Q: What do you identify as the greatest advances that have been achieved in recent years with respect to harmonization of pharmaceutical regulations?

Regulatory Harmonization

Joseph Payne,
Vice President, Regulatory Affairs & Compliance, Alcami

A: One of the more significant advances for the industry was the Mutual Recognition Agreement (MRA) between the FDA and the EU. That agreement allowed FDA and EU inspectors to utilize inspection reports and additional information generated by the other party. To accept an EU member country into the MRA, the FDA conducted a capability assessment of that country’s inspectorate. In September 2015, three FDA district offices were visited by EU officials to assess the FDA’s capabilities. As of July 11 2019, all 28 member countries have been deemed capable inspectorates and have entered into the MRA.

The MRA will undoubtedly lead to greater efficiencies for both regulatory agencies through information exchange and coordination of inspections. The agencies will be able to focus on inspecting organizations that present a higher risk to public health. While both authorities can inspect an organization at any time, the anticipated benefit to industry includes a reduction in duplicate inspections. We have already noticed several differences in our multinational on-site inspections and pre-inspection activities. This is a welcome change, and we look forward to the continuing progress in mutual recognition between the regulators governing the pharmaceutical space.

Filippo Petti,
Chief Executive Officer, Celyad

A: As a Belgian biotech company running global clinical trials advancing treatments intended to reach multiple major world markets, synchronizing regulatory bodies, including the U.S. Food and Drug Administration (FDA), the EMA and Belgium’s Federal Agency for Medicines and Health Products (FAMHP), is of the utmost importance to our business. A major advancement in recent years is increased harmonization between these agencies, especially on rapid regulatory approval of production and process updates with therapies tested globally.

A good example of such harmonization is the simultaneous approval by both the FDA and FAMHP to use our new proprietary OptimAb manufacturing process for our NKG2D-based CAR-T cell therapies CYAD-01 and CYAD-02. This dual approval allows smooth transition of this innovation from the laboratory to the clinic to ensure that we offer the most advanced solution to patients involved in our clinical trials worldwide. Synchronizing global regulators ultimately benefits the patient by allowing innovative companies to provide clinical trial sites around the world with the most up-to-date products.

Robert Nass,
Head of Quality & Regulatory Management, MilliporeSigma

A: MilliporeSigma welcomes the harmonization of regulations, which makes it easier to operate as a global life science business. On the other hand, we still see different local interpretations of global regulations, which can make things more complicated for our worldwide supply chain.

A few examples of harmonization that we recognize as great achievements:

  • Mutual recognition agreement between the European Union and the United States for medicines, now fully operational for human medicines as of 11 July 2019, following a transition phase. This will reduce the amount of inspections as it allows the authorities to rely on each other’s GMP system.

  • Medical Device Single Audit Program (MDSAP): Authorities participating in the program are the World Health Organization, the U.S. FDA and authorities from Australia, Brazil, Canada, Japan and the EU. It allows a MDSAP-recognized auditing organization to conduct a single regulatory audit of a medical device manufacturer, satisfying the requirements of the regulatory authorities participating in the program.

  • EXCiPACT™ Certification: This certification was developed in partnership with the International Pharmaceutical Excipients Council, with input coming from academic fields, industry and the U.S. FDA. MilliporeSigma played a vital role in shaping this program to define and standardize GMPs and good distribution practice (GDP) for excipients. EXCiPACT™ certification grants an independent, one-stop ”seal of approval” by third-party auditors. With EXCiPACT™ certification, a single audit will be all it takes to prove that an excipient complies with current GMP and GDP requirements. This certification for manufacturers, suppliers and distributors of pharmaceutical excipients minimizes risks to customers and helps to reduce the burden of audits and thus costs.

  • REACH (registration, evaluation, authorization and restriction of chemicals) in the EU is one of the most advanced regulations of the world, which recently reached a milestone with wave 3. This regulation provides a standard regulatory framework for Europe, which will lead the way for further global regulations.

  • PIC/S: The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme are two international instruments between countries and pharmaceutical inspection authorities. This non-binding, informal cooperative arrangement between regulatory authorities in the GMP field of medicinal products for human or veterinary use is open to any authority having a comparable GMP inspection system. Currently, there are 52 active state members.
Alex Ovadia,
Chief Executive Officer, Check-Cap

A: International agencies, such as the World Health Organization (WHO) or the International Organization for Standardization (ISO), have developed important initiatives over the years to advance global harmonized medical device regulations. The ISO has published a set of voluntary international standards, extensively adopted both at regional and national levels, in relation to product development, manufacturing, quality assurance and control to provide the different governments with a technical base for health, safety and environmental requirements. The WHO has similarly published international guides to help member states develop internationally compatible regulations. At Check-Cap, we are constantly monitoring and adopting these initiatives and guidelines to ensure that our product is being held to the highest standards in terms of patient safety, product quality and global compliance and to ensure that patients from multiple countries can access and benefit from our C-Scan technology.

Christian Krautkramer,
Senior Counsel & Head of Ethics and Compliance for Life Sciences, GE Healthcare

A: Our ability to leverage data and work done in one jurisdiction to support regulatory approval in another and to bring lifesaving biotherapeutics to market faster is certainly a big step forward. Regulatory agencies worldwide seem to use technology to enhance speed in moving drugs from application to approval. They also seem to be more receptive than ever to industry input, especially where they have a lack of internal expertise, such as new regulations around use of artificial intelligence as either a manufacturing or clinical enhancement. Hopefully, regulators will continue this momentum of cross-agency collaboration.

Claudia Stampfli,
Head of Global GMP Compliance, Lonza

A: I consider the recent full implementation of the mutual recognition agreement (MRA) between the European Union and the United States as a very positive development. This covers inspections of manufacturing sites for certain human medicines (e.g., APIs, pharmaceuticals in various dosage forms, biotechnology-derived biological products) in their respective territories. From an industry perspective, we expect a reduction in the number of regulatory inspections with the same scope, which allows us to free up resources for continuous improvement activities. The impact will primarily be in the area of surveillance and general GMP inspections, and we hope the MRA work will continue to include additional inspection types (i.e., application-related inspections) and additional product categories (e.g., ATMPs (advanced therapy medicinal products)) in the near future.

Anders Rabbe,
Chief Executive Officer, Isofol Medical

A: For our ongoing phase III clinical trial, we are having all manufacturing of drug candidate arfolitixorin completed by Recipharm, a major European contract manufacturer of pharmaceuticals. The drug product is then shipped to our distributor with several storage facilitates to ensure that all active trial sites have arfolitixorin throughout the phase III trial. It may sound simple, but one of the most impactful recent advances with respect to harmonization of pharmaceutical regulations for shipping, import/export and customs has been the digital revolution. Having the ability to schedule, register and log shipments of arfolitixorin electronically with the required officials has significantly reduced small errors that could otherwise delay the process. We look forward to integrating digital communications and electronic records to further improve these coordinated activities.

Matthew Lawrence,
Chief Executive Officer and Chief Scientific Officer, RxGen

A: The progressive harmonization of animal welfare standards and regulatory definitions of good laboratory practices (GLP) have been key to RxGen’s ability to grow and thrive in this era of rapid biomedical advances and strong stakeholder interests in research quality. With the combination of standards into a global set of practices, specific local political/regulatory jurisdictions carry reduced importance, streamlining the creation and operation within broadly applicable standard operating procedures and setting the stage for greater scientific reproducibility and animal welfare.

Daniel G. Lachapelle,
PE, Regional Leader, CRB

A: Speed and ease of communication have resulted in real global participation. Formal and informal groups are easily developed across the industry to facilitate open communication and knowledge sharing. Communication tools are readily available to enable this participation, and the result is real harmonization of pharmaceutical regulations. Scientific consensus on innovative advancements can be reached quicker due to the ability to easily communicate on a global scale and the willingness of regulatory and industry experts to openly share information. Harmonized guidelines are more readily adopted when the community has the opportunity to participate during the development of technical documents.

Veda K. Walcott,
Vice President, Global Regulatory Affairs & Compliance, Catalent

A: The harmonization of Module 3 – CMC sections by the International Council on Harmonization (ICH), has allowed a global submission approach that reduces regional submission variations, reduces regulatory authoring timelines and reduces post-market life cycle management activities. The implementation of the electronic common technical document (eCTD) is also a great achievement, as electronic submissions decrease authoring, review and publication time. The ICH and global Ministry of Health agencies are continuing to build Quality-by-Design principles to allow the identification of established conditions and continue to reduce the impact of post-market life cycle changes. These harmonization activities contribute to the pharmaceutical manufacturer’s ability to continue to meet global demand throughout the product life cycle.

Elad Kedar,
Chief Executive Officer, Orasis Pharmaceuticals

A: The harmonization of pharmaceutical regulations has become increasingly important to bring together the pharmaceutical industry and regulatory authorities. It is essential that biopharma professionals between nations can share reliable information with one another for the timely advancement of life-changing technology. For example, the development of our phase IIa and phase IIb trials was made possible through harmonization of clinical trial regulations. In our phase IIa trials, we tested our CSF-1 eye drop on more than 70 individuals, mainly in Israel. This is a multi-center, double-masked trial enrolling 150 participants with presbyopia to evaluate the efficacy and safety of CSF-1. The harmonization of pharmaceutical regulations has made it possible to efficiently transition our studies from Israel to the United States. Additionally, Orasis was granted an accelerated FDA approval process thanks to prior established global research and clinical experience of ingredients in our eye drop. Our regulatory pathway is a 505(B)(2) abbreviated pathway, allowing us faster access to the market without compromising safety. The harmonization of research from scientists and clinicians across the globe has helped fast-track the development of our product for people living with presbyopia.

Read Part 1: Global Compliance