The manufacture, monitoring, and marketing processes for a pharmaceutical after it is approved are as important as the steps involved in developing it and submitting for approval.
In fact, some unique issues can occur during the postapproval phase. These issues can be divided into three primary categories: chemistry, manufacturing, and control issues; regulatory issues; and business-related issues. As such, pharmaceutical executives should understand the issues involved in each category.
The implementation of chemistry, manufacturing, and control measures in the context of updated technology and analytical measures often causes issues for a pharmaceutical after it has been approved.
Some pharmaceutical companies have argued that it is easier to develop a new pharmaceutical than to keep up with existing technology. Officials at the Food and Drug Administration have long proposed that pharmaceutical companies that manage quality-by-design systems should be able to do so with less interference by the Food and Drug Administration.
Manufacturers have also wanted the Food and Drug Administration to streamline the process through the down-regulation of the reporting requirements for changes that are low risk.
The level of documentation that is required when changes are made to the chemistry, manufacturing, and control process of pharmaceuticals can also be an issue that occurs during the postapproval process.
In general, if the change is minor, the Food and Drug Administration only requires the pharmaceutical companies document it in their annual report or notify them via the Changes Being Effected process.
However, if the change is not minor pharmaceutical companies should use the Prior Approval Supplement to notify the Food and Drug Administration of the changes and then wait for the Food and Drug Administration to approve the change. However, many companies are uncertain as to which mechanism to use.
To address these issues, the Food and Drug Administration has issued a number of guidances. The most recent of these is SUPAC (Scale-Up and Post-approval Changes): Manufacturing Equipment Addendum, which provides a global set of recommendations on how to use the appropriate documentation to support changes in manufacturing.
This guidance, which combines four previous guidances, discusses how to notify the Food and Drug administration of changes to the size of the particles, the manner in which the particles are blended, mixed, or dried; granulation and dosing of medications; capsules made of soft gelatin; coating, printing, and drilling of pharmaceuticals; and the emulsification, deaeration, and transfer of pharmaceuticals.
Another postapproval issue involves the increasing number of rules, regulations, and risks that correlate with the performance of a pharmaceutical after it has been approved.
This has been attributed to the increased power of regulatory agencies and increased legislation. Although the Food and Drug Administration has been slow to enforce the regulations for postmarketing surveillance studies in the past, they have been taking measures to enforce the regulations and issue monetary penalties to companies that do not provide the appropriate data. In the European Union, the regulations have been much more rigid and must be followed through in appropriate manner.
Regulatory agencies also want to learn more about the safety of a product in populations that were not assessed in clinical trials, such as elderly populations, pediatric populations, or populations with comorbid conditions.
They also wish to ascertain the efficacy of pharmaceuticals in real-world populations. Although the Food and Drug Administration is still determining what steps are necessary to ensure safety and efficacy in a real-world scenario, the European Medicines Agency has issued pharmacovigilance guidelines to address the issue.
According to these guidelines, pharmaceutical companies are required to have a risk management plan for all new products. The agency will also require additional monitoring for certain products. In addition to clarifying the legal basis for postapproval safety studies, they also require postapproval efficacy studies.
Business-related issues can also affect the success of pharmaceutical companies after a pharmaceutical has been approved. Over the past forty years, the approval rate for a second new molecular entity has steadily decreased and only half of the companies that receive approval for a new molecular entity receive approval for a second one.
Although one factor is the time that it takes to develop a mew molecular entity, another factor is the likelihood that a company is going to be acquired. Most approval times average six to eight years; however, approximately half of the companies that have marketed a new molecular were acquired within five years of the first approval and before they achieved approval for a second molecular entity.
Within the previous ten years, slightly less than half of the companies that attained approval for a second molecular entity remained independent. The companies less likely to be acquired included those that manufactured pharmaceuticals for orphan conditions or infectious diseases.
Pharmaceutical executives can take a number of measures to ensure that they address postapproval issues appropriately. First, they can familiarize themselves with the appropriate guidances and make certain that their staff understand and comply with the requirements for reporting changes to chemistry, manufacturing, and control processes.
To avoid penalties, they can make certain that personnel in upper management understand the reporting requirements for postmarketing surveillance studies and impress the importance of submitting these data to the appropriate regulatory agencies on time. They can also recruit a team familiar with designing trials that reflect real-world scenarios.
To decrease the chances of being acquired (should you feel this is desirable), pharmaceutical executives can develop a marketing plan for the pharmaceutical while it is still being developed.
In addition to developing the chemical composition of the pharmaceutical and submitting it for approval the Food and Drug Administration or the European Medicines Agency, pharmaceutical executives should also understand the disease that the pharmaceutical is designed to treat, the population affected, the needs of that population, appropriate standards of care, access of patients to care, and the ability of patients, healthcare practitioners, and third-party payers to differentiate between their product and the competition.
They should perform market research to ascertain what the competition is, how the market has changed over time, whether patents for similar treatments are scheduled to expire, and how competitors would react to the launch of a new product. In addition to using analytics to predict the success of a product, pharmaceutical executives should use metrics to measure the success of a product before it is marketed and review the process after the product is marketed.
Then they can change their processes on the basis of their findings. They should however also not omit steps such as primary research, coordination across functions, and development of business cases in their haste to get a product onto the market.
Pharmaceutical executives should choose a marketing team whose experience and skills correlate with the type of product to be marketed and make certain that different departments work together. This team should customize their approach on the basis of the unique characteristics of the product and a strategy to manage the product throughout its lifecycle.
This may include countermeasures to address the marketing of generics, determining which formulation or method of delivery would be most profitable, determining a strategy for changing a product to an over-the-counter version, and determining a strategy for managing the product at the end of its lifecycle. They can also specialize in products that grant exclusivity or for which market approval can be accelerated, such as products designed to treat orphan conditions, products that address a specific unmet medical need, or products eligible for European Named Patient Programs or compassionate use programs.
By understanding the reporting mechanisms, regulations, and expectations of the Food and Drug Administration and other regulatory agencies and by developing an appropriate marketing plan for a product before it is approved, pharmaceutical executives can increase the chances of their product being successful after it is approved.
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