controlled and documented process.
The purpose of a cosmetic quality system is to ensure the quality of the product and to protect the health of the consumer. ISO 22716 is an international standard for cosmetics GMP and supplements the requirements of the European Cosmetics Directive and Regulation. This standard is a measure of an enterprise’s ability to produce and deliver high-quality, safe cosmetics for consumer use.
To the article Quality Assurance Systems and CAPA
It is the responsibility of the Ministry of Health to ascertain the intended purpose of a cosmetic product and if it fulfills that purpose as stated on the packaging. In addition, the Ministry of Health must ensure that the ingredients contained in cosmetics are worthy of use, cannot cause harm to the user, and are not known to be substances that are dangerous to the public. However, sometimes people develop irritations, sensitivities or allergies to substances found in cosmetics, such as lead, aluminum, parabens (preservatives) and more.
The purpose of proper manufacturing conditions, or good manufacturing practice (GMP), in the cosmetics industry is to ensure that cosmetics are manufactured in accordance with quality system requirements. GMP, among other things, deals with minimizing risks involved in the production process and covers all aspects of production, from starting and raw materials, vendor and supplier certification, production facilities, production processes, employee conduct and training, cleaning procedures, equipment and process validation and final product testing.
In Israel, the GMP cosmetic review procedure is carried out by the Ministry of Health.
In the US, GMP is codified in 21 CFR part 701, and in Europe as part of Directive 76/768/EEC.
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