MDA Guidance on Combination Products: Incident Reporting

Table Of Contents

Incident Reporting: Key Points 

The document further highlights the key points associated with incident reporting. First of all, the authority provides a flowchart illustrating the approach to be applied. According to the flowchart, management of incidents involving combination products includes the following stages: 

1. Receipt of the information about the incident;
2. Determination of the nature of the incident in question;
3. Notifying the related agency;
4. Conducting a rigorous investigation of the case;
5. Submitting an investigation report to the respective authority;
6. Taking the actions intended to address the issue as instructed by the primary agency (if applicable);
7. Submitting a report describing the actions taken to the primary agency. 

Once the above steps are completed, the case related to the incident will be considered closed. 

In order to assist the registration holders in following the approach described hereabove, the authority provides a table containing examples of incidents and the way they should be managed. When describing the said approach, the authority pays the most attention to interactions with each of the regulating authorities responsible for constituent parts of the combination product in question. According to the guidance, depending on the nature of an incident, the notification and investigation report should be submitted to either authority or both of them. At the same time, the primary agency will be the one providing instructions to be followed and expecting a report on the completion of the respective actions by the registration holders. As described in previous articles, a primary agency should be determined based on the component of the device responsible for the primary mode of action. 

Specific Aspects 

The document further outlines certain specific considerations related to adverse events reporting including, inter alia, the following ones:

• Drug issues (other than ADR) may include quality defect/regulatory non-compliance related to safety;
• In the event where the assessment of “nature of incident” was not agreed by the primary agency, the agency will inform the company to notify the ancillary agency and the first notification timeline will be counted for;
• In the event where the nature of incident cannot be determined, notification of incident shall be submitted to both agencies (concurrent notification). 

The Medical Device Authority (MDA), a Malaysian regulatory agency in the sphere of healthcare products, has published a guidance document dedicated to drug-medical device and medical device-drug combination products. The document provides an overview of the applicable regulatory requirements, as well as additional clarifications and recommendations to be taken into consideration by medical device manufacturers and other parties involved in order to ensure compliance thereto. At the same time, provisions of the guidance are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations. The authority also reserves the right to make changes to the guidance and recommendations provided therein, should such changes be reasonably necessary to reflect corresponding changes to the underlying regulations. 

In particular, the guidance describes different registration flows for drug-medical device and medical device-drug combination products. The document outlines specific matters related to the involvement of the two regulating authorities responsible for each of the constituent parts. The scope of the guidance covers, inter alia, the aspects related to adverse drug reactions and incident reporting. According to the guidance, in order to comply with the applicable regulatory requirements for adverse drug reaction (ADR) reporting, the parties involved should follow the approach described in the Malaysian Guideline on Good Pharmacovigilance Practices (GVP) for Product Registration Holders in its latest edition. 

Notification of Incident 

The guidance also describes in detail the way notification of incidents should be performed and outlines the applicable reporting timelines to be followed by the registration holders. According to the guidance, any and all cases resulting in harm caused to a user/patient are subject to reporting to the relevant agency, while the reporting timelines will depend on the nature of the incident and risks associated with the underlying issue. 

For events taking place in Malaysia the following reporting timeframes will apply:

• An incident related to the failure of a combination product, or issues with its labeling or instructions for use should be reported within 30 calendar days from the date the respective information was received by the responsible party;
• An incident resulting in a severe health deterioration or one that could potentially result in such consequences in case of reoccurrence should be notified to the authority within 10 calendar days from the date the responsible party became aware of it; 
• For an incident associated with a serious threat to public health, a 48-hours reporting timeframe applies. 

At the same time, the approach applicable to the events taking place abroad is slightly different, namely:

• Individual incidents are not subject to reporting on a routine basis;
• Significant safety issues impacting the benefit/risk profile of the combination product in question should be reported to the authority within 3 calendar days from the date they were identified;
• Should a combination product registered in Malaysia be subject to withdrawal or suspension of registration in any other country, the appropriate notification should be provided within 24 hours. 

Investigation Report 

Under the general rule, an investigation report should be submitted to the relevant regulating authority within 30 calendar days. Once the report is received, the primary agency may provide additional instructions and requests to be followed by the party responsible for the combination product in question. The authority would expect the registration holder to provide a follow-up report on the actions taken based on the instructions communicated by the authority. Should no feedback on the report be received from the authority within 45 calendar days from the date of its submission, such a report will be considered accepted. 

The authority also mentions that all incident notifications, as well as investigation reports, should be submitted in electronic format via email. 

In summary, the present MDA guidance describes the approach to be applied with respect to incidents associated with combination products. The document highlights the key points associated with the reporting procedures and outlines the applicable timeframes to be followed by the responsible parties. 

Sources:

MINISTRY OF HEALTH MALAYSIA -GUIDELINE FOR DRUG-MEDICAL DEVICE AND MEDICAL DEVICE-DRUG COMBINATION PRODUCTS

How Can RegDesk Help?

RegDesk is a holistic Regulatory Information Management System that provides medical device and pharma companies with regulatory intelligence for over 120 markets worldwide. It can help you prepare and publish global applications, manage standards, run change assessments, and obtain real-time alerts on regulatory changes through a centralized platform. Our clients also have access to our network of over 4000 compliance experts worldwide to obtain verification on critical questions. Global expansion has never been this simple.