Recent news reports have described the successful progress of at least one company, Varda Space Industries, in developing a space-based drug manufacturing platform and process. The FDA-related regulatory and legal questions and implications of this are intriguing. For example:  

• Will FDA need to recruit astronauts to inspect space-based manufacturing facilities? 
• What are the intellectual property opportunities and risks for space-made drugs? 
• Would a generic or biosimilar version of a space-made drug also be required to be manufactured in space?

By way of background, Varda's space-based drug manufacturing approach leverages the well-known phenomenon that crystals can be grown in much purer form and in a much more consistent fashion in micro-gravity environments. Indeed, NASA and pharmaceutical companies has been conducting protein crystal growth experiments on the International Space Station for many years, with such activities accelerating more recently.  

One of the reasons space-based drug manufacturing is so intriguing and potentially game-changing for patients and the biopharmaceutical industry, is the fact that for drug active ingredients in crystalline form (of which there are many, including blockbuster monoclonal antibody drugs such as Keytruda® (pembrolizumab)), the purity, safety, efficacy, solubility and stability (among other attributes) of the drug are dependent on the quality and consistency of the crystals. So, a drug API manufactured in space may offer significant advantages over the same API manufactured on earth. Another benefit may be that space-manufacturing of biologicals can overcome the gravity-induced effects of convection and sedimentation that make earth-bound removal of impurities much more difficult.

With a solid scientific rationale, increasingly affordable access to space, and a public health need for new (as well as improved versions of existing) drugs and biologics, it seems inevitable that space-based drug manufacturing will become a commercial reality in the very near future. The questions and challenges this will pose to FDA and the biopharmaceutical industry are complex and difficult to answer with much certainty at this time. However, below are some preliminary thoughts on the questions noted above….

FDA Inspections: An already challenging part of FDA's public health mission—cGMP inspections of drug manufacturing facilities—will be further complicated with space-based drug manufacturing. FDA routinely conducts on-site inspections of drug facilities for compliance with current Good Manufacturing Practices (cGMP) regulations, and it is intriguing (but a bit whimsical) to imagine FDA developing an astronaut corps to conduct such inspections of space-based facilities. But as a practical matter, the agency will need to rely on some method of Remote Regulatory Assessments for such purposes. However, FDA and NASA already have a Memorandum of Understanding (MOU) in place that, among other things allows the two agencies to “[d]iscuss providing technical expertise for planning, performance, or review in areas of mutual interest….” Whether or not space-based FDA inspections would be one of those “mutual interests,” in the event FDA ever does conduct an on-site inspection of a space-based facility, this author would gladly volunteer on a pro bono basis to attend such an inspection on behalf of the company! 

Patent Implications: Patents claiming various crystalline forms of APIs have been common in the pharmaceutical industry for many years, in part due to the varying clinical and physico-chemical attributes exhibited by different polymorphic forms (and mixtures of forms) of such APIs. But controversies over Orange Book listings of so-called “polymorph patents" led to FDA regulations in 2003 and 2016 governing when and how polymorph patents could be listed in the Orange Book, which in turn impacted how proposed generic versions of approved drugs are developed by sponsors and reviewed and approved by FDA. It seems plausible that space-made APIs could exhibit patentable crystalline features that could provide significant commercial and legal advantages to sponsors of new drug applications utilizing such technology.

Regulatory Impact on Generic and Biosimilar Competition. The promise of being able to create ultra-pure, or even completely novel, crystalline forms of drug APIs in space raises questions about the feasibility of developing and approving generic and biosimilar versions of such drugs. As FDA has explained in a generic drug Guidance document, 

“Polymorphic forms of a drug substance can have different chemical and physical properties, including melting point, chemical reactivity, apparent solubility, dissolution rate, optical and mechanical properties, vapor pressure and density. These properties can have a direct effect on the ability to process and/or manufacture the drug substance and the drug product, as well as on drug product stability, dissolution and bioavailability. Thus, polymorphism can affect the quality, safety and efficacy of the drug product.”

While differences in the polymorphic form of a drug API do not create a different active ingredient for purposes of FDA's generic (small molecule) drug “sameness” requirement under the Hatch-Waxman amendments, such polymorphic differences may in some cases make it difficult or impossible for a generic version to meet the bioequivalence requirement for FDA approval. Similarly, such differences may impact the biosimilarity analysis for proposed biosimilar versions of approved biologic products. The ability of an earth-bound drug company to successfully develop a bioequivalent or biosimilar version of a space-made product will likely vary on a drug-by-drug basis, but the potential may exist for APIs that simply cannot be adequately replicated anywhere but in a space-based facility. If that comes to pass, regulatory and policy changes will certainly be proposed and no doubt would be vigorously debated.