MaRS Library Step 10: Ensure post-marketing compliance
Healthcare product development is complex. It is critical to know the general product development lifecycle so that you can follow the correct path. Knowing which pitfalls to avoid will speed your time to market. This article outlines step 10 of the 10 steps to develop a healthcare product.
Once you have received regulatory clearance or approval for your healthcare product, what’s next? Beyond marketing, advertising, pricing and reimbursement, distribution, and other activities to start selling your healthcare product, it is critical to meet the manufacturer’s regulatory obligations to ensure ongoing compliance. Some obligations exist for administrative purposes; others are specifically designed for continual monitoring of the safety, quality and efficacy/effectiveness of your product in the marketplace throughout the product lifecycle.
There are many different post-marketing obligations for the manufacturer of a healthcare product. The ones discussed below are not an exhaustive list, as requirements are specific to different products in different jurisdictions. Manufacturers should identify these requirements at the point of market approval or clearance in the relevant jurisdiction(s).
- Post-market surveillance, post-approval studies or post-marketing commitments: These are studies and/or clinical trials which, at the time the licence is issued, the manufacturer commits to conduct. The intention of these studies is to gather additional information about a product’s safety, efficacy or optimal use. The product label may be amended depending on the results collected from these studies.1
- Safety reporting for drugs, biologics and medical devices: Reports onreportable adverse events (for example, death, life-threatening events) must be submitted to the appropriate regulatory agencies, in compliance with the mandatory timeline, for the ongoing evaluation of product safety. Sometimes the new safety information collected may lead to changes in product labelling or even the withdrawal of the product from the market. Other reporting requirements may include the submission of periodic reports on safety (for example, Periodic Safety Update Reports for drugs & biologics).2,3
- Establishment registration and product listing: Depending on the jurisdiction issuing the approval, local and foreign-based companies (“establishments”) that are involved in the manufacturing, packaging, labelling and testing of the drug, drug components or medical devices may be required to register their names and addresses with the local regulatory agency. Registrants may also be required to list their products.4
- Licensing requirements―environmental protection: Sites that handle chemicals or engage in operations that are potentially dangerous to the environment must register with the relevant environmental protection agencies. These sites are subject to inspection to ensure that adequate controls, containment measures and emergency response procedures are in place to prevent damage to the environment.5
- Inspections: On-site inspections will be carried out by the regulatory authorities or third parties to ensure compliance with Good Manufacturing Practice(GMP) or ISO 13485 standards. These may be scheduled or unannounced. Manufacturers must ensure continuing compliance with appropriate quality standards.For manufacturers who have products registered in foreign countries, note that the frequency of inspections by foreign regulatory authorities has been greatly reduced by the establishment of mutual recognition agreements wherein the parties accept the validity of their respective GMP inspection regimes.5
- Product licence renewal: Different products may be subject to a licence renewal process and this varies across jurisdictions. For instance, in Canada, a manufacturer holding a class II, III or IV medical device licence is required to confirm annually their intention to renew their licence by submitting a renewal form to Health Canada.6 In the EU, a marketing authorization for a medicinal product is valid for five years and it can be renewed by submitting a renewal application.7
- Changes to approved products: Changes to approved products should be evaluated to assess their impact on product quality, safety and efficacy/effectiveness. These changes should be documented properly (for example, through the company’s change-control process). Depending on the degree of impact, some changes may simply need the company to document the change being evaluated, some can be initiated after notifying the appropriate regulatory agencies, and some will require regulatory approval prior to implementation. Different mechanisms exist in different jurisdictions for reporting these changes and these can vary from an annual report to an amendment/variation application to a new licence application.8 Manufacturers should consult the guidance documents specific to the jurisdiction in order to follow the proper compliance procedures.
Did you know?
In the US, establishment registration for a drug or medical device is an administrative exercise resulting in the issuance of an Establishment Registration Number and a product listing code. However, such registration means that the site is included in the FDA database and that your establishment is subject to FDA inspection.5
Read the first step: Step 1: Classify your healthcare product
The information presented in these articles is intended to outline the general processes, principles and concepts of the healthcare product development lifecycle. Since regulatory requirements are ever-changing, it is current only as of the date of publication and not intended to provide detailed instructions for product development. Every healthcare product is unique and therefore so is its associated product development lifecycle. Specific advice should be sought from a qualified healthcare or other appropriate professional.
Published: October 17, 2012
- U.S. Food and Drug Administration. (2012, August 27). Post-Approval Studies (PAS) – Frequently Asked Questions (FAQ). Retrieved September 19, 2012, from http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/PostApprovaStudies/ucm135263.htm.
- International Conference on Harmonisation. (2003, November 12). ICH E2D: Post-approval safety data management: Definitions and standards for expedited reporting. Retrieved September 19, 2012, from http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E2D/Step4/E2D_Guideline.pdf.
- International Conference on Harmonisation. (2005, November). ICH E2C(R1): Clinical safety data management: Periodic safety update reports for marketed drugs. Retrieved September 19, 2012, from http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002780.pdf.
- U.S. Food and Drug Administration. (2012, September 10). Device registration and listing. Retrieved September 19, 2012, from http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/RegistrationandListing/default.htm.
- Tobin, J.J. & Walsh, G. (2008). Chapter 12. Oversight and vigilance. In Medical product regulatory affairs. Pharmaceuticals, diagnostics, medical devices. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA.
- Health Canada. (2012, April 1). Guidance Document – Medical Device Licence Renewal and Fees for the Right to Sell Licensed Medical Devices. Retrieved September 21, 2012, from http://www.hc-sc.gc.ca/dhp-mps/md-im/applic-demande/guide-ld/md_licren_mm_homren-eng.php.
- European Medicines Agency. Q&A: Renewals. Retrieved October 1, 2012, from http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000038.jsp&mid=WC0b01ac0580023e7c.
- Tobin, J.J. & Walsh, G. (2008). Chapter 8. Variations to the drug authorisation process. In Medical product regulatory affairs. Pharmaceuticals, diagnostics, medical devices. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA.