Measuring Progress of Regulatory Convergence and Cooperation Among Asia–Pacific Economic Cooperation (APEC) Member Economies in the Context of the COVID-19 Pandemic

Purpose Regulatory convergence and cooperation among medical product regulatory authorities are essential to delivering safe and efficacious products quickly to patients. The COVID-19 pandemic highlights the urgent need for streamlined regulatory approval processes—which can be achieved in part through regulatory convergence and cooperation—both to accelerate availability of COVID-19 vaccines, treatments and diagnostics and to maintain the availability of the existing medical products unrelated to COVID-19. Methods The Asia–Pacific Economic Cooperation (APEC) Life Sciences Innovation Forum (LSIF) established the Regulatory Harmonization Steering Committee (RHSC) in 2008 to advance regulatory convergence among APEC’s 21 member economies. Key performance indicators (KPIs) were developed in 2018 to measure convergence. Results This paper reports survey results collected from KPI tracking in March 2020 from medical product regulatory authorities in all 21 APEC economies concerning areas of regulatory practice in which they could converge and cooperate. For example, from 2008 to 2020, there was a 14.3% increase in the number of APEC member economy regulatory authorities sharing Good Manufacturing Practices (GMP) Certificates and a 28% increase in the number of regulatory authorities accepting multisite licenses in that same period. In addition, this paper explores how APEC economies could realize a maximum level of regulatory convergence and cooperation. Conclusions Convergence efforts within APEC can accelerate availability of medical products including that related to COVID-19 vaccines, treatments and diagnostics, while maintaining the availability of the existing medical products unrelated to COVID-19 vaccines and treatment. New KPIs and capability building are to be considered to enable a new era of innovation ushered in by COVID-19.

A Survey of the Regulatory Requirements for the Waiver of In Vivo Bioequivalence Studies of Generic Products in Certain Dosage Forms by Participating Regulators and Organisations of the International Pharmaceutical Regulators Programme

The requirements to waive in vivo bioequivalence studies for immediate release solid oral dosage forms based on the Biopharmaceutics Classifications System (BCS) are well known, and biowaivers[1] for other types of oral dosage forms based on pre-defined criteria may also be acceptable. Similarly, biowaivers for dosage forms such as injectable products may also be allowed if certain criteria are met. The current paper summarises the biowaiver requirements for oral solutions and suspensions, soft gelatin capsules and injectable products (intravenous injections, subcutaneous and intramuscular injections, emulsions for injection and micellar solutions for injection) among the participants of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP). A review of the requirements indicated that there was a trend towards convergence when the dosage form became less complex; however, the most common approach used by each of the jurisdictions was a case-by-case approach given that most jurisdictions do not have well defined guidelines to support all possible scenarios. Even in the simplest case of intravenous solutions, the acceptability of qualitative changes in excipients differ between the IPRP members. Notwithstanding the differences, the dissemination of the information is a first step towards regulatory convergence regarding biowaivers for certain dosage forms and should be useful for pharmaceutical companies currently developing generic medicinal products for IPRP jurisdictions.

The “New” Economics of Trade Agreements: From Trade Liberalization to Regulatory Convergence?

What incentives do governments have to negotiate trade agreements that constrain their domestic regulatory policies? We study a model in which firms design products to appeal to local consumer tastes, but their fixed costs increase with the difference between versions of their product destined for different markets. In this setting, firms' profit‐maximizing choices of product attributes are globally optimal in the absence of consumption externalities, but national governments have unilateral incentives to invoke regulatory protectionism to induce firm delocation. An efficient trade agreement requires commitments not to engage in such opportunistic behavior. A rule requiring mutual recognition of standards can be used to achieve efficiency, but one that requires only national treatment falls short. When product attributes confer local consumption externalities, an efficient trade agreement must coordinate the fine details of countries' regulatory policies.

The convergence of water, electricity and gas industries: Implications for PPP design and regulation

In several countries that have privatised their utilities, power and water are separate industries regulated by sector-specific regulators. In a parallel development, desalination has become an important source of water supply in countries where there is a shortage of cheap and clean freshwater. Where the energy source is gas, the use of gas-fired power plants to supply electricity for desalination links the water, electricity and gas industries. We use the case of the financial collapse of an integrated water and power project to illustrate the problems that can arise from such convergence, and to draw lessons for firms, Public-Private Partnerships (PPPs) and regulators. A water company had successfully tendered to build a desalination plant for a water agency that would deliver an agreed volume of water per day for a 25-year period. The technology proposed was an integrated on-site power plant to supply electricity to the desalination plant as well as to the electricity grid. The business model was for profits from electricity sales to cross-subsidise water desalination costs. However, a combination of take-or-pay LNG contracts and low spot prices in a competitive electricity market led to deep operating losses. The reasons for the collapse of the business were neither technological nor operational but arose from failure to adequately manage the market risks arising from infrastructure convergence, competition, long-term rigid contractual arrangements and missing markets. The case highlights the importance of risk assessment at bidding stage and, in particular, the risks that a cross-subsidy can create. Viewed in this context, our recommendations are for regulatory convergence for converging infrastructure sectors, multi-sector risk assessments for PPP contracts, crafting flexible PPP contracts in anticipation of future adjustments, development of more liquid hedging markets and promoting competition where feasible in infrastructure sectors.

Quality standards for biopharmaceuticals: the importance of good manufacturing practice

Regulatory standards for rDNA derived medicinal products put in place over 40 years ago provided a framework for moving forward with novel biotechnologies and biosimilars leading to their success as highly effective medicines. As biologicals and biosimilars are increasingly developed, licensed and used worldwide less experienced manufacturers and regulatory agencies need support in dealing with these highly complex products. This Commentary highlights the need for regulatory convergence and support, notes the critical role of GMP and draws attention to the comprehensive review by Sia Chong Hock et al. which strongly advocates improving harmonization of regulatory efforts especially in the Association of South East Asian Nations (ASEAN).

Concordance of Early and Late End Points for Community-acquired Bacterial Pneumonia Trials

Background While there are ongoing regulatory convergence efforts, differences remain in primary end points recommended for community-acquired bacterial pneumonia (CABP) trials. The US Food and Drug Administration (FDA) recommends assessing CABP symptom resolution at an early time point (3–5 days after randomization). Other regulatory agencies recommend assessing overall clinical response at a later time point (5–10 days after therapy ends). Methods We analyzed participant-level data from 6 recent CABP trials submitted to the FDA (n = 4645 participants) to evaluate concordance between early and late end-point outcomes. We used multivariate logistic regression to identify factors associated with discordance. Results Early and late end-point outcomes were concordant for 85.6% of participants. The proportions of early end-point responders that ultimately failed and early end-point nonresponders that ultimately succeeded were similar (6.0% vs 8.4%, respectively). Early end-point response was highly predictive of late end-point success (positive predictive value, 92.9%). Multivariate logistic regression identified early end-point responders/late end-point failures as less likely to be obese and more likely to be infected with Chlamydophila pneumoniae or Staphylococcus aureus, have received antibacterial drug therapy prior to randomization, and have severe chest pain at baseline. The most common investigator-provided reasons for failure among early end-point responders/late end-point failures were receipt of nonstudy antibacterial drug therapy and loss to follow-up. Conclusions Early and late end-point outcomes were highly concordant. These data may be useful in the continuing efforts to reach international regulatory convergence on CABP clinical trial design recommendations.