A Good Paper on Comparison of Approaches to Regulation of Different Countries

The paper titled "Ensuring Medical Device Effectiveness and Safety: A Cross-National Comparison of Approaches to Regulation" by Kramer et al. provided a systematic and in-depth comparisons of regulation of the US, EU, Japan, and China. The comparisons are based on six key features of device regulation:

1. Regulatory Authority
2. Pre-Market Evaluation
3. Adverse Event Reporting
4. Quality System Regulation
5. Post-Approval Studies
6. Post-Market Regulation Actions

Emerging strategies of post-approval surveillance were also discussed such as unique device identifier (UDI) system.

New Final Guidance of 510(K) by the FDA

On July 28, 2014, FDA issued the newest "Final Guidance of The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]" after revised draft guidance issued in Dec 28, 2011. The final guidance gives more examples than the 2011 draft guidance to better illustrate the decision-making process during a 510(k) review. It also includes a sample 510(k) summary which is more much detailed than most 510(k) summary documents found on the FDA website. Special and Abbreviated 510(k) sections were removed. FDA intends to finalize these sections separately. Although FDA states that this guidance is "not intended to implement significant policy changes," the guidance clarifies and addresses many key issues in the 510(k) program.

The US FDA requires that the manufacturers demonstrate safety and efficacy of the product, unless the devicecan be shown to be substantially equivalent (SE) to a predicate product that is legally marketed in the United States (via the 510(k)). For most new products, those without predicates, and certain high-risk products (typically Class III), a PMA is required. Certain Class I and exempted Class II medical devices are permitted to be marketed without the FDA’s prior authorization, although manufacturing(Quality System Regulations) and/or documentation controls may still apply. Some important points are summaried below:

Predicate Device

Predicate device is a the legally marketed device a legally marketed device, which is a device that (i) was legally marketed prior to May 28, 1976 (preamendments device) and for which a PMA is not required; or (ii) has been reclassified from Class III to Class II or I; or (iii) has been found SE through the 510(k) process. Although a manufacturer can identify multiple predicate devices, FDA recommends identifying a primary predicate in the submission.

Study Clinical Trials of Medical Device by FDA Bioresearch Monitoring (“BIMO”) program

FDA Bioresearch Monitoring (“BIMO”) program are to protect the rights, safety, and welfare of human research subjects and to assure the quality, reliability, and integrity of data collected. It is a good source to learn good clinical practice, responsibilities of sponsors, clinical investigators, contract research organizations, monitors, institutional review boards in clinical trials of medical devices and preparing for FDA inspections. 

FDA Launches Online National Medical Device Curriculum

FDA has launched a new learning tool for academic institutions and science and technology innovators called the National Medical Device Curriculum, to advance their understanding of FDA's medical device regulatory processes. The curriculum offers students FDA-endorsed knowledge about navigating the regulatory process, including how to design, test, and clinically evaluate devices; identify the root causes of adverse events and device malfunctions; and develop iterative device designs. The curriculum includes a series of four fictional case studies based on real-world medical device scenarios in a format similar to Harvard Business School Case Studies. 

By understanding FDA's regulatory process, innovators can accelerate the delivery of innovative medical products to patients.

FDA guidance to nanotechnology products

Nanotechnology is an emerging area which can create many new materials for medical devices, medicine, electronics and energy industries. On the other hand, more and more concerns about nanotechnology are raised about the toxicity and environmental impact of nanomaterials. 

Today, FDA issues three final guidances and one draft guidance to support the responsible development of nanotechnology products (the link).

In guidances, FDA has not established regulatory definitions of “nanotechnology,” “nanomaterial,” “nanoscale,” or other related terms. It aims to help industry when they should consider potential implications for regulatory status, safety, effectiveness, or public health impact that may arise with the application of nanotechnology in FDA-regulated products. FDA advises industry to consult with FDA early in the development process to facilitate a mutual understanding of the specific scientific and regulatory issues for their nanotechnology products.

In "Guidance for Industry Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology", FDA identifies two Points to Consider that should be used to evaluate whether FDA-regulated products involve the application of nanotechnology.

1. Whether a material or end product is engineered to have at least one external dimension, or an internal or surface structure, in the nanoscale range (approximately 1 nm to 100 nm);
2. Whether a material or end product is engineered to exhibit properties or phenomena, including physical or chemical properties or biological effects, that are attributable to its dimension(s), even if these dimensions fall outside the nanoscale range, up to one micrometer (1,000 nm).

Japan Visting

This week we have a chance to visit the factory of a well-known Japan chemical & materials company. A ond-day visiting in Tokyo and some photos nearby the hotel:

Suica

Different Needs that Guide the Design and Development of Medical Devices

The customers of medical devices are involved patient, doctor, nurse and purchasing agent who has different preference. The book Combination Products: Regulatory Challenges and Successful Product Development" (page 39) gives a summary of typical voices of customers for using combination products, which is a good reference for medical devices as well:

• Patient: Needs to be safe, should be covered by insurance, result in minimum pain with no side effects, etc. 

• Doctor: Needs to be easy to use/intuitive, have less morbidity/mortality and excellent and proven clinical benefits. Easy to place during procedure, excellent support from sales rep, overwhelming clinical superiority.

• Nurse: Easy to use, store, unwrap, dispose, clean and sterilize; minimal nurse supervision of the patient. clear instructions with plenty of pictures, ergonomic and intuitive.

• Purchasing agent: Cost-effective, reimbursable, excellent product-related service, clear codes that can easily be entered in system.

新修订的中国《医疗器械监督管理条例》Revised Version of “The Regulations for the Supervision and Administration of Medical Devices”

昨天中国发布了修订的《医疗器械监督管理条例》。条例分为8章80条（相比2000年的条例为4章48条）。

和2000年4月施行的条例（以下称旧条例）比较，一些个人感觉重要的修改总结如下： 

1. 总则

新条例第一条去掉了“为了加强对医疗器械的监督管理”。可能是为了突出“为了保证医疗器械的安全、有效”的医疗器械监督管理原则和目的。

新条例将医疗器械的定义放在了附则部分。将旧条例中医疗器械所指的“单独或者组合使用于人体的仪器、设备、器具、材料或者其他物品”改为“直接或者间接用于人体的仪器、设备、器具、体外诊断试剂及校准物、材料以及其他类似或者相关的物品”。明确了间接用于人体的体外诊断（in vitro diagnostics）试剂和医疗器械等作为医疗器械的一部分。医疗器械使用目的中相应加入了“通过对来自人体的样本进行检查，为医疗或者诊断目的提供信息”。

新条例增加了国务院和县级以上地方人民政府有关部门在各自的职责范围内负责与医疗器械有关的监督管理工作的内容。明确了有关部门如工商、卫生、质监、海关、公安等参与到医疗器械的生产、经营和使用的监督管理工作。

Imagemagick

Install Imagemagick, a powerful command line image tool, with Homebrew in my iMac.
1. install XQuartz first, download file from http://xquartz.macosforge.org
2. brew install imagemagick --with-x11
3. convert logo: logo.gif; display logo.gif

Pass FDA 's Tests

FDA websites, specially Center for Devices and Radiological Health (CDRH) is certain to the first study source for medical device industry and research. After study carefully of 21 CFR part medical device, cosmetics and drug, CDRH learn materials, I have passed serveral important tests.

Factors to consider before a innovative idea to real market success in medical device.

It is easy to find ideas that appear to have promising business potential, but ultimately very few have the potential for real market success. Many factors need considered before we determine if a idea will have real impact. Serveral considerations which may increase the chances of success in medical device development are listed:

1. A new medical device must solve a real clinical problem or substantially lowers the cost of treatment and decreases mortality or serious morbidity relative to the standard of care.
2. Understand how large the potential market (size and growth) for the new product is, and how ready the clinical users will be to adopt it.
3. Learn intellectual property. Obtain protection of own patent and avoid infrigement of other's patents.
4. Conduct clinical trials as early as possible if necessary.
5. Plan the regulatory strategy early. The better you understand the regulatory framework, the greater your chance of success.
6. Understand the reimbursement landscape.
   
   

Online Medical Devices Registration: Licensale.com

Medical device industry is highly regulated. Regulatory affairs of medical devices are complex and time-consuming procedures. Just find a unique, cloud-based, global regulatory system LICENSALE.COM from Arazy Group that simplifies international regulatory affairs.

顾客满意-ISO 9001与ISO 13485的区别

对比ISO 9001质量管理体系，ISO 13485医疗器械质量管理体系标准里没有“顾客满意”的要求，代之以“满足顾客要求”。标准中解释：“顾客满意”和“顾客感知度”在法规中作为要求来实施太过于主观。以“满足顾客要求”作为对质量管理体系绩效的测量，与ISO 13485反应当前监管法规和促进世界医疗器械监管法规协调的目标相一致。

所谓“良药苦口”，医疗器械在保证安全、有效的前提下，有时不得不对产品使用的舒适性作出折中甚至舍弃一致降低了顾客满意度。同时，一味地追求顾客满意也会对医疗器械产品的研发、制造产生不利的影响。

虽然现在的标准中未要求＂顾客满意＂，但个人认为在保证医疗器械产品安全、有效的前提下，顾客的使用舒适性应在产品研发阶段给予充分考虑。同时，对顾客使用舒适性的反馈信息的深入分析结果是下一步产品开发和改进的重要的参考。通过考虑结和最新科技成果、仔细分析和评估风险/受益及应用人因工程学原理等，提供产品的使用舒适性，才能更好的开发出顾客满意度高的、具有强大市场竞争力的产品。

Standards of Antimicrobial and Anti-biofilm Assay

In the academic research, different labs and groups have their protocols for evaluating antimicrobial/antibiofilm properties of modified surfaces/materials and antimicrobial agents. In the industrial R&D, adopting international standards is more reliable and trusty. Below is the summary of main standards for antimicrobial/antibiofilm assay used in medical device industry:

• Antimicrobial Effectiveness Tests in United States Pharmacopeia (USP) Chapter 51.
• Zone of Inhibition, MIC, MBC:  refer to standards from the Clinical and Laboratory Standards Institute (CLSI).
• ISO 22196, Measurement of Antibacterial Activity on Plastics and Other non-Porous Surfaces. (based on JIS Z 2801)
• ISO 20743, Determination of Antibacterial Activity of Textile Products.
• ASTM E2149, Standard Test Method for Determining the Antimicrobial Activity of Antimicrobial Agents Under Dynamic Contact Conditions.
• ASTM E2180, Standard Test Method for Determining the Activity of Incorporated Antimicrobial Agent(s) in Polymeric or Hydrophobic Materials.
• ASTM E2315, Standard Guide for Assessment of Antimicrobial Activity Using a Time-Kill Procedure.
• ASTM E1054, Standard Test Methods for Evaluation of Inactivators of Antimicrobial Agents.
• ASTM E1326 Standard Guide for Evaluating Nonconventional Microbiological Tests Used for Enumerating Bacteri.
• JIS (Japan Industrial Standard) Z 2801, Antimicrobial products–Test for Antimicrobial Activity and Efficacy.
• EN 1276, Chemical Disinfectants Bactericidal Activity Testing.
• EN 1040, Basic Bactericidal Activity of Chemical Disinfectant. 
• ASTM E2647, Standard Test Method for Quantification of Pseudomonas aeruginosa Biofilm Grown Using Drip Flow Biofilm Reactor with Low Shear and Continuous Flow.
• ASTM E2196, Standard Test Method for Quantification of Pseudomonas aeruginosa Biofilm Grown with Medium Shear and Continuous Flow Using Rotating Disk Reactor.
• ASTM E2562, Standard Test Method for Quantification of Pseudomonas aeruginosa Biofilm Grown with High Shear and Continuous Flow using CDC Biofilm Reactor.
• Guidances and SOPs by the European Committee on Antimicrobial Susceptibility Testing (EUCAST).