10 Practical Regulatory Questions to Ask During a Marketing Authorization Transfer Process

Pharma mergers and acquisitions have been on the rise in recent years, particularly as large pharmaceutical companies look for new sources of revenue to replace blockbuster drugs in view of the shift toward more specialized and precision treatments. In 2019, the pharmaceutical industry saw a record-breaking 1,276 merger and acquisition deals totaling $411 billion.¹ Even despite the pandemic, deals continued to close in 2020.

Mergers and acquisitions in pharma offer mutual benefits for large companies and small biotechs. The big companies rapidly expand their research and development pipelines. The emerging biotech companies gain a profitable exit strategy or the opportunity for greater brand recognition. However, with large deals come a complex Regulatory Asset Transfer process or Market Authorization Transfer (MAT) process, in which business and regulatory compliance continuity are critical considerations. During MATs, regulatory teams must weigh several operational aspects while creating a roadmap that takes them into account. Here are some key questions for regulatory teams that are necessary for planning and executing a successful MAT process.

• What are the regulatory MAT timelines in each market? Countries have specific timelines which must be considered for the overall transfer plan. For example, MAT submissions in Brazil must be completed within 180 days of the agreement execution date, and several regulated milestones must be met following approval. In addition, the acquiring company must have the capacity to conduct local quality control before releasing the product to the market which means analytical transfer to a local partner (if applicable) must be completed in timely manner.

• Do the markets require the acquiring company to have a local presence? Some countries might require the acquiring company to have a local in-country presence to act as local distributor and local regulatory agent. For instance, with the Gulf Cooperation Council (GCC), pharmaceutical companies use the services of appropriately licensed local agents and distributors to procure all necessary approvals and distribute pharmaceutical products or medical devices in the country.

• Do markets require new Marketing Authorization Holders to have official representation. These include Canada and Australia, for example, where lack of local MAH representation will prevent the product from being transferred successfully to the new MAH.

• Does the market lack local regulations? If the country the acquiring company wishes to sell in lacks local regulation, another country will need to act as the reference market. For example, some African, Asian, and Caribbean markets don’t have their own stringent safety regulations. As a result, these markets rely on the approved safety data from bigger, more robust markets such as the United Kingdom and Sweden to use as reference ensuring quality, safety, and efficacy of the products to be marketed in their territory.

• Are local product release testing or local clinical trials required? Brazil, Argentina, South Korea, and Uruguay are examples of countries that require analytical methods transfer prior to the asset transfer. Depending upon local analytical site availability, the process can take between five months to a year.
  

• Will the regulatory status of the product impact the MAT? In some cases, the asset in question for the MAT will be in the midst of a license renewal or other regulatory procedure that will need to be completed prior to the MAT, adding anywhere from a month to several years to the process.
  

• What submission documentation is required to complete the MAT? Regulatory teams should map out all of the documentation needed and how long each piece will take to finalize. Some documentation, such as regulatory forms and certifications take little time to complete, while items such as product artwork preparation and Certificates of Pharmaceutical Product can take three to five months to collect.
  

• Will product supply be available in the new markets once the MAT is complete? Product supply may need to be built up to allow market presence during the time of transition, thus necessitating a grace period for existing product sales in the seller’s livery following the transfer. It is not uncommon for acquiring companies to experience a three-to-six-month delay or more due to manufacturing schedules, capacity, or other issues such as raw materials on back order. Acquiring companies may be able to mitigate these delays by applying strong manufacturing risk management measures or resolving such issues by accessing product inventory shared between markets, such as products produced for France sold in other French-speaking countries.
  

• Which pharmacovigilance (PV) activities need to be addressed and by whom? Many pharmaceutical companies will call upon the services of a local (appropriately licensed) agent as an alternate means to procuring all necessary approvals and distributing its pharmaceutical products in the country. This is a very popular, relatively simple, method of facilitating the distribution of pharmaceutical products. Documents showing the capacity of the new holder to perform all the PV responsibilities are required.
  
  — In Europe, for instance, an updated summary of the Pharmacovigilance System of the market approval dossier, or a document identifying the qualified person responsible for Pharmacovigilance (QPPV) must be submitted as part of the transfer application package.
  
  — A comprehensive Pharmacovigilance Agreement must be prepared as soon as possible after a deal closes. Roles and responsibilities over PV matters must be clearly defined. For example, per EU and US legislation, there must be only one Global Safety Database (GSD) per active substance. Therefore, during divestment/acquisition negotiations, decision-makers must define which party will hold and maintain that database to assure compliance continuity. Decision-makers must also review individual case safety reports (ICSRs) exchange conditions, in addition to assigning responsibilities for overseeing aggregate safety report preparation review, provision of sales and clinical trial data, and off-label use data to avoid post-transaction PV issues. Failure to do so may lead to noncompliance and subsequently to regulatory action and financial impact.
  
  
• Who is in charge of the paperwork? The transfer process necessitates the transfer of all product-related documentation and data repositories, such as regulatory dossiers, databases and paper archives. Additionally, as part of the submission packages for the approval of the transfer of the holders’ rights for medical devices, pharmaceutical products, cosmetics or foods outside the U.S., companies are required to have certain documents authenticated either by apostille or by consular legalization through the embassy of the target country, such as:
  
  
• Certificate to Foreign Government (CFG)
• Certificate of Exportability (COE)
• Certificate of Pharmaceutical Product (CPP); and its
• International Organization for Standardization (ISO) certification; or
• Free Sale Certificate (CFS) to document that its products are free from defect, disease or harmful nature.

This can be a massive, time consuming and often overlooked step in the project plan of a MAT process. Moreover, for mature assets, companies have thousands of documents, many of which may be in paper format which might need to be scanned and transferred. Subsequently, documentation transfer requirements for all formats and operational aspects should be discussed at the pre-deal stage.

Having regulatory professionals at the table to ask the right questions during mergers and acquisitions can prevent an array of risks, avoid delays and ensure a successful MAT process. Bringing regulators expertise into the fold early on can help companies initiate mutually beneficial, seamless deals without unwarranted and costly challenges.

Cecile Riboud is Senior Director of Integrated Global Compliance, IQVIA.

Note

1. https://www.pharmasalmanac.com/articles/ma-fundamental-to-pharma-industry-growth#:~:text=2019%20Another%20Big%20Year,both%20deal%20value%20and%20volume.&text=Those%20deals%20added%20up%20to,that%20Dealogic%20began%20tracking%20transactions