In the interests of endeavouring to align its regulatory framework with other GHTF jurisdictions, FDA will introduce a pilot program for voluntary submission of ISO13485:2003 audit reports, with an intended start date of 5 June 2012.  

On 19 March 2012, FDA released a guidance which explains exactly how the pilot program will work and the conditions that shall apply. FDA has also recently released additional information in the form of a video and slide presentation, available here.

The program is intended to allow FDA to set “risk-based inspectional priorities” based on the submitted audit reports. The reports will be used to assist FDA in deciding whether an establishment can be removed from FDA’s routine inspection work plan for one year from the last day of the ISO 13485:2003 audit. This in effect will postpone the establishment’s bi-annual inspection for that one-year period.

It should be noted that targeted inspections conducted as part of PMA applications, “for cause” inspections or follow ups to previously conducted FDA audits will continue as per usual and will not be influenced by this pilot program.

Also to be noted is that only audit reports issued by third party auditors under the regulatory system of one of the founding members of the GHTF (Australia, Canada, Europe, Japan) will be accepted by FDA. Internal audit reports will not be accepted. Reports shall only be accepted from establishments which have existing device registrations in USA and who have quality systems compliant with FDA’s Quality System Regulations (QSR - 21CFR Part 820).

In parallel to this initiative, FDA and Health Canada are also working closely to develop a single-audit program whereby one inspection can provide evidence of compliance with both FDA’s QSR requirements as well as Canada’s CMDCAS requirements. There are plans to ultimately expand this initiative to include other GHTF members.  

It is encouraging to see these cooperative schemes move forward – it is certainly a welcome idea for manufacturers that they may one day be able to roll their periodic third party quality system audits into one!

For assistance in complying with your regulatory and quality obligations in United States and other global jurisdictions, please contact us via email: enquiries@brandwoodbiomedical.com; or give our office a call on +61 2 9906 2984.

Abhi Kannan

Consultant

Brandwood Biomedical

The Chinese State Food and Drug Administration (SFDA) has cracked down hard and fast on the pharmaceutical industry in China and declared its intention to tighten post-market compliance monitoring.  

A notification issued on the 27^th April has mandated that, effective from 1^st May, all manufacturers of

• medical grade gelatin,
• drug capsules, and
• pharmaceutical products in capsule form.

must conduct batch testing for quality control of both the raw materials sourced and final products produced. 

Moreover, each kind of capsule manufactured or placed onto the Chinese market before 30^th April is to be batch tested by its manufacturer for Chromium contents. The test results have to be made publically available by 31^st May. Any products with excessive concentration of Chromium must be recalled immediately.

The trigger that has set the SFDA on its post-market vigilance enforcement warpath is a whistle-blowing news report revealing excessive Chromium levels in 13 pharmaceutical capsules. This was publicized in mid-April and attracted widespread outrage from the general public, especially since these 13 pharmaceuticals are mostly common place drugs such as Amoxicillin.

SFDA immediately took action to pull these products from the shelf. Preliminary investigations have shown the root cause is the usage of industrial-grade gelatin as raw material instead of medical grade.

Follow-on post-market vigilance actions were swift, SFDA has:

1. cancelled 5 pharmaceutical manufacturing certificates within the week (Links: 1 2 3)
2. published findings from sample testing 135 manufacturers for compliance to standard on chromium concentration
3. shut down manufacturers with non-compliant products and confiscated products distributed
4. enforced mandatory recalls and destruction of recalled products
5. initiated legal actions against manufacturers offending the Chinese regulations on Pharmaceuticals
6. mandated batch testing by manufacturers with similar products
7. published Order 97-2012  declaring SFDA will take a more active role in trending post-market reports, analyzing of pharmaceutical adverse event reports and supervising manufacturers in taking corrective actions

Although the above items are immediately pertinent for manufacturers of medical-grade gelatin/pharmaceutical/capsule in China, their effects will ripple throughout the health industry, affecting both device and pharmaceutical manufacturers alike.

It is crucial for manufacturers to maintain regulatory compliance of products they have on the market. This can often be overlooked when other activities, such as designing and introducing new products to market, take priority. However, SFDA’s actions in the past two weeks have clearly demonstrated that regulatory authorities can and will react quickly to target non-compliance by implementing severe regulatory penalties. So do NOT wait till regulatory authorities are at your door, ask yourself these questions now:

• Are you 100% sure that products at the end of your productions line are compliant to the regulation of the jurisdiction they will be supplied in?
• Have you in place a fully functioning post-market vigilance system, including ability to receive and follow up complaints and to file adverse event reports?
• When was the last time you conducted a trend analysis on post-market data?
• Do you routinely check the quality system certification from your key component(s) suppliers?

Concerned about your post-market risks? Contact us or give our office a call on +61 2 9906 2984.  We would be pleased to help.

Lucy Xiao

Associate Consultant

While the provision of electronic IFUs will be acceptable in the future, the regulation does restrict its use to professional users only. In addition to this, it may only be provided with a few select types of medical devices, which are:

1)     active implantable medical devices and their accessories,

2)     implantable medical devices and their accessories,

3)     fixed installed medical devices,

4)     medical devices and their accessories with a built-in system visually displaying the IFU, and

5)     stand-alone software.

Manufacturers intending to replace a paper IFU with an equivalent electronic one are first required to undertake a documented risk assessment. Where the risk assessment demonstrates that providing the IFU in electronic form either maintains or improves the level of safety obtained by providing the same in paper format, only then is a manufacturer allowed to provide it in the electronic format. In the risk assessment, the following components must be assessed as a minimum:

1)     knowledge and experience of the intended users in use of the device as well as use of hardware and software to display         the IFU,

2)     characteristics of the environment in which the device is used,

3)     access to reasonable electronic resources to view the IFU by the user,

4)     protective safeguards from IFU data tampering,

5)     safety and back-up mechanisms in the event of either hardware or software failure,

6)     foreseeable medical emergency situations requiring the provision of information in paper form,

7)     impact caused by faulty Internet or website provisions and safety measures to deal with such situations, and

8)     evaluation of time period required to deliver paper version of the IFU is requested.

In conjunction, manufacturers must provide all relevant and necessary information required to access and use the electronic IFU; and also implement a system to provide IFUs in paper format free of charge within 7 calendar days of receiving a request. Manufacturers should also note that where an IFU includes instructions for the patient, that part of the IFU shall not be provided in electronic form.

This regulation comes into effect in March 2013. While it seems to be applicable to only a niche set of medical devices, the European Union appears to have established a sure and steady step forward, towards an eco-friendly medical devices industry. 

For assistance in complying with your regulatory and quality obligations in Europe and other global jurisdictions, please contact us via email: enquiries@brandwoodbiomedical.com; or give our office a call on +61 2 9906 2984.

Best Regards,

Smitha Viswanatha

Associate Consultant

Brandwood Biomedical

On February 10^th 2012, the TGA issued a public notice providing details of civil penalties in excess of AU $3.1 million handed down to Export Corporation Pty Ltd for importing and supplying nutritional and weight-loss products not listed on the Australian Register of Therapeutic Goods (ARTG).

This case, held in the Federal Court in Canberra, demonstrates that;

1. The TGA can and will act,
2. Penalties are substantial,
3. The TGA does not need to pursue prosecution - these penalties were Civil.

The TGA published enforcement guidelines in 2006 which detail changes to the Act and provides guidance on offences and penalties applicable for contraventions of the Act in order to: ”…

• help achieve the objects of the Act and the Therapeutics Goods Regulations 1990 (the Regulations) and the Therapeutics Goods (Medical Devices) Regulations 2002;
• maximise compliance with the regulatory requirements under the Act and Regulations;
• promote the supply of safe and good quality therapeutic goods; and
• maintain public confidence in the supply, manufacture, import and export of therapeutic goods. "

In determining whether to pursue criminal or civil penalties, the TGA considers the seriousness of the contravention, whether it was a persistent or one-off offence, whether it was “careless, negligent or deliberate” or driven by commercial advantage, and whether there is risk of harm or harm has already resulted. Furthermore, it considers government and public expectations and actions which will best deter re-offenders or potential offenders.

Civil penalties do not result in a criminal conviction, but can result in substantial fines for organisations that are found to be in contravention of the Act.

For assistance in complying with your regulatory and quality obligations in Australia, NZ and other global jurisdictions, please contact us via email: enquiries@brandwoodbiomedical.com; or give our office a call on +61 2 9906 2984.

Best Regards,

Gemma de Plater

Consultant

Brandwood Biomedical

The Taiwan Food and Drug Administration (TFDA) are responsible for the pre-market approvals of In Vitro Diagnostic (IVD) devices before they can be supplied commercially. Similar to regulatory requirements for Medical Devices, the safety and effectiveness for IVD devices must be validated. Depending on the classification, high risk devices must be manufactured under a certified Quality Management System.

To this end, TFDA has published the Guidance on Quality System Documentation (QSD) Requirements for IVD Devices  體外診斷試劑優良製造規範指導手冊 and the Guidance for Registration of IVD Devices  體外診斷試劑查驗登記須知 which was implemented in Dec 2010.

In addition to the above, TFDA has now made available the Guidance for Registration of IVD Devices for Home-Use家用體外診斷醫療器材查驗登記須知 .

These guidance documents are based on the US 21 CFR regulations, FDA CDRH guidance documents, European directives as well as applicable harmonised standards.

Depending on product classification, the required information includes, but not limited to:

-          Intended use and intended user

-          Theoretical basis and relevant R&D data

-          Product manuals and labelling

-          Performance evaluation by lay users (for home-use IVDs)

-          Preclinical testing

-          Quality control testing

-          Clinical Trial reports

-          GMP/QSD certification

TFDA has adopted a similar list-based classification system as the US FDA. For items on this list, Class I devices are subject to least amount of regulatory scrutiny whereas Class III devices typically require provision of detailed technical data and sometimes expert panel consultation. In spite of classification, the registration process can be simplified if the product has been registered in the US and has appropriate predicate IVD devices in Taiwan.

For innovative products that have no predicates however, TFDA have a special procedure which provides an official opinion on the applicable classification on a case-by-case basis. Products without suitable predicate devices in Taiwan may be subjected to more stringent post-market vigilance requirements, including periodical incident reporting to the TFDA. 

For more information on the regulatory pathway and optimal registration strategy in Taiwan, please contact us via email: enquiries@brandwoodbiomedical.com; or give our office a call on +61 2 9906 2984.

Best Regards,

Lucy Xiao

Associate Consultant

Brandwood Biomedical

The most common method employed by manufacturers for demonstrating conformity with the Essential Requirements is to show compliance with Harmonised Standards, as published in the Official Journal of the EU. When standards are updated to reflect changes in the ‘state-of-the-art’ and if the updated standard is accepted by the EU, a transition period will generally apply for applicability of the new standard and expiry of the old.

Europe’s Notified Body Association, NB-MED has now released a FAQ document providing guidance on issues related to the transition from 2^nd to 3^rd edition of EN 60601-1.  While Guidance and Q&A documents regarding this transition in Europe have previously been published, they have not always reflected the views and practices of Notified Bodies.

The new FAQ document released by NB-MED has been compiled by a team of experts following consultation with the industry. It attempts to address several complex questions and issues arising with the introduction of the 3rd edition of EN 60601-1 such as the requirements for legacy devices or devices already placed on the market. The FAQ confirms that legacy devices which are compliant with the 2^nd edition of the standard that require replacement after the transition period (after 1 June 2012) will need to comply with the 3^rd edition when reintroduced to the market. This will generally mean that repaired devices will require additional testing and possibly redesign to ensure compliance with the 3^rd edition before returned to customers.  

The FAQ document notes that an Amendment to the 3rd edition is already on the way, with an expected IEC publication date of September 2012. The committee states that compliance with the anticipated Amended 3rd edition before it is recognised as a harmonised standard will not be acceptable to claim presumption of conformity with the Essential Principles. However, once recognised, a transition period of 3 years can be expected to apply, in which time the manufacturer must ensure that their device is retested according to Ed 3, Amendment 1. An assessment through gap analysis and risk management alone is not considered sufficient, as the Amendment is expected to lead to a “‘new’ generation of the EN 60601-1 series”; hence retesting to the amended standard will be required. 

The FAQ document also includes detailed explanation of how the 3rd edition will affect x-ray device manufacturers, with specific information on the application of the various parts of the standard series for different categories of x-ray equipment.

Click here to view the FAQ document in full.

Health Canada will also cease to recognise the 2^nd edition of the 60601-1 from 1 June 2012, while US FDA has set a mandatory transition date of 1 June 2013. Although FDA has already recognised the 3^rd edition, it should be noted that OSHA (the US Department of Labor OS&H Administration) is yet to publish acceptance of the updated standard. If OSHA does not adopt the new standard by FDA’s transition date of 1 June 2013, manufacturers seeking NRTL approval for their medical device will need to demonstrate compliance with the 3^rd edition to satisfy FDA, while also demonstrating compliance with the 2^nd edition to gain NRTL approval.

Need advice on compliance of your medical electrical equipment? Contact us for assistance. 

Best Regards,                                                                                                                                        

Abhi Kannan                                                                                                                              

Consultant, Brandwood Biomedical

The agreement involves raising user fees to $595 million US dollars over 5 years.  This fee increase is in return for several performance goals at the FDA such as reviewing a certain percentage of pre-market applications within set time-frames and the expansion of pre-review discussions with industry.

While a doubling in pre-market review user fees may sound excessive, the real costs in the 510(k) process are in the testing and effort required to prepare the submission and the time cost in the review.  An estimate from Josh Makower indicated the costs of getting to a 510(k) as up to $24 million!  While most device developments will be much less than this, the investment to get to that point is certainly significant and the 510(k) fees (currently $4,049 US dollars) are trivial in comparison.   If the FDA raise brings genuinely faster and better FDA process, then it’s well worth it in smoother and faster time-to-market.

The manufacturer must also play their part.  You need to put yourself in the reviewer’s shoes.  Your submission needs to anticipate the reviewer’s concerns and questions, and explicitly answer them.  Clairvoyance?  No – just good planning and strategy and understanding of technical and regulatory risks during the product development and submission preparation phases. 

If you are involved with medical devices and require any form of regulatory or quality assistance, please feel free to contact us http://www.brandwoodbiomedical.com.au/contact-us/